gebhart/patrepeval huggingface dataset:
Serum response factor binding sites differ in three human cell types (2007)

The serum response factor (SRF) is essential for embryonic development and maintenance of muscle cells and neurons. The mechanism by which this factor controls these divergent pathways is unclear. Here we present a genome-wide view of occupancy of SRF at its binding sites with a focus on those that vary with cell type. We used chromatin immunoprecipitation (ChIP) in combination with human promoter microarrays to identify 216 putative SRF binding sites in the human genome. We performed independent quantitative PCR validation at over half of these sites that resulted in 146 sites we assert to be true binding sites at over 90% confidence. Nearly half of the sites are bound by SRF in only one of the three cell types we tested, providing strong evidence for the diverse roles for SRF in different cell types. We also explore possible mechanisms controlling differential binding of SRF in these cell types by assaying cofactor binding, DNA methylation, histone methylation, and histone acetylation at a subset of sites bound preferentially in smooth muscle cells. Although we did not see a strong correlation between SRF binding and epigenetics modifications, at these sites, we propose that SRF cofactors may play an important role in determining cell-dependent SRF binding sites. ELK4 (previously known as SAP-1 [SRF-associated protein-1]) is ubiquitously expressed. Therefore, we expected it to occupy sites where SRF binding is common in all cell types. Indeed, 90% of SRF sites also bound by ELK4 were common to all three cell types. Together, our data provide a more complete understanding of the regulatory network controlled by SRF.
A New Calculus for the Treatment of Optical SystemsV A More General Formulation, and Description of Another Calculus (1947)

After a brief review of the nature of the calculus, a formulation is provided for the application of the calculus to a wider class of optical systems than those postulated in the earlier papers of this series. The application is found, however, to be subject to the drastic limitation that the system must not depolarize the light passing through it. Since homogeneous crystalline plates are almost completely free of depolarization, this limitation does not exist in the previously contemplated application to piles of crystalline plates. A more powerful calculus, whose formulation is due to Soleillet and whose development is due to Perrin and Mueller, is described, and is found to be free of this limitation. Its general properties are compared with those of the calculus discussed in this series of papers.
The influence of experimental manipulations on chewing speed during in vivo laboratory research in tufted capuchins (Cebus apella) (2011)

Even though in vivo studies of mastication in living primates are often used to test functional and adaptive hypotheses explaining primate masticatory behavior, we currently have little data addressing how experimental procedures performed in the laboratory influence mastication. The obvious logistical issue in assessing how animal manipulation impacts feeding physiology reflects the difficulty in quantifying mechanical parameters without handling the animal. In this study, we measured chewing cycle duration as a mechanical variable that can be collected remotely to: 1) assess how experimental manipulations affect chewing speed in Cebus apella, 2) compare captive chewing cycle durations to that of wild conspecifics, and 3) document sources of variation (beyond experimental manipulation) impacting captive chewing cycle durations. We find that experimental manipulations do increase chewing cycle durations in C. apella by as much as 152 milliseconds (ms) on average. These slower chewing speeds are mainly an effect of anesthesia (and/or restraint), rather than electrode implantation or more invasive surgical procedures. Comparison of captive and wild C. apella suggest there is no novel effect of captivity on chewing speed, although this cannot unequivocally demonstrate that masticatory mechanics are similar in captive and wild individuals. Furthermore, we document significant differences in cycle durations due to inter-individual variation and food type, although duration did not always significantly correlate with mechanical properties of foods. We advocate that the significant reduction in chewing speed be considered as an appropriate qualification when applying the results of laboratory-based feeding studies to adaptive explanations of primate feeding behaviors.
Targeted replacement of the mycocerosic acid synthase gene in Mycobacterium bovis BCG produces a mutant that lacks mycosides. (1996)

A single gene (mas) encodes the multifunctional enzyme that catalyzes the synthesis of very long chain multiple methyl branched fatty acids called mycocerosic acids that are present only in slow-growing pathogenic mycobacteria and are thought to be important for pathogenesis. To achieve a targeted disruption of mas, an internal 2-kb segment of this gene was replaced with approximately the same size hygromycin-resistance gene (hyg), such that hyg was flanked by 4.7- and 1.4-kb segments of mas. Transformation of Mycobacterium bovis BCG with this construct in a plasmid that cannot replicate in mycobacteria yielded hygromycin-resistant transformants. Screening of 38 such transformants by PCR revealed several transformants representing homologous recombination with single crossover and one with double crossover. With primers representing the hyg termini and those representing the mycobacterial genome segments outside that used to make the transformation construct, the double-crossover mutant yielded PCR products expected from either side of hyg. Gene replacement was further confirmed by the absence of the vector and the 2-kb segment of mas replaced by hyg from the genome of the mutant. Thin-layer and radio-gas chromatographic analyses of the lipids derived from [1-14C]propionate showed that the mutant was incapable of synthesizing mycocerosic acids and mycosides. Thus, homologous recombination with double crossover was achieved in a slow-growing mycobacterium with an intron-containing RecA. The resulting mas-disrupted mutant should allow testing of the postulated roles of mycosides in pathogenesis.
Folding energy landscape of the thiamine pyrophosphate riboswitch aptamer (2012)

Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family.
An automated system for micro-batch protein crystallization and screening (1990)

An automatic sample dispenser has been constructed to aid with protein crystallization trials. This dispenser contains a bank of Hamilton syringes driven by stepper motors under computer control which is used to set up small samples (2 μl or less) for batch crystallization. Software has been written to create a series of trials which form a two-dimensional array of crystallization conditions. A specially designed fluoropolymer multibore microtip allows the very small volumes to be mixed and dispensed with great accuracy.
Unregulated activation of STAT-5, ERK1/2 and c-Fos may contribute to the phenotypic transformation from myelodysplastic syndrome to acute leukaemia (2001)

Myelodysplastic syndrome (MDS) is characterised by ineffective erythropoiesis and poor progenitor response to erythropoietin (Epo). The aim of this study was to determine the role of the Epo-R mediated signalling in the rise of MDS and whether alteration of signalling pathways contribute to the leukeamogenesis from MDS to acute leukaemia. We analysed Epo and GM-CSF induced ERK1/2 activation, c-Fos expression, STAT-5 and AP-1 DNA binding activities in mononuclear cells of umbilical cord blood (UCBMNC), normal marrow (NBMMNC) or marrow with MDS, AML with prior MDS and de novo AML. In UCBMNC and NBMMNC, Epo and GM-CSF induced the activation of STAT-5 DNA binding and ERK 1/2 activation (n = 6). In contrast, in MDS RA, both signalling pathways were activated only by GM-CSF but not by Epo (n = 7). In acute leukaemia, elevated basal activity of STAT-5 DNA binding appeared in 8/8 cases, which was independent of Epo or GM-CSF treatment. In normal and MDS samples, c-Fos and Egr-1 proteins were not detectable and the expression levels were not increased by Epo or GM-CSF treatment. In contrast, we found an elevated level of c-Fos expression in 5/8 acute leukemia cases, which was not further increased in the presence of Epo or GM-CSF. The elevated c-Fos expression was accompanied by an extremely high blast number in 5/5 cases. These results suggest that impaired ERK/MAPK activation, similarly to impaired STAT-5 activation in Epo-R signalling, may be responsible for the apoptotic process and the block of maturation in MDS RA. The results also suggest that the appearance of the constitutively activated STAT-5 DNA binding and c-Fos expression may be used as a predictor of the blastic transformation.
Assessment of feasibility and efficacy of Class IV laser therapy for postoperative pain relief in off-pump coronary artery bypass surgery patients: A pilot study (2015)

Class IV laser can be an effective technique for postoperative analgesia following OPCABG surgery through sternotomy when included as a component of MMA technique.
A structural analysis of the role of the nuclear matrix and DNA loops in the organization of the nucleus and chromosome (1984)

The interphase nucleus is characterized by a nuclear matrix structure that forms a residual scaffolding composed of approximately 10% of the total nuclear proteins. The nuclear matrix contains residual elements of the pore-complex and lamina, the nucleolus, and an intranuclear fibrous network that provides the basic shape and structure of the nucleus. In the interphase nucleus this nuclear matrix has been reported to be a central element in the organization of DNA loop domains and to contain fixed sites for DNA replication and transcription. In this study, we have analysed the role of the nuclear matrix and the DNA loop domains in the organization and structure of the number 4 human chromosome. A model is proposed that closely approximates the observed structural dimensions of this chromosome. The model is composed of 30 nm diameter filaments formed from a solenoid of six nucleosomes per turn. This 30 nm solenoid filament is organized as loops of DNA each containing approximately 60 000 base-pairs; each loop is anchored at its base to the nuclear matrix. A radial loop model containing 18 of these loops per turn forms a new unit of chromosome structure termed the miniband. Approximately 106 of these minibands are arranged along a central axis to form the final chromatid. The role of the nuclear matrix in this organization is presented. The accuracy of the proposed model is tested by comparing its features with the known properties of the number 4 human chromosome.
Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide (2002)

Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action.
An Environmentally Friendly Stimulation Fluid for High-Temperature Applications (2010)

Summary Matrix acidizing is used in carbonate formations to create flow channels from the formation to the wellbore; in sandstone formations, however, the goal is to dissolve materials that impair well performance. However, the use of acids in deep wells has some major drawbacks, including high reaction rate and corrosion to well tubulars. We have discovered a new stimulation chemical that can be used as a replacement for or in combination with acid treatments in deep wells. A polyacid whose structure allows for acidification is described. The polyacidic chelate L-glutamic acid, N, N-diacetic acid (GLDA) is manufactured from L-glutamic acid (MSG). The chelate-based fluid very effectively dissolves CaCO3, and it is less corrosive to the equipment and easy to handle. This paper discusses the reaction of the new chelate, GLDA, with calcite and compares its performance with other available chelates, including ethylenediaminetetraacetic acid (EDTA), hydroxy-ethylethylenediaminetriacetic acid (HEDTA), nitrilotriacetic acid (NTA), and ethanoldiglycine (EDG). GLDA dissolves calcite over a wide pH interval, although it is less effective than HEDTA at pH &amp;gt; 5. A unique property of GLDA is its high solubility; solutions exceeding 40 wt% can be achieved at a pH of approximately 2, whereas HEDTA solubility is limited to approximately 10 wt%. A mole of GLDA with a natural pH of approximately 1.5 is capable of dissolving up to two moles of CaCO3. Throughout the pH range, GLDA appears to be as thermally stable as HEDTA. As an additive to hydrochloric acid (HCl), GLDA is as effective as HEDTA in preventing precipitation of moderate levels of Fe3+ in spent acids. At high Fe3+ concentrations, GLDA is slightly less effective than HEDTA on a molar basis; but, to deal with high Fe3+ levels, GLDA may be better because significantly higher concentrations of it are possible in various acids. In 28 wt% HCl, HEDTA has limited solubility while GLDA's solubility exceeds 40 wt%. From an environmental standpoint, GLDA is readily biodegradable and is made from a renewable raw material, monosodium glutamate. GLDA has low toxicity and aquatic toxicity characteristics. As a replacement for HCl, GLDA is significantly safer and less corrosive.
Simultaneous quantification of free fatty acids, free sterols, squalene, and acylglycerol molecular species in palm oil by high‐temperature gas chromatography‐flame ionization detection (2005)

This paper discusses a rapid GC-FID technique for the simultaneous quantitative analysis of FFA, MAG, DAG, TAG, sterols, and squalene in vegetable oils, with special reference to palm oil. The FFA content determined had a lower SE compared with a conventional titrimetric method. Squalene and individual sterols, consisting of beta-sitosterol, stigmasterol, campesterol, and cholesterol, were accurately quantified without any losses. This was achieved through elimination of tedious conventional sample pretreatments, such as saponification and preparative TLC. With this technique, the separation of individual MAG, consisting of 16:0, 18:0, and 18:1 FA, and the DAG species, consisting of the 1,2(2,3)- and 1,3-positions, was sufficient to enable their quantification. This technique enabled the TAG to be determined according to their carbon numbers in the range of C44 to C56. Comparisons were made with conventional methods, and the results were in good agreement with those reported in the literature.
Nanocontact Printing:  A Route to Sub-50-nm-Scale Chemical and Biological Patterning (2003)

This paper describes the first example of the patterning of surfaces via nanocontact printing with chemically distinct features in the <50 nm scale over 3 × 3 mm2. These ultrasmall features are achieved via a combination of “sharp” and “hard” poly(dimethylsiloxane) stamps, keeping the contact area in the 50 nm domain, and high molecular weight inks to avoid diffusion. The patterns consist of dendrimers or proteins and can be used as a scaffold for further modification with gold nanoparticles.
EXTRACTING SEMANTIC PREDICATIONS FROM MEDLINE CITATIONS FOR PHARMACOGENOMICS (2006)

We describe a natural language processing system (Enhanced SemRep) to identify core assertions on pharmacogenomics in Medline citations. Extracted information is represented as semantic predications covering a range of relations relevant to this domain. The specific relations addressed by the system provide greater precision than that achievable with methods that rely on entity co-occurrence. The development of Enhanced SemRep is based on the adaptation of an existing system and crucially depends on domain knowledge in the Unified Medical Language System. We provide a preliminary evaluation (55% recall and 73% precision) and discuss the potential of this system in assisting both clinical practice and scientific investigation.
Nonsense mutation in open reading frame E2 of bovine papillomavirus DNA (1986)

Oligonucleotide-directed mutagenesis was used to construct a nonsense mutation in open reading frame (ORF) E2 of bovine papillomavirus DNA. A single base substitution mutation was constructed which converted a TAC codon into a TAG amber stop codon at a position in the ORF that did not overlap with any other viral ORFs. Full-length viral DNA containing the mutation induced only approximately 2% of the transformed foci of mouse C127 cells that were induced by wild-type DNA. In a different transformation assay, approximately one-half of the C127 cells which had acquired the mutant DNA gave rise to colonies containing at least some cells with transformed morphology. The constructed mutation was maintained in cell lines derived from cells which had acquired the mutant viral DNA, but the viral DNA appeared to be integrated into the host cell genome. Genetic mapping experiments proved that the constructed amber mutation caused the decrease in focus-forming activity and the integration of the mutant viral DNA. These results suggest that ORF E2 encodes a protein which is involved either directly or indirectly in some aspects of oncogenic transformation by bovine papillomavirus and in maintaining the viral DNA as a plasmid in transformed cells.
Non‐specific, general and multiple stress resistance of growth‐restricted Bacillus subtilis cells by the expression of the σB regulon (1998)

Bacillus subtilis cells respond almost immediately to different stress conditions by increasing the production of general stress proteins (GSPs). The genes encoding the majority of the GSPs that are induced by heat, ethanol, salt stress or by starvation for glucose, oxygen or phosphate belong to the sigmaB-dependent general stress regulon. Despite a good understanding of the complex regulation of the activity of sigmaB and knowledge of a very large number of general stress genes controlled by sigmaB, first insights into the physiological role of this nonspecific stress response have been obtained only very recently. To explore the physiological role of this reguIon, we and others identified sigmaB-dependent general stress genes and compared the stress tolerance of wild-type cells with mutants lacking sigmaB or general stress proteins. The proteins encoded by sigmaB-dependent general stress genes can be divided into at least five functional groups that most probably provide growth-restricted B. subtilis cells with a multiple stress resistance in anticipation of future stress. In particular, sigB mutants are impaired in non-specific resistance to oxidative stress, which requires the sigmaB-dependent dps gene encoding a DNA-protecting protein. Protection against oxidative damage of membranes, proteins or DNA could be the most essential component of sigmaB mediated general stress resistance in growth-arrested aerobic gram-positive bacteria. Other general stress genes have both a sigmaB-dependent induction pathway and a second sigmaB-independent mechanism of stress induction, thereby partially compensating for a sigmaB deficiency in a sigB mutant. In contrast to sigB mutants, null mutations in genes encoding those proteins, such as cIpP or cIpC, cause extreme sensitivity to salt or heat.
M6P/IGF2Rloss of heterozygosity in head and neck cancer associated with poor patient prognosis (2003)

This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy.
Hybrid GaAs-Nanowire–Carbon-Nanotube Flexible Photovoltaics (2010)

A simple method is described for the preparation of carbon nanotube (CNT) composite films containing Au nanoparticles, which act as adatom collection agents promoting the growth of core-shell p-n junction GaAs nanowires (NW), according to the vapor-liquid-solid mechanism. This approach for composite film formation requires no covalent modification of the CNTs. GaAs NWs obtained are randomly aligned with respect to the CNT substrate in a densely packed arrangement. Nanohybrid films, incorporating coaxial GaAs NWs as the active, light-harvesting medium are used in the fabrication of photovoltaic cells, exhibiting conversion efficiencies up to 0.32%. Doping experiments confirm that conduction is not dominated by Schottky barriers at contact interfaces. The NW/CNT solar cells are shown to retain function following bending up to a curve radius of 12.5 mm, illustrating the potential of these novel materials in flexible device applications.
Expression and post-translational processing of gastrin in heterologous endocrine cells. (1991)

The biosynthesis of gastrin involves a complex series of post-translational processing reactions that result in the formation of a biologically active secretory product. To study the mechanisms for two specific reactions in gastrin processing, namely dibasic cleavage and amidation, we infected AtT-20, GH3, and Rin5-f cells with the retroviral expression vector, pZip-NeoSV(X), containing human gastrin cDNA. We detected gastrin and its glycine extended post-translational processing intermediates (G-gly) in the media and cell extracts of successfully infected cells. Characterization of the molecular forms of gastrin in these cell lines revealed that GH3 and Rin5-f processed gastrin in a manner similar to antral G-cells but the cleavage of the Lys74-Lys75 bond that converts G34 to G17 appeared to be suppressed in AtT-20 cells. Even after conversion of this site to Arg74-Arg75 via site-directed mutagenesis, the At-20 cells synthesized G34 predominantly. All of the infected cells amidated gastrin but the gastrin/G-gly ratio, a reflection of amidation within the cells, was enhanced in GH3 and Rin5-f cells but diminished in AtT-20 cells upon treatment with dexamethasone (10(-4) M) for 3 days. The dibasic cleavage of gastrin was uneffected by dexamethasone. Our data suggest that the activities of post-translational processing reactions responsible for the synthesis of biologically active gastrin exhibit considerable tissue and substrate specificity.