gebhart/patrepeval huggingface dataset:
Design, Synthesis and Anticonvulsant Activity of the Potent Adenosine Kinase Inhibitor GP3269 (1997)

Abstract The pyrrolopyrimidine nucleoside GP3269 (12) was shown to be a potent and selective inhibitor of human adenosine kinase (IC50 = 11 nM) and to exhibit anticonvulsant activity in rats after oral administration. Synthesis of GP3269 was accomplished in 4 steps from 4-chloro-5-iodopyrrolopyrimidine (9) and the protected 5-deoxy-1-α-chlororibose (8) using a base-catalyzed nucleoside coupling reaction and the Suzuki reaction to replace the 5-iodo substituent with phenyl.
Design of a Wideband 1.5GHz to 3GHz Class EF2 Power Amplifier (2014)

International audience
Procedimiento para la preparación de oximas catalizado por un material laminar deslaminado (2007)

Referencia OEPM: P200402893.-- Fecha de solicitud: 01/12/2004.-- Titular: Ube Corporation Europe, S.A. (El Grao, Castellon, ES).
Combining machine learning and high-throughput experimentation to discover photocatalytically active organic molecules (2021)

Light-absorbing organic molecules are useful components in photocatalysts, but it is difficult to formulate reliable structure-property design rules. More than 100 million unique chemical compounds are documented in the PubChem database, and a significant sub-set of these are π-conjugated, light-absorbing molecules that might in principle act as photocatalysts. Nature has used natural selection to evolve photosynthetic assemblies; by contrast, our ability to navigate the enormous potential search space of organic photocatalysts in the laboratory is limited. Here, we integrate experiment, computation, and machine learning to address this challenge. A library of 572 aromatic organic molecules was assembled with diverse compositions and structures, selected on the basis of availability in our laboratory, rather than more sophisticated criteria. This training library was then assessed experimentally for sacrificial photocatalytic hydrogen evolution using a high-throughput, automated method. Quantum chemical calculations and machine learning were used to visualise, interpret, and ultimately to predict the photocatalytic activities of these molecules, covering a much broader chemical space than for previous polymer photocatalyst libraries. By applying unsupervised learning to the molecular structures, we identified structural features that were common in molecules with high catalytic activity. Further analysis using calculated molecular descriptors within a suite of supervised classification algorithms revealed that light absorption, exciton electron affinity, electron affinity, exciton binding energy, and singlet-triplet energy gap had correlations with the photocatalytic performance. These trained predictive models can be used in future studies as filters to deprioritise or discard would-be low-activity candidate molecules from experiments, and to prioritize more favourable candidates. As a demonstration, we used virtual <i>in silico</i> experiments to show that it was possible to halve the experimental cost of finding 50% of the most active photocatalysts by using the machine learning model as an experimental advisor. We further showed that the ML advisor trained on the 572-molecule library could be used to make predictions for an unseen set of 96 molecules, achieving equivalent predictive accuracies to those in the initial training set. This marks a step toward the machine-learning assisted discovery of molecular organic photocatalysts and the approach might also be applied to problems beyond photocatalytic hydrogen evolution, such as CO<sub>2</sub> reduction and photoredox chemistry.
ARRY-797, a Potent and Selective Inhibitor of p38 Map Kinase, Inhibits LPS-Induced IL-6 and In Vivo Growth of RPMI-8226 Human Multiple Myeloma Cells. (2006)

Abstract Multiple myeloma (MM) is characterized by the expansion of malignant plasma cells within the bone marrow. Their growth, survival, and migration are mediated in part via cytokines. Interleukin 6 (IL-6) is necessary for sustaining the in vitro growth of many MM cell lines and enhancing the proliferation of explanted human myeloma cells. The mitogen-activated protein kinase family member, p38, is activated by cytokines and growth factors and plays a significant role in inflammatory diseases. However, its role in the pathogenesis of multiple myeloma is poorly understood. Specific p38 inhibitors inhibit paracrine MM cell growth which is associated with IL-6 and VEGF secretion from bone marrow stromal cells (BMSCs). Furthermore, p38 inhibition blocks TNF-alpha-induced IL-6 secretion in BMSCs, thereby further inhibiting MM cell growth and survival. Although these data suggest an important role for p38 in MM, the direct effects of p38 inhibiton on MM has not been extensively explored. Therefore, we investigated the effects of p38 inhibition on in vitro and in vivo IL-6 production and MM cell growth in vivo after lipopolysaccaride (LPS) stimulation. LPS has been shown to induce various cytokines, including TNF-alpha and IL-6, via the p38 pathway. ARRY-797, an orally bioavailable, small molecule inhibitor of p38 directly inhibited LPS-induced IL-6 production from RPMI-8226 (IC50 = 100 pM) in vitro. In SCID-beige mice, LPS (3 μg/kg) induced IL-6 (7897 ± 827 pg/mL) and TNF-alpha (1922 ± 282 pg/mL) after 2 hours and these cytokines were inhibited by oral administration of ARRY-797 (30 mg/kg) by 91% and 95%, respectively. In MM xenograft models, ARRY-797 (30 mg/kg, BID, PO) inhibited RPMI 8226 tumor growth by 72% as a single agent and by 56% when LPS was administered to stimulate growth in vivo. In addition, ARRY-797 inhibited LPS-induced phosphorylation of p38 in RPMI-8226 xenografts. Together, these data support a role for p38 in IL-6-mediated growth of multiple myelomas. To our knowledge, ARRY-797 is the first small molecule p38 inhibitor to demonstrate single agent activity in a MM xenograft model and it has been advanced into preclinical development.
Perceived Differences in Running and Walking Shoes (1995)

Designers rely heavily on the past sales history of a particular shoe when attempting to make decisions regarding shoe characteristics of future shoes. Cushioning devices made of air, “super” gases, energy return rubber, and gel's have become popular. However, the question that needs to be asked is whether these devices are truly functional or whether they are primarily of aesthetic value. Shoe qualities such as cushioning, comfort, stability, shock absorption, and energy return play an important role during athletic activity. It is also known that the above mentioned characteristics have significant interactions with each other. Hence it is important to know the relevance of these interactions when designing shoes for a particular activity. The primary goal of this study was to investigate the interaction and relevance of shoe properties during running and walking. Four specially fabricated shoes were used in the study. The results indicate the following: • Heel cushioning and shock absorption play an important role in the overall cushioning of a midsole. • Runners perceive shoe-heel cushioning somewhat differently from those who use shoes for walking. • Heel cushioning during running seems to be influenced by shock absorption, stability and possibly rebound. • Heel cushioning during walking seems to be influenced by shock absorption and possibly rebound. Hence a good running shoe can in most cases satisfy the biomechanical needs during walking.
Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach (2015)

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance.
Effect of composition and processing conditions on the chemical and morphological evolution of PA‐6/EPM/ EPM‐g‐MA blends in a corotating twin‐screw extruder (2001)

Abstract This study investigated the effect of blend composition and processing conditions on the chemical conversion and morphological evolution of PA‐6/EPM/EPM‐ g ‐MA blends along a twin‐screw extruder. The maleic anhydride (MA) content of the modified rubber was found to decrease strongly, to a level of almost zero, and in the melting zone the particle size was dramatically reduced, from millimeters to submicrometers. Blend composition had a secondary effect on both chemical conversion and morphological development. The processing conditions, particularly the temperature profile and the screw speed, affected both the chemical conversion and the morphological evolution. Using low temperatures and low screw rotation it was possible to follow in detail the evolution of morphological development of a reactive blend in a twin‐screw extruder. © 2001 John Wiley &amp; Sons, Inc. J Appl Polym Sci 80: 1535–1546, 2001
Toward the ideal synthesis. New transition metal-catalyzed reactions inspired by novel medicinal leads (2002)

Abstract Studies in our laboratory are directed at the advancement of synthesis, biology, and medicine. This lecture will focus on new transition metal-catalyzed reactions that have been inspired by biologically potent targets such as phorbol and Taxol® and by the more general interest in producing syntheses that are concise, efficient, cost- and resource-effective, environmentally benign, quick, and simple to conductin essence, ideal. A special emphasis in our program is placed on new transition metal-catalyzed reactions that, in the absence of catalyst, would be forbidden or difficult to achieve. We have thus far reported the first examples of intramolecular metal-catalyzed [4+2], [5+2], and [4+4] cycloadditions, reactions that produce 6-, 7-, and 8-membered rings, respectively. Recent advances in our [5+2] cycloaddition studies will be presented, including new catalysts for relative and absolute stereochemical control. We will also describe recyclable catalysts that can be used in water, thereby minimizing cost and environmental concerns about solvent waste streams. New multicomponent reactions will also be presented. Finally, we will report a new [6+2] cycloaddition that produces an 8-membered ring.
Induction of erythroid differentiation in K562 cells by inhibitors of inosine monophosphate dehydrogenase. (1989)

The effects of three inhibitors of inosine monophosphate (IMP) dehydrogenase on a human erythroleukemic cell line, K562, were studied. Following incubation with these inhibitors, K562 cells underwent differentiation and accumulated hemoglobins. The induction of hemoglobin accumulation was dose dependent; maximum induction was observed at 100, 25, and 3 microM, respectively, for ribavirin, tiazofurin, and mycophenolic acid. The induction was associated with reduction of intracellular GTP content and was blocked by adding guanosine within 24 h after adding inducer. The effective dose for half-maximum induction by ribavirin was 3 times less than that for 50% inhibition of K562 proliferation; however, for tiazofurin and mycophenolic acid, it closely approximated the concentrations which suppressed cellular proliferation. Ribavirin was sequestered preferentially inside the K562 cells, and the induction by ribavirin had a greater than 30-fold increase in hemoglobin. Studies with isoelectric focusing, globin chain analyses, and immunochemical assays indicated that both A gamma and G gamma were detected and that the hemoglobin produced in the ribavirin-treated cells consisted of approximately 60% fetal hemoglobin and its acetylated equivalents. The adult-type alpha globin was found, while no beta globin chains were demonstrated. Thus, accumulation of fetal hemoglobin and production of alpha globin chain in ribavirin-treated cells are different from the pattern of hemoglobins induced by hemin.
Immune and genetic gardening of the intestinal microbiome (2014)

The mucosal immune system - consisting of adaptive and innate immune cells as well as the epithelium - is profoundly influenced by its microbial environment. There is now growing evidence that the converse is also true, that the immune system shapes the composition of the intestinal microbiome. During conditions of health, this bidirectional interaction achieves a homeostasis in which inappropriate immune responses to non-pathogenic microbes are averted and immune activity suppresses blooms of potentially pathogenic microbes (pathobionts). Genetic alteration in immune/epithelial function can affect host gardening of the intestinal microbiome, contributing to the diversity of intestinal microbiota within a population and in some cases allowing for unfavorable microbial ecologies (dysbiosis) that confer disease susceptibility.
Effects of Oxygen Vacancy Concentration on Mechanical Properties of Cerium Oxide (2006)

Nonstoichiometric compositions of ceria were created by heat treatment at 800 C at various oxygen partial pressures. The different oxygen vacancy concentrations created by this heat treatment were conserved to room temperature by fast cooling. Nanoindentation technique was used to study the elastic modulus and hardness of samples. The room temperature results indicate that the elastic modulus of ceria decreases at very low partial pressures of oxygen, but the hardness shows a maximum as a function of oxygen partial pressure. The fracture toughness was evaluated using Brazilian disk samples under mode I loading condition. The preliminary results reveal that surprisingly fracture toughness is increased at very low oxygen partial pressure. In this paper, the change in toughness is discussed in terms of pore-crack interaction, internal stresses, microcracks and phase transformation.
Induced chromosome deletions cause hypersociability and other features of Williams–Beuren syndrome in mice (2009)

The neurodevelopmental disorder Williams-Beuren syndrome is caused by spontaneous approximately 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. To functionally dissect the deletion and identify dosage-sensitive genes, we created two half-deletions of the conserved syntenic region on mouse chromosome 5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human deletion. Gene transcript levels in brain are generally consistent with gene dosage. Increased sociability and acoustic startle response are associated with PD, and cognitive defects with DD. Both PD and D/P males are growth-retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle (LV) volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders.
A statistical method for binary classification of images (2005)

The classification of documents with sparse text, and video analysis, relies on accurate image classification. We herein present a method for binary classification that accommodates any number of individual classifiers. Each individual classifier is defined by the critical point between its two means, and its relative weighting is inversely proportional to its expected error rate. Using 10 simple image analysis metrics, we distinguish a set of "natural" and "city" scenes, providing a "semantically meaningful" classification. The optimal combination of 5 of these 10 classifiers provides 85.8% accuracy on a small (120 image) feasibility corpus. When this feasibility corpus is then split into half training and half testing images, the mean accuracy of the optimum set of classifiers was 81.7%. Accuracy as high as 90% was obtained for the test set when training percentage was increased. These results demonstrate that an accurate classifier can be constructed from a large pool of simple classifiers through the use of the statistical ("Normal") classification method described herein.
Horizontal Gene Transfer of Antibiotic Resistance from Acinetobacter baylyi to Escherichia coli on Lettuce and Subsequent Antibiotic Resistance Transmission to the Gut Microbiome (2020)

Agricultural use of antibiotics is recognized by the U.S. Centers for Disease Control and Prevention as a major contributor to antibiotic-resistant infections. While most One Health attention has been on the potential for antibiotic resistance transmission from livestock and contaminated meat products to people, plant foods are fundamental to the food chain for meat eaters and vegetarians alike. We hypothesized that environmental bacteria that colonize plant foods may serve as platforms for the persistence of antibiotic-resistant bacteria and for horizontal gene transfer of antibiotic-resistant genes. Donor <i>Acinetobacter baylyi</i> and recipient <i>Escherichia coli</i> were cocultured <i>in vitro</i>, <i>in planta</i> on lettuce, and <i>in vivo</i> in BALB/c mice. We showed that nonpathogenic, environmental <i>A. baylyi</i> is capable of transferring plasmids conferring antibiotic resistance to <i>E. coli</i> clinical isolates on lettuce leaf discs. Furthermore, transformant <i>E. coli</i> from the <i>in planta</i> assay could then colonize the mouse gut microbiome. The target antibiotic resistance plasmid was identified in mouse feces up to 5 days postinfection. We specifically identified <i>in vivo</i> transfer of the plasmid to resident <i>Klebsiella pneumoniae</i> in the mouse gut. Our findings highlight the potential for environmental bacteria exposed to antibiotics to transmit resistance genes to mammalian pathogens during ingestion of leafy greens.<b>IMPORTANCE</b> Previous efforts have correlated antibiotic-fed livestock and meat products with respective antibiotic resistance genes, but virtually no research has been conducted on the transmission of antibiotic resistance from plant foods to the mammalian gut (C. S. Hölzel, J. L. Tetens, and K. Schwaiger, Pathog Dis 15:671-688, 2018, https://doi.org/10.1089/fpd.2018.2501; C. M. Liu et al., mBio 9:e00470-19, 2018, https://doi.org/10.1128/mBio.00470-18; B. Spellberg et al., NAM Perspectives, 2016, https://doi.org/10.31478/201606d; J. O'Neill, Antimicrobials in agriculture and the environment, 2015; Centers for Disease Control and Prevention, Antibiotic resistance threats in the United States, 2019). Here, we sought to determine if horizontal transmission of antibiotic resistance genes can occur between lettuce and the mammalian gut microbiome, using a mouse model. Furthermore, we have created a new model to study horizontal gene transfer on lettuce leaves using an antibiotic-resistant transformant of <i>A. baylyi</i> (Ab<sup>zeoR</sup>).
GOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase 3 trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥2 line recurrent or metastatic cervical cancer. (2018)

TPS5600 Background: Patients with recurrent and metastatic cervical carcinoma experience modest survival benefit with first-line platinum-based chemotherapy with or without bevacizumab. Those with platinum-refractory disease have a median survival of only 7 months. Cemiplimab, a human monoclonal anti-PD-1, has exhibited antitumor activity and an acceptable safety profile in a phase 1 trial of solid tumors including recurrent cervical cancer. Methods: GOG 3016/ENGOT-cx9 is an open-label, randomized (1:1), phase 3 trial of cemiplimab versus IC chemotherapy in women ≥18 years with platinum-refractory recurrent and/or metastatic cervical cancer that has progressed within 6 months of the last dose of platinum-containing chemotherapy (NCT03257267). Patients will be stratified for the primary efficacy analysis by histology and geographic region. Patients will receive cemiplimab every 3 weeks (Q3W) or IC chemotherapy, ie, pemetrexed 500 mg/m2 Q3W; topotecan 1 mg/m2 daily x5 days, every 21 days; irinotecan 100 mg/m2 days 1, 8, 15, and 22, followed by 2 weeks rest, for a 42-day (6-week cycle); gemcitabine 1000 mg/m2 days 1 and 8, every 21 days; or vinorelbine 30 mg/m2 days 1 and 8, every 21 days. Treatments will be given IV for up to 96 weeks. The primary objective is overall survival (OS). Key secondary objectives include the assessment of overall response, progression-free survival, and the frequency and severity of adverse events. Stratification factors include prior bevacizumab, histology, and ECOG status. Assuming duration of study enrollment and follow-up of 20 months and 12 months, respectively, we calculated we would need to enroll approximately 436 patients, with 330 deaths expected, to provide the study with 90% power to detect a reduction in the risk of death of at least 20% with cemiplimab, with the 1-sided type 1 error rate limited to 2.5%. An independent data monitoring committee (IDMC) will monitor the data during the study conduct. Clinical trial information: NCT03257267.
Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants (2019)

Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti-6Al-4V alloy through a hydrothermal treatment of previously NaOH-treated surfaces in calcium-citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170°C for 3 hr. The coating was approx. 1 μm thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated- and un-coated samples. However, the CaCO<sub>3</sub> coating reduced by approx. 2-5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO<sub>3</sub> and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO<sub>3</sub> coating encourage further studies on this coating for clinical applications.