gebhart/patrepeval huggingface dataset:
The Role of Polarity in the Structure of Silanes Employed in Surface Modification (2009)

Silanes that alter the chemical properties of surfaces have been studied intensively for over fifty years. In the context of coupling agents for polymer composites, biomolecule immobilization and adhesive technology, silanes have been both reviewed and have been the subject of many symposia. In contrast to silanes utilized as coupling agents in adhesive applications, silanes used to modify the surface energy or wettability of substrates under most conditions are not intended to impart chemical reactivity to the substrate. They are often referred to as non-functional silanes in order to indicate the absence of functional (reactive) groups on the organic substituent of the silane. Non-functional silanes are important since water adsorption at the interface is an important factor in coupling agent effectiveness. Although the use of non-functional silanes for surface modification is more pervasive than silanes used as coupling agents, they have been the subject of only a single review [1] which emphasizes hydrophobic surfaces. The full range of interactions of silane-treated surfaces with aqueous systems, from hydrophobic to hydrophilic, has not been reviewed. The objective of this overview is to demonstrate trends in behavior of substrates treated with non-functional silanes in aqueous environments byproviding examples of data from the literature on polar and non-polar substituted silanes and new data in which polar groups and non-polar groups are both present together as a single substituent on the silane.
Comparison of HDAC inhibitors in clinical development (2013)

At therapeutic concentrations panobinostat stimulate HIV-1 expression in latently infected cells with greater potency than other HDAC inhibitors undergoing clinical investigation. These findings warrant further investigation and panobinostat is now being advanced into clinical testing against latent HIV infection.
Design and performance of convergence routing on multiple spanning trees (2002)

This paper presents a new design, and a performance study for convergence routing in a general network with multiple spanning trees suggested as a switch-based LAN. In particular, a new algorithm for constructing two edge-disjoint spanning trees of a given network is presented, and the resulting trees are used for convergence routing (a variant of deflection routing with destination convergence guaranteed). It is shown empirically that convergence routing on two edge-disjoint spanning trees yields a better bound than a single spanning tree, on the maximum route length. The construction of the two edge-disjoint spanning trees is done with specific strategies for achieving certain tree properties that improve the system's performance.
Kinetic study of hybridoma cell growth in continuous culture. I. A model for non‐producing cells (1991)

The kinetic behavior of a nonproducing hybridoma clone AFP-27-NP was investigated in continuous culture under glucose-limited conditions. A total of more than 21, 000 h of cultures were operated at dilution rates ranging from 0.01 to 0.06 h(-1). The viable cell concentrations, dead cell concentrations, and cell volumes all varied with the dilution rate. A steady-state model was developed based on the biomass concentration and the glucose concentration. The specific growth rate as a function of glucose concentration is described by a model similar to the Monod model with a threshold glucose concentration and a minimum specific growth rate incorporated; the model is meaningful only at glucose concentrations and specific growth rates above these levels. A death rate is included in the model which is described by an inverted Monod-type function of glucose concentration. The yield coefficient based on glucose is constant in the lower range of specific growth rates and changes to a new constant value in the upper region of specific growth rates. No maintenance term for glucose consumption was needed; in the plot of specific glucose consumption rate vs. specific growth rate, the line intercepted the specific growth rate axis at a value close to the minimum growth rate. The values for the model parameters were determined from regression analysis of the steady-state data. The model predictions and experimental results fit very well.
Direct Regulation of Mitochondrial RNA Synthesis by Thyroid Hormone (1999)

We have analyzed the influence of in vivo treatment and in vitro addition of thyroid hormone on in organello mitochondrial DNA (mtDNA) transcription and, in parallel, on the in organello footprinting patterns at the mtDNA regions involved in the regulation of transcription. We found that thyroid hormone modulates mitochondrial RNA levels and the mRNA/rRNA ratio by influencing the transcriptional rate. In addition, we found conspicuous differences between the mtDNA dimethyl sulfate footprinting patterns of mitochondria derived from euthyroid and hypothyroid rats at the transcription initiation sites but not at the mitochondrial transcription termination factor (mTERF) binding region. Furthermore, direct addition of thyroid hormone to the incubation medium of mitochondria isolated from hypothyroid rats restored the mRNA/rRNA ratio found in euthyroid rats as well as the mtDNA footprinting patterns at the transcription initiation area. Therefore, we conclude that the regulatory effect of thyroid hormone on mitochondrial transcription is partially exerted by a direct influence of the hormone on the mitochondrial transcription machinery. Particularly, the influence on the mRNA/rRNA ratio is achieved by selective modulation of the alternative H-strand transcription initiation sites and does not require the previous activation of nuclear genes. These results provide the first functional demonstration that regulatory signals, such as thyroid hormone, that modify the expression of nuclear genes can also act as primary signals for the transcriptional apparatus of mitochondria.
Identification and molecular analysis of glgS, a novel growth‐phase‐regulated and rpoS‐dependent gene involved in glycogen synthesis in Escherichia coli (1992)

The putative stationary-phase sigma factor (sigma S) encoded by rpoS is essential for glycogen synthesis, but is not required for the transcription of glgC and glgA, which encode ADP-glucose-pyrophosphorylase and glycogen synthase, respectively. Using a mini-Mu random chromosomal library and a screen for glycogen overproduction, we identified a novel gene (glgS) involved in glycogen synthesis. glgS maps at 66.6 min (3247 kb) on the chromosome and constitutes a monocistronic operon. It encodes a hydrophilic and highly charged small protein, with a molecular weight of 7886, which is strongly expressed in minicells. Experiments with single-copy chromosomal glgS::lacZ gene fusions indicated that glgS expression is controlled by sigma S as well as by cAMP. Two transcriptional start sites were mapped in the upstream regulatory region of glgS. The glgSp1 transcript was absent in a cya mutant, whereas an rpoS mutant did not synthesize the glgSp2 transcript. Although glycogen synthesis is strongly stimulated by overproduction of GlgS and is inhibited by a glgS null mutation, glgS does not affect the expression of the glgCAP operon. Its potential role in the metabolic control of glycogen synthesis is discussed. Also, evidence is presented to show that the amount of glycogen accumulated in vivo in early stationary-phase cells is mainly determined by sigma S-controlled gene expression and allosteric activation of GlgC, whereas the absolute levels of expression of glgCAP as well as the intracellular concentration of cAMP are of minor importance.
Rearrangements of Synaptic Connections in Visual Cortex Revealed by Laser Photostimulation (1994)

Assessing patterns of synaptic connections in the developing mammalian neocortex has relied primarily on anatomical studies. In a physiological approach described here, the patterns of synaptic connections in slices of developing ferret visual cortex were determined with scanning laser photostimulation. Functional synaptic inputs to pyramidal cells in cortical layers 2 and 3 originating from sites close to the neuronal cell body appeared at least 2 weeks before eye opening, prior to the formation of long-range horizontal connections. Extensive long-range horizontal connections appeared in the next 10 days of development. The number of local connections peaked at the time of eye opening; the number of these connections subsequently declined to the level found in the adult while the specificity of long-distance connections increased. Thus, the relative influence of local connections on the activity of layer 2 and layer 3 neurons declines as the cortex matures while the influence of longer range connections increases substantially.
Patient Characteristics and ICU Organizational Factors That Influence Frequency of Pulmonary Artery Catheterization (2000)

Organizational characteristics of ICUs, insurance reimbursement, and race, as well as clinical variables, are associated with variation in practice patterns regarding pulmonary artery catheter use. Understanding such influences, combined with studies measuring clinical and economic outcomes, can contribute to the development of policies for the rational use of pulmonary artery catheters. JAMA. 2000;283:2559-2567
Critical Evaluation of Current Treatments in Metastatic Colorectal Cancer (2005)

Fluorouracil (FU) has been the mainstay of treatment for metastatic colorectal cancer (mCRC) for many years. However, in recent years, newer chemotherapeutic agents, particularly irinotecan (Campostar; Pfizer Pharmaceuticals, New York, NY, http://www.pfizer.com) and more recently oxaliplatin (Eloxatin; Sanofi-Aventis Inc., New York, NY, http://www.sanofi-aventis.com), have been shown to improve survival in combination with FU-based therapies. These agents were therefore incorporated into first- and second-line treatment strategies. The development of targeted agents that are tumor specific with better toxicity profiles than chemotherapeutic agents has widened the spectrum of therapies for this disease. The U.S. Food and Drug Administration (FDA) recently approved two targeted agents for treating mCRC: an antivascular endothelial growth factor monoclonal antibody (mAb), bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com), in combination with first-line 5-FU-based chemotherapy regimens and the human epidermal growth factor receptor (HER-1/EGFR)-targeted mAb cetuximab (Erbitux; ImClone Systems, Inc., New York, NY, http://www.imclone.com) as monotherapy or in combination with irinotecan as second-line therapy in refractory cancer. These newer, more effective agents are improving clinical outcome for patients with mCRC. However, as the number of agents has increased, choosing the most effective treatment strategy has become increasingly complex. This review discusses the role of the individual agents in the treatment of mCRC and identifies the most effective regimens.
Characterization of a human pluripotent stem cell‐derived model of neuronal development using multiplexed targeted proteomics (2015)

SRM-based protein profiling enabled establishment of the reproducibility and physiological relevance of the hPSC-derived neuronal model. Combined with the successful quantification of proteins relevant to neurodevelopmental diseases, this validates the platform for use as a model to enable neuroscience drug discovery.
Phosphorylation of caldesmon by ERK MAP kinases in smooth muscle (2000)

Phosphorylation of h-caldesmon has been proposed to regulate airway smooth muscle contraction. Both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases phosphorylate h-caldesmon in vitro. To determine whether both enzymes phosphorylate caldesmon in vivo, phosphorylation-site-selective antibodies were used to assay phosphorylation of MAP kinase consensus sites. Stimulation of cultured tracheal smooth muscle cells with ACh or platelet-derived growth factor increased caldesmon phosphorylation at Ser789 by about twofold. Inhibiting ERK MAP kinase activation with 50 microM PD-98059 blocked agonist-induced caldesmon phosphorylation completely. Inhibiting p38 MAP kinases with 25 microM SB-203580 had no effect on ACh-induced caldesmon phosphorylation. Carbachol stimulation increased caldesmon phosphorylation at Ser789 in intact tracheal smooth muscle, which was blocked by the M(2) antagonist AF-DX 116 (1 microM). AF-DX 116 inhibited carbachol-induced isometric contraction by 15 +/- 1.4%, thus dissociating caldesmon phosphorylation from contraction. Activation of M(2) receptors leads to activation of ERK MAP kinases and phosphorylation of caldesmon with little or no functional effect on isometric force. P38 MAP kinases are also activated by muscarinic agonists, but they do not phosphorylate caldesmon in vivo.
Role of specific hemagglutinin amino acids in the immunogenicity and protection of H5N1 influenza virus vaccines (2005)

If H5N1 influenza viruses become transmissible among humans, vaccination will offer the most effective option to limit their spread. Two human vaccine candidates recently generated by reverse genetics are based on antigenically different hemagglutinin (HA) glycoproteins derived from the A/HK/213/03 (H5N1) and A/Vietnam/1203/04 (H5N1) viruses. Their HA1 amino acid sequences differ at 10 positions, one of which (N154) introduces a potential glycosylation site in A/Vietnam/1203/04 (H5N1). To assess the impact of five amino acids in the putative antigenic sites on immunogenicity and immune protection, we generated a series of whole-virus vaccines that differed only in one or two HA amino acids. Sera from ferrets vaccinated with these inactivated preparations had high virus neutralization titers, but their hemagglutination inhibition (HI) titers were usually low. Interestingly, a recombinant virus in which the HA amino acid S223 (characteristic of 2004 viruses) was converted to N223 (as in A/HK/213/03) resulted in higher HI titers. This observation indicates that specific HA residues, such as N223, increase the sensitivity of the HI assay by altering receptor specificity and/or antibody-antigen binding. Ferrets vaccinated with mutant vaccine viruses were protected against lethal challenge with wild-type A/Vietnam/1203/04 virus. Our results suggest that inclusion of the N223 residue in the HA glycoproteins of diagnostic reference viruses may facilitate the evaluation of vaccine efficacy in humans.
Pharmacology of cannabinoid receptor ligands. (1999)

Mammalian tissues contain at least two types of cannabinoid receptor, CB1 and CB2, both coupled to G proteins. CB1 receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB2 receptors occur in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this endogenous cannabinoid system has been paralleled by a renewed interest in possible therapeutic applications of cannabinoids, for example in the management of pain and in the suppression of muscle spasticity/spasm associated with multiple sclerosis or spinal cord injury. It has also prompted the development of a range of novel cannabinoid receptor ligands, including several that show marked selectivity for CB1 or CB2 receptors. This review summarizes current knowledge about the in vitro pharmacological properties of important CB1 and CB2 receptor ligands. Particular attention is paid to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [35S]GTPgammaS binding assays, and to selected examples of how these pharmacological properties can be influenced by chemical structure. The in vitro pharmacological properties of ligands that can potently and selectively oppose the actions of CB1 or CB2 receptor agonists are also described. When administered by themselves, some of these ligands produce effects in certain tissue preparations that are opposite in direction to those produced by cannabinoid receptor agonists and the possibility that the ligands producing such inverse cannabimimetic effects are inverse agonists rather than pure antagonists is discussed.
Structure and expression of a human gene coding for a 71 kd heat shock ‘cognate’ protein (1987)

In all eukaryotes examined so far, hsp70 gene families include cognate genes (hsc70) encoding proteins of about 70 Kd which are expressed constitutively during normal growth and development. We have investigated the structural relationship of heat-inducible and cognate members of the human hsp70 gene family. Among several human genomic clones isolated using Drosophila hsp/hsc70 probes, one contained an hsc70 gene. Its complete sequence is reported here. It is split by eight introns and encodes a predicted protein of 70899 d that would be 81% homologous to hsp70. Structural comparisons with corresponding genes from other species provide one of the most striking examples of gene conservation. Isolation of a corresponding cDNA clone, RNA-mapping and in vitro translation data demonstrate that the gene is expressed constitutively and directs the synthesis of a 71 kd protein. The latter is very likely to be identical to a clathrin uncoating ATPase recently identified as a member of the hsp70-like protein family.
Notizen: Zur Biosynthese von Steroid-Derivaten im Pflanzenreich 3. Mitt.1: Spirostanol-Biogenese aus Cholesteringlucosid (1966)

Article Notizen: Zur Biosynthese von Steroid-Derivaten im Pflanzenreich 3. Mitt.1: Spirostanol-Biogenese aus Cholesteringlucosid was published on May 1, 1966 in the journal Zeitschrift für Naturforschung B (volume 21, issue 5).
Cellular proteins bind to the 3' end of Sindbis virus minus-strand RNA (1992)

Forty-four nucleotides at the 5' terminus of the genomic RNA of Sindbis virus can form a stable stem-loop structure and have been shown previously to be important for viral replication. The structure formed by the complement of this sequence at the 3' end of the minus-strand RNA has been proposed to be a promoter for RNA replication and as such might be bound in a specific fashion by proteins of either cellular or viral origin. Short oligonucleotide probes (either 62 or 132 nucleotides) representing the 3'-terminal sequence of the minus strand were prepared. When added to extracts from infected or uninfected cells, these probes were bound by cellular proteins, as evidenced by a shift in the electrophoretic mobility of the (labeled) oligonucleotide. Competition experiments confirmed the specificity of the interaction. Proteins of apparent molecular sizes 42 and 44 kDa, and to a lesser extent 52 kDa, could be cross-linked to the minus-sense probes by UV irradiation. A mutant minus-strand probe identical to the longer probe except for a single-nucleotide deletion corresponding to nucleotide 5 in the genomic RNA, which is lethal for the virus, was also found to bind the same proteins as the wild-type probe. The half-life of the mutant probe-cellular protein complex was threefold longer than that of the wild-type complex, however, indicating that the mutant probe was bound more tightly than the wild-type probe. We hypothesize that the binding of cellular factors may be transiently required for initiation of transcription of plus-strand RNA from the minus-strand template and that overly tight binding of such factors is deleterious for RNA replication.
RNA aptamers that bind L-arginine with sub-micromolar dissociation constants and high enantioselectivity (1996)

A completely randomized RNA pool as well as a degenerate pool comprised of an RNA sequence which binds citrulline with a dissociation constant of 0 muM were used to select for tight binding arginine specific RNA aptamers. A modified in vitro selection scheme, based on affinity chromatography was applied to allow the enrichment of high affinity solution binders. The selection scheme included a negative selection with the non-cognate ligand citrulline, and a heat denaturation step prior to affinity elution with an excess of the cognate ligand arginine. After 20 cycles the majority of the pools bound specifically to the arginine matrix even after denaturation/renaturation in the presence of 20 mM of a non-cognate amino acid. When denatured and eluted in the presence of 20 mM arginine, the selected RNAs quantitatively washed off the column. These RNA aptamers were cloned and sequenced. Equilibrium dialysis performed with the most abundant clone among the selected sequence revealed Kd values of 330 nM for the RNA/arginine affinity, which is nearly a 200-fold improvement over the tightest binding arginine binding RNAs known to date. Arginine recognition by this RNA is highly enantioselectice: L- arginine is bound 12 000-fold better than D-arginine. Chemical modification analysis revealed that the secondary structure of the aptamer might contain a pseudoknot motif. Our tight binding arginine aptamers join a number of natural and in vitro selected RNAs which recognize arginine. The RNAs described here compare in their binding affinity with the tightest binding RNA aptamers for low molecular weight molecules isolated in other in vitro selection experiments.
Regulation of class III (Vps34) PI3Ks (2007)

The class III PI3K (phosphoinositide 3-kinase), Vps34 (vacuolar protein sorting 34), was first identified as a regulator of vacuolar hydrolase sorting in yeast. Unlike other PI3Ks, the Vps34 lipid kinase specifically utilizes phosphatidylinositol as a substrate, producing the single lipid product PtdIns3P. While Vps34 has been studied for some time in the context of endocytosis and vesicular trafficking, it has more recently been implicated as an important regulator of autophagy, trimeric G-protein signalling, and the mTOR (mammalian target of rapamycin) nutrient-sensing pathway. The present paper will focus on studies that describe the regulation of hVps34 (human Vps34) intracellular targeting and enzymatic activity in yeast and mammalian cells.
Germ cell-specific expression of green fluorescent protein in transgenic rainbow trout under control of the rainbow trout vasa-like gene promoter (2000)

A technique to identify and isolate live fish primordial germ cells (PGCs) has not been established, in spite of the importance of purified germ cells for molecular and cellular studies. In rainbow trout, the distribution of vasa transcripts is restricted to the germ cell lineage, making this transcript a useful indicator of PGCs. Therefore, in this study, we cloned and characterized the rainbow trout vasa-like gene (RtVLG) regulatory regions and produced transgenic trout carrying the green fluorescent protein (GFP) gene driven by the RtVLG regulatory regions (p vasa-GFP) in order to identify live PGCs in vivo. In transgenic trout carrying the p vasa-GFP construct, cells showing green fluorescence were first observed at the mid-blastula stage; however, no cell-type-specific expression was observed at this stage. At the eyed stage, about 30% of the transgenic embryos showed specific GFP expression in PGCs, and at the hatching stage, about 70% of the transgenic embryos did so. An immunohistochemical study of hatching stage embryos revealed that the GFP-expressing cells are located in genital ridges. This transgenic trout, having visualizable PGCs, will make it possible to isolate live PGCs for in vitro studies and to study the ontogeny of PGCs including sex differentiation in live embryos.