gebhart/patrepeval huggingface dataset:
A Comprehensive Survey of Ras Mutations in Cancer (2012)

All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers.
Antiinflammatory effects of polypeptide growth factors. Platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor inhibit the cytokine-induced expression of the alternative complement pathway activator factor B in human fibroblasts. (1990)

The synthesis of complement components in human fibroblasts is modulated by mediators of inflammation such as cytokines. In particular, interleukin-1 (IL-1) and tumor necrosis factor (TNF) induce time- and dose-dependent increases in the synthesis of complement proteins factor B (FB), C3, and factor H (FH). Polypeptide growth factors are also soluble mediators released during inflammation and able to modulate many fibroblast functions. We have studied the effects of polypeptide growth factors platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) on the synthesis of complement proteins in cultured human fibroblasts. PDGF, EGF, and FGF alone did not affect the level of synthesis of any of the complement proteins analyzed, but simultaneous incubation of PDGF, EGF, or FGF with IL-1 and TNF resulted in a dose-dependent inhibition of the cytokine-enhanced expression of FB. Inhibition of FB synthesis was observed between 4 and 8 h of exposure to PDGF and persisted for 4 h after the removal of the growth factor. Analysis of steady-state levels of specific FB mRNA suggested that PDGF-induced inhibition of FB synthesis is mediated at a pretranslational level and that it requires new protein synthesis. The effect of the growth factors was limited to FB, with marginal or no inhibition on the cytokine-enhanced synthesis of C3 and FH, excluding the possibility that the inhibitory effects of PDGF, EGF, and FGF on FB synthesis were due to a negative modulation of the growth factors on cytokine cell membrane receptors. Specific inhibition of cytokine-induced increases in FB synthesis by the growth factors may represent down regulation of the acute inflammatory process, further permitting progression to processes of tissue repair and remodeling. Study of the interactions between cytokines and growth factors in the regulation of synthesis of complement proteins may also provide a system for investigating mechanisms of signal transduction of both polypeptide growth factors and cytokines.
Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus (2000)

Previous studies have indicated that the autoimmune phenomenon might be caused by an imbalance of T helper cell (Th) cytokines. We measured the plasma concentrations of three novel proinflammatory cytokines interleukin (IL)-17, IL-18, IL-12 and a key Th2 cytokine IL-4 in patients with systemic lupus erythematosus (SLE) and correlated the ratio of proinflammatory/Th2 cytokines with SLE disease activity index (SLEDAI). Plasma IL-12, IL-17, IL-18 and IL-4 concentrations of 36 SLE patients and 18 sex- and age-matched control subjects were measured by enzyme linked immunosorbent assay. All were significantly higher in SLE patients than control subjects (IL-12, mean+/-s.d. of 166.7+/-84.5 vs 93.5+/-39.2 pg/ml, P<0.001; IL-17, 76.5+/-45.7 vs 37.6+/-35.3 pg/ml, P=0.002; IL-18, 368.7+/-199. 5 vs 141.1+/-47.1 pg/ml, P<0.001; and IL-4, 27.1+/-15.3 vs 17.3+/-7. 2 pg/ml, P<0.05), and IL-18/IL-4 ratio correlated positively and significantly with SLEDAI score (r=0.435, P=0.006). We propose that SLE is characterized by an elevation of both Th1 and Th2 cytokines: the elevation of proinflammatory cytokine IL-12, IL-17 and IL-18 may trigger the inflammatory process in SLE and the elevation of IL-18/IL-4 ratio suggests an imbalance of cytokine profile to mediate the inflammatory response.
How Did Everyone Get Diagnosed with Major Depressive Disorder? (2015)

Psychiatric diagnoses often reflect a matrix of sociological factors associated with professional prestige, economic forces, and cultural fashions. Diagnostic systems conceptualize the same underlying psychosocial problems in very different ways during various time periods. Since the publication of the third edition of the Diagnostic and Statistical Manual (DSM-III) in 1980, psychological distress resulting from social circumstances that previously was viewed as a general problem of nerves, neuroses, and anxiety was transformed into the specific diagnosis of major depressive disorder. Several factors, including the contrasting ways in which DSM-III defined anxiety and depression, the necessity of using explicit diagnoses to obtain professional legitimacy and reimbursement for services, and the marketing practices of the pharmaceutical industry, account for why depression replaced anxiety as the diagnosis most suitable for treated mental health conditions. Beneath the changing veneer of psychiatric labels, however, lies the same mélange of psychic ills that resist the precise labels current diagnostic fashions strive to impose upon them.
Histidine residue in the zinc-binding motif of aminopeptidase A is critical for enzymatic activity. (1993)

The murine BP-1 antigen (also called 6C3) is a homodimeric, phosphorylated cell surface glycoprotein that is expressed on immature B-lineage cells, bone marrow stromal cell lines, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. The amino acid sequence deduced from a BP-1 cDNA predicted a type II integral membrane protein with a zinc-binding motif (His-Glu-Xaa-Xaa-His) found in zinc-dependent metallopeptidases, and functional analysis suggested that BP-1 is aminopeptidase A [APA; L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 3.4.11.7]. Here we constructed an expression vector in which the BP-1 cDNA was placed downstream from the SR alpha promoter and used this construct to transfect COS-7 and Ltk- cells. Both transfectants expressed the BP-1 antigen on the cell surface and APA activity. The enzymatic activity of recombinant APA was increased by Ca2+ and inhibited by Zn2+, consistent with previous reports with purified APA. Point mutation of one of the histidine residues in the zinc-binding motif to phenylalanine completely abolished APA enzymatic activity, suggesting the structure of the zinc-binding motif of APA is critical for catalytic activity. Both wild-type and mutant BP-1 were glycosylated, transported to the cell surface, and possessed molecular weights similar to native BP-1 molecules on the murine 18.81 pre-B-cell line. The successful expression of both wild-type and mutant APA should allow more precise analysis of the diverse physiological roles of this ectoenzyme.
Applying ILMD technique with time scaling for CFD simulation of diesel engine (2006)

Detailed mechanisms describing ignition, flame propagation and pollutant formation typically involve several hundred species and elementary reactions, prohibiting their use in practical three-dimensional engine simulations. Conventionally reduced mechanisms often fail to predict minor radicals and pollutant precursors. The ILDM-method is an automatic reduction of a detailed mechanism, which assumes local equilibrium with respect to the fastest time scales identified by a local eigenvector analysis. In the reactive flow calculation, the species compositions are constrained to these manifolds. Conservation equations are solved for only a small number of reaction progress variables, thereby retaining the accuracy of detailed chemical mechanisms. This gives an effective way of coupling the details of complex chemistry with the time variations due to turbulence. A standard and RNG k-e model is used to model the turbulent flow field. Turbulence-chemistry interactions are taken into account by integrating the chemical source terms over a presumed probability density function (pdf ). The standard KIVA III code along with the above models for chemistry and turbulence were used to simulate the flow in a single cylinder of a DI diesel engine. Since no equilibrium or partial-equilibrium approach is involved, accurate concentrations of O radicals and soot-precursors (C2H2 &amp; C3H3) can be obtained from the ILDM.
Nuclei multiplexing with barcoded antibodies for single-nucleus genomics (2019)

Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or are frozen, and opens the way to human genetics studies, clinical trials, and precise cell atlases of large organs. However, such applications are currently limited by batch effects, processing, and costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies to uniquely label nuclei from distinct samples. Comparing human brain cortex samples profiled with or without hashing antibodies, we demonstrate that nucleus hashing does not significantly alter recovered profiles. We develop DemuxEM, a computational tool that detects inter-sample multiplets and assigns singlets to their sample of origin, and validate its accuracy using sex-specific gene expression, species-mixing and natural genetic variation. Our approach will facilitate tissue atlases of isogenic model organisms or from multiple biopsies or longitudinal samples of one donor, and large-scale perturbation screens.
Nanocomposite solar cells based on conjugated polymer / PbSe quantum dot (2005)

We report a novel type of nanocomposite of conjugated polymer (regio-regular polythiophene) with infrared-sensitive, PbSe quantum dots (QD), which have size-tunable lowest-energy absorption bands between 0.3 and 1 eV. Thin film devices show very good diode characteristics and sizable photovoltaic response with an open circuit voltage, <i>Voc</i>, of ~ 0.3-0.4 V and short circuit current density, J<sub>sc</sub>, of ~ 0.2mA/cm<sup>2</sup>, which is significantly higher than recently reported in PbS QD-based devices. This is the evidence of a quite efficient photoinduced charge transfer between the polymer and QD, with infrared sensitivity. Photocurrent under reverse bias is significantly enhanced to J<sub>ph</sub> ~ 1 mA/cm<sup>2</sup> indicating that the polythiophene/PbSe QD system can be used as effective infrared photodetectors. Detailed spectroscopic studies of photoresponse over a wide spectral range are presented. Quenching of photoluminescence by PbSe QDs has also been studied to gain more understanding of energy and charge transfer in this system.
Post-traumatic stress disorder and declarative memory functioning: a review. (2011)

Declarative memory dysfunction is associated with post-traumatic stress disorder (PTSD). This paper reviews this literature and presents two frameworks to explain the nature of this dysfunction: that memory deficits are a product of neurobiological abnormalities caused by PTSD and/or that pre-existing memory deficits serve as a risk factor for the development of PTSD following trauma exposure. Brain regions implicated in declarative memory deficits include the hippocampus and prefrontal cortex, and imaging and biochemistry studies as they relate to memory dysfunction are described. Prospective and twin studies provide support for a risk factor model.
A Bacillus thuringiensis Crystal Protein with Selective Cytocidal Action to Human Cells (2004)

Bacillus thuringiensis crystal proteins, well known to be toxic to certain insects but not pathogenic to mammals, are used as insecticidal proteins in agriculture and forest management. We here identified a crystal protein that is non-insecticidal and non-hemolytic but has strong cytocidal activity against various human cells with a markedly divergent target specificity, e.g. highly cytotoxic to HepG2 and Jurkat and less cytotoxic to the normal hepatocyte (HC) and HeLa. In slices of liver and colon cancer tissues, the toxin protein preferentially killed the cancer cells, leaving other cells unaffected. The cytocidal effect of the protein is non-apoptotic with swelling and fragmentation of the susceptible cells, although the apoptotic process does occur when the cell damage proceeded slowly. The amino acid sequence deduced from the nucleotide sequence of the cloned gene of the protein has little sequence homology with the insecticidal crystal proteins of B. thuringiensis. These observations raise the presence of a new group of the B. thuringiensis toxin and the possibility of new applications for the protein in the medical field.
Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? (2012)

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome of hemolysis, thrombocytopenia, and renal insufficiency. Genetic mutations in the alternate pathway of complement are well recognized as the cause in more than 60% of patients affected by this thrombotic microangiopathy. The identification of aHUS as a disease of the alternate pathway of complement enables directed therapeutic intervention both in the acute and chronic setting and may include one or all of the following: plasma therapy, complement blockade, and liver transplantation. Because aHUS shares many of the presenting characteristics of the other thrombotic microangiopathies, and confirmatory genetic results are not available at the time of presentation, the diagnosis relies heavily on the recognition of a clinical syndrome consistent with the diagnosis in the absence of signs of an alternate cause of thrombotic microangiopathy. Limited understanding of the epidemiology, genetics, and clinical features of aHUS has the potential to delay diagnosis and treatment. To advance our understanding, a more complete characterization of the unique phenotypical features of aHUS is needed. Further studies to identify additional genetic loci for aHUS and more robust biomarkers of both active and quiescent disease are required. Advances in these areas will undoubtedly improve the care of patients with aHUS.
Thiophen als Strukturelement physiologisch aktiver Substanzen, 15. Mitt. Das Thiophenanalogon eines anxiolytisch wirksamen 1,2,4‐Triazolo[4,3‐b]pyridazins (1985)

Abstract Ausgehend von Trifluoressigsäure ( 2 ) wird der Trifluormethyl‐substituierte Thiophenaldehyd 12 synthetisiert. Aus diesem wird das gewünschte Produkt 1 hergestellt.
Genomic Structure of an Economically Important Cyanobacterium, Arthrospira (Spirulina) platensis NIES-39 (2010)

A filamentous non-N(2)-fixing cyanobacterium, Arthrospira (Spirulina) platensis, is an important organism for industrial applications and as a food supply. Almost the complete genome of A. platensis NIES-39 was determined in this study. The genome structure of A. platensis is estimated to be a single, circular chromosome of 6.8 Mb, based on optical mapping. Annotation of this 6.7 Mb sequence yielded 6630 protein-coding genes as well as two sets of rRNA genes and 40 tRNA genes. Of the protein-coding genes, 78% are similar to those of other organisms; the remaining 22% are currently unknown. A total 612 kb of the genome comprise group II introns, insertion sequences and some repetitive elements. Group I introns are located in a protein-coding region. Abundant restriction-modification systems were determined. Unique features in the gene composition were noted, particularly in a large number of genes for adenylate cyclase and haemolysin-like Ca(2+)-binding proteins and in chemotaxis proteins. Filament-specific genes were highlighted by comparative genomic analysis.
Metabolism of vasopressin. (1985)

The clearance of vasopressin (VP) by the kidneys and splanchnic viscera was studied in the anesthetized dog. VP is bound to plasma protein, 10% at basal plasma VP levels and 40% at plasma VP concentrations greater than 20 microU/ml. The urinary clearance of VP is 70-100% of the glomerular filtration rate; the renal organ clearance of the hormone is 20-30% greater than its urinary clearance. There is evidence that the renal organ clearance of VP is affected by changes in both glomerular filtration rate and renal blood flow. The renal clearance of VP is a result of glomerular filtration, degradation, or reabsorption in the proximal nephron, and secretion into the distal nephron. In the short term, the renal clearance of VP is unaffected either by changes in the plasma VP concentration over a broad range or by moderate hemorrhage. The splanchnic clearance of VP is accomplished almost equally by the intestine and the liver. Because the sum of the splanchnic and renal clearances of VP is less than estimates of its metabolic clearance rate, there may be a physiologically significant clearance of VP by organs in addition to the kidneys and splanchnic viscera.
A Novel Thiourea Ligand Applied in the Pd‐Catalyzed Heck, Suzuki and Suzuki Carbonylative Reactions (2004)

Abstract A novel C 2 symmetrical and sterically bulky thiourea ligand 1 has been successfully applied to Heck, Suzuki and Suzuki‐type carbonylative coupling reactions under aerobic conditions. Since the metal‐sulfur bond in the thiourea complexes is stronger than the metal‐phosphorus bond of typical phosphine complexes, thiourea ligands generally do not easily dissociate from the metal center under catalytic conditions, which establishes the thiourea 1 ‐based palladium complexes as effective catalysts for the palladium‐catalyzed cross‐coupling reactions.
Photoreceptor Deactivation and Retinal Degeneration Mediated by a Photoreceptor-Specific Protein Kinase C (1991)

The protein kinase C (PKC) family of serine-threonine kinases has been implicated in the regulation of a variety of signaling cascades. One member of this family, eye-PKC, is expressed exclusively in the Drosophila visual system. The inaC (inactivation-no-afterpotential C) locus was shown to be the structural gene for eye-PKC. Analysis of the light response from inaC mutants showed that this kinase is required for the deactivation and rapid desensitization of the visual cascade. Light adaptation was also defective in inaC mutant flies. In flies carrying the retinal degeneration mutation rdgB, absence of eye-PKC suppressed photoreceptor cell degeneration. These results indicate that eye-PKC functions in the light-dependent regulation of the phototransduction cascade in Drosophila.
Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine (2010)

Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403-2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161-171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12-17, 2007; Sunami et al. in Anal Biochem 357(1):128-136, 2006; Ishikawa et al. in FEBS Lett 576(3):387-390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238-241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations.
Dna isolated from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus is rich in guanine-cytosine content. (1982)

DNA fragments were isolated from DNA/anti-DNA antibody immune complexes of systemic lupus erythematosus. Hybridization experiments indicated that DNA isolated from immune complexes originates from human nuclear DNA. Two classes of DNA were identified by polyacrylamide gel electrophoresis. The m.w. of small fragments was 25,000 with 30 to 40 base pairs, and that of large fragments was 100,000 with 150 base pairs. The average guanine-cytosine (G-C) content in the small fragments was 55% of total bases, and that in the large fragments was 45%. Compared with the average 38% G-C content of total human DNA, the antigen DNA is rich in G-C content. Such unusually high G-C content can alter DNA structure, which may serve as the target for antibody production.
Positively Charged Residues at Positions 12, 17, and 18 of Glucagon Ensure Maximum Biological Potency (1998)

Glucagon is a peptide hormone that plays a central role in the maintenance of normal circulating glucose levels. Structure-activity studies have previously demonstrated the importance of histidine at position 1 and the absolute requirement for aspartic acid at position 9 for transduction of the hormonal signal. Site-directed mutagenesis of the receptor protein identified Asp64 on the extracellular N-terminal tail to be crucial for the recognition function of the receptor. In addition, antibodies generated against aspartic acid-rich epitopes from the extracellular region competed effectively with glucagon for receptor sites, which suggested that negative charges may line the putative glucagon binding pocket in the receptor. These observations led to the idea that positively charged residues on the hormone may act as counterions to these sites. Based on these initial findings, we synthesized glucagon analogs in which basic residues at positions 12, 17, and 18 were replaced with neutral or acidic residues to examine the effect of altering the positive charge on those sites on binding and adenylyl cyclase activity. The results indicate that unlike N-terminal histidine, Lys12, Arg17, and Arg18 of glucagon have very large effects on receptor binding and transduction of the hormonal signal, although they are not absolutely critical. They contribute strongly to the stabilization of the binding interaction with the glucagon receptor that leads to maximum biological potency.