gebhart/patrepeval huggingface dataset:
Telechelics by Carbocationic Techniques (2018)

This chapter demonstrates that carbocationic polymerization has been developed to the stage where a large number of telechelics, which are not accessible by other methods, can be synthesized. In order to synthesize telechelics from methylpropene via a typical cationic mechanism, it is essential that the initiation, the propagation, and the termination or transfer reactions can be controlled. Telechelics with olefinic end-groups are useful intermediates for a wide variety of telechelic derivates. The reaction of the iodine-terminated telechelic with hexamethylenediamine (HMDA) leads to polymers with higher molar masses than the starting telechelics. The reaction of the iodine-terminated telechelic with HMDA leads to polymers with higher molar masses than the starting telechelics. These results indicate that the telechelic polymer reacted with both ends of HMDA to induce a chain extension reaction. Polymethylpropene carrying a tert-chloride end-group has been quantitatively converted to a variety of derivatives. Divinylbenzene usually yields insoluble cross-linked polymers from radical and anionic polymerizations.
Acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase. Evidence for a transmembrane acetylation mechanism. (1985)

The lysosomal membrane enzyme acetyl-CoA: alpha-glucosaminide N-acetyltransferase catalyzes the transfer of an acetyl group from acetyl-CoA to terminal alpha-linked glucosamine residues of heparan sulfate. The reaction mechanism was examined using highly purified lysosomal membranes from rat liver. The reaction was followed by measuring the acetylation of a monosaccharide acetyl acceptor, glucosamine. The enzyme reaction was optimal above pH 5.5, and a 2-3-fold stimulation of activity was observed when the membranes were assayed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicated that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. Further evidence to support this mechanism was provided by characterization of the enzyme half-reactions. Membranes incubated with acetyl-CoA and [3H]CoA were found to produce acetyl-[3H]CoA. This exchange was optimal at pH values above 7.0. Treating membranes with [3H] acetyl-CoA resulted in the formation of an acetyl-enzyme intermediate. The acetyl group could then be transferred to glucosamine, forming [3H]N-acetylglucosamine. The transfer of the acetyl group from the enzyme to glucosamine was optimal between pH 4 and 5. The results suggest that acetyl-CoA does not cross the lysosomal membrane. Instead, the enzyme is acetylated on the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate.
Mass Spectrometric and Gas Chromatographic Evidence for Some New Components in the Gas Phase of Tobacco Smoke (1970)

The gas phase of fresh tobacco smoke was injected onto an open-tubular gas chromatography column at low temperature. Mass spectra and retention data for components eluted on temperature programming suggest the presence of six new compounds: 1,1-, 1,2-cis-, and 1,2-trans- dimethylcyclopropanes; 1-chloro-5-methylhexane; 1,3,5-hexatriene; and 2-methyl-1-octene
Filtrage conditionnel pour le suivi de points dans des sequences d'images (2003)

National audience
Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE (2023)

Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin and mucin-domain containing family of proteins (TIM-1, -3, -4) decorate immune cells and act as key checkpoint inhibitors in cancer. However, their dense O-glycosylation remains enigmatic both in terms of glycoproteomic landscape and structural dynamics, primarily due to the challenges associated with studying mucin domains. Here, we present a mucinase (SmE) and demonstrate its ability to selectively cleave along the mucin glycoprotein backbone, similar to others of its kind. Unlike other mucinases, though, SmE harbors the unique ability to cleave at residues bearing extremely complex glycans which enabled improved mass spectrometric analysis of several mucins, including the entire TIM family. With this information in-hand, we performed molecular dynamics (MD) simulations of TIM-3 and -4 to demonstrate how glycosylation affects structural features of these proteins. Overall, we present a powerful workflow to better understand the detailed molecular structures of the mucinome.
Film Cooling Measurements for Cratered Cylindrical Inclined Holes (2007)

Film cooling performance is studied for cylindrical holes embedded in craters. Different crater geometries are considered for a typical crater depth. Cratered holes may occur when blades are coated with thermal barrier coating layers by masking the hole area during TBC spraying resulting in hole surrounded by TBC layer. The film performance and behavior is expected to be different for the cratered holes compared to standard cylindrical holes. Detailed heat transfer coefficient and film effectiveness measurements are obtained simultaneously using a single test transient IR thermography technique. The study is performed at a single mainstream Reynolds number based on free-stream velocity and film hole diameter of 11000 at four different coolant-to-mainstream blowing ratios of 0.5, 1.0, 1.5 and 2.0. The results show that film cooling effectiveness is slightly enhanced by cratering of holes but a substantial increase in heat transfer enhancement negates the benefits of higher film effectiveness. Three different crater geometries are studied and compared to a baseline flush cylindrical hole, a trenched hole, and a typical diffuser shaped hole. CFD simulation using Fluent was also performed to determine the jet-mainstream interactions associated with the experimental surface measurements.
Phosphor sensitized thermally activated delayed fluorescence organic light-emitting diodes with ideal deep blue device performances (2019)

Phosphorescence sensitized thermally activated delayed fluorescent organic light-emitting diodes realized a high external quantum efficiency of 24.8% and deep blue color coordinates of (0.131, 0.107).
State-to-state reactive scattering amplitudes from single-arrangement propagation with absorbing potentials (1990)

A new paradigm is presented for calculation of reactive state-to-state transition amplitudes. The wave function is propagated in one arrangement (either reagents or the sought products, the choice being at one’s convenience); other arrangements are blocked with an absorbing potential. Reactive information is then obtained from the integral expression for the T matrix (〈ψ‖H−H0‖Ψ〉). The approach is exemplified on a collinear system, yielding accurate transition probabilities that are insensitive to the parameters of the absorbing potential. Expressions for the complete T matrix in the new reactive IOS are then derived, based solely on an IOS assumption in one of the arrangements, without a need to invoke matching procedures between different arrangements.
Role of disulfide bonds in biologic activity of human interleukin-6. (1991)

We have examined the functional importance of the two disulfide bonds formed by the four conserved cysteines of human interleukin (IL-6). Using a bacterial expression system, we have synthesized a series of recombinant IL-6 mutants in which the constituent cysteines of the first (Cys45-Cys51), second (Cys74-Cys84), or both disulfide bonds of recombinant human interleukin-6 were replaced by other amino acids. Each mutant was partially purified and tested in four representative bioassays. While mutants lacking Cys45 and Cys51 retained activity similar to nonmutated recombinant IL-6, the activity of mutants lacking Cys74 and Cys84 was significantly reduced, especially in assays involving human cell lines. These results indicate that the first disulfide bond of human interleukin-6 is not required for maintenance of normal biologic activity. However, the fact that mutants lacking Cys45 and Cys51 were more active than corresponding cysteine-free mutants indicates that the disulfide bond formed by these residues contributes to biologic activity in the absence of the second disulfide bond. Competition binding studies with representative mutants indicate that their affinity for the human IL-6 receptor parallels their biologic activities on human cells.
Rapid Production of Recombinant Allergens in <i>Nicotiana benthamiana</i> and Their Impact on Diagnosis and Therapy (2001)

We conclude that this plant expression system offers a viable alternative to fermentation-based production of allergens in bacteria or yeasts.
ADAMTS10-mediated tissue disruption in Weill–Marchesani syndrome (2018)

Fibrillin microfibrils are extracellular matrix assemblies that form the template for elastic fibres, endow blood vessels, skin and other elastic tissues with extensible properties. They also regulate the bioavailability of potent growth factors of the TGF-β superfamily. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)10 is an essential factor in fibrillin microfibril function. Mutations in fibrillin-1 or ADAMTS10 cause Weill-Marchesani syndrome (WMS) characterized by short stature, eye defects, hypermuscularity and thickened skin. Despite its importance, there is poor understanding of the role of ADAMTS10 and its function in fibrillin microfibril assembly. We have generated an ADAMTS10 WMS mouse model using Clustered Regularly Spaced Interspaced Short Palindromic Repeats and CRISPR associated protein 9 (CRISPR-Cas9) to introduce a truncation mutation seen in WMS patients. Homozygous WMS mice are smaller and have shorter long bones with perturbation to the zones of the developing growth plate and changes in cell proliferation. Furthermore, there are abnormalities in the ciliary apparatus of the eye with decreased ciliary processes and abundant fibrillin-2 microfibrils suggesting perturbation of a developmental expression switch. WMS mice have increased skeletal muscle mass and more myofibres, which is likely a consequence of an altered skeletal myogenesis. These results correlated with expression data showing down regulation of Growth differentiation factor (GDF8) and Bone Morphogenetic Protein (BMP) growth factor genes. In addition, the mitochondria in skeletal muscle are larger with irregular shape coupled with increased phospho-p38 mitogen-activated protein kinase (MAPK) suggesting muscle remodelling. Our data indicate that decreased SMAD1/5/8 and increased p38/MAPK signalling are associated with ADAMTS10-induced WMS. This model will allow further studies of the disease mechanism to facilitate the development of therapeutic interventions.
The roles of EGF and Wnt signaling during patterning of the C. elegans Bγ/δ Equivalence Group (2009)

ceh-13/labial/Hox1 expression in Bgamma is regulated by the EGF pathway and downstream factors lin-1/ETS lin-31/Forkhead and sur-2/MED23. Wnt signaling is required for proper Bgamma division, perhaps to orient the Bgamma mitotic spindle. Our results suggest that dbl-1/dpp is not required for VPC and P12 specification, highlighting another difference among these EGF-dependent equivalence groups.
Surface-Normal Dual-Polarization Coherent Receiver Using Dielectric Metasurface (2023)

Spatially scalable surface-incidence dual-polarization (DP) coherent receiver with a dielectric metasurface and photodetector array is proposed. The designed metasurface is fabricated on a silicon-on-quartz chip to demonstrate ideal wave-mixing functionalities required for DP coherent detection.
Structural Basis of Telomeric RNA Quadruplex−Acridine Ligand Recognition (2011)

Human telomeric DNA is now known to be transcribed into noncoding RNA sequences, termed TERRA. These sequences, which are believed to play roles in the regulation of telomere function, can form higher-order quadruplex structures and may themselves be the target of therapeutic intervention. The crystal structure of a TERRA quadruplex-acridine small-molecule complex at a resolution of 2.60 Å, is reported here and contrasts remarkably with the structure of the analogous DNA quadruplex complex. The bimolecular RNA complex has a parallel-stranded topology with propeller-like UUA loops. These loops are held in particular conformations by multiple hydrogen bonds involving the O2' hydroxyl groups of the ribonucleotide sugars and play an active role in binding the acridine molecules to the RNA quadruplex. By contrast, the analogous DNA quadruplex complex has simpler 1:1 acridine binding, with no loop involvement. There are significant loop conformational changes in the RNA quadruplex compared to the native TERRA quadruplex (Collie, G. W.; Haider, S. M.; Neidle, S.; Parkinson, G. N. Nucleic Acids Res. 2010, 38, 5569 - 5580), which have implications for the future design of small molecules targeting TERRA quadruplexes, and RNA quadruplexes more generally.
Perturbing the acetylation status of the Type IV pilus retraction motor, PilT, reduces Neisseria gonorrhoeae viability (2018)

Post-translational acetylation is a common protein modification in bacteria. It was recently reported that Neisseria gonorrhoeae acetylates the Type IV pilus retraction motor, PilT. Here, we show recombinant PilT can be acetylated in vitro and acetylation does not affect PilT ultrastructure. To investigate the function of PilT acetylation, we mutated an acetylated lysine, K117, to mimic its acetylated or unacetylated forms. These mutations were not tolerated by wild-type N. gonorrhoeae, but they were tolerated by N. gonorrhoeae carrying an inducible pilE when grown without inducer. We identified additional mutations in pilT and pilU that suppress the lethality of K117 mutations. To investigate the link between PilE and PilT acetylation, we found the lack of PilE decreases PilT acetylation levels and increases the amount of PilT associated with the inner membrane. Finally, we found no difference between wild-type and mutant cells in transformation efficiency, suggesting neither mutation inhibits Type IV pilus retraction. Mutant cells, however, form microcolonies morphologically distinct from wt cells. We conclude that interfering with the acetylation status of PilT<sub>K117</sub> greatly reduces N. gonorrhoeae viability, and mutations in pilT, pilU and pilE can overcome this lethality. We discuss the implications of these findings in the context of Type IV pilus retraction regulation.
Descending GABAergic Neurons of the RVM That Mediate Widespread Bilateral Antinociception (2023)

Summary Neurons projecting from the rostral ventromedial medulla (RVM) to the spinal dorsal horn are critical elements of endogenous pain control systems. Here, we describe a GABA/glycinergic pathway that predominantly innervates the superficial dorsal horn. Anatomical and optogenetic tracing of these neurons from a single unilateral site of the lumbar spinal cord indicated that these neurons give rise to a dense bilateral innervation of the spinal cord along its entire rostrocaudal axis. Chemogenetic activation of these neurons caused a bilateral and widespread reduction in heat, cold, and mechanical sensitivity, while their silencing with tetanus toxin induced allodynia and spontaneous pain-like aversive behaviors. Consistent with a continuous role in the prevention of spontaneous pain, many descending RVM GABAergic neurons were found to be tonically active. This pathway may therefore be relevant for widespread conditioned analgesia, while its dysfunction may underlie chronic widespread pain syndromes.
Widespread Dispersion of Adeno-Associated Virus Serotype 1 and Adeno-Associated Virus Serotype 6 Vectors in the Rat Central Nervous System and in Human Glioblastoma Multiforme Xenografts (2005)

The transduction patterns of recombinant adeno-associated virus serotype 1 (AAV1) and serotype 6 (AAV6) vectors were assessed in human glioblastoma multiforme (GBM) cell lines, in human GBM biopsy spheroids, and in tumor xenografts growing in nude rat brains. All the cell lines tested (A172, D37, GaMg, HF66, and U373Mg) were found to be permissive to both AAV1 and AAV6 vectors, and thus displayed a transduction pattern similar to AAV2 vectors. For every cell line tested, the transduction efficiency displayed by AAV2 vectors was better than by isogenic and isopromoter AAV1 vectors. Transduction efficiency was dependent on the viral particle number used, suggesting that the receptors for these vectors are widely distributed in GBM tissues. Interestingly, AAV1, AAV2, and AAV6 vectors were able to infect and transduce the same cells when added simultaneously to monolayer cultures. Infection of human GBM biopsy spheroids with AAV1 and AAV6 vectors resulted in transgene expression both at the surface layers and in the core of the spheroids. Following injection of AAV1 and AAV6 vectors into human GBM biopsy xenografts growing in nude rat brains, reporter gene expression was seen both in the periphery as well as in the central regions of the tumors. When injected into the normal rat brain, both AAV1 and AAV6 vectors were found to transduce several central nervous system (CNS) regions. The presented results suggest a potential therapeutic role for AAV1 and AAV6 vectors in gene therapy for GBM and also for other CNS malignancies.
Management of Diabetic Retinopathy (2007)

Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR. Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments.
Bound Analysis of Imperative Programs with the Size-change Abstraction (extended version) (2012)

The size-change abstraction (SCA) is an important program abstraction for termination analysis, which has been successfully implemented in many tools for functional and logic programs. In this paper, we demonstrate that SCA is also a highly effective abstract domain for the bound analysis of imperative programs. We have implemented a bound analysis tool based on SCA for imperative programs. We abstract programs in a pathwise and context dependent manner, which enables our tool to analyze real-world programs effectively. Our work shows that SCA captures many of the essential ideas of previous termination and bound analysis and goes beyond in a conceptually simpler framework.
Sensitivity analysis aimed at blood vessels detection using interstitial optical tomography during brain needle biopsy procedures (2015)

A brain needle biopsy procedure is performed for suspected brain lesions in order to sample tissue that is subsequently analysed using standard histopathology techniques. A common complication resulting from this procedure is brain hemorrhaging from blood vessels clipped off during tissue extraction. Interstitial optical tomography (iOT) has recently been introduced by our group as a mean to assess the presence of blood vessels in the vicinity of the needle. The clinical need to improve safety requires the detection of blood vessels within 2 mm from the outer surface of the needle, since this distance is representative of the volume of tissue that is aspirated durirng tissue extraction. Here, a sensitivity analysis is presented to establish the intrinsic detection limits of iOT based on simulations and experiments using brain tissue phantoms. It is demonstrated that absorbers can be detected with diameters >300 μm located up to >2 mm from the biopsy needle core for bulk optical properties consistent with brain tissue.
CYP Inhibition-Mediated Drug-Drug Interactions (2010)

Adverse drug reaction is a frequent cause of drug withdrawals from the market. The drug-drug interaction (DDI) potential of new drug candidates is an increasing safety concern of pharmaceutical companies. DDIs frequently occur between coadministered drugs on a pharmacokinetic ground and sometimes create life-threatening conditions. The unexpected increase of the exposure of a drug is most frequently evoked by the inhibition of metabolic enzymes. While the inhibition of CYPs by new drug candidates is unwanted, one has to recognize that several currently marketed successful drugs with relatively clean record of drug-drug interactions are time-dependent inhibitors of drug metabolic enzymes. Therefore, the correct and high throughput prediction of drug-drug interaction propensity of new chemical entities (NCEs) at an affordable cost is a major interest of pharmaceutical research. False negatives and positives, also the misinterpretation of otherwise flawlessly generated data are equally costly or hazardous. While screening methods for the detection of CYP inhibition are available now, the quantitative estimation of DDI potential and its PK effect leaves an ample room for improvement. This is reflected in the great research activity focused on the establishment of correct in vitro-in vivo correlations. The impressing number of recent publications and methods recommended in this field provide an increasingly solid ground for the selection of lead compounds and development candidates. Keywords: Drug-drug interaction, CYP450, IVIVE, CYPs, of new chemical entities (NCEs), isozymes, cisapride, mibefradil, terfenadine, nefazodone, toxicology, lucocorticoides, biotransformation, Metabolism-based inhibitor (MBI), xenobiotic compounds, CYP monooxygenases, Fluoxetine, paroxetine, fraction metabolized (fm,CYP), conjugases, allosteric feature, Competitive inhibition, metabolite-intermediate complex (MIC), macrolide antibiotics, erythromycin, clarithromycin, troleandomycin, carbamazepine, cyclosporine, midazolam, ritonavir, microsomal monooxygenases, idiosyncratic reactions, Cholestasis, proinflammatory cytokines, antagonize nuclear receptors, ketoconazole, neuropathic pain, poor metabolizer (PM), extensive metabolizer (EM), ultrarapid metabolizer (UM), Ethynyl groups, ethynylestradiol, acetyl salicylic acid, hepatic inlet concentration, metabolite, pregnane X receptor, ultrarapid metabolizer
Phosphonium-Boronate Amino Acid Derivatives as Fluoride Pincers for 18F-Labelling (2014)

GRAPHICAL ABSTRACT
Purifying polluted water through hemodialysis filters for poor villages without electricity: the Easy Water for Everyone approach and experience (2020)

Abstract Given the need for treating polluted drinking water, our NGO Easy Water for Everyone has produced pure water in remote villages without power and achieved health benefits. With the goal of reaching more needy populations we report our experience and successful implementation in Ghana. In 20 villages polluted water is pumped every few days to an elevated water tank connected to a filtration device leading to a faucet. Repurposed hemodialyzers with polysulfone membranes, having a filter pore size of 0.003 micrometres, prevent passage of pathogens. Gravity from a 3 m height pushes water through the membrane whenever the faucet is open. Backflushing of the hemodialyzer membrane three times daily removes built-up organic material and maintains flow rates of 250 L/hour for at least two years. Filtered water has been culture-negative. Management of problems and optimization are reported. The five-year cost per village of &amp;lt;1,500 population averaged &amp;lt;2 US$ per day.