gebhart/patrepeval huggingface dataset:
Small-Molecule Lead-Finding Trends across the Roche and Genentech Research Organizations (2022)

The origin of small-molecule leads that were pursued across the independent research organizations Roche and Genentech from 2009 to 2020 is described. The identified chemical series are derived from a variety of lead-finding methods, which include public information, high-throughput screening (both full file and focused), fragment-based design, DNA-encoded library technology, use of legacy internal data, in-licensing, and de novo design (often structure-based). The translation of the lead series into in vivo tool compounds and development candidates is discussed as are the associated biological target classes and corresponding therapeutic areas. These analyses identify important trends regarding the various lead-finding approaches, which will likely impact their future application in the Roche and Genentech research groups. They also highlight commonalities and differences across the two independent research organizations. Several caveats associated with the employed data collection and analysis methodologies are included to enhance the interpretation of the presented information.
Cardiovascular effects of peptide kinin B2 receptor antagonists in rats (2002)

Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate (HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B2 receptor antagonist, namely icatibant (0.1-1 micromol/kg as a bolus) and MEN1 1270 (0.1-1 micromol/kg as a bolus or 1 micromol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 micromol/kg did not change BP but at 0.1 micromol/kg increased HR at 30 min from administration. MEN1 1270 at 0.1 or 0.3 micromol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 micromol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 micromol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN1 1270 at 1 micromol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN1 1270 (1 micromol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN1 1270 (0.1 micromol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN1 1270 was more rapid than that of icatibant. These results indicate that kinin B2 receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN1 1270 could be putatively attributed to kinetic characteristics.
Supplementary Movie 3 from Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities (2023)

Supplementary Movie 3 from Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities
Involvement of nitric oxide in target-cell lysis and DNA fragmentation induced by murine natural killer cells (1996)

Although it has been recognized for sometime that target cells destroyed by natural killer (NK) cells die largely by apoptosis, the underlying mechanisms are not fully understood. The aim of the present study was to examine the role of nitric oxide (NO) in mediating murine NK-cell-induced killing of YAC-1 lymphoma cells. NK calls induced extensive release of 125I-DNA and 51Cr from YAC-1 cells. The target killing ability of NK cells was associated with an increased production of NO as measured by concentrations of nitrite in the culture medium. That YAC-1 killing resulted, in part, from the production of NO was confirmed by the significant protection of cell lysis in L-arginine-depleted medium and by approximately 30 % attenuation of cell lysis and DNA fragmentation by an inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME) in a culture medium containing 1 mmol/L L-arginine. Fluorescence microscopic examination of YAC-1 cells showed the presence of changes in nuclear morphology characteristic for apoptosis. The percentage of apoptotic cells was markedly decreased by L-NAME. Further evidence for apoptosis is provided by the specific pattern of internucleosomal DNA fragmentation both in the absence and presence of L-NAME. During target-cell killing, an increased oxidation of intracellularly trapped dichlorofluorescein was observed in cells labeled with an antimouse NK-cell monoclonal antibody, as measured by flow cytometry. These increases were effectively prevented by L-NAME, but not W-13, an inhibitor of calmodulin. The ability of NO to induce cell lysis and DNA fragmentation in YAC-1 cells was further demonstrated by exposing tumor cells to chemically generated NO. Taken together, these observations suggest a role for NO as one of the mediators of NK-cell-mediated DNA fragmentation and cell lysis.
Synchronous Picosecond Sonoluminescence. (1995)

Abstract : If acoustic cavitation is produced in a liquid, the implosion of cavities can heat the internal contents of the bubble to incandescent temperatures. The electromagnetic emissions associated with this energy concentration can often be seen with the naked eye. This phenomenon, in which light is generated by sound is called sonoluminescence. A particular form of this phenomenon is called single-bubble sonoluminescence. This form is much easily to study because the fundamental bubble dynamics that leads to bubble collapse and the associated electromagnetic emissions can be ascertained. Also, in single bubble sonoluminescence it is likely that the bubble collapse is spherically symmetric, resulting in an amplification of this already violent phenomenon. The intent of this project is to investigate the phenomenon of single bubble sonoluminescence, and from knowledge gained here, to be able to provide useful information concerning the more general phenomenon of multiple-bubble sonoluminescence.
Introduction (2016)

The Information and Communications Technology (ICT) sector was born in the twenty-first century out of a consolidation of two major industry sectors of the last century, the telecommunications industry and the computing industry. This book is designated to harness the momentum of the mobile telecommunications industry to a fifth generation of technologies. These technologies will allow completing the consolidation of services, content distribution, communications and computing into a complex distributed environment for connectivity, processing, storage, knowledge and intelligence. This consolidation is responsible for a blurring of roles across the board, with computing and storage being embedded in communication infrastructure, process control being distributed across the Internet and communication functions moving into centralized cloud environments.
Preparation and Chemical Composition of Orange Oil Concentrates (1983)

ABSTRACT Flavor and color concentrates were prepared by a vacuum distillation process from cold pressed Valencia and midseason orange oils and were analyzed quantitatively by gas chromatography. Twenty‐five major and minor constituents were identified by mass spectrometry. The influence of the concentration process on oxygenated flavor compounds, primarily aldehydes and alcohols, was evaluated. Aldehydes and color values were determined by chemical and spectrophotometric methods. When compared with midseason orange oils, 25–35% higher concentration of oxygenated flavor compounds and of total aldehydes were found in Valencia orange oils. Midseason oils had 20–30% higher color values when compared with Valencia oils. Cold pressed oils concentrated to 25‐fold had an increase in color value of 20‐fold, while the concentration of oxygenated flavor compounds increased about 10 times.
Modeling of zinc energy storage system for integration with renewable energy (2009)

Utility scale energy storage devices have been considered for integration with renewable energy systems to improve their sustainability and dispatch. In this paper, we analyze and model an advanced zinc energy storage device (ZESS), for grid level applications. This energy storage system has high energy and power density, high efficiency and long life. A series of tests have been conducted on the ZESS in order to develop an electrical model that describes its behavior. The modeling is based on the observation that, at constant temperature, both the open circuit voltage of the ZESS and its internal resistance are exclusive functions of its state of charge (SOC). Since the value of the SOC is crucial to the developed model, and due to the inexistence of charge sensors, Kalman filtering is used to estimate the SOC of the ZESS at any operating point. The model and the SOC estimator are necessary blocks to use when integrating the ZESS with some renewable energy system so that the controller can decide whether the ZESS should store/release energy from/to the system.
Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature (2018)

Hidradenitis suppurativa (HS) is a chronic skin disease of the pilo-sebaceous apocrine unit characterized by significant inflammation and an impaired quality of life. The pathogenesis of HS remains unclear. To determine the HS skin and blood transcriptomes and HS blood proteome, patient data from previously published studies were analysed and integrated from a cohort of patients with moderate to severe HS (n = 17) compared to healthy volunteers (n = 10). The analysis utilized empirical Bayes methods to determine differentially expressed genes (DEGs) (fold change (FCH) >2.0 and false discovery rate (FDR) <0.05), and differentially expressed proteins (DEPs) (FCH>1.5, FDR<0.05). In the HS skin transcriptome (lesional skin compared to non-lesional skin), there was an abundance of immunoglobulins, antimicrobial peptides, and an interferon signature. Gene-sets related to Notch signalling and Interferon pathways were differentially activated in lesional compared to non-lesional skin. CIBERSORT analysis of the HS skin transcriptome revealed a significantly increased proportion of plasma cells in lesional skin. In the HS skin and blood transcriptomes and HS blood proteome, gene-sets related to the complement system changed significantly (FDR<0.05), with dysregulation of complement-specific DEGs and DEPs. These data point towards an exaggerated immune response in lesional skin that may be responding to commensal cutaneous bacterial presence and raise the possibility that this may be an important driver of HS disease progression.
Supplemental Figure 2 from AGS16F Is a Novel Antibody Drug Conjugate Directed against ENPP3 for the Treatment of Renal Cell Carcinoma (2023)

&lt;p&gt;Supplemental Figure 2. AGS16-7.8 does not inhibit the enzymatic activity of purified ENPP3.&lt;/p&gt;
Heat pumps for subway stations heat supply (2019)

Приведен обзор перспектив внедрения теплонасосного оборудования для теплоснабжения станций метрополитена за счет использования теплоты вторичных энергоресурсов, в первую очередь - теплоты воздуха, удаляемого из вентиляционных шахт. Даны некоторые оценки экономической целесообразности таких проектов.
DEVELOPMENT OFBEAUVERIA BASSIANAFOR CONTROL OF GRASSHOPPERS AND LOCUSTS (1997)

Abstract Recognition of the potential of Beauveria bassiana (Balsamo) Vuillemin as a control agent of grasshoppers and locusts occurred as early as 1936, in South Africa. Field testing of B . bassiana as an inundative control agent of grasshoppers and locusts has been facilitated by development of a solid substrate method for mass-production of the fungus and has resulted in the registration of a strain against grasshoppers in the United States. In some, but not all field trials, application has resulted in substantial reductions in grasshopper populations. Numerous environmental constraints, including temperature and ultraviolet (UV) radiation, may limit field efficacy of the fungus. Laboratory studies suggest that low humidity does not limit the ability of the fungus to initiate disease. Sunlight is the major cause of mortality of conidia on leaf surfaces. The incorporation of UVB protectants in formulations can increase conidial survival; however, these have not yet been evaluated for their effects on field efficacy of B . bassiana against insects. Thermoregulation by grasshoppers has been implicated in resistance to mycosis. Results of laboratory studies indicate that grasshoppers infected with B . bassiana preferentially seek temperatures between 40 and 42 °C and these temperatures are inhibitory to disease development. In field-cage trials, a higher prevalence and more rapid development of disease were observed in grasshoppers placed in shaded cages than in grasshoppers placed in cages exposed to full sunlight. In laboratory experiments simulating grasshopper thermoregulation during daylight periods, application of both Metarhizium flavoviride Gams and Rozsypal and B . bassiana simultaneously resulted in a final prevalence of disease that was greater than M . flavoviride alone in the hot temperature environment, and equal to B . bassiana alone in the cool temperature environment. Incorporation of sublethal levels of Dimilin with conidia of B . bassiana increased efficacy of the fungus against grasshoppers in laboratory and field trials. Once environmental constraints are better quantified, it may be possible to overcome them through improved formulation, strain selection, genetic or phenotypic manipulation, and inoculum targeting. Ultimately, success of B . bassiana as a microbial control agent will depend on our ability to overcome environmental and other constraints and/or to predict its efficacy under various environmental conditions.
Lithium Ion Solvation: Amine and Unsaturated Hydrocarbon Solvates of Lithium Hexamethyldisilazide (LiHMDS) (1996)

6Li, 15N, and 13C NMR spectroscopic studies of 6Li−15N labeled lithium hexamethyldisilazide ([6Li,15N]LiHMDS) solvated by more than 20 different mono-, di-, and trialkylamines (and ammonia) are described. LiHMDS dimers solvated by the least hindered trialkylamines and most dialkylamines exchange ligands by a dissociative mechanism that is sufficiently slow to observe discrete mono-, di-, and mixed-solvated dimers. Dimers solvated by the hindered trialkylamines and unhindered monoalkylamines undergo rapid ligand substitutions by relatively rapid dissociative and associative mechanisms (respectively). Mono- and disolvated dimers can be observed for the monoalkylamines at <1.0 equiv of ligand (per Li). The monomers that form at elevated trialkylamine concentrations are suggested to be di- and trisolvated. The relationship between ligand structure and lithium amide aggregation state is a complex and sensitive function of amine alkyl substituents. The dialkylamines prove to be remarkably similar to dialkyl ethers as ligands for the LiHMDS dimer despite pronounced differences expected for nitrogen- and oxygen-based coordination. A greater relative promotion of monomer formation by the dialkylamines than the dialkyl ethers can be traced to disproportionate monomer stabilization by the amines. Hydrocarbon-dependent aggregation effects are discussed in terms of primary and secondary shell solvation.
High-dose factor VIII inhibits factor VIII–specific memory B cells in hemophilia A with factor VIII inhibitors (2005)

Hemophilia A in its severe form is a life-threatening hemorrhagic disease that is caused by mutations in the factor VIII (FVIII) gene (symbol F8). About 25% of patients who receive replacement therapy develop neutralizing antibodies that inhibit the function of substituted FVIII. Long-term application of high doses of FVIII has evolved as an effective therapy to eradicate the antibodies and to induce long-lasting immune tolerance. Little is known, however, about the immunologic mechanisms that cause the down-modulation of anti-FVIII antibodies by high doses of FVIII. We report that high doses of FVIII inhibit the restimulation of FVIII-specific memory B cells and their differentiation into antibody-secreting plasma cells in vitro and in vivo in a murine model of hemophilia A. The inhibition of memory B-cell responses is irreversible and not mediated by FVIII-specific T cells. Furthermore, it seems to involve the activation of caspases. We conclude that the inhibition of FVIII-specific memory B cells might be an early event in the down-modulation of anti-FVIII antibodies in patients with hemophilia A who receive high doses of FVIII.
Neutrophils Protect Against Staphylococcus aureus Endocarditis Progression Independent of Extracellular Trap Release (2022)

Neutrophils protect against IE independent of NET release. Absence of <i>S. aureus</i> coagulases, but not nucleases, reduced IE severity and increased NET levels. Staphylocoagulase-induced fibrin likely hampers NETs from constraining infection and the resultant tissue damage, a hallmark of valve destruction in IE.
A Scalable and Regioselective Synthesis of 2-Difluoromethyl Pyridines from Commodity Chemicals (2014)

A scalable de novo synthesis of difluoromethyl pyridines from inexpensive materials is reported. The pyridyl subunit is built around the difluoromethyl group rather than a late stage introduction of this moiety. This user-friendly approach allows access to a diverse range of substitution patterns on all positions on the ring system and on the difluoromethyl group.
Simulation of dissolution of matter and flow in restricted geometries (2012)

Numerical analysis has been utilized for several decades1 for solving problems where conventional analytical equations fail due to e.g. complex geometry of the dissolution vessel2. Furthermore, numerical analysis enables the visualization of the formed concentration gradients that persist during dissolution testing. Numerical analysis utilizing finite element modeling (FEM) can thus help to elucidate the dissolution process that is occurring in highly complex geometries. The FEM method can be computationally solved by the coupling of a laminar flow problem with a transport problem. The model can be solved as a stationary study by evaluating the Navier-Stokes equation for the fluid flow and the mass balance equation for the transport problem. A FEM simulation was subsequently performed for a flow through cell geometry designed for dissolution testing and the calculated dissolution rate was compared to the experimentally obtained dissolution rate. It was found that the FEM method provided excellent agreement with the experimentally obtained data. Thus, the FEM method provides new possibilities for the investigation of dissolution processes in complex geometries and encompasses the capability to visualize various phenomena related to the dissolution mechanisms. This platform could in future also be suitable for studying more complex dissolution phenomena where micelles are present in the solvent phase. Future simulations supported by dissolution studies will also explore compounds that exhibit solvent mediated recrystallization. 1. Bredehoe.Jd; Pinder, G. F. Mass-Transport in Flowing Groundwater. Water Resources Research 1973, 9, 194-210. 2. Kaunisto, E.; Nilsson, B.; Axelsson, A. Drug dissolution rate measurements - evaluation of the rotating disc method. Pharmaceutical Development and Technology 2009, 14, 400-408.
Surface analysis insight note: Analysis of X‐ray photoelectron spectroscopy images with summary statistics (2023)

Developments in X‐ray photoelectron spectroscopy (XPS) instrumentation and the need for spatial information in surface characterization have led to advances in XPS imaging and related image processing techniques. In this Insight Note, we demonstrate the use of summary statistics as simple, but effective, tools for understanding XPS hyperspectral images (data cubes) prior to more advanced image processing. An XPS image obtained from a silicon surface patterned with different thicknesses of oxide was analyzed with three summary statistics: a tool in the MATLAB programming environment, the mean, and pattern recognition entropy (PRE). The MATLAB tool largely separates the spectra into two groups. The mean does a somewhat better job differentiating between the spectra, and PRE is even more effective. The results of the MATLAB summary statistic are confirmed by plotting the average and standard deviation spectra of different regions of the image it produces. The results of the mean and PRE summary statistics are confirmed by evenly segmenting the results and examining the average and standard deviation spectra of these segments. Fitting these average spectra demonstrates the greater effectiveness of the PRE summary statistic in segmenting the spectra into chemically distinct groups.
Novel biocompatible nanofibers for wound dressing applications (2014)

Wounds, due to burns, cuts, surgery and chronic infections, have major socioeconomic impact [1]. With over 25 billion dollars annual cost of non-healing wounds, alternative wound healing strategies are urgently needed [2]. One of the major trends witnessed by the Global Wound Dressing market is the increasing demand for advanced, combination dressings for the treatment of various chronic and acute wounds [3]. In a combination wound dressing, the antimicrobial agent (such as antibiotics), wound healing therapeutics, and promoting growth factors are loaded within a matrix, which allows their sustained and prolonged release. Combination wound dressing allows delivery of the therapeutics needed for efficient wound healing in a single dressing that does not need to be changed frequently and sometimes is biodegradable.
Protein tyrosine kinase inhibitory properties of planar polycyclics obtained from the marine sponge Xestospongia cf. carbonaria and from total synthesis (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein tyrosine kinase inhibitory properties of planar polycyclics obtained from the marine sponge Xestospongia cf. carbonaria and from total synthesisKhisal A. Alvi, Jaime Rodriguez, Maria Cristina Diaz, Robert Moretti, Robert S. Wilhelm, Rita H. Lee, Doris L. Slate, and Phillip CrewsCite this: J. Org. Chem. 1993, 58, 18, 4871–4880Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/jo00070a023https://doi.org/10.1021/jo00070a023research-articleACS PublicationsRequest reuse permissionsArticle Views859Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts