gebhart/patrepeval huggingface dataset:
A neural-specific GAP-43 core promoter located between unusual DNA elements that interact to regulate its activity (1992)

In an effort to identify cis-acting elements that respond to signals controlling different stages of neural differentiation, we have analyzed the promoter and surrounding regulatory sequences of the rat GAP-43 gene. Expression of this gene is both neural specific and, within neurons, strongly modulated by signals related to axon integrity. Expression analysis in cell lines and primary rat cortical cultures demonstrates that neural-selective gene expression can be directed by a 386 base pair GAP-43 promoter fragment that contains canonical TATA and CCAAT box consensus sequences. A short region of homology with other neural-specific genes, identified upstream of the core promoter, is not essential for selective expression in neuronal cells. Within cortical cell cultures, expression is strongly modulated by two interacting elements on either side of the promoter, each of which contains a sequence with the potential to adopt an unusual DNA conformation. While each of these flanking elements reduces expression when added alone to the core promoter, each counteracts the negative influence of the other when both elements are present.
Advances in the Chemistry of Mannich Bases (1973)

In this review, the progress in the chemistry of Mannich bases in the years 1960-1970 is reported in depth. The first part of the review deals with the synthesis of the bases and discusses separately the types of substrates undergoing the reaction. The second part contains a discussion of Mannich base reactions. whereby these bases are regarded as easily accessible intermediates for the synthesis of various products. 1. Synthesis of Mannich Bases 1.1. Structure 1.2. Reactants and Reaction Conditions 1.3. Mechanism, Orientation, and By-products 1.4. C-Aminomethylation Reactions 1.5. N-, S-, Se-, and P-Aminomethylation Reactions 1.6. Optically Active Mannich Bases 2. Reactions of Mannich Bases 2.1. Deaminomethylation 2.2. Deamination 2.3. Substitution of the Amino Group (X-Alkylation) 2.4. Reduction 2.5. Reaction with Organometallic Compounds 2.6. Cyclization 2.7. Miscellaneous Reactions
More economical synthesis of mesoporous MCM-41 (2014)

CHEMTECH
Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro (1989)

To develop a purification strategy for isolating the most primitive hematopoietic stem cells present in normal human marrow we have combined cell separation techniques with an assay for cells that initiate sustained hematopoiesis in vitro in the presence of irradiated human marrow adherent cells. These "feeders" were established by subculturing 2- to 6-week-old primary long-term marrow culture adherent layers at a density of 3 x 10(4) irradiated cells per square centimeter. Test "long-term culture (LTC)-initiating cells" were plated on top of the feeders and the cocultures then maintained as standard long-term marrow cultures with half-media changes and removal of half of the nonadherent cells each week. The total number of myeloid, erythroid, and multilineage clonogenic progenitors present after 5 weeks was used to provide a quantitative assessment of the number of LTC-initiating cells originally added. Using this assay, the density, light scatter, and two cell surface antigen properties of LTC-initiating cells have been defined and compared with cells capable of directly forming colonies in methylcellulose. While the majority of the clonogenic cells were found in the high forward light scatter (FLS) "blast" window, LTC-initiating cells had significantly lower FLS properties and in this respect were more similar to lymphocytes. LTC-initiating cells also expressed less HLA-DR antigen than clonogenic cells. The majority of LTC-initiating cells were found in the top 2% of the CD34 (My10) fluorescence profile, whereas clonogenic cells were found throughout the top 5% of the CD34 fluorescence profile. By combining low FLS, low orthogonal light scatter (OLS), low HLA-DR expression, and high CD34 expression, a population could be obtained that was enriched for LTC-initiating cells approximately 800-fold over unseparated marrow. This population contains only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retains 50% to 60% of the LTC-initiating cells present in the original marrow. The ability to purify these two populations independently shows that the LTC and clonogenic assays identify distinct, although not necessarily nonoverlapping cell types in human marrow. Since clonogenic cells are derived from LTC-initiating cells, the LTC assay clearly detects a more primitive population. The availability of a simple approach that allows the purification of such cells by three orders of magnitude in high yield should be useful for the investigation of early events in hematopoiesis as well as for the definitive isolation of human hematopoietic stem cells with long-term in vivo repopulating potential.
Synthesis and Structural Investigation of C4‐ and C2‐Symmetric Molecular Scaffolds Based on Imidazole Peptides (2007)

Abstract The syntheses of a C 4 ‐ and a C 2 ‐symmetric scaffold are presented. The first is composed of four imidazole units, while the second contains two imidazole and two oxazole moieties. The synthesis of the key building block for both systems has been fundamentally improved. Starting from these scaffolds, various platforms possessing two or four arms can easily be prepared. The structures of the scaffolds, together with that of a C 4 ‐symmetric oxazole scaffold, were investigated in the solid state and in the gas phase. We found that these 24‐membered cyclic peptides exist as two different structure types. In one case (type I), the nitrogen atoms of the azole units pointing into the interior of the macrocycle form a square, whereas in the second case (type II), they form a parallelogram. The type of molecular structure does not depend on the symmetry of the system, but on the type of azole used. Cyclic systems composed of four imidazole units are present in the type I structure, whereas systems consisting of four oxazole units exhibit the type II nature. Structure type II is also present in cycles composed of two oxazole units and two imidazole units. The existence of the different structure types can be explained in terms of the different orbital energies of the imidazole and oxazole systems. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine small intestine (2012)

Physiological studies of intact crypt epithelium have been limited by problems of accessibility in vivo and dedifferentiation in standard primary culture. Investigations of murine intestinal stem cells have recently yielded a primary intestinal culture in three-dimensional gel suspension that recapitulates crypt structure and epithelial differentiation (Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, Van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Nature 459: 262-265, 2009). We investigated the utility of murine intestinal crypt cultures (termed "enteroids") for physiological studies of crypt epithelium by focusing on the transport activity of the cystic fibrosis transmembrane conductance regulator Cftr. Enteroids had multiple crypts with well-differentiated goblet and Paneth cells that degranulated on exposure to the muscarinic agonist carbachol. Modified growth medium provided a crypt proliferation rate, as measured by 5-ethynyl-2'-deoxyuridine labeling, which was similar to proliferation in vivo. Immunoblots demonstrated equivalent Cftr expression in comparisons of freshly isolated crypts with primary and passage 1 enteroids. Apparent enteroid differences in mRNA expression of other transporters were primarily associated with villous epithelial contamination of freshly isolated crypts. Microelectrode analysis revealed cAMP-stimulated membrane depolarization in enteroid epithelium from wild-type (WT) but not Cftr knockout (KO) mice. Morphological and microfluorimetric studies, respectively, demonstrated Cftr-dependent cell shrinkage and lower intracellular pH in WT enteroid epithelium in contrast to Cftr KO epithelium or WT epithelium treated with Cftr inhibitor 172. We conclude that crypt epithelium of murine enteroids exhibit Cftr expression and activity that recapitulates crypt epithelium in vivo. Enteroids provide a primary culture model that is suitable for physiological studies of regenerating crypt epithelium.
Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia (2016)

Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.
Potent and Specific Inhibition of HIV Envelope-Mediated Cell Fusion and Virus Binding by G Quartet-Forming Oligonucleotide (ISIS 5320) (1994)

We have previously reported identification of a phosphorothioate oligonucleotide TTGGGGTT (ISIS 5320) as a potent inhibitor of HIV infection in vitro. The oligonucleotide forms a parallel-stranded, tetrameric guanosine quartet (G-quartet) structure that specifically binds to the HIV envelope glycoprotein (gp120) and inhibits both cell-to-cell and virus-to-cell infection at submicromolar concentrations. In the current study we demonstrate that the tetramer inhibits the infection of laboratory-derived isolates of HIV-1 and HIV-2 in a variety of phenotypically distinct, established human cell lines and a panel of biologically diverse clinical isolates in fresh human peripheral blood lymphocytes and macrophages. The compound was also active against all drug-resistant virus isolates tested. In combination with AZT, ISIS 5320 exhibits additive to slightly synergistic anti-HIV activity. Cell-based mechanism of action studies demonstrate that the compound inhibits the binding of infectious virus and virus-infected cells to uninfected target cells by binding to the cationic V3 loop of the envelope glycoprotein. The G-quartet structure is a potential candidate for use in anti-HIV chemotherapy.
Collection development in the electronic library (1993)

Until recently, bzzilding library collections lzas meant acquiring materials and housing thenz locally. Librarians have constrzzcted a well-defined methodology for plannirzg the development of collections. TIze predonzinant model was "the bigger, the better."
Orthotopic Growth of Human Glioma Cells Quantitatively and Qualitatively Influences Radiation-Induced Changes in Gene Expression (2005)

The effect of radiation on gene expression has been most frequently studied using tissue culture models. To determine the influence of experimental growth condition on radiation-induced changes in gene expression, microarray analysis was done on two human glioma cell lines (U87 and U251) grown in tissue culture and as s.c. or i.c. xenografts. Compared with tissue culture, the number of genes, whose expression was affected by radiation in both cell lines, was increased in the s.c. xenografts and further increased in the orthotopic tumors. Furthermore, in each growth condition, radiation modulated the expression of a different set of genes. In addition, whereas there were few commonly affected genes after irradiation of U87 and U251 in tissue culture, there were 729 common changes after orthotopic irradiation. These results indicate that the influence of the orthotopic environment on radiation-induced modulation of gene expression in glioma cells was both quantitative and qualitative. Moreover, they suggest that investigations of the functional consequence of radiation-induced gene expression will require accounting for experimental growth conditions.
Money Out of Thin Air: The nationwide Narrowband pcs Auction (1995)

The Federal Communications Commission held its first auction of radio spectrum at the Nationwide Narrowband PCS Auction in July 1994. The simultaneous multiple‐round auction, which lasted five days, was an ascending bid auction in which all licenses were offered simultaneously. This paper describes the auction rules and how bidders prepared for the auction. The full history of bidding is presented. Several questions for auction theory are discussed. In the end, the government collected $617 million for ten licenses. The auction was viewed by all as a huge success an excellent example of bringing economic theory to bear on practical problems of allocating scarce resources.
A new member of the DP family, DP-3, with distinct protein products suggests a regulatory role for alternative splicing in the cell cycle transcription factor DRTF1/E2F. (1995)

Integrating cell cycle progression with transcription provides an important level of control during proliferation. The cellular transcription factor DRTF1/E2F is implicated in this integration process by virtue of its physical interaction and control by key regulators of proliferation, such as retinoblastoma protein, cyclins and cyclin-dependent kinases and regulation of target genes required for cell cycle progression. Generic DRTF1/E2F DNA binding activity arises when a member of two distinct families of proteins, DP and E2F, interact as DP/E2F heterodimers. Here, we report the isolation and characterisation of a new member of the murine DP family, called DP-3 (also referred to as human DP-2). In contrast to previously characterised members of the DP and E2F families, processing of DP-3 RNA provides an important level of control by generating at least four distinct DP-3 proteins, of which three have been isolated, called alpha, beta and gamma. Processing events, which we show are both tissue- and cell-restricted, can occur either in the 5' region of DP-3 RNA and determine whether translation begins at one or two potential intiating codons, or within the coding sequence, producing variations in internal domains of the DP-3 proteins. The DP-3 proteins studied can co-operate with E2F-1 in DNA binding activity and trans activation of E2F site-dependent transcription. This analysis of DP-3, which has uncovered a hitherto unexpected and surprising level of complexity, documents a new member of the DP family and novel levels of control which may influence the activity DRTF1/E2F and hence cell cycle progression.
Epitopes for human CD4+ cells on diphtheria toxin: Structural features of sequence segments forming epitopes recognized by most subjects (1995)

The sequence regions of diphtheria toxin (DTX) recognized by CD4+ T cells of seven healthy humans of different major histocompatibility complex haplotypes were identified. Overlapping synthetic peptides, screening the DTX sequence, were used to test in proliferation assays unselected blood CD4+ cells, or DTX-specific CD4+ lines propagated by stimulation with DTX of blood mononuclear cells. Blood CD4+ cells and DTX-specific CD4+ lines gave consistent results. Although each subject had an individual pattern of peptide recognition, six peptide sequences (residues 271-290, 321-340, 331-350, 351-370, 411-430 and 431-450) were recognized by all subjects. In the native DTX molecule, these sequence regions are flanked by sequence loops exposed on the DTX surface. They overlap uncharged segments of the DTX sequence. These structural properties may be general requirements for immunodominance in CD4+ cell sensitization in humans.
The Molecular Basis of -Thalassemia (2013)

The β-thalassemias are characterized by a quantitative deficiency of β-globin chains underlaid by a striking heterogeneity of molecular defects. Although most of the molecular lesions involve the structural β gene directly, some down-regulate the gene through distal cis effects, and rare trans-acting mutations have also been identified. Most β-thalassemias are inherited in a Mendelian recessive fashion but there is a subgroup of β-thalassemia alleles that behave as dominant negatives. Unraveling the molecular basis of β-thalassemia has provided a paradigm for understanding of much of human genetics.
A Direct Catalytic Asymmetric Mannich-type Reaction via a Dinuclear Zinc Catalyst:  Synthesis of Either anti- or syn-α-Hydroxy-β-Amino Ketones (2006)

The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.
Antithyroid drugs interact with renal medullary prostaglandin H synthase. (1984)

The antithyroid drugs propylthiouracil and methimazole exert their effects on the thyroid gland by inhibiting thyroid peroxidase. In addition to this effect, these drugs have been reported to inhibit prostaglandin production in both the thyroid gland and the kidney. The purpose of our studies was to evaluate the mechanism of the effects of these drugs on prostaglandin production. Both propylthiouracil and methimazole reversibly inhibited prostaglandin E2 production in both inner medullary slices and isolated renal papillary collecting tubule cells. The inhibition of arachidonic acid-induced increases in PGE2 production indicated that the effects of methimazole and propylthiouracil were on the enzyme complex prostaglandin H synthase, and not on the phospholipase mechanisms responsible for the release of arachidonic acid from tissue phospholipids. Propylthiouracil inhibited both arachidonic acid and hydrogen peroxide-dependent binding of 14C-N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide to protein, indicating that the effect of propylthiouracil is on the hydroperoxidase and not on the cyclooxygenase component of prostaglandin H synthase. Our data also indicate the potential of the antithyroid drugs for inhibition of metabolism of drugs and xenobiotics by prostaglandin H synthase. Metabolism of both methimazole and propylthiouracil by the hydroperoxidase component of prostaglandin H synthase was demonstrated. It is proposed that this interaction with the hydroperoxidase component of prostaglandin H synthase is at least in part the mechanism by which propylthiouracil and methimazole inhibit prostaglandin production. The inhibition of tissue peroxidase provides these agents with the capability to prevent the peroxidatic metabolism of drugs and xenobiotics.
Alcohol-Based Handrub: Evaluation of Technique and Microbiological Efficacy with International Infection Control Professionals (2004)

Technique is of crucial importance in hand antisepsis. Major deficiencies were detected among even highly trained HCWs. Training should be provided before switching from handwashing to the alcohol handrub
New Modulatory α Subunits for Mammalian ShabK+ Channels (1997)

Two novel K+ channel alpha subunits, named Kv9.1 and Kv9.2, have been cloned. The Kv9.2 gene is situated in the 8q22 region of the chromosome. mRNAs for these two subunits are highly and selectively expressed in the nervous system. High levels of expressions are found in the olfactory bulb, cerebral cortex, hippocampal formation, habenula, basolateral amygdaloid nuclei, and cerebellum. Interestingly Kv9.1 and Kv9.2 colocalized with Kv2.1 and/or Kv2.2 alpha subunits in several regions of the brain. Neither Kv9.1 nor Kv9.2 have K+ channel activity by themselves, but both modulate the activity of Kv2.1 and Kv2.2 channels by changing kinetics and levels of expression and by shifting the half-inactivation potential to more polarized values. This report also analyzes the changes in electrophysiological properties of Kv2 subunits induced by Kv5.1 and Kv6.1, two other modulatory subunits. Each modulatory subunit has its own specific properties of regulation of the functional Kv2 subunits, and they can lead to extensive inhibitions, to large changes in kinetics, and/or to large shifts in the voltage dependencies of the inactivation process. The increasing number of modulatory subunits for Kv2.1 and Kv2.2 provides an amazingly new capacity of functional diversity.
The Heterogeneous Cationic Polymerization of Aromatic Alkenes by Aluminum Triflate (1997)

Aluminium triflate is a very convenient initiator for the polymerization of styrenic monomers. The systems investigated in this work call upon the use of that strong Lewis acid suspended in non polar solvents. The behaviour of 4-methylstyrene and indene as representative monomers for the C9 petroleum cut was explored both in heterogeneous homopolymerization and copolymerization conditions. Initiation was found to take place only through cocatalysis and monomer transfer was an important chain-braking event at room temperature. The low DPs thus obtained were deemed interesting in the context of the preparation of resinous materials. After the study of these batch reactions, a continuous mode was tested and the results showed that the catalyst operates adequately, but needs frequent regenerations.
Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria (2014)

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis due to the lack of CD55 and CD59 on affected erythrocytes. The anti-C5 antibody eculizumab has proven clinically effective, but uncontrolled C3 activation due to CD55 absence may result in opsonization of erythrocytes, possibly leading to clinically meaningful extravascular hemolysis. We investigated the effect of the peptidic C3 inhibitor, compstatin Cp40, and its long-acting form (polyethylene glycol [PEG]-Cp40) on hemolysis and opsonization of PNH erythrocytes in an established in vitro system. Both compounds demonstrated dose-dependent inhibition of hemolysis with IC50 ∼4 µM and full inhibition at 6 µM. Protective levels of either Cp40 or PEG-Cp40 also efficiently prevented deposition of C3 fragments on PNH erythrocytes. We further explored the potential of both inhibitors for systemic administration and performed pharmacokinetic evaluation in nonhuman primates. A single intravenous injection of PEG-Cp40 resulted in a prolonged elimination half-life of >5 days but may potentially affect the plasma levels of C3. Despite faster elimination kinetics, saturating inhibitor concentration could be reached with unmodified Cp40 through repetitive subcutaneous administration. In conclusion, peptide inhibitors of C3 activation effectively prevent hemolysis and C3 opsonization of PNH erythrocytes, and are excellent, and potentially cost-effective, candidates for further clinical investigation.