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Matches in Ghent University Academic Bibliography for { ?s <http://schema.org/abstract> ?o. }

• 01GMDBNZQQGFYESWN9DE4J51T2 abstract "The research study presented in this paper concerns an experimental electricity-powered apparatus for applying fire-like heat flux to bench-scale samples. It consists of various elements, of which the most important are ceramic heating pads used to impose a defined heat flux on the exposed side of the sample mounted in a steel holder. The test method allows to control the heating pads’ temperature as well as to adjust the distance between the heating pads and the specimen to obtain heat fluxes up to 150 kW/m2. The thickness of the convective boundary layer at the heating pads’ surface is estimated to be around 3 cm, significantly lower than in case of gas-fired radiant panels. The performance of the apparatus was analysed in a case study on soda-lime-silica glass specimen. Experimental results were compared to numerical modelling. This analysis showed that a thermal exposure compared to the ISO 834 fire curve can be imposed on the exposed side of the specimen. There are many research possibilities for future applications of the presented experimental methodology: among others, tests with bigger specimens with heating pads surface up to 1.34 m2, and tests in controlled atmosphere.".
• 01GMDD1V9CATQCS4J4CNJJ2W3Z abstract "A measurement setup is designed and constructed to experimentally investigate the thermohydraulic performance of a novel direct rotor cooling method for an interior permanent magnet synchronous machine, where oil is pumped through weight saving channels of the rotor iron close to the magnets. The setup consist of a stationary rotor assembly where heat is dissipated in an aluminum sleeve surrounding the rotor outer surface. Measurements are performed for different oil inlet temperatures, flow rates and heat losses. It is shown that tangential temperature variations can be neglected and axial variations are as expected. The conductive resistance within the rotor assembly is similar for each measurement point as the differences are within the measurement uncertainty. The convective resistance decreases with an increasing flow rate, inlet temperature and heat dissipation. From correlations in scientific literature, it is expected that the convective resistance will further reduce with increasing rotational speed of the rotor. A comparison of these results to a standard hollow shaft cooling method shows a great potential of the novel direct rotor cooling method to further increase the power density of electric machines.".
• 01GMDD9HXVA31JQA3DPWM8DK8A abstract "Purpose There has been a growing interest in the environmental trade-off between renovation and reconstruction. Life cycle assessment (LCA) is a widely recognized method to quantify environmental impacts of buildings. However, the existing standards do not provide guidelines for defining the reference system period (RSP) and system boundaries (SB) to allow for a fair, robust, and consistent comparison of renovation and reconstruction. Hence, this research establishes guidelines for defining the RSP and SB. Methods From literature, existing approaches are gathered for defining the RSP when comparing buildings with different service lives and for defining the SB when an existing building is the starting point of an assessment. Eight criteria are then elaborated for defining the RSP and SB. For example, the RSP approach should differentiate between buildings from different construction periods, and the SB approach should be robust for time-related uncertainties. Therefore, the building's and building materials' service lives and replacement rates are varied; the standard deviation (sigma) between the results then determines the robustness. Subsequently, the extent to which the approaches meet the predefined criteria is assessed. Finally, guidelines are established for defining the RSP and SB when comparing renovation with reconstruction. Results and discussion Three RSP approaches are selected: the RSP is equal to (i) the RSP of new building, (ii) the difference between the total service life of the building (TSLB) and the building age, or (iii) a service life extension. Furthermore, three SB approaches are selected: (i) the environmental impact is considered at the moment of production, (ii) the moment of occurrence, or (iii) equally divided over different life cycles. As none of the SB approaches meet all predefined criteria, three partial allocation approaches are conceived based on a linear, concave, and convex model. The concave model gives the most robust results (sigma= 0.11), but is less consistent with the reality of emissions. The convex model is, in contrast, most consistent with the reality of emissions, but is less robust (sigma= 0.16-0.19). Conclusions Based on the literature review and results, the authors recommend to define the RSP based on the difference between the TSLB and the building age for comparing renovation with reconstruction. For defining the SB in case of building materials that are retained over multiple life cycles, it is recommended to include the impact through a convex partial allocation model to compare the environmental impact of renovation and reconstruction in a robust and consistent way.".
• 01GMDF9ZQPACV43Z84SNJTSNVG abstract "Background: This paper aimed to evaluate the effects of iliotibial band (ITB) activation and gastrocnemius activation on knee kinematics and stability. A quantitative analysis needs to determine the effect of ITB and gastrocnemius activation in each of the six degrees of freedom of the knee joint. Methods: Four cadaveric knee specimens were tested during squat motions with physiological loads. The quadriceps and hamstring muscles were activated in each situation. The ITB was intermittently activated using an actuator and a cable pulley system. The gastrocnemius was activated anatomically as part of the triceps surae complex together with the soleus and the plantaris muscle. During the squat motion, the Achilles tendon has increased tension which induced muscle activation in the calf muscles thus creating the activated situation. Results: Introduction of the ITB resulted in a reduced laxity width during extension and an external tibial rotation (2.4 degrees). The femur shifted less posterior in the lateral compartment when the ITB was activated. Activation of gastrocnemius as part of the calf muscles led to an increased laxity width. Conclusions: Knee stability and knee joint kinematics are affected significantly by the activation of the ITB and the gastrocnemius as part of the triceps surae complex. This points to the importance of muscles and stabilizing tissue structures such as the ITB in the evaluation of knee joint kinematics both in vitro and in vivo. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).".
• 01GMDG35GYA1TFQ7T899GN12QX abstract "β-carotene is a carotenoid with provitamin A activity and other health benefits, which needs to become bioavailable upon oral intake to exert its biological activity. A better understanding of its behaviour and stability in the gastrointestinal tract and means to increase its bioavailability are highly needed. Using an in vitro gastrointestinal digestion method coupled to an intestinal cell model, we explored the stability, gastrointestinal bioaccessibility and cellular uptake of β-carotene from microparticles containing carotenoid extracts derived from mango by-products. Three types of microparticles were tested: one with the carotenoid extract as such, one with added inulin and one with added fructooligosaccharides. Overall, β-carotene was relatively stable during the in vitro digestion, as total recoveries were above 68 %. Prebiotics in the encapsulating material, especially inulin, enhanced the bioaccessibility of β-carotene almost 2-fold compared to microparticles without prebiotics. Likewise, β-carotene bioaccessibility increased proportionally with bile salt concentrations during digestion. Yet, a bile salts level above 10 mM did not contribute markedly to β-carotene bioaccessibility of prebiotic containing microparticles. Cellular uptake experiments with non-filtered gastrointestinal digests yielded higher absolute levels of β-carotene taken up in the epithelial cells as compared to uptake assays with filtered digests. However, the proportional uptake of β-carotene was higher for filtered digests (24 – 31 %) than for non-filtered digests (2 – 8 %). Matrix-dependent carotenoid uptake was only visible in the unfiltered medium, thereby pointing to possible other cellular transport mechanisms of non-micellarized carotenoids, besides the concentration effect. Regardless of a filtration step, inulin-amended microparticles consistently resulted in a higher β-carotene uptake than regular microparticles or FOS-amended microparticles. In conclusion, encapsulation of carotenoid extracts from mango by-products displayed chemical stability and release of a bioaccessible β-carotene fraction upon gastrointestinal digestion. This indicates the potential of the microparticles to be incorporated into functional foods with provitamin A activity.".
• 01GMDHWY886SVCH3TBTWY56YZK abstract "Feral Atlas invites you to explore the ecological worlds created when nonhuman entities become tangled up with human infrastructure projects. Seventy-nine field reports from scientists, humanists, and artists show you how to recognize “feral” ecologies, that is, ecologies that have been encouraged by human-built infrastructures, but which have developed and spread beyond human control. These infrastructural effects, Feral Atlas argues, are the Anthropocene. Playful, political, and insistently attuned to more-than-human histories, Feral Atlas does more than catalog sites of imperial and industrial ruin. Stretching conventional notions of maps and mapping, it draws on the relational potential of the digital to offer new ways of analyzing—and apprehending—the Anthropocene; while acknowledging danger, it demonstrates how in situ observation and transdisciplinary collaboration can cultivate vital forms of recognition and response to the urgent environmental challenges of our times.".
• 01GMDTXMXCWCN5Z9E5XMFCHKRH abstract "Buildings are fundamental components of urban areas and they play a vital role in supporting human activities in daily life. Understanding the actual building functions is essential for many urban applications, such as city management, urban planning, and optimization of transportation systems. Existing studies for inferring building functions are mainly based on a building's own features, and ignore its "geographic context" (e.g., the influences of nearby buildings). This paper introduces a novel geo-aware neural network to infer the functions of individual buildings. To this end, the proposed model integrates information about the built environment and human ac-tivity of a target building and its "geographic context". The model further includes a geo-aware position embedding generator and transformer encoders to better capture the complex relationships between buildings. The evaluation results demonstrate that the proposed model outperforms all baselines and achieves a classifi-cation accuracy of 90.8%. Meanwhile, the proposed model works well even with a small amount of training dataset and has a good transferability to another urban area. In summary, the proposed model is an effective and reliable approach for inferring the functions of individual buildings and has high potential for city management and sustainable urban planning.".
• 01GMDW6Y1Y7A3241RYCFD0RCJ7 abstract "Paratylenchus ilicis n. sp. was found associated with holly in the Netherlands and was described based on morphology, morphometrics, rRNA and mitochondrial cox1 genes, phylogenetic relationships with other Paratylenchus species, host information and geographical distribution. This species can be morphologically diagnosed based on its light brown, slightly obese to obese females with tubercles on cuticle, lateral bands widening into an ovoid field around vulva level, stylet length of 70 mm to 100 mm, outstretched to reflexed ovary, rounded sperm-filled spermatheca, vagina opening into a thick-walled rounded space, absence of vulval flaps and vulva at 89% to 95% of body length, very short tail in all life stages, and a characteristic finger-like tail tip in juveniles (J2). The new species is morphologically closest to Cacopaurus pestis but differs based on the absence of a scutellum-like differentiation in the lateral field, the ovaries that can be outstretched or reflexed, and the finger-like tail tip in J2. Furthermore, both species were found to be molecularly distant from one another, found in different habitats, and are associated with different hosts. The high morphological similarity between Cacopaurus and Paratylenchus and our phylogenetic analyses, revealing that the former is embedded within different Paratylenchus clades and thus polyphyletic, provide new evidences for the synonymization of Cacopaurus with Paratylenchus.".
• 01GMDWEE3D0TKND78CS1MCGYD2 abstract "The root-lesion nematode, Pratylenchus thornei, and the crown rot fungus, Fusarium culmorum, cause tremendous damage to a wide range of grain crops, resulting in significant economic losses in the global yield production. The presence of both pathogens simultaneously in cereal fields puts more pressure on breeding programs, restricting new resistant cultivars to express their potential. This study investigated 150 spring wheat lines of the 18KASIB-CORE nursery for their host suitability to P. thornei and F. culmorum, inoculated singly or in combination. Forty-eight lines were resistant to P. thornei, while 16 lines were moderately resistant to F. culmorum. Among these, nine lines maintained their resistance reaction against the complex disease involving both pathogens, while only four lines provided resistance against individual and combined infestations. Infestation scenarios of both pathogens were monitored for each resistant variety and predicted using both reproduction factor and disease index. Pratylenchus thornei downgraded all resistant lines to F. culmorum, facilitating infestation and making their severity more pronounced (169% cumulative damage) with a negative impact on yield performance. These findings are useful for improving nematode x fungus resistance in wheat and selecting promising germplasm for breeding purposes against both diseases.".
• 01GMDWYYM4575QDHYA0E5YJCHR abstract "Potato cyst nematodes (PCNs), the umbrella term for Globodera rostochiensis and G. pallida, coevolved with their Solanaceous hosts in the Andean Mountain region. From there, PCN proliferated worldwide to virtually all potato production areas. PCN is a major factor limiting the potato production in Indonesia. In our survey, only G. rostochiensis was found. Fourteen field populations were collected on Java and Sumatra, and unique variants were called by mapping resequencing data on a G. rostochiensis reference genome. A phylogenetic tree based on 1.4 million unique variants showed a genotypic separation between the outgroup, a Scottish Ro1 population, and all Indonesian populations. This separation was comparable in size with the genotypic distinction between the Javanese and the Sumatran PCN populations. Next, variants within PCN effector gene families SPRYSEC, 1106, 4D06, and venom allergen-like protein (VAL) that all interfere with the host innate immune system were compared. Distinct selective pressures acted on these effector families; while SPRYSECs (4,341 single-nucleotide polymorphisms [SNPs]/insertions or deletions of bases [indels]) behaved like neutral genes, the phylogenetic trees of 1106, 4D06, and VAL proteins (235, 790, and 150 SNPs/indels, respectively) showed deviating topologies. Our data suggest that PCN was introduced on Java not too long after the introduction of potato in the middle of the eighteenth century. Soon thereafter, the pathogen established on Sumatra and started to diversify independently. This scenario was corroborated by diversification patterns of the effector families 1106, 4D06, and VAL. Our data demonstrate how genome resequencing data from a nonindigenous pathogen can be used to reconstruct the introduction and diversification process.".
• 01GMDX5558B2TGAHRBQ56Z9DMK abstract "The family Criconematidae is a remarkable group of nematodes, containing roughly 600 nominal root-ectoparasitic species, of which many species are known to be significant agricultural pests. Strikingly, our phylogenetic analyses based on 18S, D2-D3 of 28S rRNA, and COI mtDNA sequences of criconematid species, supported by tree topology tests (SH and AU tests), revealed that almost all studied genera, including Criconema, Ogma, Crossonema, Discocriconema, Hemicriconemoides, Criconemoides, Mesocriconema, and Lobocriconema, are not monophyletic groups, a finding that is partly contrary to those of previous studies on these groups. Our results suggest that key morphological characters used in the classification of Criconematidae are the consequence of convergent evolution. It is clear from our studies that the species status of at least 40 sequences of criconematid species from GenBank must be either revised or reconsidered, with analyses based on a polyphasic approach that includes different tree- and distance-based molecular species-delimitation methods (bPTP, GMYC, ABGD1, and ABGD2). Our studies found the ABGD2 output of the automatic barcode method to agree remarkably well with established species delimitations, while in general, the four species-delimitation results corresponding to three barcode regions forwarded significantly more putative species compared to those originally considered. This study also characterised for the first time the populations of Criconemoides myungsugae and Discocriconemella hensungica associated with Vietnamese ginseng, one of the most precious and rare ginseng varieties in the world. Although these populations are morphologically in agreement with the original descriptions of C. myungsugae and D. hengsungica, their molecular data display notable variations compared to the sequences deposited in GenBank. These species demonstrate clearly the immense molecular variations that can be observed in several species of the family Criconematidae.".
• 01GME0BFGB9G30228S412TYSXE abstract "Although nascent entrepreneurs' opportunity exploration and exploitation activities are crucial for later venture evolution and performance, it is unclear why some nascent entrepreneurs engage more in these new venture creation activities than others. Building upon role identity theory, this study advances a nascent entrepreneur's various role identity aspirations as drivers of these activities. In particular, we argue that inventor, founder, and developer role identity aspirations are linked differently to the range of opportunity exploration and exploitation activities nascent entrepreneurs undertake. We use a two-stage Poisson model with sample selection correction on a random sample of 1582 inhabitants of Flanders, Belgium. The first stage estimates an individual's probability to engage in nascent entrepreneurship. The second stage tests the relationships between an individual's role identity aspirations and the range of exploration and exploitation activities undertaken, conditional on being a nascent entrepreneur, which holds for 162 individuals in our sample. We find that while some role identity aspirations are related to the range of opportunity exploration activities undertaken, others primarily affect the range of exploitation activities. Our findings have important implications for literature on new venture creation and entrepreneurial opportunities, for identity literature, and for nascent entrepreneurs wanting to start a venture.".
• 01GME1HPSCPWSC1F9WSBX1EFV6 abstract "Pharmacogenomics (PGx) studies the relationship between the patient genetic background and drug therapy. This dissertation aims to define which PGx tests are present on the market and which improvements are needed to these PGx tests to capture all essential variants and make them widely applicable in clinical practice. Therefore, in the first part, different PGx-specific tests, direct-to-customers assays, and exome sequencing were compared with the genetic variants in gene-drug interactions described in public databases. The studied tests could assay most of these genetic variants, mainly single nucleotide variants (SNVs). However, more complex and important haplotypes were missing. Therefore, in the second part of this dissertation, two new targeted sequencing technologies were tested to see to what extent they could call and phase the different variants into haplotypes for important pharmacogenes. First, the TLA technology was performed on four complex pharmacogenes and sequenced on the Illumina and ONT platforms. Both sequencing methods had a low on-target percentage, and not all positions in the genes were entirely covered. Nevertheless, CYP2D6, sequenced with the ONT platform, resulted in the correct genotype. However, less than half of the variants were phased correctly for the other studied genes. Second, we optimized the nanopore Cas9-targeted sequencing method to enrich the CYP2D6-CYP2D7 region. Although the low on-target percentage and low sequencing throughput, this method, combined with a newly developed analysis pipeline, resulted in the discovery of an inserted CYP2D6-CYP2D7 hybrid that goes undetected by other assays.".
• 01GMEHGFEM6A1068KJ5R0JHGEN abstract "Introduction: The COVID-19 pandemic had severe consequences on the physical and mental health of the general population. Containment measures to reduce the spread of the disease led to lockdowns and diminished social interaction. One vulnerable group were older adults. For them, new technological advancements such as socially assistive robots (SARs), could prove to be an effective intervention. Objectives: The aim of this study was to gain a deeper understanding of the experiences of older adults with a SAR, including its effect on loneliness and its contribution to meaningful time use/activities. Method: Inductive thematic analysis was used. After a two week intensive period, in-depth interviews were conducted to gain a deeper understanding of the experiences of older adults with SAR, whom were living in assisted living facilities during the first lockdown in Flanders, Belgium. Results: Four themes were identified: 1. The robot as a companion, alleviating feelings of loneliness and social isolation. 2. The robot as an addition and alternative to meaningful activities. 3. The technical aspects of the robot, and how it compared to accustomed technology. 4. Notable barriers and areas of improvement. Conclusion: The robot proved to be promising in terms of alleviating feelings of loneliness and social isolation, and was found to be both a motivating and facilitating presence towards meaningful activity for the participating older adults. Longer term, the ability to personalize the SAR and increase its mobility would be a valuable addition.".
• 01GMEJSCD2H4M7NTPQB6J6DPXC abstract "Deze dissertatie biedt een eerste gedetailleerd inzicht in de constituentenvolgorde van enkelvoudige declaratieve zinnen in de Servische Gebarentaal (SZJ). Als introductie op SZJ wordt eerst een beschrijving gegeven van de talige situatie van doven in Servië door de taalattitudes van doven en hun leerkrachten op een dovenschool te onderzoeken. Daarna verschuift de aandacht naar het onderwijsbeleid met betrekking tot SZJ vanaf het begin van de jaren 2000 tot 2021 om de plaats van SZJ in het dovenonderwijs te duiden. Vervolgens wordt de in deze studie toegepaste theoretische benadering gepresenteerd, die voornamelijk is ingebed in de cognitief-functionele taalkunde en op gebruik gebaseerde theorie. Het hoofdstuk over de methodologie geeft een beschrijving van het SZJ-corpus dat speciaal voor dit proefschrift werd gecreëerd. Aangezien SZJ een nauwelijks onderzochte taal is, moest een corpus worden samengesteld. Dat bestaat uit zinnen die in een experimentele setting uitgelokt werden aan de hand van het materiaal van Volterra et al. (1984), uit meer naturalistische data die zijn verzameld aan de hand van het beeldverhaal Kikker, waar ben je? (Mayer 1969), de stille film Quatre à voyager (Theunen & Faton 1983) en vrije conversaties. Er wordt een opdeling van de deelnemers gegeven in drie leeftijdsgroepen op basis van veranderingen in het onderwijsbeleid die een invloed uitgeoefend hebben op het dovenonderwijs in Servië, samen met de leeftijd waarop de deelnemers SZJ verwierven en het gender van de deelnemers. Voor deze studie zijn 2220 zinnen geïdentificeerd. Van deze 2220 zinnen werden er 1717 bestempeld als niet-locatieve zinnen, 222 werden geanalyseerd als locatieve zinnen in termen van GROUND en FIGURE, en 281 als attributieve zinnen zonder werkwoord (bijv. GESCHENK MOOI). De bevindingen wijzen erop dat SVO weliswaar de meest voorkomende volgorde lijkt te zijn in enkelvoudige declaratieve zinnen met expliciete manuele argumenten, maar dat de meest voorkomende volgordes V en SV zijn. Een hoog aantal zinnen met niet-expliciete manuele argumenten wijst erop dat factoren als werkwoordstype, werkwoordmodificatie en constructed action een belangrijke rol spelen bij de constituentenvolgorde in SZJ. Bovendien zou de prevalentie van zinnen met niet-expliciete argumenten een gevolg kunnen zijn van het contact tussen het SZJ en het Servisch, een pro-drop taal. Attributieve zinnen zonder werkwoord kwamen vaker voor in de verhalen en de vrije conversaties dan in de Volterra dataset. Deze bevinding komt overeen met observaties over het wijdverbreide gebruik van zinnen zonder werkwoord in face-to-face gesproken interacties (vgl. Givón 2009). De meest voorkomende volgorde in locatieve zinnen is GROUND-eerst-dan-FIGURE, een bevinding die typisch is voor de visuele modaliteit inherent aan gebarentalen. De multivariate analyse waarin de significantie van werkwoordstype, omkeerbaarheid, topicaliteit en sociale factoren zoals gender, leeftijd en verwervingsleeftijd op de afhankelijke variabele (S)V(O) werden getest, toonde aan dat werkwoordstype en gender het meest robuuste effect hebben op de keuze van (S)V(O). Depicting werkwoorden bleken (S)V(O) niet te verkiezen, terwijl vrouwen (S)V(O) prefereerden. Dit zou een gevolg kunnen zijn van het feit dat vrouwen de voorkeur geven aan die talige vormen die als prestigieus worden ervaren (Cheshire 1998). Aangezien in het dovenonderwijs in Servië nog steeds overwegend “Servisch met gebaren” als onderwijstaal wordt gebruikt, kan dit door de Servische dovengemeenschap als een prestigieuze variëteit worden beschouwd. Uit het corpus van deze dissertatie blijkt dat gebarentaligen gebruik maken van verschillende representatiestrategieën om uitingen te produceren. Sommige van deze uitingen gebruiken expliciete manuele gebaren om deelnemers en processen in een zin te identificeren (cf. Hodge 2013). Aan de andere kant zijn er uitingen die voornamelijk gebruik maken van enactment en die een mix van min of meer geconventionaliseerde gebaren gebruiken. SZJ lijkt een systeem te zijn dat een mengeling van vertellen, indicating en depicting inhoudt waarmee dus rekening gehouden moet worden in de beschrijving en analyse.".
• 01GMEJSCD2H4M7NTPQB6J6DPXC abstract "This thesis offers a first detailed insight into constituent order in simple declarative clauses in Serbian Sign Language (SZJ). By way of introduction to SZJ, first an account of the language situation of deaf people in Serbia is given by examining language attitudes of deaf people and their teachers in a deaf school. The focus then shifts towards examining education policy with respect to SZJ from the early 2000s until 2021 to account for the place of SZJ in deaf education. Next, the theoretical approach applied in this study which mainly draws from cognitive-functional linguistics and usage-based theory is presented. The methodology chapter provides the description of the SZJ corpus which was created specifically for this thesis. As SZJ is an under-investigated language, a corpus had to be compiled. It consists of clauses elicited in an experimental setting by means of the Volterra et al. (1984) material, more naturalistic data which are gathered by means of the picture story Frog, Where are You? (Mayer 1969), the silent film Quatre à voyager (Theunen & Faton 1983), and free conversations. The classification of participants into three age groups based on the changes in educational policy which affected deaf education in Serbia is given along with the age the participants acquired SZJ and the participants’ gender. There are 2220 identified clauses for the purposes of this study. Of these 2220 clauses 1717 were labelled as non-locative clauses, 222 were analysed as locative clauses in terms of ground and figure, and 281 as verbless attributive clauses (e.g. present pretty). The findings suggest that while SVO seems to be the most frequently attested order in simple declarative clauses with core arguments manually expressed, the most frequent orders are verb-only and SV. A high number of clauses with manually non-overt core arguments indicate that factors such as verb type, verb modification, and constructed action play an important role in constituent order in SZJ. Furthermore, the prevalence of clauses with inferred arguments could be a result of contact of SZJ with the Serbian language, a pro-drop language. Verbless attributive clauses were found to be more prevalent in the narratives and free conversations than in the Volterra dataset. This finding aligns with observations about the widespread use of verbless clauses in face-to-face spoken interactions (cf. Givòn 2009). The most frequent ordering in locative clauses is GROUND-first-then-FIGURE, which is a finding typical of the visual modality inherent to sign languages. Multivariate analysis which tested the significance of verb type, reversibility, topicality, and social factors such as gender, age, and age of acquisition on the dependent variable (S)V(O) revealed verb type and gender to have the most robust effect on the choice of (S)V(O). Depicting verbs were found to disfavour (S)V(O) while women were found to favour (S)V(O). This could be a result of women preferring those forms of a language which tend to be perceived as prestigious (Cheshire 1998). As deaf education in Serbia still predominantly uses signing in Serbian word order as the language of instruction, it may be regarded as a prestigious variety by the Serbian deaf community. It seems from what could be observed in this thesis’ corpus that signers rely on various representational strategies for producing utterance units. Some of these units use overt manual signs to identify participants and processes in a clause (cf. Hodge 2013). On the other hand, there are utterance units which use primarily enactment and use a mixture of more or less conventionalised signs. SZJ thus seems to be a system which involves a mixture of telling, indicating and depicting and needs to be accounted for as such.".
• 01GMEKN4ZRMWEVEZX6S89Q0EB3 abstract "INTRODUCTION The prevalence of chronic kidney disease is increasing worldwide, particularly affecting older adults. It is a complex progressive disease that in its end-stage necessitates renal replacement therapy (RRT) through kidney transplantation or dialysis. It carries a high disease and treatment burden, impacting patients’ ‘life participation’ substantially. Self-management, or the process through which patients are able to cope with the disease in the context of their daily lives, is essential in patients undergoing RRT. Though self-management includes medical-, emotional-, and role-management, current intervention programmes mainly focus on medical-management and to a lesser degree emotional-management. Role-management (i.e. how to fulfil life roles, engage in meaningful activity and social relations) is pivotal in supporting ‘life participation’, yet evidence in RRT-care is lacking. METHOD This protocol, based on Medical Research Council guidelines, guides the development of a role-management programme that can be deployed in a nephrology department. First, a systematic review will examine current evidence. Second, an ethnographic study will explore practical theory. Third, an initial role-management programme will be developed based on the previous phases, aided by expert/stakeholder perspectives. A usability study will assess feasibility. Finally, a definite version of the programme will be evaluated through a randomized controlled trial. CONCLUSION In recent years, ‘life participation’ has become an increasingly important outcome in RRT. It carries the highest priority for patients and caregivers, contrasting the current focus on medical priorities in standard care. Patients want to stay as meaningfully active as possible, as long as possible. A role-management programme could prove beneficial.".
• 01GMFTQ0233KB71D6BSB9DZB7Z abstract "Teaching Point: A thrombosed calcified aneurysm of the splenic vein is a rare complication of pancreatitis.".
• 01GMG1E9TH999K9SG8M883C7RW abstract "Introduction: No information is available in Belgium on life expectancy adjusted for health-related quality of life (HRQoL). Quality-adjusted life expectancy (QALE) captures the multidimensionality of health by accounting for losses in mortality and HRQoL linked to physical, mental, and social impairments. The objective of this study is to estimate for Belgium QALE, the changes in QALE between 2013 and 2018 and the contribution of mortality, HRQoL and its dimensions to this trend. Methods: The Belgian Health Interview Survey (BHIS), a representative sample of the general population, included the EQ-5D-5L instrument in 2013 and 2018. The tool assesses HRQoL comprising five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) using a 5-level severity scoring to define a large variety of health states. The Sullivan method was used to compute at different ages QALE by gender using mortality data from the Belgian statistical office and average EQ-5D scores from the BHIS. QALE was calculated for 2013 and 2018, and changes in QALE over time were decomposed into mortality and ill-health effect. Results: In 2018, QALE at age 15 years (QALE(15)) was 56.3 years for women and 55.8 years for men, a decrease from 2013 by 0.7 year for women and a stagnation for men. In men, the decrease in mortality counterbalanced the decline in HRQoL. The decline in QALE in women is driven by a decrease in mortality rates that is too small to compensate for the substantial decline in HRQoL before the age of 50 years. In women at older ages, improvements in HRQoL are observed. In women, QALE(15) is decreasing due to an increase in pain/discomfort, anxiety/depression and problems in usual activities. In men at age 15, the pain/discomfort and anxiety/depression domains contributed to the stagnation. QALE(65) increased somewhat, due to an improvement in self-care and mobility for both genders, and usual activities and anxiety/depression in men only. Conclusion: The strength of QALE as member of the family of composite indicators, the health expectancies, is the multidimensional structure of the underlying health component, including both ill-health with different health domains as levels of severity. The ability to decompose differences in the health expectancy not only into a mortality and health component but also into the different health dimensions allows to better inform on general population health trends. Next, compared to other health expectancy indicators, QALE is more sensitive to changes at younger ages.".
• 01GMGEVBGZP3BFAVTVBPPP4S8V abstract "Assisted return (AR) is a widespread policy tool offering financial support and counselling to returning migrants. Policymakers present it as a durable solution vis-à-vis undocumented migrants and rejected asylum seekers. However, AR has been proven to display the concurrence of care and control typical of contested humanitarianism. This concurrence takes different shapes across nation states. Our paper looks at how Sweden, Finland, the UK, Italy, Spain, and Portugal concretely configure care and control in their AR programmes, by focusing particularly on accessibility criteria, the landscape of the actors implementing the measure and their main implementation strategies. We finally find that the care and control balance of a particular layer within the AR national system can hardly be appreciated without considering the (lack of) life opportunities available to the potential beneficiaries of the measure, both within the confines and outside of it. Therefore, our comparative research ultimately conveys that what we call the intrinsic humanitarianism of AR—or its internal care-control balance—can give insight into the durability of the measure only when associated with what we term the extrinsic humanitarianism of AR—namely its broader relationship with forced return. In order words, AR ultimately appears migration control in disguise if it is not coupled with the enlargement of dignified life chances for migrants.".
• 01GMGJK1SNWWCRZC9GYAKMR3V1 abstract "In this paper we describe the use of two mathematical constructs in developing objective measures of explainability. The first one is measure theory, which has a long and interesting history, and which establishes abstract principles for comparing the size of general sets. At least some of the underpinnings of this theory can equally well be applied to evaluate the degree of explainability of given explanations. However, we suggest that it is meaningless, or at least undesired, to construct objective measures that allow the comparison of any two given explanations. Explanations might be non compatible, in the sense that integrating such explanations results in decreasing rather than increasing explainability. In other words, explainability is best considered as a partial order relation. Notwithstanding the use of partial order relations and measure theory, it is unwise to unconditionally apply these mathematical concepts to the field of explainability. It is demonstrated that the law of diminishing returns from economics offers a neat way to make these concepts applicable to the domain of explainability. The legal field is used as an illustration of the presented ideas.".
• 01GMGJQNJ129DYKKT97V80YQ5D abstract "The attempt to concretely define the concept of explainability in terms of other vaguely described notions, is doomed to fail. We argue that a rigorous numeric measure is needed to take a significant step forward. Such a measure would allow the objective comparison of machine learning models that are explainable to varying degrees. In the longer term, a numeric measure might make it possible to compare humans and machines in terms of explanatory capacities, thereby establishing a very specific kind of Turing test. We introduce some notions and rigorous definitions related to explainability, in particular completeness and consistency. The objective of this paper is that the introduced terms can act as a concrete starting point for the construction of a mathematically expressed measure of explainability. We also show how the idea of model selection, where a model is chosen from a candidate set by optimizing the trade-off between complexity and goodness of fit, can be applied to select explainable models.".
• 01GMGTXBFTXBPE2SAHRFWFREHC abstract "Endogenous bioelectrical signals are one of the most relevant cues to determine tissue function in electrosensitive tissues and thus play a vital role in the tissue regeneration process. In this regard, piezoelectricity is considered as one of the key functionalities in biomaterials to electrically stimulate tissue regeneration. However, the integration of biocompatibility, biodegradability and 3D structure with pronounced piezoelectric activity to support tissues repair remains a challenge. Furthermore, the mere presence of a matrix for cell growth is often not sufficient for a good cell adhesion and proliferation; this often requires other components, which would provide additional functionalities, for example, improve cell adhesion and proliferation, provide antibacterial protection, etc (polymers, nano- and micro- particles, biological molecules, such as enzymes, and antibiotics). That stimulates development of hybrid polymer-based materials incorporating both organic and inorganic components. Composite biodegradable and piezoelectric polymer-based materials are emerging as a very potent and promising class of materials due to their diverse properties, which are proved to be a viable tool for tissue engineering applications for the formation of the extracellular matrix (ECM), avoiding a second surgery, and providing electrical stimulation. In this work, novel hybrid 3-D electrospun scaffolds are developed to improve cell adhesion and proliferation, biomimetic mineralization, and antibacterial activity. These scaffolds are based on biodegradable natural poly(3-hydroxybutyrete) polymer, which has piezoelectric properties relevant for a close contact to bone tissue. Specifically in this thesis work: 1) it has been demonstrated, for the first time to the best of our knowledge, that under dynamically applied mechanical stress, piezoelectric PHB-based scaffolds are capable of providing an enhanced biomimetic mineralization and more homogenous growth of the inorganic bone phases, such as calcium carbonate, resulting in an improved cell adhesion and proliferation; 2) design of composite PHB-based scaffolds is pursued by functionalizing it with CaCO3 particles and subsequent drug immobilization, which results in an enhanced osteoblastic cell adhesion/proliferation and 17 pronounced antibacterial effects; 3) surface functionalization of electrospun PHB-based scaffolds is performed close to surface monomolecular level by a non-destructive diazonium approach, leading to preserved piezoresponses and an improved wettability, which are important for cell adhesion for regenerative tissue engineering; 4) design of hybrid biodegradable PHB-based scaffolds are pursued by their functionalization with reduced graphene oxide (rGO) nanoflakes, resulting in an enhanced surface potential and piezoresponses, demonstrating improved cell adhesion and proliferation under static and dynamic mechanical conditions; 5) investigation of the biodegradation process and studies of its impact on the composition, structure, physio-mechanical and electromechanical properties of hybrid PHB-rGO scaffolds with an enhanced piezoresponses are performed. Our results emphasize the added value of hybrid biodegradable and piezoelectric polymer-based materials and approaches, particularly involving functionalization by microparticles, surface chemistry and bioactive molecules. Such new materials are envisioned to find applications in tissue engineering, biomedicine, and biology.".
• 01GMJF3GN8NWBB3JP709KSPPG6 abstract "The pan-European power grid is experiencing an increasing penetration of Variable Renewable Energy (VRE). The fluctuating and non-dispatchable nature of VRE hinders them in providing the Ancillary Service (AS) needed for the reliability and stability of the grid. Therefore, Energy Storage Systems (ESS) are needed along the VRE. Among the different ESS, a particularly viable and reliable option is Pumped Hydro Storage (PHS), given its cost-effective implementation and considerable lifespan, in comparison to other technologies. Traditional PHS plants with Francis turbines operate at a high head difference. However, not all regions have the necessary topology to make these plants cost-effective and efficient. Therefore, the ALPHEUS project will introduce low-head PHS for regions with a relatively flat topography. In this paper, a grid-forming controlled converter coupled with low-head PHS that can contribute to the grid stability is introduced, emphasising its ability to provide different AS, especially frequency control, through the provision of fast Frequency Containment Reserve (fFCR) as well as synthetic system inertia. This paper is an extended version of the paper “The Contribution of Low-head Pumped Hydro Storage to a successful Energy Transition”, which was presented at the 19th Wind Integration Workshop 2020.".
• 01GMKGQFJC1F25515K3KGH3SWK abstract "Wireless sensor networks (WSNs) are considered part of an environmentally friendly technology leading to more timely and cost-effective production and management of farms. Despite the potential of WSNs to agricultural development in the global South, outreach is still very limited, also in Iran. Therefore, in order to facilitate the adoption of WSNs, it is necessary to identify the factors influencing and challenging the adoption of this technology. This exploratory study uses a qualitative approach to identify the main barriers WSN outreach is facing. In the results, we distinguish facts that we define as issues or barriers that were identified by others from fears that are not supported by evidence so far, at the level of the farmers, the government actors as well as the technology itself. Facts include communication barriers such as internet access, farmers’ knowledge levels and rigidity to change as well as the government’s top-down organisation of the extension programme and support levels. Fears are mainly expressed on the technology itself and relate to costs, a lack of access, the complexity of use and reliability of the data. We provide a nuanced view of how fears need to be acknowledged and facts are to be tackled.".
• 01GMKJCZHNMYB5EKBZVN4Z6GSG abstract "Grassland is the primary land use in China but has experienced severe degradation in recent decades due to overgrazing and conversion to agricultural production. Here, we conducted a field experiment in northeastern Inner Mongolia to test the effectiveness of sown pastures in lowering the grazing pressure on grasslands and raising the quality of marginal soils. Alfalfa and smooth bromegrass monocultures and mixture were sown in a marginal cropland field in Hulunber in June 2016. Biomass productivity, soil physicochemical, and biological properties were monitored annually from 2016 to 2020. The results showed that the marginal cropland soil responded consistently positively to sown pastures for major soil properties. Soil organic carbon (SOC) and total nitrogen (TN) increased by 48 and 21%, respectively, from 2016 to 2020 over the 0-60 cm soil depth range. Soil microbes responded proactively too. The soil microbial biomass C (SMBC) and N (SMBN) increased by 117 and 39%, respectively, during the period of 2016-2020. However, by the end of the experiment, the soil of a natural grassland field, which was included in the experiment as a control, led the sown pasture soil by 28% for SOC, 35% for TN, 66% for SMBC, and 96% for SMBN. Nevertheless, the natural grassland soil's productive capacity was inferior to that of the sown pasture soil. The average aboveground biomass productivity of sown pastures was measured at 8.4 Mg ha(-1) in 2020, compared to 5.0 Mg ha(-1) for natural grassland, while the root biomass of sown pastures was averaged at 7.5 Mg ha(-1), leading the natural grassland by 15%. Our analyses also showed that the sown pastures' biomass productivity advantage had a much-neglected potential in natural grassland protection. If 50% of the available marginal cropland resources in Hulunber under the current environmental protection law were used for sown pastures, the livestock grazing pressure on the natural grasslands would decrease by a big margin of 38%. Overall, these results represent systematic empirical and analytical evidence of marginal cropland soil's positive responses to sown pastures, which shows clearly that sown pasture is a valid measure both for soil rehabilitation and biomass production.".
• 01GMKKPWY9MM157WNVPKDA69E5 abstract "Introduction: Grasslands are the most important land use in China and have experienced extensive degradation in the past few decades due to overgrazing. However, regionally viable solutions to grazing intensity alleviation remained elusive to date. Methods: Here, we evaluated the grazing intensity effects of sown alfalfa pastures in northern China using an experiment-modeling combined approach that involved six sites in field experiments and five provinces in DNDC modeling of sown alfalfa pasture’s forage production and carbon sequestration potentials in marginal lands. Results: Our results showed that the sown alfalfa pasture’s dry-matter yield varied between 4.5 and 9.0 Mg ha-1 under rainfed and irrigated conditions, respectively, from 2025 to 2035. If half of the available marginal lands were mobilized for alfalfa forage production, these yield levels meant that livestock grazing intensity on natural grasslands may drop 8-13% under rainfed and 20-33% under irrigated conditions. Our results also showed that marginal land’s soil organic carbon contents were systematically higher under sown alfalfa pasture than under fallow management by a big margin of 8.5 and 9.9 g kg-1 (i.e., +79 and +95%), under rainfed and irrigated conditions, respectively, during 2025-2035. Discussion: Overall, these results demonstrated that sown alfalfa pasture on marginal lands represents an effective grassland conservation pathway over the short- to medium-term time horizon based on current technologies.".
• 01GMKR6QC41E70SV6DX5359HSA abstract "Full 3D inversion of time-domain Airborne ElectroMagnetic (AEM) data requires specialists' expertise and a tremendous amount of computational resources, not readily available to everyone. Consequently, quasi-2D/3D inversion methods are prevailing, using a much faster but approximate (1D) forward model. We propose an appraisal tool that indicates zones in the inversion model that are not in agreement with the multidimensional data and therefore, should not be interpreted quantitatively. The image appraisal relies on multidimensional forward modeling to compute a so-called normalized gradient. Large values in that gradient indicate model parameters that do not fit the true multidimensionality of the observed data well and should not be interpreted quantitatively. An alternative approach is proposed to account for imperfect forward modeling, such that the appraisal tool is computationally inexpensive. The method is demonstrated on an AEM survey in a salinization context, revealing possible problematic zones in the estimated fresh-saltwater interface.".
• 01GMKRGV4NG5KZKFXR03EF1MTQ abstract "The inversion of time-domain AEM data with full 3D inversion requires specialists’ expertise and a huge amount of computational resources, not readily available to everyone. Consequently, quasi-2D/3D inversion methods are prevailing, using a much faster but approximate (1D) forward model. The question remains whether the obtained inversion results are reliable and can be interpreted quantitatively. We propose an appraisal tool for quasi-2D/3D methods that indicate zones in the inversion model that are not in agreement with the multidimensional (2D/3D) forward model and therefore, should not be interpreted in a quantitative fashion. The image appraisal step only requires one full 2.5D or 3D forward and one multidimensional Jacobian computation on a coarse mesh to compute a so-called normalized gradient. Large values in that gradient indicate model parameters that do not fit the true multidimensionality of the observed data well and should not be interpreted quantitatively. We demonstrate our method on a real AEM survey in a salinization context, revealing problematic zones in the fresh-saltwater interface. Interestingly, the problematic zones are not necessarily at larger depths, but where the interface is changing. The advantage of our approach is that all computations are feasible on a single laptop.".
• 01GMMMDKYQ0Y7ZZQ14A3YS52AP abstract "During the initial outbreak of the global COVID-19 pandemic, many countries imposed a total lockdown (containment at home). Although it was still allowed in Belgium to be physically active or exercise with people from your household in the vicinity of your home, engaging in sports or physical activity in a group or club context was no longer permitted. To examine whether a lack of physical activity was potentially threatening to the mental well-being of citizens and vice versa, the present study examined concurrent and reciprocal relationships between physical activity and anxiety, depressive symptoms, and sleep quality during the COVID-19 lockdown in a 9-week longitudinal design. In a sample of 983 Belgian adults (75.1% female; Mage = 43.78, range = 18–82 years), we explored these relationships at both the between- and within-person levels through random intercept cross-lagged panel models. The findings indicate that more physical activity was associated with lower symptoms of anxiety and depression and better sleep quality, a finding observed both at the between-person (across weeks; βanxiety = − 0.25, βdepression = − 0.30, βsleep quality = 0.24, p < .001) and within-person level (within weeks; βanxiety = − 0.10, βdepression = − 0.14, βsleep quality = 0.11, p < .05). Moreover, at the within-person level, an increase in feelings of anxiety and depression at one moment predicted lower levels of physical activity one week later (βanxiety = − 0.04, βdepression = − 0.06, p < .05). Since poor mental health poses a threat to the maintenance of physical activity, the current findings suggest that it is critical to invest in the mental health of individuals during distressing times.".
• 01GMMNJAH3NG9QC14E8P3955MQ abstract "Studies on strategic parliamentary opposition often focus on broader behavioral patterns or party‐level variation. This article analyzes differences at the individual level, more notably between male and female opposition members of parliament. Using rational‐choice perspectives of opposition activity and theories of gendered political behavior, we hypothesize that female opposition members focus less on ideological conflicts (with or between coalition parties) and more on their party’s core issues. Furthermore, we expect them to more frequently target female ministers, in part because of the nature of their respective portfolios. Our analysis of all parliamentary questions tabled by opposition members in the Belgian Federal Parliament between 2007 and 2019 (N = 48,735) suggests that female members of parliament seem more likely to focus on issues that are salient to their party and less on conflictual matters between coalition partners. These results provide new empirical insights into strategic opposition behavior and gendered differences in the legislature.".
• 01GMMP2RRSDBSWWTBDY7H8CJSH abstract "The book offers an archaeological and historical synthesis of the results obtained by the excavations of François Thureau-Dangin (1929–1931) and by the more recent excavations of the universities of Melbourne (1988–1999) and Liège (2000–2010). It presents a comprehensive and diachronic view of the evolution of the site, which, by its position on the Euphrates at an important crossroads of ancient communication routes, was at the heart of a game of cultural and political interference between Mesopotamia, the Mediterranean world and Asia Minor.".
• 01GMMPTRSWZATYERPW5E2JXDE1 abstract "This paper offers a case study of uninscribed scarabs in Egyptian blue. It addresses the initial occurrence of scarabs in this material in Lebanon and uses finds from Middle Bronze Age Sidon as stepping stones for the interpretation of more problematic finds from Byblos.".
• 01GMMQ41G0DKKZP467MPC9T5MD abstract "Prebiotics are dietary substrates which promote host health when utilized by desirable intestinal bacteria. The most commonly used prebiotics are non-digestible oligosaccharides but the prebiotic properties of other types of nutrients such as polyphenols are emerging. Here, we review recent evidence showing that amino acids (AA) could function as a novel class of prebiotics based on: (i) the modulation of gut microbiota composition, (ii) the use by selective intestinal bacteria and the transformation into bioactive metabolites and (iii) the positive impact on host health. The capacity of intestinal bacteria to metabolize individual AA is species or strain specific and this property is an opportunity to favor the growth of beneficial bacteria while constraining the development of pathogens. In addition, the chemical diversity of AA leads to the production of multiple bacterial metabolites with broad biological activities that could mediate their prebiotic properties. In this context, we introduce the concept of “Aminobiotics,” which refers to the functional role of some AA as prebiotics. We also present studies that revealed synergistic effects of the co-administration of AA with probiotic bacteria, indicating that AA can be used to design novel symbiotics. Finally, we discuss the difficulty to bring free AA to the distal gut microbiota and we propose potential solutions such as the use of delivery systems including encapsulation to bypass absorption in the small intestine. Future studies will need to further identify individual AA, dose and mode of administration to optimize prebiotic effects for the benefit of human and animal health.".
• 01GMMSNS7YHVVD84S3FKWS2V3B abstract "IntroductionDe-institutionalization of psychiatric care has greatly increased the role of family members in the recovery pathways of Persons labeled as Not Criminally Responsible (PNCR). However, the role of family members in supporting PNCR in forensic psychiatric care remains understudied. Scarce evidence indicates that PNCR have to deal with stigma and endure specific burdens (i.e., symptom-specific, financial, social, and emotional). Recovery-focused research showed that recovery in both persons with a severe mental illness and family members develop in parallel with each other and are characterized by similar helpful principles (e.g., hope and coping skills). As such, the recovery pathways of PNCR often goes hand in hand with the recovery pathway of their family members. During the family recovery process, family members often experience not being listened to or being empowered by professionals or not being involved in the decision-making process in the care trajectory of their relative. Therefore, the aim of this study is to capture how family members experience the care trajectories of their relatives, more specifically by looking at family recovery aspects and personal advocacy of family members. MethodsSemi-structured interviews were conducted with 21 family members of PNCR from 14 families. A thematic analysis confirms that family members suffer from stigma and worry significantly about the future of their relative. ResultsRegarding the care trajectory of PNCR, family members experienced barriers in multiple domains while trying to support their relative: involvement in care and information sharing, visiting procedures, transitions between wards, and the psychiatric and judicial reporting by professionals. In addition, family members emphasized the importance of (social) support for themselves during the forensic psychiatric care trajectories and of a shared partnership. DiscussionThese findings tie in with procedural justice theory as a precondition for family support and family recovery within forensic psychiatric care.".
• 01GMMX6XDDHKTERBZHW3D8RDAA abstract "The lack of label-free high-throughput screening technologies presents a major bottleneck in the identification of active and selective biocatalysts, with the number of variants often exceeding the capacity of traditional analytical platforms to assess their activity in a practical time scale. Here, we show the application of direct infusion of biotransformations to the mass spectrometer (DiBT-MS) screening to a variety of enzymes, in different formats, achieving sample throughputs equivalent to similar to 40 s per sample. The heat map output allows rapid selection of active enzymes within 96-well plates facilitating identification of industrially relevant biocatalysts. This DiBT-MS screening workflow has been applied to the directed evolution of a phenylalanine ammonia lyase (PAL) as a case study, enhancing its activity toward electron-rich cinnamic acid derivatives which are relevant to lignocellulosic biomass degradation. Additional benefits of the screening platform include the discovery of biocatalysts (kinases, imine reductases) with novel activities and the incorporation of ion mobility technology for the identification of product hits with increased confidence.".
• 01GMMX6XDWB3W81N5XZWBG8N91 abstract "Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards beta-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto-N-biose towards galectins can be 'turned on/off' by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved. The panel of fluoro-glycans were obtained by a chemoenzymatic approach, exploiting BiGalK and BiGalHexNAcP enzymes from Bifidobacterium infantis which are shown to tolerate fluorinated glycans, introducing structural diversity which would be very laborious by chemical methods alone. These results demonstrate that integrating non-natural, fluorinated glycans into nanomaterials can encode unprecedented selectivity with potential applications in biosensing.".
• 01GMMX6XE3Q895CPJKX3DAJHNA abstract "Given there is an optimal lipophilicity range for orally bioavailable drugs, structural modifications applied in the drug development process are not only focused on optimizing bioactivity but also on fine-tuning lipophilicity. Fluorine introduction can be used for both purposes. Insights into how fluorine introduction affects lipophilicity are thus of importance, and systematic series of fluorinated compounds with measured octanol-water partition coefficients are a powerful way to enhance our qualitative understanding in this regard and are essential as input for computational log P estimation programs. Here, we report a detailed comparison of all possible vicinal and skipped (1,3-substituted) fluorination motifs when embedded in structurally equivalent environments (X-CFnH2-n-CFmH2-m-X versus X-CFnH2-n-CH2-CFmH2-m-X, with n,m not equal 0 and X = CH2OH) to compounds with isolated fluorination (n not equal 0; m = 0, and including X-CH2-CFnH2-n-CH2-X, n = 0-2). It is shown that skipped fluorination is more powerful for log P reduction purposes compared to single or vicinal fluorination. Efficient stereoselective syntheses of the compounds with skipped fluorination motifs are reported, which where relevant can be made enantioselective using known chiral building blocks. These compounds, and some intermediates, will be of interest as advanced fluorinated building blocks.".
• 01GMMX6XEP0W38HTM4MS9C5N2M abstract "The highly strained cubane system is of great interest as a scaffold and rigid linker in both pharmaceutical and materials chemistry. A straightforward approach is reported for the scale-up of a [2+2] photocycloaddition step using convenient home-made flow photoreactors to access dimethyl 1,4-cubanedicarboxylate on decagram-scale in 33-40% yield over 8 steps. The process is demonstrated on 3.4 g.h(-1) input with 30 minutes residence time, enabling to reduce the process time and to avoid the use of batch photoreactors. Completion of the characterisation of the photocycloadduct and its hydrates is reported.".
• 01GMMX72B6PKE6063ESY4RDHF1 abstract "Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorinated monosaccharides, leading to the first examples of polyfluorinated substrates accepted by this class of enzymes. We have discovered four new N-acetylhexosamine kinases with a different substrate scope, thus expanding the number of homologs available in this subclass of kinases. Lastly, we have solved the crystal structure of a galactokinase in complex with 2-deoxy-2-fluorogalactose, giving insight into changes in the active site that may account for the specificity of the enzyme toward certain substrate analogs.".
• 01GMMX72BCKD9DPHMMBQ2B23DF abstract "A systematic comparison of lipophilicity modulations upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl substituents, at a single carbon atom, is provided using directly comparable, and easily accessible model compounds. In addition, comparison with relevant linear chain derivatives is provided, as well as lipophilicity changes occurring upon chain extension of acyclic precursors to give cyclopropyl containing compounds. For the compounds investigated, fluorination of the isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent.".
• 01GMMX72BG5RPP0RFKXBE5E3EJ abstract "This review provides an extensive summary of the effects of carbohydrate fluorination with regard to changes in physical, chemical and biological properties with respect to regular saccharides. The specific structural, conformational, stability, reactivity and interaction features of fluorinated sugars are described, as well as their applications as probes and in chemical biology.".
• 01GMMX777Z875W9TGMTBAS9DXJ abstract "The first synthesis of 3-deoxy-3-fluoro-l-fucose is presented, which employs ad- tol-sugar translation strategy, and involves an enzymatic oxidation of 3-deoxy-3-fluoro-l-fucitol. Enzymatic activation (FKP) and glycosylation using an alpha-1,2 and an alpha-1,3 fucosyltransferase to obtain two fluorinated trisaccharides demonstrates its potential as a novel versatile chemical probe in glycobiology.".
• 01GMMX7784DC6XJNHWA56DTA3W abstract "Fluorinated carbohydrates, where one (or more) fluorine atom(s) have been introduced into a carbohydrate structure, typically through deoxyfluorination chemistry, have a wide range of applications in the glycosciences. Fluorinated derivatives of galactose, glucose, N-acetylgalactosamine, N-acetylglucosamine, talose, fucose and sialic acid have been employed as either donor or acceptor substrates in glycosylation reactions. Fluorinated donors can be synthesised by synthetic methods or produced enzymatically from chemically fluorinated sugars. The latter process is mediated by enzymes such as kinases, phosphorylases and nucleotidyltransferases. Fluorinated donors produced by either method can subsequently be used in glycosylation reactions mediated by glycosyltransferases, or phosphorylases yielding fluorinated oligosaccharide or glycoconjugate products. Fluorinated acceptor substrates are typically synthesised chemically. Glycosyltransferases are most commonly used in conjunction with natural donors to further elaborate fluorinated acceptor substrates. Glycoside hydrolases are used with either fluorinated donors or acceptors. The activity of enzymes towards fluorinated sugars is often lower than towards the natural sugar substrates irrespective of donor or acceptor. This may be in part attributed to elimination of the contribution of the hydroxyl group to the binding of the substrate to enzymes. However, in many cases, enzymes still maintain a significant activity, and reactions may be optimised where necessary, enabling enzymes to be used more successfully in the production of fluorinated carbohydrates. This review describes the current state of the art regarding chemoenzymatic production of fluorinated carbohydrates, focusing specifically on examples of the enzymatic production of activated fluorinated donors and enzymatic glycosylation involving fluorinated sugars as either glycosyl donors or acceptors.".
• 01GMMX7789H859SCMNQSZNX15G abstract "Optimization of compound lipophilicity is a key aspect of drug discovery. The aim of this work was to compare the lipophilicity modulations induced by 16 distinct known and novel fluoroalkyl motifs on three parent models. Fifty fluorinated compounds, with 28 novel experimental aliphatic log P values, are involved in discussing various lipophilicity trends. As well as confirming known trends, a number of novel lipophilicity-reducing motifs are introduced. Tactics to reduce lipophilicity are discussed, such as "motif extensions" and "motif rearrangements", including with concomitant extension of the carbon chain, as well as one- and two-fluorine 'deletions' within perfluoroalkyl groups. Quantum chemical log P calculations (SMD-MN15) based on solvent-dependent three-dimensional (3D) conformational analysis gave excellent correlations with experimental values, superior to Clog P predictions based on 2D structural motifs. The availability of a systematic collection of data based on a small number of parent molecules illustrates the relative lipophilicity modulations of aliphatic fluorination motifs.".
• 01GMMX7C533K47MG9YYC9J76GE abstract "The highly strained cubane system is of great interest as a scaffold and rigid linker in both pharmaceutical and materials chemistry. The first electrochemical functionalisation of cubane by oxidative decarboxylative ether formation (Hofer-Moest reaction) was demonstrated. The mild conditions are compatible with the presence of other oxidisable functional groups, and the use of flow electrochemical conditions allows straightforward upscaling.".
• 01GMMX7C58V5KM9SA6WNHKVKTE abstract "This is the first paper in a sequential pair devoted to the enzyme mutarotase (aldose 1-epimerase; EC 5.1.3.3). Here, the broader context of the physiological role of mutarotase, among those enzymes considered to be part of 'metabolic structure', is reviewed. We also summarise the current knowledge about the molecular mechanism and substrate specificity of the enzyme, which is considered in the context of the binding of fluorinated glucose analogues to the enzyme's active site. This was done as a prelude to our experimental studies of the anomerisation of fluorinated sugars by mutarotase that are described in the following paper.".
• 01GMMX7C5CVT7RDFXQG6CWZ2Q6 abstract "Five F-19-substituted glucose analogues were used to probe the activity and mechanism of the enzyme mutarotase by using magnetisation-exchange NMR spectroscopy. The sugars (2-fluoro-2-deoxy-D-glucose, FDG2; 3-fluoro-3-deoxyD-glucose, FDG3; 4-fluoro-4-deoxy-D-glucose, FDG4; 2,3-difluoro-2,3-dideoxy-D-glucose, FDG23; and 2,2,3,3-tetrafluoro-2,3-dideoxy-D-glucose (2,3-dideoxy-2,2,3,3-tetrafluoro-D-erythro-hexopyranose), FDG2233) showed separate F-19 NMR spectroscopic resonances from their respective alpha- and beta-anomers, thus allowing two-dimensional exchange spectroscopy measurements of the anomeric interconversion at equilibrium, on the time scale of a few seconds. Mutarotase catalysed the rapid exchange between the anomers of FDG4, but not the other four sugars. This finding, combined with previous work identifying the mechanism of the anomerisation by mutarotase, suggests that the rotation around the C1-C2 bond of the pyranose ring is the rate-limiting reaction step. In addition to D-glucose itself, it was shown that all other fluorinated sugars inhibited the FDG4 anomerisation, with the tetrafluorinated FDG2233 being the most potent inhibitor. Inhibition of mutarotase by F-sugars paves the way for the development of novel fluorinated compounds that are able to affect the activity of this enzyme in vitro and in vivo.".
• 01GMMX7H22D446SD2WNEPA0NAG abstract "The dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important receptor of the immune system. Besides its role as pathogen recognition receptor (PRR), it also interacts with endogenous glycoproteins through the specific recognition of self-glycan epitopes, like Le(x). However, this lectin represents a paradigmatic case of glycan binding promiscuity, and it also has been shown to recognize antigens with alpha 1-alpha 2 linked fucose, such as the histo blood group antigens, with similar affinities to Le(x). Herein, we have studied the interaction in solution between DC-SIGN and the blood group A and B antigens, to get insights into the atomic details of such interaction. With a combination of different NMR experiments, we demonstrate that the Fuc coordinates the primary Ca2+ ion with a single binding mode through 3-OH and 4-OH. The terminal alpha Gal/alpha GalNAc affords marginal direct polar contacts with the protein, but provides a hydrophobic hook in which V351 of the lectin perfectly fits. Moreover, we have found that alpha Gal, but not alpha GalNAc, is a weak binder itself for DC-SIGN, which could endow an additional binding mode for the blood group B antigen, but not for blood group A.".
• 01GMMX7H29135DE8KMFRXKA1EB abstract "Fluorinated carbohydrates have been employed as probes for fundamental studies of protein-carbohydrate interactions, but also in the development of mechanism-based enzyme inhibitors. There is a continuing demand for novel fluorinated carbohydrate probes. Whereas most examples so far involved monodeoxyfluorinated sugars, multiply deoxyfluorinated sugars have gained much interest. Here we report the synthesis and characterisation of novel vicinal dideoxy-difluorinated D-galactoses with fluorination at the 3,4-positions, and at the 2,3-positions, the latter in both the pyranose and furanose forms. This includes a successful pyranose-into-furanose isomerisation protocol.".
• 01GMMX7H2DZP8MW9S6CBY2T74H abstract "A fluorine nuclear magnetic resonance (F-19-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The strategy employed allows not only screening of a mixture of compounds, but also obtaining valuable information on the specific sugar-protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc, and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, is also detected for the first time. The combination of the F-19 with standard proton saturation transfer difference (H-1-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture.".
• 01GMMX7NYYC318FZJT0FNJRRT3 abstract "There is an increasing interest in investigating how polyfluorination of carbohydrates modifies their physical and biological properties. An example that has caught much attention is 2,3,4-trideoxy-2,3,4-trifluoroglucose. Four syntheses of this compound have been reported, which are either low yielding or long (13 or more steps). We report a 6-step synthesis of 2,3,4-trideoxy-2,3,4-trifluoroglucose starting from levoglucosan. The solution-phase structure of an intermediate, 1,6-anhydro-2,4-dideoxy-2,4-difluoroallose, features a rare example of a bifurcated F center dot center dot center dot H(O)center dot center dot center dot F hydrogen bond and is compared to its crystal structure.".
• 01GMMX7NZ3RTAXDCMCJP5ZJ5NQ abstract "Fluorination has become an effective tool to optimize physicochemical properties of bioactive compounds. One of the applications of fluorine introduction is to modulate the lipophilicity of the compound. In our group, we are interested in the study of the impact of fluorination on lipophilicity of aliphatic fluorohydrins and fluorinated carbohydrates. These are not UV-active, resulting in a challenging lipophilicity determination. Here, we present a straightforward method for the measurement of lipophilicity of fluorinated compounds by F-19 NMR spectroscopy. This method requires no UV-activity. Accurate solute mass, solvent and aliquot volume are also not required to be measured. Using this method, we measured the lipophilicities of a large number of fluorinated alkanols and carbohydrates.".
• 01GMMX7NZ7BHYQK5VBSPMWSBHD abstract "Fluorination is commonly employed to optimize bioactivity and pharmaco-kinetic properties of drug candidates. Aliphatic fluorination often reduces the lipophilicity (log P), but polyfluoroalkylation typically increases lipophilicity. Hence, identification of polyfluorinated motifs that nonetheless lead to similar or even reduced lipophilicities is of interest to expand the arsenal of medicinal chemistry tools in tackling properties such as compound metabolic stability or off-target selectivity. We show that changing a CF3-group of a perfluoroalkyl chain to a methyl group leads to a drastic reduction in lipophilicity. We also show that changing a C-F bond of a trifluoromethyl group, including when incorporated as part of a perfluoroalkyl group, to a C-Me group, leads to a reduction in log P, despite the resulting chain elongation. The observed lipophilicity trends were identified in fluorinated alkanol models and reproduced when incorporated in analogues of a drug candidate, and the metabolic stability of these motifs was demonstrated.".
• 01GMMX7NZC6DR68A738C24R3E0 abstract "We have developed a new approach, to our knowledge, to quantify the equilibrium exchange kinetics of carrier-mediated transmembrane transport of fluorinated substrates. The method is based on adapted kinetic theory that describes the concentration dependence of the transmembrane exchange rates of two competing, simultaneously transported species. Using the new approach, we quantified the kinetics of membrane transport of both anomers of three monofluorinated glucose analogs in human erythrocytes (red blood cells) using F- 19 NMR exchange spectroscopy. An inosine-based glucose-free medium was shown to promote survival and stable metabolism of red blood cells over the duration of the experiments (several hours). Earlier NMR studies only yielded the apparent rate constants and transmembrane fluxes of the anomeric species, whereas we could categorize the two anomers in terms of the catalytic activity (specificity constants) of the glucose transport protein GLUT1 toward them. Differences in the membrane permeability of the three glucose analogs were qualitatively interpreted in terms of local perturbations in the bonding of substrates to key amino acid residues in the active site of GLUT1. The methodology of this work will be applicable to studies of other carrier-mediated membrane transport processes, especially those with competition between simultaneously transported species. The GLUT1-specific results can be applied to the design of probes of glucose transport or inhibitors of glucose metabolism in cells, including those exhibiting the Warburg effect.".
• 01GMMX7TW00PDYTBH7MVJQKQ2W abstract "The diastereoselective synthesis of fluorinated building blocks that contain chiral fluorine substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syndiastereomer. Both targets were synthesised using an epoxide opening strategy.".
• 01GMMX7ZRFFR2CN4Z6672RB9DY abstract "A three-step synthesis of enantiomerically enriched 1,1,1-trifluoro-2-propanamine based on the use of a chiral sulfinamide auxiliary is described. The reduction of the geometrically pure Z-sulfinimine (NOE, HOE) with NaBH4 or L-Selectride leads to the corresponding (R)- or (S)-configured amine derivatives (X-ray crystallographic analysis) with 92-96% de. The typical models to explain the stereoselection for these reducing agents fail to rationalize the obtained stereoselectivities, and an in situ imine isomerization is proposed to occur. The direct use of the hydrochloric acid salt (with excess Et3N) of this poorly nucleophilic amine for epoxide opening reactions is not possible due to the higher nucleophilicity of chloride. Hence, a novel triflate salt is introduced, synthesized through ready sulfinamide hydrolysis with trimethylsilyl triflate, which can be used directly, without the need of isolating the pure amine beforehand. (C) 2017 Elsevier Ltd. All rights reserved.".
• 01GMMX7ZRK8CVP15GABJKG70XS abstract "Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH center dot center dot center dot O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine.".
• 01GMMX7ZRQGSQVA16EZEZXB79Q abstract "Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donating capacity (designated by pK(AHY)) when OH center dot center dot center dot F intramolecular hydrogen-bond (IMHB) interactions occur, as opposed to an increase in pK(AHY) due to the fluorine electronegativity. This work has now been extended to a wider range of aliphatic beta-fluorohydrins with increasing degrees of conformational flexibility. We show that the observed differences in pK(AHY) between closely related diastereomers can be fully rationalized by subtle variations in populations of conformers able to engage in OH center dot center dot center dot F IMHB, as well as by the strength of these IMHBs. We also show that the Kenny theoretical V-alpha(r) descriptor of H-bond acidity accurately reflects the observed variations and a calibration equation extended to fluorohydrins is proposed. This work clearly underlines the importance of the weak OH center dot center dot center dot F IMHB in the modulation of alcohol H-bond donating capacity.".
• 01GMMX84N78ZENQ9G2Z4ACSPFH abstract "The synthesis of a novel dideoxydifluorinated fluorosugar is described starting from levoglucosan. The fluorine atoms were introduced sequentially through 3,4-epoxide opening and retentive 3-OH deoxofluorination. This latter process was accompanied by a rearrangement process involving the 2-OBn group, which is consistent with previous results of Karban et. al. (Beilst. J. Org. Chem. 2016, 12, 750), who observed a similar rearrangement involving a 2-azido group.".
• 01GMMX84NBVCMKYK5RSCPN5HFP abstract "Background: Galactose oxidase (GOase) catalyses the highly selective oxidation of terminal galactosides on a wide range of natural glycoconjugates and has found wide applications in biotechnology - particularly in biocatalysis. GOase is copper dependent and uses oxygen to oxidise the C6-primary alcohol of galactose and produces hydrogen peroxide. The enzyme activity can be conveniently assessed by a colorimetric assay.".
• 01GMMX84NF9S2DTWF5NTXDNQZC abstract "The conformational preferences of o-cresols driven by fluorination were thoroughly investigated from a theoretical point of view with quantum-chemical methods, and the results were compared to those recently reported for benzyl alcohols. The key conformers of both families exhibit a six-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement in the strength of the IMHB is observed in -fluoro-o-cresols, owing to a simultaneous increase in the hydrogen bond (HB) basicity of the aliphatic fluorine and the HB acidity of the aromatic hydroxyl relative to that observed for o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the cases of the di- and trifluorinated derivatives, the occurrence of a three-centered HB is emphasized, and its features are discussed. The impact of these structural predilections on the HB properties of o-cresol was characterized from the estimation of the HB acidity parameter, pK(AHY), weighted according to their conformational populations. We found that -fluorination led to a decrease in the HB acidity of the hydroxyl group (in contrast with the o-fluorination of benzyl alcohols), whereas ,-difluorination resulted in no significant variation in pK(AHY). Finally, an increase in the HB acidity was predicted upon methyl perfluorination, which was confirmed experimentally. Theoretical descriptors based on atoms in molecules, noncovalent interactions, and natural bond orbital analyses allowed rationalization of the predicted trends and revealed a relationship with the strength of the established OH center dot center dot center dot F IMHB.".
• 01GMMX89HYNAYED53DPFNGVZNY abstract "Carbohydrates typically have low affinities to protein binding sites, and the development of carbohydrate mimetics with improved binding is therefore of interest. Tetrafluorination of monosaccharides is one of the strategies currently under investigation for that purpose. The synthesis of the required tetrafluorinated monosaccharides is achieved by a fluorinated building block approach. The enantioselective synthesis of tetrafluorinated hexose derivatives is described here, in both pyranose and furanose forms. In particular, the optimization of the enantioselective synthesis of the previously reported 2,3-dideoxy-2,2,3,3-tetrafluoro-D-threo-hexopyranose 3, 2,3-dideoxy-2,2,3,3-tetrafluoro-D-threo-hexofuranose 4, and 2,3-dideoxy2,2,3,3-tetrafluoro-D-erythro-hexopyranose 5 is described as is the synthesis of two novel sugar derivatives, 3,4-dideoxy-3,3,4,4-tetrafluoro-D-threo-hexopyranose 6 and 3,4-dideoxy-3,3,4,4-tetrafluoro-D-eiythro-hexopyranose 7. The key step of all syntheses is a perfluoroalkyl lithium-mediated C-C bond formation, either intramolecular or intermolecular, which proceeds in good to excellent yields. NMR and X-ray crystallographic analyses of the tetrafluorinated methyl pyranoside derivatives confirm their C-4(1) conformation.".
• 01GMMX89J3D7WP4VMQEEXSQR32 abstract "A second-generation synthesis of (-)-luminacin D based on an early stage introduction of the trisubstituted epoxide group is reported, allowing access to the natural product in an improved yield and a reduced number of steps (5.4%, 17 steps vs 2.6%, 19 steps). A full account of the optimization work is provided, with the reversal of stereoselection in the formation of the C4 alcohol in equally excellent diastereoselectivity as the key improvement.".
• 01GMMX89J7ESR7RAM8KEJWHP3V abstract "In plants, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan-II (RG-II). Incubation of 4-day-old light-grown Arabidopsis seedlings or tobacco BY-2 cells with 8-azido 8-deoxy Kdo (Kdo-N-3) followed by coupling to an alkyne-containing fluorescent probe resulted in the specific in muro labelling of RG-II through a copper-catalysed azide-alkyne cycloaddition reaction. CMP-Kdo synthetase inhibition and competition assays showing that Kdo and D-Ara, a precursor of Kdo, but not L-Ara, inhibit incorporation of Kdo-N-3 demonstrated that incorporation of Kdo-N-3 occurs in RG-II through the endogenous biosynthetic machinery of the cell. Co-localisation of Kdo-N-3 labelling with the cellulose-binding dye calcofluor white demonstrated that RG-II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo-N-3 and an alkynated derivative of L-fucose that incorporates into rhamnogalacturonan I, co-localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click-mediated labelling with Kdo-N-3 provides an efficient method to study the synthesis and redistribution of RG-II during root growth.".
• 01GMMX89K2CWT000X5WH09688E abstract "Property tuning by fluorination is very effective for a number of purposes, and currently increasingly investigated for aliphatic compounds. An important application is lipophilicity (logP) modulation. However, the determination of logP is cumbersome for non-UV-active compounds. A new variation of the shake-flask logP determination method is presented, enabling the measurement of log P for fluorinated compounds with or without UV activity regardless of whether they are hydrophilic or lipophilic. No calibration curves or measurements of compound masses/aliquot volumes are required. With this method, the influence of fluorination on the lipophilicity of fluorinated aliphatic alcohols was determined, and the log P values of fluorinated carbohydrates were measured. Interesting trends and changes, for example, for the dependence on relative stereochemistry, are reported.".
• 01GMMX8EEPN7ESEMFXPS1QGHFE abstract "Fluorination is commonly exercised in compound property optimization. However, the influence of fluorination on hydrogen-bond (HB) properties of adjacent functional groups, as well as the HB-accepting capacity of fluorine itself, is still not completely understood. Although the formation of OH center dot center dot center dot F intramolecular HBs (IMHBs) has been established for conformationally restricted fluorohydrins, such interaction in flexible compounds remained questionable. Herein is demonstrated for the first time-and in contrast to earlier reports-the occurrence of OH center dot center dot center dot F IMHBs in acyclic saturated g-fluorohydrins, even for the parent 3-fluoropropan-1-ol. The relative stereochemistry is shown to have a crucial influence on the corresponding (h1)J(OH center dot center dot center dot F) values, as illustrated by syn- and anti-4-fluoropentan-2-ol (6.6 and 1.9 Hz). The magnitude of OH center dot center dot center dot F IMHBs and their strong dependence on the overall molecular conformational profile, fluorination motif, and alkyl substitution level, is rationalized by quantum chemical calculations. For a given alkyl chain, the "rule of shielding" applies to OH center dot center dot center dot F IMHB energies. Surprisingly, the predicted OH center dot center dot center dot F IMHB energies are only moderately weaker than these of the corresponding OH center dot center dot center dot OMe. These results provide new insights of the impact of fluorination of aliphatic alcohols, with attractive perspectives for rational drug design.".
• 01GMMX8EF83H50CA7Z2RBJFGAD abstract "The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o-fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OHF interaction, secondary CHF and/or CHO interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors.".
• 01GMMX8EFHZAPZDSCAV1A07RSV abstract "A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. Very high affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. Crystal structure analysis was conducted on a number of PI analogues in complex with HIV-1 protease.".
• 01GMMX8R9275W206QA6QBTBN5B abstract "UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F-4-Galp) and UDP-Galf (UDP-F-4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F-4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation (E-4) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics.".
• 01GMMX8X5J717QNNX5KAHF5SCR abstract "A comprehensive conformational analysis of both 2,3-difluorobutane diastereomers is presented based on density functional theory calculations in vacuum and in solution, as well as NMR experiments in solution. While for 1,2-difluoroethane the fluorine gauche effect is clearly the dominant effect determining its conformation, it was found that for 2,3-difluorobutane there is a complex interplay of several effects, which are of similar magnitude but often of opposite sign. As a result, unexpected deviations in dihedral angles, relative conformational energies and populations are observed which cannot be rationalised only by chemical intuition. Furthermore, it was found that it is important to consider the free energies of the various conformers, as these lead to qualitatively different results both in vacuum and in solvent, when compared to calculations based only on the electronic energies. In contrast to expectations, it was found that vicinal syn-difluoride introduction in the butane and by extension, longer hydrocarbon chains, is not expected to lead to an effective stabilisation of the linear conformation. Our findings have implications for the use of the vicinal difluoride motif for conformational control.".
• 01GMMX8X5Q5VEDF5N7VZCHJN9X abstract "A four-step, three-stage synthesis of the API ropinirole hydrochloride has been developed from a commercially available naphthalene derivative. The new route has half the step-count and twice the overall yield of the current manufacturing process. Key features of the synthesis are a regioselective Birch reduction and an ozonolysis with concomitant ring closure to induce the required ring contraction.".
• 01GMMX971PS0GTX5TQS93QFZF6 abstract "A total synthesis of paroxetine is reported, with a diastereo-selective and diastereoconvergent cobalt-catalysed sp(3)-sp(2) coupling reaction involving a 3-substituted 4-bromo-N-Bocpiperidine (Boc = tert-butoxycarbonyl) substrate as a key step. A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.".
• 01GMMX9BVTYV3110AVT03WNN3N abstract "The Reformatsky reaction of ethyl bromodifluoroacetate to alpha-oxygenated sulfinylimines is described. Using Honda-Reformatsky conditions, the reaction proceeds with double diastereodifferentiation, with the configuration of the sulfinyl group determining the stereochemical course of the reaction. Excellent diastereoselectivities (>94:6) are obtained for the matched cases. In contrast, reaction with sulfinylimines derived from unsubstituted alkanals proceeded with virtually no diastereoselectivity.".
• 01GMMX9BW2Y2V07N9BWEEY4SNY abstract "Carbohydrate-aromatic interactions are highly relevant for many biological processes. Nevertheless, experimental data in aqueous solution relating structure and energetics for sugar-arene stacking interactions are very scarce. Here, we evaluate how structural variations in a monosaccharide including carboxyl, N-acetyl, fluorine, and methyl groups affect stacking interactions with aromatic DNA bases. We find small differences on stacking interaction among the natural carbohydrates examined. The presence of fluorine atoms within the pyranose ring slightly increases the interaction with the C-G DNA base pair. Carbohydrate hydrophobicity is the most determinant factor. However, gradual increase in hydrophobicity of the carbohydrate does not translate directly into a steady growth in stacking interaction. The energetics correlates better with the amount of apolar surface buried upon sugar stacking on top of the aromatic DNA base pair.".
• 01GMMX9BW6E4WCJPKH2EKZT5ZH abstract "Very high diastereoselectivity can be achieved by 1,3-chelation-controlled allylation of aldehydes that possess a non-chelating -ether substituent, even if the -position is a quaternary centre and/or a spiro-epoxide. This reaction was used as a key step in an enantioselective synthesis of the angiogenesis inhibitor luminacinD.".
• 01GMMX9GRPAE9S4X5NXDSVF2XB abstract "Tetrafluorinated analogues of both UDP-galactopyranose and UDP-galactofuranose have been synthesized and assayed against UDP-galactopyranose mutase, a key enzyme for Mycobacterium tuberculosis cell wall biosynthesis. Competition assays and STD-NMR spectroscopy techniques have evidenced not only the first unambiguous case of affinity enhancement through local sugar polyfluorination, but also showed that tetrafluorination can still have a beneficial effect on binding when monofluorination at the same position does not.".
• 01GMMX9GS08SR94FCH7CTQ2A17 abstract "Convenient access to homochiral fluoroalkenes is described via a Julia-Kocienski olefination reaction. The required homochiral fluorosulfone is synthesized by a Mitsunobu reaction from readily available enantiopure secondary alcohols.".
• 01GMMX9ZF1JQZBVQSF7P8SR00C abstract "A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. High affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. A number of PIs have been synthesized that show equivalent and greater activity for HIV-1 mutant strains as compared to wild-type HIV-1. The activity on the purified enzyme was confirmed for a selection of analogues.".
• 01GMMX9ZF6XA3EDXYADTZRBFJ9 abstract "Galactose oxidase (GOase) was shown to oxidise several C2/C3 fluorinated galactose analogues. Interestingly, the enzyme was able to distinguish between the 2,3-tetrafluorinated galactose and its epimeric glucose analogue, and this represents the first reported biotransformation of a heavily fluorinated sugar.".
• 01GMMXA4BMR19DFY7488GF4NRB abstract "The crystal structure of a reducing dibenzylated tetrafluorinated galactose derivative is reported. The compound crystallized as the alpha-anomer, and a single OH center dot center dot center dot O hydrogen bond dominates the crystal packing, leading to a helical arrangement containing two galactose derivatives per turn. Interestingly, the helices are cross-linked by ArC-H center dot center dot center dot F contacts, but without significant Ar-Ar interactions.".
• 01GMMXA4BXE5T5NMN176ZW17AG abstract "A large-scale synthesis of meso-2,3-difluoro-1,4-butanediol in 5 steps from (Z)-but-2-enediol is described. Crystallographic analysis of the diol and the corresponding benzyl ether reveals an anti conformation of the vicinal difluoride moiety. Monosilylation of the diol is high-yielding but all attempts to achieve chain extension through addition of alkyl Grignard and acetylide nucleophiles failed.".
• 01GMMXA98FK6SYPS62A9EWW8YV abstract "A general steroid synthesis is presented that relies on prior formation of three stereogenic centers (C8, C13, and C14) on a D ring template, followed by C- and B-ring cyclizations. The assembly of the key D ring template, achieved by a 3-component conjugate addition/alkylation process, allows introduction of structural variety as required. The method is illustrated by the total synthesis of estrone via a C-ring closing metathesis and a B-ring Heck cyclization.".
• 01GMMXA98RBRRSZSF8RFVF7K0H abstract "The formation of carboxylic esters via reaction of carboxylic acids with O-alkylisoureas proceeds in excellent yields with very short reaction times when conducted in a monomode microwave synthesizer. Efficient processes were developed using preformed or commercially available isoureas derived from primary and secondary alcohols, with a reaction time of only 5 min or less. It was demonstrated that under these microwave conditions, ester formation proceeded in good yields with clean inversion of configuration where appropriate. The process was validated using menthol, a hindered substrate for S(N)2 reactions. In addition, starting from primary alcohols, ester formation was successfully accomplished using ail in situ isourea formation procedure. A polymer-assisted solution-phase procedure was also developed by employing preformed solid-supported isoureas and by an efficient "catch and release" ester formation procedure whereby primary alcohols were caught on resin as isoureas by reaction with immobilized carbodiimide and released as esters by subsequent treatment with a carboxylic acids.".
• 01GMMXAK260S5HT69XF54E1ACB abstract "A perfluoroalkylidene lithium mediated cyclisation approach for the enantioselective synthesis of a tetrafluorinated aldose (ribose) and of a tetrafluorinated ketose (fructose), both in the furanose and in the pyranose form, is described.".
• 01GMMXAQYN10EP83N25DKRCAAS abstract "A convenient synthesis of carbanuclecosides, with both enantiomers equally accessible, is reported. The key step is a tandem linchpin cyclization process to give access to substituted carbafuranose derivatives having the correct relative stereochemistry for subsequent nucleobase introduction with inversion of configuration at C 1. This was illustrated by the synthesis of 2',3'-dideoxycarbathymidine via a convergent nucleobase introduction and of 2',3'-dideoxy-6'-hydroxycarbauridine via a linear nucleobase introduction. Both methods relied on Mitsunobu chemistry, and the first example of the Mukaiyama modification of the Mitsunobu reaction involving nucleobases as nucleophiles is reported.".
• 01GMMXAWVGPS2PDNPJDGHSCE1Z abstract "Polyfluorinated carbohydrates have emerged as interesting probes to investigate "polar hydrophobicity" effect(s) in protein-carbohydrate interactions. A convenient enantioselective synthesis of tetrafluorinated analogues of two of the most important monosaccharides, D-glucose and D-galactose, is reported, as well as our first results regarding the glycosylation of these sugar analogues.".
• 01GMMXAWVSSFM7Z7532C8W24EN abstract "This contribution gives on overview of the literature regarding the Sharpless Asymmetric Dihydroxylation of alkenes which contain a perfluoroalkyl (R-F = CnF2n+1) or a perfluoroalkylidene (R(CF2)(n)) substituent (hereafter termed "fluorinated alkenes"). Modifications required for these unreactive substrates towards OsO4-mediated dihydroxylation are highlighted, as well as a comparison of enantioselectivities with the corresponding nonfluorinated alkenes.".
• 01GMMXB1R7KJB5ACVJKSFDRE0F abstract "An efficient, enantioselective synthesis of a disubstituted bis-THF scaffold 5 is described, as well as an efficient differentiation of the 1,3-diol unit.".
• 01GMMXB1RBMW6PHFCZ1BYY4YGE abstract "The synthesis of an achiral skipped bis(1,3-diene) substrate was achieved, which was shown to undergo an enantioselective, diastereotopic group-selective, intramolecular Diels-Alder reaction.".
• 01GMMXB1RFKKRJ4M1F262E9BQV abstract "A concise synthesis of highly functionalized cyclopentane derivatives via a Brook rearrangement mediated stereoselective linchpin cyclization reaction involving tert-butyldimethylsilyl-1,3-dithianyllithium and homochiral 1,4-bis-epoxides is described.".
• 01GMMXB6MZ0HXCF2XJ339EQJ6P abstract "A straightforward three-step synthesis of a solid-supported IBX amide resin was achieved using inexpensive and commercially available 2-iodobenzoic acid chloride and Merrifield resin. A high apparent loading of 0.63 mmol g(-1) was obtained. Oxidation of a range of alcohols to the corresponding carbonyl compounds proved very straightforward using 1.2 equiv of the resin. Recycling of the resin was also possible with minimal loss of activity after two reoxidations.".
• 01GMMXBBHSYDJ34NAZY15E9ZYF abstract "Polymer-supported O-alkylisoureas were prepared by reaction of an alcohol with a polymer-supported carbodiimide under copper(II) catalysis. These reagents were used to transform carboxylic acids into the corresponding methyl, benzyl, allyl, and p-nitrobenzyl esters in a highly chemoselective manner in high yields and in very high purity after simple resin filtration and solvent evaporation. The reactions could be carried out using both conventional or microwave heating, with reaction times as short as 3-5 min in the latter case, without compromising yield, purity, or chemoselectivity. Unfortunately, the corresponding solid-supported tert-butyl isoureas could not be prepared.".
• 01GMMXBGEKNCZ79H50KVH84494 abstract "On the basis of our previously described selective protection of arabitol as its 1,2:4,5-bis-pentylidene acetal 5, we report a straightforward synthesis of the novel "pseudo"-C-2-symmetric 3-azido-1,2:4,5-diepoxypentane building block 4 in 6 steps from arabitol. Using a similar synthetic route, an improved synthesis of the C-2-symmetrical 1,2:4,5-bis-epoxypentane building block I is described, also in 6 steps from arabitol. Both enantiomers of 1 and 4 are accessible, and all reactions involved are easily amenable for large-scale synthesis.".
• 01GMMXBNBBGQYPFGN8QBZMEWVJ abstract "The benefits of microwave irradiation are described for a number of important reactions such as amid and ester formation and dehydration of formamide to the corresponding isonitriles. Not only were reaction times dramatically reduced but the transformations were less prone to side reactions and decomposition.".
• 01GMMXBNBFXT1EPP4RWFGCJF1G abstract "Graphics".
• 01GMMXBNBFXT1EPP4RWFGCJF1G abstract "Polymer-supported O-methyl, O-benzyl, and O-allyl-isoureas were prepared by copper(II)-catalyzed reaction of polymer-supported carbodiimide with the corresponding alcohols. These polymer-supported reagents were successfully employed to convert a series of carboxylic acids to methyl, benzyl, or allyl esters, in good yields. The products were obtained with high purity (>95% by NMR) after a simple resin filtration-solvent evaporation sequence.".
• 01GMMXBNBKKT1ZBM6CZXZVYQ72 abstract "A short synthesis of the homochiral disubstituted butenolide 1 is described in four steps from arabitol. The key steps are the selective kinetic protection of arabitol and the cyclization of 11 to form the butenolide ring. This last transformation represents a rare example of a fully stereoselective cyclitive desymmetrization process of a "pseudo"-C-2-symmetric substrate.".
• 01GMMXBT8101ZE64MG9B93RAF3 abstract "Alcohols can be converted in high yields to the corresponding alkyl halides in a one-pot procedure via the corresponding O-alkylisourea; very short reaction times are possible when microwave irradiation is used.".
• 01GMMXBT85PXNT0Y3T885PDV74 abstract "Microwave-assisted beta-alkylations of several carboxylic acids have been performed with three different beta-alkylisoureas. All reactions are significantly faster compared to conventionally heated reactions, while retaining high chemoselectivity. The combination of microwave technology with the use of the solid-supported isourea 3 enables the synthetic chemist to obtain the pure methyl esters starting from the corresponding acids in less than an hour.".

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