gebhart/patrepeval huggingface dataset:
Determining Effects of Non-synonymous SNPs on Protein-Protein Interactions using Supervised and Semi-supervised Learning (2014)

Single nucleotide polymorphisms (SNPs) are among the most common types of genetic variation in complex genetic disorders. A growing number of studies link the functional role of SNPs with the networks and pathways mediated by the disease-associated genes. For example, many non-synonymous missense SNPs (nsSNPs) have been found near or inside the protein-protein interaction (PPI) interfaces. Determining whether such nsSNP will disrupt or preserve a PPI is a challenging task to address, both experimentally and computationally. Here, we present this task as three related classification problems, and develop a new computational method, called the SNP-IN tool (non-synonymous SNP INteraction effect predictor). Our method predicts the effects of nsSNPs on PPIs, given the interaction's structure. It leverages supervised and semi-supervised feature-based classifiers, including our new Random Forest self-learning protocol. The classifiers are trained based on a dataset of comprehensive mutagenesis studies for 151 PPI complexes, with experimentally determined binding affinities of the mutant and wild-type interactions. Three classification problems were considered: (1) a 2-class problem (strengthening/weakening PPI mutations), (2) another 2-class problem (mutations that disrupt/preserve a PPI), and (3) a 3-class classification (detrimental/neutral/beneficial mutation effects). In total, 11 different supervised and semi-supervised classifiers were trained and assessed resulting in a promising performance, with the weighted f-measure ranging from 0.87 for Problem 1 to 0.70 for the most challenging Problem 3. By integrating prediction results of the 2-class classifiers into the 3-class classifier, we further improved its performance for Problem 3. To demonstrate the utility of SNP-IN tool, it was applied to study the nsSNP-induced rewiring of two disease-centered networks. The accurate and balanced performance of SNP-IN tool makes it readily available to study the rewiring of large-scale protein-protein interaction networks, and can be useful for functional annotation of disease-associated SNPs. SNIP-IN tool is freely accessible as a web-server at http://korkinlab.org/snpintool/.
Donation Frequency, Iron Loss, and Risk of Cancer Among Blood Donors (2008)

Repeated blood donation was not associated with increased or decreased risk of cancer overall. The lack of consistency across latency periods casts doubt on an apparent association between reduced cancer risk and iron loss in men. The positive association between frequent plasma donation and risk of non-Hodgkin lymphoma deserves further exploration.
The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage (1998)

Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules.
The Mutual Habit Modification of Sodium Chloride and Dipolar Ions (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Mutual Habit Modification of Sodium Chloride and Dipolar IonsCharles P. Fenimore and Arthur. ThrailkillCite this: J. Am. Chem. Soc. 1949, 71, 8, 2714–2717Publication Date (Print):August 1, 1949Publication History Published online1 May 2002Published inissue 1 August 1949https://pubs.acs.org/doi/10.1021/ja01176a033https://doi.org/10.1021/ja01176a033research-articleACS PublicationsRequest reuse permissionsArticle Views128Altmetric-Citations23LEARN 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-Alertsclose Get e-Alerts
Freezing of Aqueous Solutions of Glycosylated Bovine Beta-Casein (1998)

Abstract Genetic engineering of milk proteins allows control of their physicochemical properties in foods and dairy products during processing, storage, and consumption. Robust methods for the estimation of the quality and function of the proteins during downstream processing are sought. The focus of this study is a systematic microscopic investigation of the freezing of sub-microliter pendent droplets of buffer solution of glycosylated bovine beta-casein. The freezing and crystallization is observed with a scanning confocal microscope fitted with a stage cooled with vapor boiled off a liquid nitrogen dewar. Four liquid samples (with glycosylated bovine beta-casein concentrations of 35, 125, 500, and 1000 μg/ml) are compared against the control (10 mg/ml of wild type non-glycosylated bovine beta-casein). The freezing of similar size samples consisting of de-ionized water, ice-nucleating mixture (Pseudomonas syringae), and pure buffer solution is also examined for comparison. Higher concentrations of the engineered-beta casein result in increasing antifreeze action, corresponding to depression of the freezing point, and thermal stabilization of the supercooled liquid. This conclusion is supported by a non-parametric statistical analysis based on the Jonckheere test. A freezing point assay can thus be made to assess the quality of glyco-bovine beta-casein.
Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma (2013)

There were high expressions of serum exosomal miR-17-5p and miR-21 in PC patients. Examination of serum exosomal microRNA is a useful serum biomarker for PC diagnosis other than serum-free microRNA. It is postulated that exosomal miR-17-5p participates in the progression of PC.
Leukemia initiated by hemopoietic stem cells expressing the v-abl oncogene. (1991)

We report a mouse model with which to study leukemogenesis initiated by a specific genetic change introduced into a primary lymphoid-myeloid pluripotent stem cell. Fetal liver hemopoietic cells were infected with a high titer of helper-free Abelson murine leukemia virus (A-MuLV) and were used to reconstitute lethally irradiated mice. Two weeks later, progenies of a single primitive hemopoietic stem cell carrying a specifically integrated A-MuLV proviral DNA could be detected in both colony-forming units in spleen and myeloid colony-forming cells in the bone marrow. Beginning at 3 weeks after transplantation, the recipients developed elevated leukocyte counts, splenomegaly, and increase of blast cells in the peripheral blood. Multiple clones of A-MuLV-infected cells were infused into each recipient. However, in the same animal, DNA extracted from various affected organs and from factor-independent lymphoid and myeloid immortalized cells all contained an identical, specifically integrated proviral genome. The A-MuLV-infected stem cells differentiated into various lineages of hemopoietic cells. Our data show that the expression of the v-abl oncogene in a primary lymphoid-myeloid hemopoietic stem cell directly initiates leukemogenesis by stimulating factor-independent growth. The monoclonal-type disease development seen in these animals may require the occurrence of an additional genetic event.
Regulatory Elements in the 5′-Flanking Region and the First Intron Contribute to Transcriptional Control of the Mouse Alpha 1 Type I Collagen Gene (1989)

We have identified two blocks of regulatory sequences located in the 5'-flanking region and the first intron of the mouse alpha 1 type I collagen (COL1A1) gene. Both blocks were found to contain positive as well as negative regulatory elements. Sequences located within 222 base pairs upstream of the transcription start site showed a strong stimulatory effect on the COL1A1 promoter and were sufficient for tissue-specific regulation of the COL1A1 gene. The combined upstream and intron regulatory sequences showed a marked inhibition of COL1A1 promoter activity in fibroblasts. This finding suggests that additional, more remote regulatory sequences may be required for establishing the high level of activity of the endogenous COL1A1 gene in fibroblastoid cells.
Site-Specific Incorporation of <i>p</i>-Propargyloxyphenylalanine in a Cell-Free Environment for Direct Protein−Protein Click Conjugation (2010)

The tyrosine analog p-propargyloxyphenylalanine (pPa), like tyrosine, has limited water solubility. It has been postulated that this limited solubility has contributed to reduced cellular uptake of pPa and thus reduced in vivo incorporation of pPa into proteins. Using a cell-free protein synthesis system (CFPS) to circumvent cellular uptake, pPa has been incorporated site-specifically into proteins with high specificity at yields up to 27 times greater than the highest previously reported yield. The alkyne group present on proteins incorporated with pPa provides a reactive residue for site-specific bioconjugation with the copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition (CuAAC). Previously, incorporation of another CuAAC-compatible unnatural amino acid p-azido-l-phenylalanine (pAz) was demonstrated with CFPS. However, incorporation of pPa may be preferred over pAz due to the instability of the pAz's aryl-azido moiety upon UV or near-UV light exposure. Also, the ability to incorporate site-specifically both reactants of the CuAAC (the alkyne group of pPa and the azido group of pAz) into proteins enables direct site-specific conjugation of heterologous proteins. We have demonstrated (for the first time to our knowledge) a one-step, linker-less, site-specific, direct protein-to-protein conjugation using CuAAC and unnatural amino acids.
Molecular characterization of planktic cyanobacteria of Anabaena, Aphanizomenon, Microcystis and Planktothrix genera. (2001)

Toxic and non-toxic cyanobacterial strains from Anabaena, Aphanizomenon, Calothrix, Cylindrospermum, Nostoc, Microcystis, Planktothrix (Oscillatoria agardhii), Oscillatoria and Synechococcus genera were examined by RFLP of PCR-amplified 16S rRNA genes and 16S rRNA gene sequencing. With both methods, high 16S rRNA gene similarity was found among planktic, anatoxin-a-producing Anabaena and non-toxic Aphanizomenon, microcystin-producing and non-toxic Microcystis, and microcystin-producing and non-toxic Planktothrix strains of different geographical origins. The respective sequence similarities were 99.9-100%, 94.2-99.9% and 99.3-100%. Thus the morphological characteristics (e.g. Anabaena and Aphanizomenon), the physiological (toxicity) characteristics or the geographical origins did not reflect the level of 16S rRNA gene relatedness of the closely related strains studied. In addition, cyanobacterial strains were fingerprinted with repetitive extragenic palindromic (REP)- and enterobacterial repetitive intergenic consensus (ERIC)-PCR. All the strains except two identical pairs of Microcystis strains had different band profiles. The overall grouping of the trees from the 16S rRNA gene and the REP- and ERIC-PCR analyses was similar. Based on the 16S rRNA gene sequence analysis, four major clades were formed. (i) The clade containing filamentous heterocystous cyanobacteria was divided into three discrete groups of Anabaena/Aphanizomenon, Anabaena/Cylindrospermum/ Nodularia/Nostoc and Calothrix strains. The three other clades contained (ii) filamentous non-heterocystous Planktothrix, (iii) unicellular non-heterocystous Microcystis and (iv) Synechococcus strains.
LATENT CLASS ANALYSIS: A GENERAL SOLUTION AND AN EMPIRICAL EVALUATION (1951)

P. == (V N2) D. (V N2)' * Substituting (3.12) into (3.13) , P. = BAD. A' E' . Let Q == A D. A' Then from (3.14) P. = B Q B' Premultiplying (3.16) by E', and postmultiplying by E, we
A Technique of Scan Blindness Elimination for Planar Phased Array Antenna using Miniaturized EBG (2014)

In this paper, the planar phased array antenna scan blindness characteristic has been analyzed and a novel technique of eliminating the scan blindness for the phased array antenna has been introduced. The scan blindness of the center element has been used to present the entire phased array characteristic. The array scan blindness characteristics have been simulated and analyzed using CST Microwave Studio (CST MWS). The 5×3 planar phased array antenna radiation patterns against the pattern elevation angle direction has been simulated and compiled. The array’s scan blindness has been determined at the angle of approximately 47⁰. The miniaturized capacitive loaded Electromagnetic Band Gap (EBG) has been developed and introduced between the array elements to eliminate the problem. Based on the simulated results, it is shown that the use of a miniaturized EBG is effective in reducing the surface wave effects and eliminates the scan blindness in the array radiation pattern. This novel finding is very useful to improve the antenna directive efficiency for the directional radar and satellite application.
Stereochemical studies. <b>58</b>. Saturated heterocycles. <b>39</b>. Preparation and steric structures of dihydro‐1,3‐oxazines, 1,3‐oxazin‐2‐ones and 1,3‐oxazine‐2‐thiones fused with norbornane and norbornene (1983)

Abstract 3‐ endo ‐Aminobicyclo[2.2.1]hept‐5‐ene‐2‐ endo ‐carboxylic acid ( 1 ), prepared from endo ‐norborn‐5‐ene‐2,3‐dicarboxylic acid anhydride, and the analogous saturated cis‐exo ‐amino acid ( 3 ) were reduced with lithium aluminum hydride to the aminoalcohols 2 and 4 ; the latter were cyclized by means of arylimino ethers to methylene‐bridged tetrahydro‐ ( 6a‐c ) and hexahydro‐3,1‐benzoxazines ( 7b‐d ), respectively. The endo ( 2 ) and exo ( 4 ) aminoalcohols were converted to methylene‐bridged tetrahydro‐3,1‐benzoxazin‐2‐one ( 9 ) and hexahydro‐3,1‐benzoxazin‐2‐one ( 12 ) with ethyl chloroformate and sodium methoxide; treatment of the alcohols with carbon disulfide gave, via the dithiocarbamates, the corresponding 2‐thiones ( 11, 13 ). The structures were confirmed by ir and nmr spectroscopy.
Structures of Prostacyclin Synthase and Its Complexes with Substrate Analog and Inhibitor Reveal a Ligand-specific Heme Conformation Change (2007)

Prostacyclin synthase (PGIS) is a cytochrome P450 (P450) enzyme that catalyzes production of prostacyclin from prostaglandin H(2). PGIS is unusual in that it catalyzes an isomerization rather than a monooxygenation, which is typical of P450 enzymes. To understand the structural basis for prostacyclin biosynthesis in greater detail, we have determined the crystal structures of ligand-free, inhibitor (minoxidil)-bound and substrate analog U51605-bound PGIS. These structures demonstrate a stereo-specific substrate binding and suggest features of the enzyme that facilitate isomerization. Unlike most microsomal P450s, where large substrate-induced conformational changes take place at the distal side of the heme, conformational changes in PGIS are observed at the proximal side and in the heme itself. The conserved and extensive heme propionate-protein interactions seen in all other P450s, which are largely absent in the ligand-free PGIS, are recovered upon U51605 binding accompanied by water exclusion from the active site. In contrast, when minoxidil binds, the propionate-protein interactions are not recovered and water molecules are largely retained. These findings suggest that PGIS represents a divergent evolution of the P450 family, in which a heme barrier has evolved to ensure strict binding specificity for prostaglandin H(2), leading to a radical-mediated isomerization with high product fidelity. The U51605-bound structure also provides a view of the substrate entrance and product exit channels.
Face localization and authentication using color and depth images (2005)

This paper presents a complete face authentication system integrating both two-dimensional (color or intensity) and three-dimensional (3-D) range data, based on a low-cost 3-D sensor, capable of real-time acquisition of 3-D and color images. Novel algorithms are proposed that exploit depth information to achieve robust face detection and localization under conditions of background clutter, occlusion, face pose alteration, and harsh illumination. The well-known embedded hidden Markov model technique for face authentication is applied to depth maps and color images. To cope with pose and illumination variations, the enrichment of face databases with synthetically generated views is proposed. The performance of the proposed authentication scheme is tested thoroughly on two distinct face databases of significant size. Experimental results demonstrate significant gains resulting from the combined use of depth and color or intensity information.
Rheology and Screen-Printing Performance of Model Silver Pastes for Metallization of Si-Solar Cells (2018)

Further strong growth of solar energy conversion based on PV (photovoltaic) technology requires constant improvement to increase solar cell efficiency. The challenge in front-side metallization of Si-solar cells is to print uniform fine lines with a high aspect ratio to achieve higher efficiencies simultaneously with a reduced consumption of raw materials. An in-depth understanding of the relationship between paste composition, rheology and screen-printed line morphology is essential. Three model pastes with similar silver content and corresponding vehicles differing in their thixotropic agent content were investigated. Rheological properties (yield stress, viscosity, wall slip velocity, structural recovery, and fracture strain) were determined using steady and oscillatory shear, as well as elongational flow rheometry. Pastes were screen-printed at various speeds through a layout screen including line widths between 20 and 55 µm. Dried fingers were analyzed with respect to line width, aspect ratio (AR) and cross-sectional area. Our investigations reveal that minor changes of thixotropic agent result in substantial variations of the paste’s flow properties. However, this only weakly affects the line morphology. Irrespective of printing speed or finger opening, AR is slightly increasing; i.e., the screen-printing process is robust against changes in paste rheology.
A chemical with proven clinical safety restores Down syndrome-related phenotypes via DYRK1A inhibition (2016)

DYRK1A is important in neuronal development and function, and its excessive activity is considered a significant pathogenic factor in Down syndrome and Alzheimer's disease. Thus, inhibition of DYRK1A has been suggested to be a new strategy to modify the disease. Very few compounds, however, have been reported to act as inhibitors, and their potential clinical uses require further evaluation. Here, we newly identify CX-4945, the safety of which has been already proven in the clinical setting, as a potent inhibitor of DYRK1A that acts in an ATP-competitive manner. The inhibitory potency of CX-4945 on DYRK1A (IC50=6.8 nM) in vitro was higher than that of harmine, INDY or proINDY, which are well-known potent inhibitors of DYRK1A. CX-4945 effectively reverses the aberrant phosphorylation of Tau, amyloid precursor protein (APP) and presenilin 1 (PS1) in mammalian cells. To our surprise, feeding with CX-4945 significantly restored the neurological and phenotypic defects induced by the overexpression of minibrain, an ortholog of human DYRK1A, in the Drosophila model. Moreover, oral administration of CX-4945 acutely suppressed Tau hyperphosphorylation in the hippocampus of DYRK1A-overexpressing mice. Our research results demonstrate that CX-4945 is a potent DYRK1A inhibitor and also suggest that it has therapeutic potential for DYRK1A-associated diseases.
Routes of FA delivery to cardiac muscle: modulation of lipoprotein lipolysis alters uptake of TG-derived FA (2003)

Long-chain fatty acids (FA) supply 70-80% of the energy needs for normal cardiac muscle. To determine the sources of FA that supply the heart, [(14)C]palmitate complexed to bovine serum albumin and [(3)H]triolein [triglyceride (TG)] incorporated into Intralipid were simultaneously injected into fasted male C57BL/6 mice. The ratio of TG to FA uptake was much greater for hearts than livers. Using double-labeled Intralipid with [(3)H]cholesteryl oleoyl ether (CE) and [(14)C]TG, we observed that hearts also internalize intact core lipid. Inhibition of lipoprotein lipase (LPL) with tetrahydrolipstatin or dissociation of LPL from the heart with heparin reduced cardiac uptake of TG by 82 and 64%, respectively (P < 0.01). Palmitate uptake by the heart was not changed by either treatment. Uptake of TG was 88% less in hearts from LPL knockout mice that were rescued via LPL expression in the liver. Our data suggest that the heart is especially effective in removal of circulating TG and core lipids and that this is due to LPL hydrolysis and not its bridging function.
Conformal hybrid finite difference time domain and finite volume time domain (1994)

A hybrid method that combines the finite difference time domain (FDTD) and the finite volume time domain (FVTD) methods is presented. The FVTD, based on a conformal and unstructured grid is used in the near vicinity of the surface of a scatterer, and the FDTD is used to model the fields in the surrounding area. The two are coupled together through interpolation. The vertex-based FVTD allows for more convenient and accurate interpolations than a conformal FDTD method. The hybrid method is validated through two examples-the scattering by a PEC cube and sphere-by comparison with the direct FDTD solution, and with an exact Mei series solution for the spherical case.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
An efficient selection system for packaging herpes simplex virus amplicons. (1998)

Due to their simplicity and flexibility of genomic construction, herpes simplex virus (HSV) amplicon-based vectors are attractive vehicles for gene delivery. However, a significant problem faced in the generation of amplicon stocks is the low amplicon to helper virus (A/H) ratio. In order to improve the proportion of amplicons generated, a selection system for amplicon production was developed in which the HSV thymidine kinase (TK) gene is inserted into an amplicon plasmid and an HSV mutant with both TK and glycoprotein H (gH) genes deleted is used as a helper virus. Using a protocol in which amplicon stocks are passaged 2-3 times in BHK cells of TK- and gH+ genotype in the presence of selection medium containing methotrexate, stock preparations with high A/H ratio (up to 5:1) and high amplicon titre (>1 x 10(9) infectious units/ml) were generated. In vitro characterization demonstrated that a high level of biologically functional products can be efficiently produced from these amplicon constructs.