gebhart/patrepeval huggingface dataset:
Neural Stem Cells (2003)

This review focuses on the nature and functional properties of stem cells of the adult mammalian central nervous system (CNS). It has recently been shown that cell turnover, including neurons, does occur in the mature CNS, thanks to the persistence of precursor cells that possess the functional characteristics of bona-fide neural stem cells (NSCs) within restricted brain areas. We discuss how the subventricular zone of the forebrain (SVZ) is the most active neurogenetic area and the richest source of NSCs. These NSCs ensure a life-long contribution of new neurons to the olfactory bulb and, when placed in culture, can be grown and extensively expanded for months, allowing the generation of stem cell lines, which maintain stable and constant functional properties. A survey of the differentiation potential of these NSCs, both in vitro and in vivo, outlines their extreme plasticity that seems to outstretch the brain boundaries, so that these neuroectodermal stem cells may give rise to cells that derive from developmentally distinct tissues. A critical discussion of the latest, controversial findings regarding this surprising phenomenon is provided.
Methods in Arabidopsis Research (1992)

One of the ways to make consistent progress in a particular field of biology consists in choosing a good model system on which to focus the experimental efforts of the scientific community. It has taken a long time for scientists interested in various aspects of the life of plants to reach some sort of consensus. With the advent and impact of molecular biology, the small weed Arabidopsis is now the object of rapidly growing scientific attention. Since it is reasonable to assume that the general molecular mechanisms that are responsible for the physiological, cellular and biochemical properties of plants will be essentially conserved in all plants, it follows that these mechanisms should also operate in Arabidopsis and hence that its genome should contain most of the genes that we need to know about if we want to understand the genetic determination of the life processes in plants.Arabidopsis has a small genome and well documented genetic studies are available. It is easy to grow in large numbers and mutants defining important genetically controlled mechanisms are either available, or can readily be obtained. Various methods to introduce and express isolated homologous or heterologous genes are available. It is therefore realistic and desirable to aim at exploring the genome of this plant in very great detail. As will be illustrated in this book all the elements for such a grand strategy are in place.More and more scientists are therefore willing to accept the obvious and very real practical disadvantages resulting from its small size when experiments call for the isolation of proteins, membranes, subcellular fractions etc, in order to benefit from its extraordinary experimental advantages as a model system in molecular genetics. One can safely predict that in the next decade studies with Arabidopsis will provide major breakthroughs in our understanding of most aspects of plant physiology and developmental biology. The importance of this knowledge for plant breeding and therefore for a sustainable highly productive agriculture cannot be overestimated. We therefore expect that this book will provide valuable guidelines to all those who are planning experiments aimed at understanding various aspects of plant growth, productivity and interactions with the environment. The book offers a wealth of methodical and theoretical information as well as valuable references. It should be of use to students, teachers, as well as advanced researchers and those breeders who want to use molecular techniques in breeding.
NADPH Regeneration by Glucose Dehydrogenase fromGluconobacter scleroidesforl-Leucovorin Synthesis (1992)

A new process for (6S)-tetrahydrofolate production from dihydrofolate was designed that used dihydrofolate reductase and an NADPH regeneration system. Glucose dehydrogenase from Gluconobacter scleroides KY3613 was used for recycling of the cofactor. The reaction mixture contained 200 mM dihydrofolate, 220 mM glucose, 2 mM NADP, 14.4 U/ml dihydrofolate reductase, and 14.4 U/ml Glucose dehydrogenase, and the reaction was complete after incubation at pH 8.0, and 40 degrees C for 2.5 hr. With (6S)-tetrahydrofolate as the starting material, l-leucovorin was synthesized via a methenyl derivative. The purity of the l-leucovorin was 100%, and its diastereomeric purity was greater than 99.5% d.e. as the (6S)-form.
Inactivation of pepsin by diphenyldiazomethane. (1965)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Optical network for real-time face recognition (1993)

An optical network is described that is capable of recognizing at standard video rates the identity of faces for which it has been trained. The faces are presented under a wide variety of conditions to the system and the classification performance is measured. The system is trained by gradually adaptingphotorefrac tive holograms.
Gene mutations and three‐dimensional structural analysis in 13 families with severe factor X deficiency (2002)

Factor X (FX) deficiency is a rare autosomal recessive disorder. The phenotype and genotype of 15 Iranian patients with FX deficiency from 13 unrelated families with a high frequency of consanguinity were analysed. Five different assays identified four patients from three families with a discrepancy between low-FX coagulant activity (FX:C) and higher-FX antigen (FX:Ag) (a type II deficiency). The remaining 11 patients had parallel reductions of FX:C and FX:Ag (a type I deficiency). Nine different homozygous candidate mutations were identified, of which eight were novel. The four type II cases were associated with an Arg(-1)Thr missense mutation in the prepropeptide: Arg(-1) is highly conserved in all vitamin K-dependent proteins. Four type I mutations (Gly78Asp, Cys81Tyr, Gly94Arg and Asp95Glu) were localized to the EGF-1 and EGF-2 domains, for which molecular views showed that the protein folding would be disrupted. The type I mutation Gly222Asp was localized in the catalytic domain of FX, and is sufficiently close to the Asp-His-Ser catalytic triad to disrupt its correct protein folding. The two type I splice site mutations were IVS1+3, A-->T and IVS2-3, T-->G. These novel homozygous FX mutations were consistent with their phenotypes and agree with experimental data from knockout mice, indicating that FX is an essential protein for survival.
Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells (1997)

This review focuses on how immunogens trapped by FDC in the form of Ag-Ab complexes productively signal B cells. In vitro. Ag-Ab complexes are poorly immunogenic but in vivo immune complexes elicit potent recall responses. FDC trap Ag-Ab complexes and make immune complex coated bodies or "iccosomes". B cells endocytose iccosomes, the Ag is processed, and T-cell help is elicited. In vitro, addition of FDC bearing appropriate Ag-Ab complex to memory T and B cells provoke potent recall responses (IgG and IgE). FDC also provide nonspecific costimulatory signals which augment B-cell proliferation and Ab production. B cell-FDC contact is important and interference with ICAM-1-LFA-1 interactions reduces FDC-mediated costimulation. Preliminary data suggest that a costimulatory signal may be delivered via CR2L on FDC binding CR2 on B cells. FDC can also stimulate B cells to become chemotactically active and can protect lymphocytes from apoptosis. FDC also appear to be rich in thiol groups and may replace reducing compounds such as 2 mercaptoethanol in cultures. In short, FDC-Ag specifically signals B cells through BCR, and FDC provide B cells with iccosomal-Ag necessary for processing to elicit T-cell help. In addition, FDC provide nonspecific signals that are important to promote B-cell proliferation, maintain viability, and induce chemotactic responsiveness.
Interaction of Antithrombin with Sulfated, Low Molecular Weight Lignins (2009)

Antithrombin, a major regulator of coagulation and angiogenesis, is known to interact with several natural sulfated polysaccharides. Previously, we prepared sulfated low molecular weight variants of natural lignins, called sulfated dehydrogenation polymers (DHPs) (Henry, B. L., Monien, B. H., Bock, P. E., and Desai, U. R. (2007) J. Biol. Chem. 282, 31891-31899), which have now been found to exhibit interesting antithrombin binding properties. Sulfated DHPs represent a library of diverse noncarbohydrate aromatic scaffolds that possess structures completely different from heparin and heparan sulfate. Fluorescence binding studies indicate that sulfated DHPs bind to antithrombin with micromolar affinity under physiological conditions. Salt dependence of binding affinity indicates that the antithrombin-sulfated DHP interaction involves a massive 80-87% non-ionic component to the free energy of binding. Competitive binding studies with heparin pentasaccharide, epicatechin sulfate, and full-length heparin indicate that sulfated DHPs bind to both the pentasaccharide-binding site and extended heparin-binding site of antithrombin. Affinity capillary electrophoresis resolves a limited number of peaks of antithrombin co-complexes suggesting preferential binding of selected DHP structures to the serpin. Computational genetic algorithm-based virtual screening study shows that only one sulfated DHP structure, out of the 11 present in a library of plausible sequences, bound in the heparin-binding site with a high calculated score supporting selectivity of recognition. Enzyme inhibition studies indicate that only one of the three sulfated DHPs studied is a potent inhibitor of free factor VIIa in the presence of antithrombin. Overall, the chemo-enzymatic origin and antithrombin binding properties of sulfated DHPs present novel opportunities for potent and selective modulation of the serpin function, especially for inhibiting the initiation phase of hemostasis.
Glucagon-like peptide 1 stimulates insulin gene promoter activity by protein kinase A-independent activation of the rat insulin I gene cAMP response element. (2000)

Glucagon-like peptide 1 (GLP-1), a hormonal activator of adenyl cyclase, stimulates insulin gene transcription, an effect mediated by the cAMP response element (CRE) of the rat insulin I gene promoter (RIP1). Here we demonstrate that the signaling mechanism underlying stimulatory effects of GLP-1 on insulin gene transcription results from protein kinase A (PKA)-independent activation of the RIP1 CRE. Although GLP-1 stimulates cAMP production in rat INS-1 insulinoma cells, we find accompanying activation of a -410-bp RIP1 luciferase construct (-410RIP1-LUC) to exist independently of this second messenger. GLP-1 produced a dose-dependent stimulation of -410RIP1-LUC (EC50 0.43 nmol/l), an effect reproduced by the GLP-1 receptor agonist exendin-4 and abolished by the antagonist exendin(9-39). Activation of RIP1 by GLP-1 was not affected by cotransfection with dominant-negative Gs alpha, was not blocked by cAMP antagonist Rp-cAMPS, and was insensitive to PKA antagonist H-89. Truncation of -410RIP1-LUC to generate -307-, -206-, and -166-bp constructs revealed 2 segments of RIP1 targeted by GLP-1. The first segment, not regulated by forskolin, was located between -410 and -307 bp of the promoter. The second segment, regulated by both GLP-1 and forskolin, included the CRE and was located between -206 and -166 bp. Consistent with these observations, stimulatory effects of GLP-1 at RIP1 were reduced after introduction of delta-182 and delta-183/180 inactivating deletions at the CRE. The action of GLP-1 at -410RIP1-LUC was also reduced by cotransfection with A-CREB, a genetically engineered isoform of the CRE binding protein CREB, which dimerizes with and prevents binding of basic-region-leucine-zipper (bZIP) transcription factors to the CRE. In contrast, the action of GLP-1 at the CRE was not blocked by cotransfection with M1-CREB, an isoform that lacks a consensus serine residue serving as substrate for PKA-mediated phosphorylation. On the basis of these studies, it is proposed that PKA-independent stimulatory actions of GLP-1 at RIP1 are mediated by bZIP transcription factors related in structure but not identical to CREB.
A Small Molecule Inhibits Akt through Direct Binding to Akt and Preventing Akt Membrane Translocation (2010)

The Akt pathway is frequently hyperactivated in human cancer and functions as a cardinal nodal point for transducing extracellular and intracellular oncogenic signals and, thus, presents an exciting target for molecular therapeutics. Here we report the identification of a small molecule Akt/protein kinase B inhibitor, API-1. Although API-1 is neither an ATP competitor nor substrate mimetic, it binds to pleckstrin homology domain of Akt and blocks Akt membrane translocation. Furthermore, API-1 treatment of cancer cells results in inhibition of the kinase activities and phosphorylation levels of the three members of the Akt family. In contrast, API-1 had no effects on the activities of the upstream Akt activators, phosphatidylinositol 3-kinase, phosphatidylinositol-dependent kinase-1, and mTORC2. Notably, the kinase activity and phosphorylation (e.g. Thr(P)(308) and Ser(P)(473)) levels of constitutively active Akt, including a naturally occurring mutant AKT1-E17K, were inhibited by API-1. API-1 is selective for Akt and does not inhibit the activation of protein kinase C, serum and glucocorticoid-inducible kinase, protein kinase A, STAT3, ERK1/2, or JNK. The inhibition of Akt by API-1 resulted in induction of cell growth arrest and apoptosis selectively in human cancer cells that harbor constitutively activated Akt. Furthermore, API-1 inhibited tumor growth in nude mice of human cancer cells in which Akt is elevated but not of those cancer cells in which it is not. These data indicate that API-1 directly inhibits Akt through binding to the Akt pleckstrin homology domain and blocking Akt membrane translocation and that API-1 has anti-tumor activity in vitro and in vivo and could be a potential anti-cancer agent for patients whose tumors express hyperactivated Akt.
Distinct regions of the human granulocyte-colony-stimulating factor receptor cytoplasmic domain are required for proliferation and gene induction. (1993)

Using two different cell systems, we show that the cytoplasmic domain of the granulocyte-colony-stimulating factor receptor (G-CSFR) may be composed of at least two functional regions. The first, within the membrane-proximal 57 amino acids, is absolutely required to deliver a proliferative signal. This region contains two sequence motifs conserved between members of the hematopoietin receptor family. The second functional region resides between amino acids 57 and 96. This region is required for the induction of acute-phase plasma protein gene expression when the G-CSFR is transfected into human hepatoma cell lines. The G-CSFR-transfected hepatoma cells respond to G-CSF by increasing the production of the same set of plasma proteins as stimulated by interleukin-6, suggesting that the two cytokines share a common signal transduction pathway.
MutantX-S: scalable malware clustering based on static features (2013)

The current lack of automatic and speedy labeling of a large number (thousands) of malware samples seen everyday delays the distribution of malware signatures, leading to a low detection rate of new malware samples in the wild. In this paper, we design, implement and evaluate a novel, scalable framework, called MutantX-S, that can efficiently cluster a large number of samples into families based on programs’ static features, i.e., code instruction sequences. MutantX-S is a unique combination of several novel techniques to address the practical challenges of malware clustering. Specifically, it exploits the instruction format of x86 architecture and represents a binary program as a sequence of opcodes, facilitating the extraction of N-gram features. It also exploits the hashing trick recently developed in the machine learning community to reduce the dimensionality of the extracted feature vectors, thus significantly lowering the memory and computation costs of clustering. Our comprehensive evaluation on a MutantX-S prototype using a database of more than 100,000 malware samples has shown its ability to correctly cluster over 80 % of input samples within 2 hours, achieving a good balance between accuracy and scalability. Applying MutantX-S on malware samples created at different times, we also demonstrate that MutantX-S achieves high accuracy (around 0.75–0.8) in predicting family labels for unknown malware. 1.
Selective in Vivo Inhibition of Mitogen-activated Protein Kinase Activation Using Cell-permeable Peptides (2002)

The extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinases (MAPKs), is essential for cellular proliferation and differentiation, and thus there exists great interest to develop specific and selective inhibitors of this enzyme. Whereas small molecule inhibitors PD098095 and U0126 have been used to study MAPK/ERK kinase (MEK), their target selectivity has been questioned recently. The cross-reactivity of ATP-directed inhibitors with other protein kinases prompted us to develop structure-based selective peptide inhibitors of ERK activation. Based on a MEK1-derived peptide, we developed inhibitors of ERK activation in vitro and in vivo. The inclusion of either an alkyl moiety or a membrane-translocating peptide sequence facilitated the cellular uptake of the peptide inhibitor and prevented ERK activation in 4-phorbol 12-myristate 13-acetate-stimulated NIH 3T3 cells or nerve growth factor-treated PC12 cells in a concentration-dependent manner. In addition, cell-permeable peptides inhibited ERK-mediated activation of the transcriptional activity of ELK1. The peptides did not have an inhibitory effect on the activity of two other closely related classes of MAPKs, c-Jun amino-terminal kinase or p38 protein kinase. Thus, these peptides may serve as valuable tools for investigating ERK activation and for selective investigation of ERK-mediated responses. With the knowledge of other kinase interacting domains, it would be possible to design cell-permeable inhibitors for investigating diverse cellular signaling mechanisms and for possible therapeutic applications.
Prediction of the Coding Sequences of Unidentified Human Genes. XX. The Complete Sequences of 100 New cDNA Clones from Brain Which Code for Large Proteins in vitro (2001)

To accumulate information on the coding sequences of unidentified genes, we have carried out a sequencing project of human cDNA clones which encode large proteins. We herein present the entire sequences of 100 cDNA clones of unidentified human genes, named KIAA1776 and KIAA1780-KIAA1878, from size-fractionated cDNA libraries derived from human fetal brain, adult whole brain, hippocampus and amygdala. Most of the cDNA clones to be entirely sequenced were selected as cDNAs which were shown to have coding potentiality by in vitro transcription/translation experiments, and some clones were chosen by using computer-assisted analysis of terminal sequences of cDNAs. Three of these clones (fibrillin2/KIAA1776, MEGF10/KIAA1780 and MEGF11/KIAA1781) were isolated as genes encoding proteins with multiple EGF-like domains by motif-trap screening. The average sizes of the inserts and corresponding open reading frames of eDNA clones analyzed here reached 4.7 kb and 2.4 kb (785 amino acid residues), respectively. From the results of homology and motif searches against the public databases, the functional categories of the predicted gene products of 54 genes were determined; 93% of these predicted gene products (50 gene products) were classified as proteins related to cell signaling/communication, nucleic acid management, or cell structure/motility. To collect additional information on these genes, their expression profiles were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.
[Immunomodulating effect of killed, apathogenic Escherichia coli, strain Nissle 1917, on the macrophage system]. (1991)

The influence of formaldehyde-killed Escherichia coli strain Nissle 1917 (SK 22) on macrophages of C57BL/6 mice was investigated in vitro. It has been shown that SK 22 activated macrophages derived from bone marrow produced Interleukin-6 with high efficiency. In addition, SK 22 stimulated macrophages to secrete tumor necrosis factor, as measured by a bioassay. Furthermore, macrophages were activated by SK 22 to produce a 3 fold amount of oxygen radicals compared to the spontaneous oxygen radical production. In contrast to this finding, the phagocytic capacity of these macrophages was only slightly increased. The specific lysis of P 815 tumor cells by peritoneal macrophages after coincubation with SK 22 was measured using tumor cells prelabelled with radioactive 51Cr. The results of the in vitro experiments presented clearly show that the E. coli preparation SK 22 is an efficient immunomodulator of the unspecific immune system.
Mutations in Diphtheria Toxin Separate Binding from Entry and Amplify Immunotoxin Selectivity (1987)

Monoclonal antibodies linked to toxic proteins (immunotoxins) can selectively kill some tumor cells in vitro and in vivo. However, reagents that combine the full potency of the native toxins with the high degree of cell type selectivity of monoclonal antibodies have not previously been designed. Two heretofore inseparable activities on one polypeptide chain of diphtheria toxin and ricin account for the failure to construct optimal reagents. The B chains (i) facilitate entry of the A chain to the cytosol, which allows immunotoxins to efficiently kill target cells, and (ii) bind to receptors present on most cells, which imparts to immunotoxins a large degree of non-target cell toxicity. This report identifies point mutations in the B polypeptide chain of diphtheria toxin that block binding but allow cytosol entry. Three mutants of diphtheria toxin have 1/1,000 to 1/10,000 the toxicity and 1/100 to 1/8,000 the binding activity of diphtheria toxin. Linking of either of two of the inactivated mutant toxins (CRM103, Phe508; CRM107, Phe390, Phe525) to a monoclonal antibody specific for human T cells reconstitutes full target-cell toxicity--indistinguishable from that of the native toxin linked to the same antibody--without restoring non-target cell toxicity. This separation of the entry function from the binding function generates a uniquely potent and cell type-specific immunotoxin that retains full diphtheria toxin toxicity, yet is four to five orders of magnitude less toxic than the native toxin is to nontarget cells.
Seven-co-ordination in metal complexes of quinquedentate macrocyclic ligands. Part 6. Magnesium complexes of macrocyclic ligands containing nitrogen and oxygen donor atoms (1977)

Reaction of 2,6-diacetylpyridine or 2,6-diformylpyridine with 3,6-dioxaoctane-1,8-diamine in methanol in the presence of MgCl2·6H2O gves complexes [MgL(OH2)2]Cl2·H2O of 15-membered quinquedentate N2O2 macrocycles (L) in high yield. Simple metathetical reactions lead to derivatives containing other anions including neutral complexes having axially co-ordinated thiocyanate. On the basis of various physical properties, the complexes are assigned seven-co-ordinate, probably pentagonal-bipyramidal, structures. Control experiments show that in the absence of a salt of Mg2+ the macrocycles are formed in only small yield or not at all. The Ca2+ ion is ineffective in oromotina the synthesis of these macrocvcles, as is Mg2+ in the synthesis of three related quadridentate N4 and N3O macrocycles.