gebhart/patrepeval huggingface dataset:
Immunotherapy in lung cancer. (2014)

Immunotherapy has emerged in recent years as a promising therapeutic approach in lung cancer. Two approaches are of particular interest: immune checkpoint inhibition, which aims to counteract the physiologic mechanisms of immune tolerance co-opted by some tumors, and vaccine therapy, which enables enhanced exposure to tumor antigen. Immune checkpoint therapies include the monoclonal antibody blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) with ipilimumab, as well as antibody blockade of the programmed cell death-1 (PD-1) receptor and the PD-1 ligand. These immune checkpoint therapies have been evaluated in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with early evidence of activity. Vaccines include antigen specific therapies which induce specific antitumor immunity against relevant tumor-associated antigens. In lung cancer, these include the melanoma-associated antigen-A3 (MAGE-A3), membrane-associated glycoprotein (MUC-1), and the epidermal growth factor receptor (EGFR). Whole tumor vaccines have also been evaluated in lung cancer and influence the patient's immune system to allow recognition of the tumor as foreign creating de novo immunity. This review summarizes the evidence to date for the efficacy and safety of immunotherapies in lung cancer.
On the substrate specificity of α-crystallin as a molecular chaperone (1995)

alpha-Crystallin, the major protein of the ocular lens, acts as a molecular chaperone by preventing the thermal aggregation of proteins. However, in contrast with many other heat shock proteins, alpha-crystallin fails to protect proteins from aggregation during refolding reactions. Our results indicate that alpha-crystallin has substrate specificity different from other chaperones and recognizes specific non-native intermediates formed on the denaturation pathway only, with no affinity for intermediates formed on the refolding pathway.
Multiple Lysine Mutations in the C-Terminal Domain of p53 Interfere with MDM2-Dependent Protein Degradation and Ubiquitination (2000)

To investigate the effect of mutations in the p53 C-terminal domain on MDM2-mediated degradation, we introduced single and multiple point mutations into a human p53 cDNA at four putative acetylation sites (amino acid residues 372, 373, 381, and 382). Substitution of all four lysine residues by alanines (the A4 mutant) and single lysine-to-alanine substitutions were functional in sequence-specific DNA binding and transactivation; however, the A4 mutant protein was resistant to MDM2-mediated degradation, whereas the single lysine substitutions were not. Although the A4 mutant protein and the single lysine substitutions both bound MDM2 reasonably well, the single lysine substitutions underwent normal MDM2-dependent ubiquitination, whereas the A4 protein was inefficiently ubiquitinated. In addition, the A4 mutant protein was found in the cytoplasm as well as in the nucleus of a subpopulation of cells, unlike wild-type p53, which is mostly nuclear. The partially cytoplasmic distribution of A4 mutant protein was not due to a defect in nuclear import because inhibition of nuclear export by leptomycin B resulted in nuclear accumulation of the protein. Taken together, the data suggest that mutations in the putative acetylation sites of the p53 C-terminal domain interfere with ubiquitination, thereby regulating p53 degradation.
Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members (1997)

In the intracellular death program, hetero- and homodimerization of different anti- and pro-apoptotic Bcl-2-related proteins are critical in the determination of cell fate. From a rat ovarian fusion cDNA library, we isolated a new pro-apoptotic Bcl-2 gene, Bcl-2-related ovarian killer (Bok). Bok had conserved Bcl-2 homology (BH) domains 1, 2, and 3 and a C-terminal transmembrane region present in other Bcl-2 proteins, but lacked the BH4 domain found only in anti-apoptotic Bcl-2 proteins. In the yeast two-hybrid system, Bok interacted strongly with some (Mcl-1, BHRF1, and Bfl-1) but not other (Bcl-2, Bcl-xL, and Bcl-w) anti-apoptotic members. This finding is in direct contrast to the ability of other pro-apoptotic members (Bax, Bak, and Bik) to interact with all of the anti-apoptotic proteins. In addition, negligible interaction was found between Bok and different pro-apoptotic members. In mammalian cells, overexpression of Bok induced apoptosis that was blocked by the baculoviral-derived cysteine protease inhibitor P35. Cell killing induced by Bok was also suppressed following coexpression with Mcl-1 and BHRF1 but not with Bcl-2, further indicating that Bok heterodimerized only with selective anti-apoptotic Bcl-2 proteins. Northern blot analysis indicated that Bok was highly expressed in the ovary, testis and uterus. In situ hybridization analysis localized Bok mRNA in granulosa cells, the cell type that underwent apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover.
Tin Oxide Dependence of the CO2 Reduction Efficiency on Tin Electrodes and Enhanced Activity for Tin/Tin Oxide Thin-Film Catalysts (2012)

The importance of tin oxide (SnO(x)) to the efficiency of CO(2) reduction on Sn was evaluated by comparing the activity of Sn electrodes that had been subjected to different pre-electrolysis treatments. In aqueous NaHCO(3) solution saturated with CO(2), a Sn electrode with a native SnO(x) layer exhibited potential-dependent CO(2) reduction activity consistent with previously reported activity. In contrast, an electrode etched to expose fresh Sn(0) surface exhibited higher overall current densities but almost exclusive H(2) evolution over the entire 0.5 V range of potentials examined. Subsequently, a thin-film catalyst was prepared by simultaneous electrodeposition of Sn(0) and SnO(x) on a Ti electrode. This catalyst exhibited up to 8-fold higher partial current density and 4-fold higher faradaic efficiency for CO(2) reduction than a Sn electrode with a native SnO(x) layer. Our results implicate the participation of SnO(x) in the CO(2) reduction pathway on Sn electrodes and suggest that metal/metal oxide composite materials are promising catalysts for sustainable fuel synthesis.
Elevation of ELISA D-Dimer Levels in Patients with Primary Pulmonary Hypertension (2002)

These results suggest the possible involvement of endogenous fibrinolysis in the pathophysiology of PPH.
Buckytubes and Derivatives: Their Growth and Implications for Buckyball Formation (1993)

Transmission electron microscopy (TEM) observations of graphite tubules (buckytubes) and their derivatives have revealed not only the previously reported buckytube geometries but also additional shapes of the buckytube derivatives. Detailed cross-sectional TEM images reveal the cylindrical cross section of buckytubes and the growth pattern of buckytubes as well as their derivatives. These observations of frozen growth stages of buckytubes and derivatives suggest a helical growth mechanism analogous to that of crystal growth via screw dislocations. The helicacy of buckytubes is analyzed by electron diffraction whereas the anisotropy of electronic structure is revealed by momentum transfer resolved electron energy loss spectrometry. Based on the TEM observations, it is proposed that buckytubes act as precursors to closed-shell fullerene (buckyball) formation and the possible steps in buckyball formation are outlined. In arc evaporation experiments in which residue rods (containing various amounts of buckytubes) were used as the starting anode for fullerene production, the amount of buckytubes in the rod was correlated with fullerene yield.
Nanopod Formation through Gold Nanoparticle Templated and Catalyzed Cross-linking of Polymers Bearing Pendant Propargyl Ethers (2010)

A novel method for synthesizing polymer nanopods from a linear polymer bearing pendant propargyl ether groups, using gold nanoparticles as both the template and the catalyst for the cross-linking reaction, is reported. The transformations involved in the cross-linking process are unprecedented on the surface of a gold particle. A tentative cross-linking mechanism is proposed.
Targeting Retroviral Vectors to Vascular Lesions by Genetic Engineering of the MoMLV gp70 Envelope Protein (1997)

Targeted gene delivery to vascular lesions is a major challenge in the development of gene therapy protocols for cardiovascular diseases. One approach would be to enable retroviral vectors to accumulate at sites of vascular injury and enhance local vector concentration. An early step in wound repair is the adhesion of platelets to collagen exposed from damaged vasculature. Hence, the Moloney murine leukemia virus (MoMLV) envelope (env) protein was engineered to incorporate a high-affinity collagen-binding domain derived from von Willebrand clotting factor, and expressed in Escherichia coli and in mammalian cells. The chimeric env protein bound tightly to collagen, and virions bearing this collagen-binding env protein exhibited viral titers approaching those of virions expressing wild-type (WT) env protein. The chimeric virions were concentrated on collagen matrices, and they retained their infectivity under conditions in which virions bearing WT env protein were washed away. Targeted delivery of the chimeric env protein to injured mouse aorta and selective binding of the collagen-targeted virions to injured rabbit artery were observed. In comparative studies, vascular smooth muscle cell transduction was demonstrated in catheter-injured carotid arteries following infusion of collagen-targeted virions but not of virions bearing WT env protein. Taken together, these observations demonstrate the ability of collagen-targeted virions to localize gene delivery to sites of vascular injury.
Flexible page segmentation using the background (2002)

This paper introduces a new method for document page segmentation. This method is based on the analysis of the background white space that surrounds the printed regions on the page. It does not make any assumptions about the shape of the regions as opposed to most earlier approaches which assume that printed regions are rectangular. It is capable of identifying and describing regions of complex shapes more accurately than existing methods. It requires no a priori knowledge. The background white space is covered with tiles and the contour of each region is identified by tracing through these white tiles that encircle it. The method can segment page images with severe skew without skew correction. The white tiles on the image can also be used in subsequent document analysis processes such as the classification of the image regions.
Layer-by-Layer Epitaxial Growth of Scalable WSe2 on Sapphire by Molecular Beam Epitaxy (2017)

Molecular beam epitaxy (MBE) provides a simple but powerful way to synthesize large-area high-quality thin films and heterostructures of a wide variety of materials including accomplished group III-V and II-VI semiconductors as well as newly developing oxides and chalcogenides, leading to major discoveries in condensed-matter physics. For two-dimensional (2D) materials, however, main fabrication routes have been mechanical exfoliation and chemical vapor deposition by making good use of weak van der Waals bonding nature between neighboring layers, and MBE growth of 2D materials, in particular on insulating substrates for transport measurements, has been limited despite its fundamental importance for future advanced research. Here, we report layer-by-layer epitaxial growth of scalable transition-metal dichalocogenide (TMDC) thin films on insulating substrates by MBE and demonstrate ambipolar transistor operation. The proposed growth protocol is broadly applicable to other TMDCs, providing a key milestone toward fabrication of van der Waals heterostructures with various 2D materials for novel properties and functionalities.
Predicting player churn in the wild (2014)

Free-to-Play or “freemium” games represent a fundamental shift in the business models of the game industry, facilitated by the increasing use of online distribution platforms and the introduction of increasingly powerful mobile platforms. The ability of a game development company to analyze and derive insights from behavioral telemetry is crucial to the success of these games which rely on in-game purchases and in-game advertising to generate revenue, and for the company to remain competitive in a global marketplace. The ability to model, understand and predict future player behavior has a crucial value, allowing developers to obtain data-driven insights to inform design, development and marketing strategies. One of the key challenges is modeling and predicting player churn. This paper presents the first cross-game study of churn prediction in Free-to-Play games. Churn in games is discussed and thoroughly defined as a formal problem, aligning with industry standards. Furthermore, a range of features which are generic to games are defined and evaluated for their usefulness in predicting player churn, e.g. playtime, session length and session intervals. Using these behavioral features, combined with the individual retention model for each game in the dataset used, we develop a broadly applicable churn prediction model, which does not rely on game-design specific features. The presented classifiers are applied on a dataset covering five free-to-play games resulting in high accuracy churn prediction.
Acyclovir in the treatment of aplastic anemia (1988)

Eight patients with idiopathic severe aplastic anemia received acyclovir as the initial treatment to ascertain if this antiviral therapy could be effective. Three patients showed improvement, but only one had a sustained recovery. The responses could be coincidental, but it seems that some patients can benefit from acyclovir. More studies are needed on the role of viruses and antiviral therapy in relation to severe aplastic anemia.
The Involvement of Glutamate in the Pathophysiology of Depression (2005)

In spite of more than 40 years of thorough studies, conventional antidepressants still have many limitations that hinder the effective treatment of depression. It seems that a breakthrough in the therapy of depression will require going beyond a monoamine-based theory of depression. Converging lines of evidence indicate that the glutamatergic system might be a promising target for a novel antidepressant therapy. Both ionotropic glutamate receptor ligands (functional NMDA receptor antagonists and AMPA receptor potentiators) and compounds acting at metabotropic glutamate receptors (mGluRs; group I mGluR antagonists, group II antagonists and group III agonists) produce antidepressant-like activity in several preclinical and some clinical studies. In this review, current knowledge and crucial hypotheses concerning the role of glutamate in the pathophysiology of depression are discussed.
Sleep Monitoring Based on a Tri-Axial Accelerometer and a Pressure Sensor (2016)

Sleep disorders are a common affliction for many people even though sleep is one of the most important factors in maintaining good physiological and emotional health. Numerous researchers have proposed various approaches to monitor sleep, such as polysomnography and actigraphy. However, such approaches are costly and often require overnight treatment in clinics. With this in mind, the research presented here has emerged from the question: "Can data be easily collected and analyzed without causing discomfort to patients?" Therefore, the aim of this study is to provide a novel monitoring system for quantifying sleep quality. The data acquisition system is equipped with multimodal sensors, including a three-axis accelerometer and a pressure sensor. To identify sleep quality based on measured data, a novel algorithm, which uses numerous physiological parameters, was proposed. Such parameters include non-REM sleep time, the number of apneic episodes, and sleep durations for dominant poses. To assess the effectiveness of the proposed system, three participants were enrolled in this experimental study for a duration of 20 days. From the experimental results, it can be seen that the proposed monitoring system is effective for quantifying sleep quality.
Management of chronic immune thrombocytopenic purpura in children and adults. (1998)

Chronic immune thrombocytopenic purpura (ITP) is characterized by macrophage destruction of platelets, primarily in the spleen, and occurs in both adults and children. Historically, splenectomy is often required, especially in adults with chronic ITP; however, several medical options have been used successfully prior to splenectomy or when this procedure has either failed or been refused by the patient. These include corticosteroids, intravenous immunoglobulin (IVIg), intravenous anti-D, danazol, vinca alkaloids, and other immunosuppressive agents such as azathioprine and cyclophosphamide. Platelet transfusions have been used in emergency situations. Several therapies that have been reported, but that are rarely used in chronic ITP, include cyclosporine A, interferon-alpha (IFN-alpha), plasma exchange, staphylococcal protein A immunoadsorption, combination chemotherapy, dapsone, ascorbic acid, and colchicine. Each of these approaches to treatment of chronic ITP are discussed.
5′-C-Malonyl RNA: Small Interfering RNAs Modified with 5′-Monophosphate Bioisostere Demonstrate Gene Silencing Activity (2015)

5'-Phosphorylation is a critical step in the cascade of events that leads to loading of small interfering RNAs (siRNAs) into the RNA-induced silencing complex (RISC) to elicit gene silencing. 5'-Phosphorylation of exogenous siRNAs is generally accomplished by a cytosolic Clp1 kinase, and in most cases, the presence of a 5'-monophosphate on synthetic siRNAs is not a prerequisite for activity. Chemically introduced, metabolically stable 5'-phosphate mimics can lead to higher metabolic stability, increased RISC loading, and higher gene silencing activities of chemically modified siRNAs. In this study, we report the synthesis of 5'-C-malonyl RNA, a 5'-monophosphate bioisostere. A 5'-C-malonyl-modified nucleotide was incorporated at the 5'-terminus of chemically modified RNA oligonucleotides using solid-phase synthesis. In vitro silencing activity, in vitro metabolic stability, and in vitro RISC loading of 5'-C-malonyl siRNA was compared to corresponding 5'-phosphorylated and 5'-nonphosphorylated siRNAs. The 5'-C-malonyl siRNAs showed sustained or improved in vitro gene silencing and high levels of Ago2 loading and conferred dramatically improved metabolic stability to the antisense strand of the siRNA duplexes. In silico modeling studies indicate a favorable fit of the 5'-C-malonyl group within the 5'-phosphate binding pocket of human Ago2MID domain.
Binding of Zn2+ to a Ca2+ loop allosterically attenuates the activity of factor VIIa and reduces its affinity for tissue factor (2000)

The protease domain of coagulation factor VIIa (FVIIa) is homologous to trypsin with a similar active site architecture. The catalytic function of FVIIa is regulated by allosteric modulations induced by binding of divalent metal ions and the cofactor tissue factor (TF). To further elucidate the mechanisms behind these transformations, the effects of Zn2+ binding to FVIIa in the free form and in complex with TF were investigated. Equilibrium dialysis suggested that two Zn2+ bind with high affinity to FVIIa outside the N-terminal gamma-carboxyglutamic acid (Gla) domain. Binding of Zn2+ to FVIIa, which was influenced by the presence of Ca2+, resulted in decreased amidolytic activity and slightly reduced affinity for TF. After binding to TF, FVIIa was less susceptible to zinc inhibition. Alanine substitutions for either of two histidine residues unique for FVIIa, His216, and His257, produced FVIIa variants with decreased sensitivity to Zn2+ inhibition. A search for putative Zn2+ binding sites in the crystal structure of the FVIIa protease domain was performed by Grid calculations. We identified a pair of Zn2+ binding sites in the Glu210-Glu220 Ca2+ binding loop adjacent to the so-called activation domain canonical to serine proteases. Based on our results, we propose a model that describes the conformational changes underlying the Zn2+-mediated allosteric down-regulation of FVIIa's activity.
Particle size measurement: the equivalent spherical diameter (1988)

Abstract In particle size analysis, it is commonplace to analyse data for anisodiametric particles as if the particles were spheres. Expressions are given herein for the equivalent spherical diameters (ESD) for discs, rods and the more general oblate and prolate spheroids. The dependence of the ESD on the true major dimension and axial ratio differs with the physical basis of measurement, and identity of the ESD values from different methods cannot be expected. A comparison between any two sets of experimental data leads to estimation of the minor particle dimension and a quantitative measure of the particle non-sphericity.
Role of Anthocyanidin Reductase, Encoded by BANYULS in Plant Flavonoid Biosynthesis (2003)

Condensed tannins (CTs) are flavonoid oligomers, many of which have beneficial effects on animal and human health. The flavanol (-)-epicatechin is a component of many CTs and contributes to flavor and astringency in tea and wine. We show that the BANYULS (BAN) genes from Arabidopsis thaliana and Medicago truncatula encode anthocyanidin reductase, which converts anthocyanidins to their corresponding 2,3-cis-flavan-3-ols. Ectopic expression of BAN in tobacco flower petals and Arabidopsis leaves results in loss of anthocyanins and accumulation of CTs.
Expression of Liver X Receptor Target Genes Decreases Cellular Amyloid β Peptide Secretion (2003)

A hallmark of Alzheimer's disease is the deposition of plaques of amyloid beta peptide (Abeta) in the brain. Abeta is thought to be formed from the amyloid precursor protein (APP) in cholesterol-enriched membrane rafts, and cellular cholesterol depletion decreases Abeta formation. The liver X receptors (LXR) play a key role in regulating genes that control cellular cholesterol efflux and membrane composition and are widely expressed in cells of the central nervous system. We show that treatment of APP-expressing cells with LXR activators reduces the formation of Abeta. LXR activation resulted in increased levels of the ATP-binding cassette transporter A1 (ABCA1) and stearoyl CoA desaturase, and expression of these genes individually decreased formation of Abeta. Expression of ABCA1 led to both decreased beta-cleavage product of APPSw (i.e. C99 peptide) and reduced gamma-secretase-cleavage of C99 peptide. Remarkably, these effects of ABCA1 on APP processing were independent of cellular lipid efflux. LXR and ABCA1-induced changes in membrane lipid organization had favorable effects on processing of APP, suggesting a new approach to the treatment of Alzheimer's disease.