gebhart/patrepeval huggingface dataset:
Acute modulation of calcium currents and synaptic transmission by gabapentinoids (2010)

Gabapentin and pregabalin are anticonvulsant drugs that are extensively used for the treatment of several neurological and psychiatric disorders. Gabapentinoids (GBPs) are known to have a high affinity binding to α2δ-1 and α2δ-2 auxiliary subunit of specific voltage-gated calcium channels. Despite the confusing effects reported on Ca (2+) currents, most of the studies showed that GBPs reduced release of various neurotransmitters from synapses in several neuronal tissues. We showed that acute in vitro application of pregabalin can reduce in a dose dependent manner synaptic transmission in both neuromuscular junctions and calyx of Held-MNTB excitatory synapses. Furthermore presynaptic Ca (2+) currents treated with pregabalin are reduced in amplitude, do not show inactivation at a clinically relevant low concentration of 100 μM and activate and deactivate faster. These results suggest novel modulatory role of acute pregabalin that might contribute to better understanding its anticonvulsant/analgesic clinical effects.
Construction of Hydrolytically-Degradable Thin Films via Layer-by-Layer Deposition of Degradable Polyelectrolytes (2002)

Hydrolytically degradable, multilayered films ranging from 10 to 100 nm have been constructed by the layer-by-layer deposition of degradable polycations and oppositely charged polyanions. Polycations play dual roles in these systems, serving as structural components of the film as well as transient elements designed to trigger release; polyanions serve as structural components and as entities to be released or delivered. The films erode in a controlled manner under physiological conditions and are suitable for the incorporation and subsequent controlled release of functional polyanions such as DNA.
Synthesis of Titanium Dioxide (TiO<SUB>2</SUB>) Nanomaterials (2006)

Titanium dioxide (TiO2) is a promising material for many emerging applications. Even more promising are the benefits offered by the material when its length scale is reduced to the nanometer range. Nanomaterials usually exhibit unique properties resulting from either the extremely large surface area-to-volume ratio or the quantum confinement effect of energy carriers. In this article we present an overview of recent progress in the synthesis of TiO2 nanomaterials. The topics include synthesis of TiO2 nanoparticles, nanorods, nanowires, nanotubes, and mesoporous/nanoporous materials using different preparation approaches such as sol-gel, sol, hydrothermal, solvothermal, and vapor deposition. The applications of TiO2 nanomaterials are also briefly summarized.
Intramolecular Charge Transfer Complexes as Fluorescence Probes for UV and Visible Light Induced Acrylate Polymerization (1994)

Intramolecular charge transfer complexes (ICTC) of derivatives of 1- diaminonaphthalene-5-sulfonamide (DANSYL AMIDE) such as 1-dimethylamino- naphthalene-5-sulfonyl-n-butylamide (1,5-DASB) and 2-dimethylamino-naphthalene- 5-sulfonyl-n-butylamide (2,5DASB), were used as fluorescence probes for cure monitoring of photocurable polymer systems. This technique is based upon the difference in fluorescence intensity from the parallel and perpendicular conformations of the excited state of the complex, and is based on the dependence of the relative population of each conformation on the microviscosity of the system. As the curing reaction proceeds, the steady state fluorescence emission spectra of the probes were all found to exhibit hypsochromic spectral shifts due to the increase in matrix microviscosity. A linear correlation between the fluorescence intensity ratios (R=Ipar. / Iper.) and the extent of polymerization, measured by transmission FTIR spectrometry, was obtained for different types of acrylated polymers, cured with UV or visible (VIS) initiators. Intramolecular charge transfer, Visible light induced acrylate polymerization.
Effect of heat stress during the dry period on mammary gland development (2011)

Heat stress during the dry period negatively affects hepatic metabolism and cellular immune function during the transition period, and milk production in the subsequent lactation. However, the cellular mechanisms involved in the depressed mammary gland function remain unknown. The objective of the present study was to determine the effect of heat stress during the dry period on various indices of mammary gland development of multiparous cows. Cows were dried off approximately 46 d before expected calving and randomly assigned to 2 treatments, heat stress (HT, n=15) or cooling (CL, n=14), based on mature equivalent milk production. Cows in the CL treatment were provided with sprinklers and fans that came on when ambient temperatures reached 21.1°C, whereas HT cows were housed in the same barn without fans and sprinklers. After parturition, all cows were housed in a freestall barn with cooling. Rectal temperatures were measured twice daily (0730 and 1430 h) and respiration rates recorded at 1500 h on a Monday-Wednesday-Friday schedule from dry off to calving. Milk yield and composition were recorded daily up to 280 d in milk. Daily dry matter intake was measured from dry off to 42 d relative to calving. Mammary biopsies were collected at dry off, -20, 2, and 20 d relative to calving from a subset of cows (HT, n=7; CL, n=7). Labeling with Ki67 antigen and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling were used to evaluate mammary cell proliferation and apoptosis, respectively. The average temperature-humidity index during the dry period was 76.6 and not different between treatments. Heat-stressed cows had higher rectal temperatures in the morning (38.8 vs. 38.6°C) and afternoon (39.4 vs. 39.0°C), greater respiration rates (78.4 vs. 45.6 breath/min), and decreased dry matter intake (8.9 vs. 10.6 kg/d) when dry compared with CL cows. Relative to HT cows, CL cows had greater milk production (28.9 vs. 33.9 kg/d), lower milk protein concentration (3.01 vs. 2.87%), and tended to have lower somatic cell score (3.35 vs. 2.94) through 280 d in milk. Heat stress during the dry period decreased mammary cell proliferation rate (1.0 vs. 3.3%) at -20 d relative to calving compared with CL cows. Mammary cell apoptosis was not affected by prepartum heat stress. We conclude that heat stress during the dry period compromises mammary gland development before parturition, which decreases milk yield in the next lactation.
Stable Histone Deacetylase Complexes Distinguished by the Presence of SANT Domain Proteins CoREST/kiaa0071 and Mta-L1 (2001)

Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones. Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes. In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601. Complex cII (15 S) contained >/=15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2. The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex. A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers. We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly.
Synthesis and Antiviral Activity of New 3,4-Dihydro-2-Alkoxy-6-Benzyl-4-Oxopyrimidines (DABOs), Specific Inhibitors of Human Immunodeficiency Virus Type 1 (1995)

3,4-Dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs) have emerged as non-nucleoside inhibitors of human immunodeficiency virus type 1 [Artico et al. (1993), Antiviral Chem Chemother 4: 361-368]. With a view to increasing their potency, a new series of DABO derivatives, differently substituted at positions C-2 and/or C-5 of the pyrimidine ring and 3′ or 3′,5′ of the benzyl moiety, have been synthesized. DABOs were prepared by reacting O-methylisourea with the appropriate methyl 2-alkyl-4-phenylacetylacetate, with formation of 3,4-dihydro-2-methoxy-6-arylmethyl-4-oxopyrimidines. Subsequent displacement of the methoxy group linked at the 2-position of the pyrimidine ring by treatment with alkoxy and cycloalkoxy potassium salts led to the required derivatives. In vitro, the most potent compounds were 12e and 12p, which had an EC 50 of 0.8 μM and a selective index of 400.
Effects of Nanosized Adsorbing Material on Electrochemical Properties of Sulfur Cathodes for Li/S Secondary Batteries (2004)

In order to prevent polysulfide dissolution into liquid electrolytes and to promote the Li/S redox reaction nanosized which has the catalytic effect of chemical bond dissociating and is expected to have an adsorbing effect due to the effect of retaining liquid electrolyte of MgO in a Li/iron sulfide secondary battery,16 was prepared by the sol-gel method as an electrochemically inactive additive for an elemental sulfur cathode for Li/S rechargeable batteries. The Li/S battery using an elemental sulfur cathode with a nanosized added showed the improvement of not only the discharge capacity but also cycle durability (maximum discharge capacity: 1185 mAh/g sulfur, The rate capability of the sulfur cathode was also increased with the addition of the nanosized From the results, it is confirmed that the nanosized had the polysulfide adsorbing effect and the catalytic effect of promoting Li/S redox reaction. Furthermore, it is found that the nanosized also increased the porosity of the sulfur cathode. © 2004 The Electrochemical Society. All rights reserved.
Marijuana Smoking vs Cannabinoids for Glaucoma Therapy (1998)

Development of drugs based on the cannabinoid molecule or its agonists for use as topical or oral antiglaucoma medications seems to be worthy of further pursuit. Among the latter chemicals, some have no known adverse psychoactive side effects. Smoking of marijuana plant material for the reduction of elevated IOP in glaucoma is ill-advised, given its toxicological profile.
A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition (2013)

RAF inhibitors such as vemurafenib and dabrafenib block BRAF-mediated cell proliferation and achieve meaningful clinical benefit in the vast majority of patients with BRAF(V600E)-mutant melanoma. However, some patients do not respond to this regimen, and nearly all progress to therapeutic resistance. We used a pooled RNA interference screen targeting more than 16,500 genes to discover loss-of-function events that could drive resistance to RAF inhibition. The highest ranking gene was NF1, which encodes neurofibromin, a tumor suppressor that inhibits RAS activity. NF1 loss mediates resistance to RAF and mitogen-activated protein kinase (MAPK) kinase kinase (MEK) inhibitors through sustained MAPK pathway activation. However, cells lacking NF1 retained sensitivity to the irreversible RAF inhibitor AZ628 and an ERK inhibitor. NF1 mutations were observed in BRAF-mutant tumor cells that are intrinsically resistant to RAF inhibition and in melanoma tumors obtained from patients exhibiting resistance to vemurafenib, thus showing the clinical potential for NF1-driven resistance to RAF/MEK-targeted therapies.
Nanoscale patterning with block copolymers (2006)

The self-assembly processes of block copolymers offer interesting strategies to create patterns on nanometer length scales. The polymeric constituents, substrate surface properties, and experimental conditions all offer parameters that allow the control and optimization of pattern formation for specific applications. We review how such patterns can be obtained and discuss some potential applications using these patterns as (polymeric) nanostructures or templates, e.g. for nanoparticle assembly. The method offers interesting possibilities in combination with existing high-resolution lithography methods, and could become of particular interest in microtechnology and biosensing.
Design, Synthesis and Evaluation of Fluorocarbons and Surfactants for in Vivo Applications New Perfluoroalkylated Polyhydroxylated Surfactants (1988)

The progress achieved since the advent of Fluosol-DA is summarized in this paper, with special focus on the synthesis and evaluation of more adequate, reliable, industrially feasible fluorocarbons, structure/property relationships--molecular weight being recognized as the pre-eminent determining factor of both the fluorocarbon's excretion rate and the emulsion's stability-, the preparation of significantly more concentrated, more efficacious emulsions, etc. The key to further progress and better mastery of the emulsions' characteristics, especially in relation to increased shelf-life, prolonged i.v. persistence, and versatility, now lies in the development of new surfactants, better adapted to this objective. New families of well defined, monodisperse perfluoroalkylated polyhydroxylated surfactants derived from sugars and related compounds have been synthesized and fully characterized. Preliminary evaluation of their surface-active properties, emulsion stabilizing capacity and biocompatibility are reported.
Introduction of the Maleimide Function onto Resin-Bound Peptides:  A Simple, High-Yield Process Useful for Discriminating among Several Lysines (1996)

Incorporation of epsilon-Adpoc-lysine as a residue in solid phase peptide synthesis allows selective deprotection of this residue on the resin-bound peptide relative to other acid labile groups such as Boc. Premature resin cleavage is avoided. A maleimide group, a useful thiol-capture reagent, was readily introduced by reacting the liberated amino function with an acylating agent containing the maleimide functionality. Acidic cleavage from the resin, with an appropriate scavenging system, afforded peptides that are derivatized with a maleimide functionality on a specific lysine. This is advantageous for producing peptide-carrier conjugates of defined specificity, useful as immunogens, by maleimide-thiol coupling. The derivatization and resin removal chemistries appear to proceed in excellent yield with respect to the maleimide group. The structures were confirmed by tandem mass spectrometry.
Mechanism of the formation of contractile ring in dividing cultured animal cells. II. Cortical movement of microinjected actin filaments. (1990)

The contractile ring in dividing animal cells is formed primarily through the reorganization of existing actin filaments (Cao, L.-G., and Y.-L. Wang. 1990. J. Cell Biol. 110:1089-1096), but it is not clear whether the process involves a random recruitment of diffusible actin filaments from the cytoplasm, or a directional movement of cortically associated filaments toward the equator. We have studied this question by observing the distribution of actin filaments that have been labeled with fluorescent phalloidin and microinjected into dividing normal rat kidney (NRK) cells. The labeled filaments are present primarily in the cytoplasm during prometaphase and early metaphase, but become associated extensively with the cell cortex 10-15 min before the onset of anaphase. This process is manifested both as an increase in cortical fluorescence intensity and as movements of discrete aggregates of actin filaments toward the cortex. The concentration of actin fluorescence in the equatorial region, accompanied by a decrease of fluorescence in polar regions, is detected 2-3 min after the onset of anaphase. By directly tracing the distribution of aggregates of labeled actin filaments, we are able to detect, during anaphase and telophase, movements of cortical actin filaments toward the equator at an average rate of 1.0 micron/min. Our results, combined with previous observations, suggest that the organization of actin filaments during cytokinesis probably involves an association of cytoplasmic filaments with the cortex, a movement of cortical filaments toward the cleavage furrow, and a dissociation of filaments from the equatorial cortex.
Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. (1986)

Salmonella typhimurium is a facultative intracellular pathogen capable of surviving within phagocytic cells of the reticuloendothelial system. To identify the genes important for intracellular survival, 9516 independent Tn10 insertional mutations were isolated in a virulent strain of S. typhimurium. By using an in vitro assay for survival within macrophages, 83 Tn10 mutants have been identified that have a diminished capacity for intracellular survival (designated MS or macrophage survival mutants). All of the MS mutants are less virulent than the parent strain in vivo, demonstrating that, for Salmonella, survival within the macrophage is essential for virulence. Thirty-seven of the MS mutants have been characterized as to their phenotype, including several mutations that confer sensitivity to specific microbiocidal mechanisms of the macrophage.
Neurosteroid Analogues. 18. Structure–Activity Studies ofent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone (2013)

A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on γ-aminobutyric acid type A (GABAA) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4α-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABAA receptor function.
Transglutaminases: multifunctional cross‐linking enzymes that stabilize tissues (1991)

Transglutaminases catalyze the posttranslational modification of proteins by transamidation of available glutamine residues. This action results primarily in the formation of epsilon-(gamma-glutamyl)lysine cross-links but includes the incorporation of polyamines into suitable protein substrates as well. The covalent isopeptide crosslink is stable and resistant to proteolysis, thereby increasing the resistance of tissue to chemical, enzymatic, and mechanical disruption. The plasma transglutaminase, factor XIIIa, is formed at sites of blood coagulation and impedes blood loss by stabilizing the fibrin clot. The squamous epithelium constituting the protective callus layer of skin is formed by the action of keratinocyte transglutaminase (TGK) and epidermal transglutaminase (TGE). The tissue transglutaminase (TGC) is a cytoplasmic enzyme present in many cells including those in the blood vessel wall. TGC function is unknown, although it could function to stabilize intra- and extra-cellular molecules in a wide variety of physiologic or pathologic processes. The amino acid sequences of factor XIII, TGC, and TGK establish them as a homologous gene family and also reveal a striking homology to the erythrocyte membrane protein, band 4.2. This review summarizes the current information on structures, functions, and evolution of the most prominent members of this gene family.
Cytokine Networks Involved in the Regulation of Haemopoietic Stem Cell Proliferation and Differentiation (2007)

Additive and synergistic interactions between haemopoietic growth factors and cytokines can be demonstrated in vitro in clonogenic and suspension cultures of murine and human bone marrow. Purification of early stem cells by combinations of purging with cytotoxic agents (5-fluorouracil, 4-hydroperoxy-cyclophosphamide) and selection with monoclonal antibodies for CD34+, CD33- cells permits analysis of factor interactions at the level of the primitive pluripotential stem cell. Interactions between interleukins, tumour necrosis factor and the colony-stimulating factors can be monitored. In vivo, IL-1 alone, or in combination with G-CSF produces accelerated reconstitution of haemopoiesis after chemotherapy, irradiation and bone marrow transplantation in murine and primate systems. IL-1 elicits cytokine cascades that may have positive or negative actions on lymphohaemopoiesis. Induction of products of the cyclooxygenase and lipooxygenase pathways, as well as tumour necrosis factor and TGF-beta, modulate haemopoiesis.
Direct evidence that interferon-beta mediates enhanced HLA-class I expression in measles virus-infected cells. (1993)

Viral infection results in enhancement of HLA-class I expression in a number of cell types, including glial cells, which normally do not express these molecules. This enhancement may occur through a direct interaction between a viral component and the HLA-class I gene or indirectly through virus-induced soluble factors produced by infected cells. These include cytokines such as IFN-gamma, IFN-alpha/beta, and TNF-alpha, known to enhance class I expression. Measles virus (MV) infection of a human glioma cell line (U-105 MG) and of primary human umbilical vein endothelial cells enhances the expression of HLA-class I molecules on these cells. The enhancement of HLA-class I is dependent on infectious virus, as antibody-neutralized MV has no effect on class I expression. In this study, we demonstrate the presence of an HLA-class I-enhancing factor in supernatants from MV-infected cells. The supernatant class I-enhancing factor is not IFN-gamma, IFN-alpha, or TNF-alpha because MV-infected cells did not produce measurable levels of these cytokines as detected by immunoassay or polymerase chain reaction. In contrast, IFN-beta is produced by the infected cells and the supernatant class I-enhancing factor could be entirely neutralized by antibodies to IFN-beta, but not antibodies to IFN-alpha, TNF-alpha, or non-immune sera. Furthermore, preincubation of cells with neutralizing antibodies to IFN-beta prior to infection blocked MV enhancement of HLA-class I completely in the U-105 MG cells and by as much as 74% in the umbilical vein endothelial cells. The results of these experiments provide direct evidence that enhanced HLA-class I expression in MV-infected cells is mediated primarily by IFN-beta.