gebhart/patrepeval huggingface dataset:
Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders (2018)

The serine hydrolase monoacylglycerol lipase (MGLL) converts the endogenous cannabinoid receptor agonist 2-arachidonoylglycerol (2-AG) and other monoacylglycerols into fatty acids and glycerol. Genetic or pharmacological inactivation of MGLL leads to elevation in 2-AG in the central nervous system and corresponding reductions in arachidonic acid and eicosanoids, producing antinociceptive, anxiolytic, and antineuroinflammatory effects without inducing the full spectrum of psychoactive effects of direct cannabinoid receptor agonists. Here, we report the optimization of hexafluoroisopropyl carbamate-based irreversible inhibitors of MGLL, culminating in a highly potent, selective, and orally available, CNS-penetrant MGLL inhibitor, 28 (ABX-1431). Activity-based protein profiling experiments verify the exquisite selectivity of 28 for MGLL versus other members of the serine hydrolase class. In vivo, 28 inhibits MGLL activity in rodent brain (ED<sub>50</sub> = 0.5-1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model. ABX-1431 (28) is currently under evaluation in human clinical trials.
Review article: the clinical role of anti‐TNFα antibody treatment in Crohn's disease (2000)

The recent licensing of anti-TNFalpha antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically-engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long-term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application.
The Pharmacologic Approach to the Treatment of Obesity (1997)

Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.
Ground state and edge excitations of a quantum Hall liquid at filling factor 2/3 (2008)

We present a numerical study of fractional quantum Hall liquid at Landau-level filling factor $\ensuremath{\nu}=2/3$ in a microscopic model including long-range Coulomb interaction and edge confining potential based on the disk geometry. We find that the ground state is accurately described by the particle-hole conjugate of a $\ensuremath{\nu}=1/3$ Laughlin state. We also find that there are two counterpropagating edge modes, and the velocity of the forward-propagating mode is larger than the backward-propagating mode. The velocities have opposite responses to the change in the background confinement potential. On the other hand changing the two-body Coulomb potential has qualitatively the same effect on the velocities; for example, we find that increasing layer thickness (which softens of the Coulomb interaction) reduces both the forward mode and the backward mode velocities.
2-Factor authentication with 2D Barcodes (2011)

An improved user-friendly secure authentication scheme using 2D barcodes is proposed in this paper. The proposed scheme uses a known mobile device as a second factor to decode an encrypted message transferred as a 2D barcode and read via a camera on the mobile device. A one-time passcode is produced from this for authentication. Elliptic curve public-key codes are used on a PKI-SIM card to encrypt a challenge as well as additional temporal data. The proposed scheme improves the security and usability of multi-factor authentication and transaction verification without requiring increased investment in hardware or user training.
HDAC4 Promotes Growth of Colon Cancer Cells via Repression of p21 (2008)

The class II Histone deacetylase (HDAC), HDAC4, is expressed in a tissue-specific manner, and it represses differentiation of specific cell types. We demonstrate here that HDAC4 is expressed in the proliferative zone in small intestine and colon and that its expression is down-regulated during intestinal differentiation in vivo and in vitro. Subcellular localization studies demonstrated HDAC4 expression was predominantly nuclear in proliferating HCT116 cells and relocalized to the cytoplasm after cell cycle arrest. Down-regulating HDAC4 expression by small interfering RNA (siRNA) in HCT116 cells induced growth inhibition and apoptosis in vitro, reduced xenograft tumor growth, and increased p21 transcription. Conversely, overexpression of HDAC4 repressed p21 promoter activity. p21 was likely a direct target of HDAC4, because HDAC4 down-regulation increased p21 mRNA when protein synthesis was inhibited by cycloheximide. The importance of p21 repression in HDAC4-mediated growth promotion was demonstrated by the failure of HDAC4 down-regulation to induce growth arrest in HCT116 p21-null cells. HDAC4 down-regulation failed to induce p21 when Sp1 was functionally inhibited by mithramycin or siRNA-mediated down-regulation. HDAC4 expression overlapped with that of Sp1, and a physical interaction was demonstrated by coimmunoprecipitation. Chromatin immunoprecipitation (ChIP) and sequential ChIP analyses demonstrated Sp1-dependent binding of HDAC4 to the proximal p21 promoter, likely directed through the HDAC4-HDAC3-N-CoR/SMRT corepressor complex. Consistent with increased transcription, HDAC4 or SMRT down-regulation resulted in increased histone H3 acetylation at the proximal p21 promoter locus. These studies identify HDAC4 as a novel regulator of colon cell proliferation through repression of p21.
Understanding RealWorld Indoor Scenes with Synthetic Data (2016)

Scene understanding is a prerequisite to many high level tasks for any automated intelligent machine operating in real world environments. Recent attempts with supervised learning have shown promise in this direction but also highlighted the need for enormous quantity of supervised data- performance increases in proportion to the amount of data used. However, this quickly becomes prohibitive when considering the manual labour needed to collect such data. In this work, we focus our attention on depth based semantic per-pixel labelling as a scene understanding problem and show the potential of computer graphics to generate virtually unlimited labelled data from synthetic 3D scenes. By carefully synthesizing training data with appropriate noise models we show comparable performance to state-of-the-art RGBD systems on NYUv2 dataset despite using only depth data as input and set a benchmark on depth-based segmentation on SUN RGB-D dataset.
Members of the YABBY gene family specify abaxial cell fate in Arabidopsis (1999)

Lateral organs produced by shoot apical and flower meristems exhibit a fundamental abaxial-adaxial asymmetry. We describe three members of the YABBY gene family, FILAMENTOUS FLOWER, YABBY2 and YABBY3, isolated on the basis of homology to CRABS CLAW. Each of these genes is expressed in a polar manner in all lateral organ primordia produced from the apical and flower meristems. The expression of these genes is precisely correlated with abaxial cell fate in mutants in which abaxial cell fates are found ectopically, reduced or eliminated. Ectopic expression of either FILAMENTOUS FLOWER or YABBY3 is sufficient to specify the development of ectopic abaxial tissues in lateral organs. Conversely, loss of polar expression of these two genes results in a loss of polar differentiation of tissues in lateral organs. Taken together, these observations indicate that members of this gene family are responsible for the specification of abaxial cell fate in lateral organs of Arabidopsis. Furthermore, ectopic expression studies suggest that ubiquitous abaxial cell fate and maintenance of a functional apical meristem are incompatible.
Discovery of a Potent and Selective in Vivo Probe (GNE-272) for the Bromodomains of CBP/EP300 (2016)

The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC<sub>50</sub> = 0.02 μM, BRET IC<sub>50</sub> = 0.41 μM, BRD4(1) IC<sub>50</sub> = 13 μM) that retained the best balance of cell potency, selectivity, and in vivo PK. Compound 59 showed a marked antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model.
Three-part inventions: intracellular signaling and induced proximity (1996)

Everyone has had the experience of stoking a fire; putting the logs close together causes flames to appear from previously dying embers. In a similar way, mere proximity might mediate qualitative biological responses. We discuss natural molecules that appear to have arisen to bring two proteins together and illustrate how this simple mechanism can be used to control a wide variety of biological processes.
The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex (2001)

The E2F transcription factors play a key role in the regulation of cellular proliferation and terminal differentiation. E2F6 is the most recently identified and the least well understood member of the E2F family. It is only distantly related to the other E2Fs and lacks the sequences responsible for both transactivation and binding to the retinoblastoma protein. Consistent with this finding, E2F6 can behave as a dominant negative inhibitor of the other E2F family members. In this study, we continue to investigate the possible role(s) of E2F6 in vivo. We report the isolation of RYBP, a recently identified member of the mammalian polycomb complex, as an E2F6-interacting protein. Mapping studies indicate that RYBP binds within the known "repression domain" of E2F6. Moreover, we demonstrate that endogenous E2F6 and polycomb group proteins, including RYBP, Ring1, MEL-18, mph1, and the oncoprotein Bmi1, associate with one another. These findings suggest that the biological properties of E2F6 are mediated through its ability to recruit the polycomb transcriptional repressor complex.
Shaping geometric objects by cumulative translational sweeps (1987)

This paper introduces the cumulative translational sweep (CTS) as a tool for shaping geometric objects. It describes how it may be applied, in combination with Boolean operations, to stimulate growth and shrinking over the boundary regions of polyhedral models, and how, by creating additional facets, it may be used to achieve global rounding effects along model edges and around their vertices. CTSs are examined in terms of a conceptual framework that describes their effects as Minkowski sums—of the polyhedra to be swept, with convex polyhedra from the class of mathematical objects known as zonotopes. Included is a discussion of applications in the OYSTER program, a CAD system for the simulation of semiconductor wafer fabrication.
Dynamically weighted ensemble neural networks for classification (2002)

Combining the outputs of several neural networks into an aggregate output often gives improved accuracy over any individual output. The set of networks is known as an ensemble or committee. This paper presents an ensemble method for classification that has advantages over other techniques for linear combining. Normally, the output of an ensemble is a weighted sum whose weights are fixed, having been determined from the training or validation data. Our ensembles are weighted dynamically, the weights determined from the respective certainties of the network outputs. The more certain a network seems to be of its decision, the higher the weight.
[The developments of medical monitoring techniques]. (2002)

Based on analyzing the problems of the existing medical monitoring systems and the clinical needs in medicine the main development aspects of modern medical monitoring techniques are discussed in the paper. Then the urgent needs of monitoring techniques are presented here.
Real‐time monitoring of high‐gravity corn mash fermentation using in situ raman spectroscopy (2013)

In situ Raman spectroscopy was employed for real-time monitoring of simultaneous saccharification and fermentation (SSF) of corn mash by an industrial strain of Saccharomyces cerevisiae. An accurate univariate calibration model for ethanol was developed based on the very strong 883 cm(-1) C-C stretching band. Multivariate partial least squares (PLS) calibration models for total starch, dextrins, maltotriose, maltose, glucose, and ethanol were developed using data from eight batch fermentations and validated using predictions for a separate batch. The starch, ethanol, and dextrins models showed significant prediction improvement when the calibration data were divided into separate high- and low-concentration sets. Collinearity between the ethanol and starch models was avoided by excluding regions containing strong ethanol peaks from the starch model and, conversely, excluding regions containing strong saccharide peaks from the ethanol model. The two-set calibration models for starch (R(2) = 0.998, percent error = 2.5%) and ethanol (R(2) = 0.999, percent error = 2.1%) provide more accurate predictions than any previously published spectroscopic models. Glucose, maltose, and maltotriose are modeled to accuracy comparable to previous work on less complex fermentation processes. Our results demonstrate that Raman spectroscopy is capable of real time in situ monitoring of a complex industrial biomass fermentation. To our knowledge, this is the first PLS-based chemometric modeling of corn mash fermentation under typical industrial conditions, and the first Raman-based monitoring of a fermentation process with glucose, oligosaccharides and polysaccharides present.
Intrahepatic cholestasis of pregnancy (2009)

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.
Effect of microwave irradiation on reaction of furo[3,2-b]pyrrole and furo[2,3-b]pyrrole-2-carbaldehydes with some active methylene compounds (2000)

The synthesis of methyl 4-(methoxymethyl)furo [3,2-b]pyrrole-5-carboxylate (1d) and methyl 2formyl-4-(methoxymethyl)furo[3,2-b]pyrrole-5-carboxylate (2d) is described. The effect of microwave irradiation on the condensation reactions of methyl 2-formylfuro[3,2-b]pyrrole-5carboxylates 2a-2d and methyl 2-formylfuro[2,3-b]pyrrole-5-carboxylates 3a-3d with active methylene compounds as are: 2-thioxothiazolidine-4-one (rhodanine), 2-thioxoimidazolidine-4one (thiohydantoine), and 3-amino-2-thioxothiazolidine-4-one (3-aminorhodanine) was studied and compared with "classical" conditions. The results show that microwave irradiation shortens the reaction time while maintaining comparable yields.
Interaction of PEO-PS-PEO Block Copolymers with Ionic Surfactants in Aqueous Solution (1997)

Abstract The formation of polyelectrolyte type complex by the interaction between ionic (anionic and cationic) surfactant and block copolymer in water was observed from viscosity measurements. Interaction between the two was also examined from conductance and surface tension measurements were two transitions, one below and one above the critical micelle concentration, CMC, of the surfactants were observed. A possible mechanism for such an interaction is proposed.
Accurate diagnosis of carriers of deletions and duplications in Duchenne/Becker muscular dystrophy by fluorescent dosage analysis. (1996)

We have developed a semiautomated approach to amplify 25 exons of the dystrophin gene using two fluorescent multiplex PCR assays which detect over 98% of reported deletions and 90% of duplications causing Duchenne/Becker muscular dystrophy. The 5' multiplex detects 11 exons from the proximal deletion hotspot of the gene while the 3' multiplex detects 14 exons from the central deletion hotspot. The PCR products are accurately sized and quantified by a fluorescent DNA sequencer after only 18 cycles of amplification. The amount of product amplified from each exon in a multiplex is divided by that from each of the other exons, and this ratio is compared with those from control samples to obtain a series of dosage quotients (DQ), from which the copy number of each exon is determined. No overlap was observed between the DQ values obtained from single and double copy loci. The assays can be used to screen both affected males and at risk female relatives for a mutation. The method has been evaluated as a female carrier test by conducting a blind trial on 150 coded samples. Sixty-three deletion carriers, two duplication carriers, and 84 normal female controls were all correctly identified, showing that carrier diagnosis is possible even in families where the nature of the mutation is unknown. Additionally the analysis showed a non-pathogenic duplication involving the muscle specific promoter and exon 1. Together these two multiplex assays detect over 70% of all mutations in the dystrophin gene, greatly simplifying and partly automating molecular diagnosis in Duchenne and Becker muscular dystrophy.
Trichomonas vaginalis: why we should be screening (2001)

Vaginal trichomoniasis, or infection with the parasite Trichomonas vaginalis, is a very common sexually transmitted infection (STI) which infects disadvantaged populations. It is of major public health concern worldwide. It has a strong association with adverse pregnancy outcomes and HIV transmission and yet is readily treatable with effective single dose, low cost treatment. Trichomoniasis should be considered in the diagnosis of vaginitis and should be part of any STI screen. Mass screening and treatment strategies for Trichomonas infection have the potential globally to be the single most cost effective achievable strategy for the reduction of HIV incidence. A greater understanding of the pathogenesis (including virulence factors) of this parasite is required if we are to combat this parasite effectively. (author abstract)
Expression of recombinant exoenzyme S of Pseudomonas aeruginosa (1995)

The structural gene for the 49-kDa form of exoenzyme S (exoS) isolated from Pseudomonas aeruginosa 388 was expressed in both Escherichia coli and P. aeruginosa PA103. Expression of exoS in E. coli under the transcriptional regulation of the T7 promoter yielded a soluble cytosolic protein with an apparent molecular mass of 49 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Expression of exoS in P. aeruginosa PA103 under the transcriptional regulation of the 0.9 kbp of Pseudomonas chromosomal DNA flanking the 5' end of exoS yielded a nitrilotriacetic acid-inducible extracellular protein with an apparent molecular mass of 49 kDa. Recombinant ExoS (rExoS) reacted with the anti-49-kDa form of exoenzyme S immunoglobulin G, existed as an aggregate as determined by gel filtration chromatography, and ADP-ribosylated soybean trypsin inhibitor at a specific activity that was similar (within twofold) to that of native exoenzyme S. Allelic exchange of exoS with a tetracycline gene cartridge yielded a strain of P. aeruginosa 388 that did not express detectable amounts of either ExoS in an immunoblot analysis using the anti-49-kDa form of exoenzyme S immunoglobulin G or ADP-ribosyltransferase activity under standard enzyme assay conditions. Expression of catalytically active rExoS in E. coli demonstrated that exoS was necessary and sufficient for the factor-activating exoenzyme S-dependent ADP-ribosyltransferase activity of exoenzyme S. Expression of nitrilotriacetic acid-inducible rExoS in P. aeruginosa PA103 demonstrated that the 0.9 kbp of Pseudomonas chromosomal DNA flanking the 5' end of exoS encoded a functional exoenzyme S promoter. Expression analysis and allelic exchange experiments suggest that the 49- and 53-kDa forms of exoenzyme S are encoded by separate genes.
Adult T-Cell Leukemia/Lymphoma (2014)

Adult T-cell leukemia/lymphoma is a rare mature CD4(+) T-cell neoplasm caused by the retrovirus human T-lymphotrophic virus type 1. At present there are approximately 20 million people infected globally with this virus, and most of these individuals belong to the endemic areas in southern Japan, Africa, the Caribbean basin, and Latin America. In the United States, it is usually seen in immigrants from these endemic regions. Adult T-cell leukemia/lymphoma predominantly affects the adult population and is rare in children. Adult T-cell leukemia/lymphoma has 4 subtypes: acute, lymphomatous, chronic, and smoldering. Clinically, the first 2 variants are classified as aggressive, and the latter two are classified as indolent. Given the rare occurrence and diagnostic challenges associated with adult T-cell leukemia/lymphoma, this review will highlight its salient features to aid in recognition of this entity and perform a comprehensive diagnostic workup.
Visible electroluminescent subwavelength point source of light (1992)

A structure has been devised to generate a visible point source of electroluminescently produced light with subwavelength dimensions. This submicron (0.3 μm) spot of light is created by the combination of a standard dc electroluminescent powder, ZnS:MnCu, that is introduced into the tip of a glass micropipette coated with a transparent coating of conducting indium oxide as the anode and an appropriate electrode placed inside the pipette as the cathode.