gebhart/patrepeval huggingface dataset:
The role of phospholipids and factor Va in the prothrombinase complex. (1980)

The kinetic parameters of the conversion of bovine prothrombin into thrombin by activated bovine blood clotting factor X (Xa) have been determined in the absence and presence of Ca2+, activated bovine factor V (Va) and phospholipid (dioleoylphosphatidylcholine/dioleoylphosphatidylserine, 1:1; mol/mol). In the absence of accessory components, the Km for prothrombin is 131 microM, which is well above its concentration in bovine plasma of about 1.5 microM. The Vmax of thrombin formation is 0.61 mol min-1 mol of Xa-1 under these conditions. In the presence of 7.5 microM phospholipid, the Km drops to 0.058 microM and the Vmax slightly increases to 2.25 mol min-1 mol of Xa. For the complete prothrombinase complex (Xa, Va, Ca2+, and 7.5 microM phospholipid), a Km for prothrombin of 0.21 microM and a Vmax of 1919 mol min-1 mol of Xa-1 is found. The Vmax of thrombin formation slightly increases when more phospholipid is present in our experiments and there is a considerable increase of the Km for prothrombin at higher phospholipid concentrations. Preliminary calculations show that the prothrombin density at the phospholipid surface at the Km is independent of the phospholipid concentration. This indicates that the Km measured in the presence of phospholipid has to be regarded as an apparent Km and the local prothrombin concentration determines the kinetics of activation. Prothrombin activation by prothrombinase complexes of different compositions was followed by gel electrophoresis in the presence of sodium dodecyl sulfate. Both in the absence and presence of phospholipid but without factor Va, prethrombin 2 is the main product formed during the initial stages of steady state prothrombin activation. In the presence of factor Va, thrombin is the main end product and minute amounts of prethrombin 2 are formed. This shift in the reaction pathway of prothrombin activation caused by factor Va will contribute to the observed increase of the Vmax measured in the presence of factor Va.
Evaluation of developmental competence, nuclear and ooplasmic maturation of calf oocytes (1996)

In this study we evaluated nuclear and ooplasmic maturation of prepuberal calf oocytes to determine a possible cause for their low developmental competency. Calf oocytes resumed meiosis and arrested at the MII stage at rates similar to that of adult animals; however, zygotes derived from calf oocytes cleaved and developed at significantly lower rates. Ooplasmic maturation was assessed during oocyte maturation and fertilization. Transmission electron microscopy revealed that a majority of calf oocytes exhibited some delay in organelle migration and redistribution following maturation. Immunofluorescence microscopy showed that following IVF, a higher percentage of calf oocytes had abnormal chromatin and microtubule configurations than those of adult cattle. These anomalies were characterized by delayed formation of sperm aster and asynchronous pronuclear formation. Microfluorometry was used to characterize the Ca2+ responses of calf oocytes to the addition of agonists or after IVF. The addition of thimerosal demonstrated the presence of Ca2+ stores in calf oocytes. Injection of near threshold concentrations of inositol 1,4,5-trisphosphate (InsP3), used to test the sensitivity of the InsP3R, released significantly less Ca2+ in calf than in cow oocytes, whereas higher concentrations of InsP3 (500 microM) released maximal [Ca2+]i in both oocytes. These results suggested that the Ca2+ content of intracellular stores was similar, but the sensitivity of the InsP3R may be different. Following insemination, calf oocytes exhibiting [Ca2+]i oscillations displayed comparable amplitude and intervals to cow oocytes; however, a significantly higher number of fertilized calf oocytes failed to show oscillations. Our findings suggest that the low developmental competence of calf oocytes can be attributed, at least in part, to incomplete or delayed ooplasmic maturation.
The NLC Software Requirements Methodology (2001)

We describe the software requirements and development methodology developed for the NLC control system. Given the longevity of that project, and the likely geographical distribution of the collaborating engineers, the planned requirements management process is somewhat more formal than the norm in high energy physics projects. The short term goals of the requirements process are to accurately estimate costs, to decompose the problem, and to determine likely technologies. The long term goal is to enable a smooth transition from high level functional requirements to specific subsystem and component requirements for individual programmers, and to support distributed development. The methodology covers both ends of that life cycle. It covers both the analytical and documentary tools for software engineering, and project management support.
HLA‐DQA, ‐DQB AND ‐DRB ALLELE CONTRIBUTION TO NARCOLEPSY SUSCEPTIBILITY (1997)

The association of narcolepsy with HLA class I antigens and HLA class II alleles was studies in a series of Spanish narcoleptic patients. The haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was found to be significantly associated with the disease, while the haplotype DRB1*0701-DRB4*01-DQA1*0201-DQB1*02 might confer a slight protective effect against narcolepsy. Gene dose-effect was not seen in any of the involved alleles, and linkage disequilibrium between the positively associated alleles was found to be stronger in patients than in controls. Statistical analysis applied to identify the HLA allele truly responsible for the association did not clearly discriminate between the contribution of DRB1*1501 and that of DQB1*0602, but it proved that the association with DQA1*0102 is secondary to that with DRB1*1501/DQB1*0602. Analysis of the diagnostic value of typing for the narcolepsy-associated alleles demonstrated a very high negative predictive value and revealed that this test can be convenient for exclusion of narcolepsy in cases when the diagnosis is not evident after clinical evaluation and the marker haplotype is absent. Finally, a family study indicated that narcolepsy is a multifactorial disorder that involves HLA genes under an incomplete penetrance model, with possible influences from environmental factors or other genes different to HLA genes.
Protein-tyrosine Phosphatase Shp-1 Is a Negative Regulator of IL-4- and IL-13-dependent Signal Transduction (1998)

Binding of interleukin (IL)-4 to its transmembrane receptor results in the Jak-mediated tyrosine phosphorylation of a number of protein components of the IL-4 signaling cascade, including Jak1, Jak2, Jak3, Tyk2, IL-4Ralpha, IRS-1, IRS-2, and Stat6 in appropriate cell types. However, the protein-tyrosine phosphatases (PTPs) that dephosphorylate these proteins and terminate signaling remained unidentified. We have noted that IL-4-dependent activation of Stat6 is sustained longer in fibroblasts than in lymphoid cells. Because Shp-1, an SH2 domain-containing PTP, is expressed primarily in hematopoietic cells, we examined whether Shp-1 activity could regulate IL-4-dependent cell signaling. Expression of an Shp-1 transgene in NIH 3T3 cells markedly reduces both IL-4-dependent Stat6 activation and Stat6-mediated transcription of IL-4-responsive genes. In accord with this, IL-4 treatment of bone marrow-derived macrophages from viable motheaten mice that express substantially reduced levels of Shp-1 activity show remarkably enhanced activation of Stat6. In addition, Stat6 activation by IL-4 is significantly enhanced in pre-B cells derived from motheaten (Shp-1 null mutant) mice compared with normal pre-B cells derived from control animals. These data clearly implicate Shp-1 in the negative regulation of the IL-4/IL-13-activated Jak-Stat pathway.
A Trial of Two Cognitive-Behavioural Methods of Treating Drug-Resistant Residual Psychotic Symptoms in Schizophrenic Patients: I. Outcome (1993)

Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive-behavioural treatments to alleviate residual hallucinations and delusions. Forty-nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow-up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect.
Anti-Inflammatory Activity of 2,4,6-Trihydroxy-α-<i>p</i>-Methoxyphenyl- acetophenone (Compound D-58) (2000)

&lt;i&gt;Background:&lt;/i&gt; Active oxygen radicals as well as a variety of cytosolic protein tyrosine kinases play a role in the regulation of prostaglandin E&lt;sub&gt;2&lt;/sub&gt; (PGE&lt;sub&gt;2&lt;/sub&gt;), a key inflammatory mediator, released by skin cells in response to irradiation with ultraviolet B light (UVB). Identification of chemical compounds that can interrupt such events may provide a basis for the development of potent anti-inflammatory agents. &lt;i&gt;Objective:&lt;/i&gt; To investigate the effect of a novel genistein analog, 2,4,6-trihydroxy-α-&lt;i&gt;p&lt;/i&gt;-methoxyphenylacetophenone, with antioxidant property (compound D-58), on UVB-induced inflammatory responses. &lt;i&gt;Methods:&lt;/i&gt; Epidermal cell cultures were irradiated with UVB both in the presence and absence of compound D-58 and the PGE&lt;sub&gt;2&lt;/sub&gt; released in the medium was determined by ELISA. For in vivo studies, skin inflammation was induced in mice either by carrageenan challenge of the air pouch or by an acute exposure of skin to UVB radiation. The resulting inflammatory mediator release, skin edema and the histological changes of the skin were determined both in the presence and absence of compound D-58. &lt;i&gt;Results:&lt;/i&gt; Compound D-58 treatment effectively inhibited the development of edema and histological changes in the skin of UVB-irradiated mice as well as the release of PGE&lt;sub&gt;2&lt;/sub&gt; in vitro as well as in vivo. &lt;i&gt;Conclusion:&lt;/i&gt; Compound D-58 (2,4,6-trihydroxy-α-&lt;i&gt;p&lt;/i&gt;-methoxyphenylacetophenone) has potent anti-inflammatory properties.
Effectiveness of correlation analysis in identifying protein residues undergoing correlated evolution (1997)

Various methods for detecting correlation between sites were evaluated by ascertaining their ability to discriminate positively correlated sites from background correlation at randomly evolved sites. A model for generating pairwise correlations of different degrees is also described. An assortment of physicochemical vectors and similarity and difference matrices were used to discriminate correlated change. There was little difference in effectiveness between the different matrices, but there were significant differences between the matrices and the physicochemical vectors. It is shown that all methods investigated exhibit significant inability to screen out background correlation, particularly in the presence of phylogenetic relatedness between the sequences. Methods using the matrices are unable to distinguish positively correlated from negatively correlated, or compensatory, replacements.
Liposomes and polymersomes: a comparative review towards cell mimicking (2018)

Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.
The potential role of the EGFR/ERBB2 heterodimer in breast cancer (2007)

Epidermal growth factor receptor (EGFR) and ErbB2 are the best-characterised members of the ErbB family of receptor tyrosine kinases. Both receptors are frequently deregulated in human cancers and both are targets for anticancer drugs. ErbB2 amplification and overexpression are associated with a poor prognosis in breast cancer patients. Over the last decade, evidence has revealed that ErbB2 interacts with EGFR in order to achieve its full oncogenic potential. Therefore, assessment of EGFR and ErbB2 coexpression can potentially predict the outcome of the disease as well as success of therapies better than the assessment of single receptors. Moreover, it is not single-agent therapies, targeting one receptor, but combinations or several receptor-targeted therapies that may be the best way to fight cancer.
Mining the Web's link structure (1999)

The Web is a hypertext body of approximately 300 million pages that continues to grow at roughly a million pages per day. Page variation is more prodigious than the data's raw scale: taken as a whole, the set of Web pages lacks a unifying structure and shows far more authoring style and content variation than that seen in traditional text document collections. This level of complexity makes an "off-the-shelf" database management and information retrieval solution impossible. To date, index based search engines for the Web have been the primary tool by which users search for information. Such engines can build giant indices that let you quickly retrieve the set of all Web pages containing a given word or string. Experienced users can make effective use of such engines for tasks that can be solved by searching for tightly constrained key words and phrases. These search engines are, however, unsuited for a wide range of equally important tasks. In particular, a topic of any breadth will typically contain several thousand or million relevant Web pages. How then, from this sea of pages, should a search engine select the correct ones-those of most value to the user? Clever is a search engine that analyzes hyperlinks to uncover two types of pages: authorities, which provide the best source of information on a given topic; and hubs, which provide collections of links to authorities. We outline the thinking that went into Clever's design, report briefly on a study that compared Clever's performance to that of Yahoo and AltaVista, and examine how our system is being extended and updated.
ハワイ州政府による一ケア・マネジメント・プログラム廃止がもたらした影響(1)ケース・スタディに見るアメリカ合衆国における社会福祉の現状 (2003)

It was observed that sedentary lifestyle, diabetes mellitus, high BMI (≥ 30 kg/m<sup>2</sup>), good socioeconomic status, and hypertension are independent risk factors for the development of CAVD compared to those with a normal aortic valve in the Afghan population.
In Vivo Robustness Analysis of Cell Division Cycle Genes in Saccharomyces cerevisiae (2006)

Intracellular biochemical parameters, such as the expression level of gene products, are considered to be optimized so that a biological system, including the parameters, works effectively. Those parameters should have some permissible range so that the systems have robustness against perturbations, such as noise in gene expression. However, little is known about the permissible range in real cells because there has been no experimental technique to test it. In this study, we developed a genetic screening method, named "genetic tug-of-war" (gTOW) that evaluates upper limit copy numbers of genes in a model eukaryote Saccharomyces cerevisiae, and we applied it for 30 cell-cycle related genes (CDC genes). The experiment provided unique quantitative data that could be used to argue the system-level properties of the cell cycle such as robustness and fragility. The data were used to evaluate the current computational model, and refinements to the model were suggested.
A DNA damage signal is required for p53 to activate gadd45. (2000)

We provide direct evidence that overexpression of p53 is not sufficient for robust p53-dependent activation of the endogenous gadd45 gene. When p53 was induced in TR9-7 cells in the absence of DNA damage, waf1/p21 and mdm2 mRNA levels were increased, but a change in gadd45 mRNA was barely detectable. Activation of the gadd45 gene was observed when camptothecin was added to cells containing p53 in the absence of a further increase in the p53 level. Phosphorylation of p53 at serine 15 and acetylation at lysine 382 were detected after drug treatment. It has been suggested that p53 posttranslational modification is critical during activation. However, inhibition of these modifications by wortmannin was not sufficient to block the transactivation of gadd45. Interestingly, after camptothecin treatment, increased DNase I sensitivity was detected at the gadd45 promoter, suggesting that an undetermined DNA damage signal is involved in inducing chromatin remodeling at the gadd45 promoter while cooperating with p53 to activate gadd45 transcription.
Past, Present and Future of Brain Stimulation (2010)

Recent technological advances including brain imaging (higher resolution in space and time), miniaturization of integrated circuits (nanotechnologies), and acceleration of computation speed (Moore’s Law), combined with interpenetration between neuroscience, mathematics, and physics have led to the development of more biologically plausible computational models and novel therapeutic strategies. Today, mathematical models of irreversible medical conditions such as Parkinson’s disease (PD) are developed and parameterised based on clinical data. How do these evolutions have a bearing on deep brain stimulation (DBS) of patients with PD? We review how the idea of DBS, a standard therapeutic strategy used to attenuate neurological symptoms (motor, psychiatric), has emerged from past experimental and clinical observations, and present how, over the last decade, computational models based on different approaches (phase oscillator models, spiking neuron network models, population-based models) have started to shed light onto DBS mechanisms. Finally, we explore a new mathematical modelling approach based on neural field equations to optimize mechanisms of brain stimulation and achieve finer control of targeted neuronal populations. We conclude that neuroscience and mathematics are crucial partners in exploring brain stimulation and this partnership should also include other domains such as signal processing, control theory and ethics.
Photoprocesses of Thiacarbocyanine Monomers, Dimers, and Aggregates Bound to Polyanions (2002)

The photophysical and photochemical properties of thiacarbocyanine I and the methyl 2 and ethyl 3 meso derivatives in aqueous solution were studied in the presence of poly(styrenesulfonate) (PSS), poly(acrylic acid) (PAA), or poly(methacrylic acid) (PMA). When the ratio of polyanion residue to dye concentrations (r) is increased, a monomer/dimer equilibrium in neat water is shifted toward bound H-aggregates (high dye loading conditions), dimers, and monomers (low dye loading). The photodeactivation properties of 1-3 depend significantly on these ground-state equilibria. The fluorescence quantum yield (Phif) is strongly enhanced for low dye loading and reduced when bound aggregates and dimers are present, r = 3-30 and (0.2-2) x 10(3), respectively. For 1 the quantum yield of trans --&gt; cis photoisomerization. (Phi(t-c)) is also reduced by aggregation. The quantum yield of intersystem crossing (Phi(isc)) is enhanced for bound dimers, the value is largest for 3. In the redox reactions via the triplet state of 3, ascorbic acid and p-benzoquinone serve as electron donor and acceptor, respectively. The photoinduced electron transfer is less efficient for bound monomers than for bound dimers. For the three polyanions comparable effects were found; especially, the ground-state equilibria and the Phi(f), Phi(isc), and Phi(t-c) values depend in a well-defined manner on,the parameter r.
Isolation and sequencing of the replication region of Mycobacterium avium plasmid pLR7 (1995)

The Mycobacterium avium plasmid pLR7 is representative of a group of small plasmids that are common in isolates from AIDS patients with disseminated M. avium infections. Determination of the functions of these and other plasmids has been hampered by the lack of methods for genetic manipulation of M. avium. In this study, the region of pLR7 capable of replication was identified and sequenced. Fragments of pLR7 were cloned into a pUC18 derivative carrying a kanamycin resistance marker and introduced into a plasmid-free M. avium strain by electroporation. The origin of replication was located on a 1.8-kb PvuII-to-SmaI fragment. An open reading frame encoding a putative Rep protein was identified. Two other open reading frames were identified in this region. A shuttle vector, pMB351, was constructed with the pLR7 origin of replication, pUC18, and the kanamycin resistance gene from Tn5. This vector was successfully transformed into M. avium, Mycobacterium tuberculosis, and Mycobacterium bovis.
Semiconductor Nanocrystals Hybridized with Functional Ligands: New Composite Materials with Tunable Properties (2010)

Semiconductor nanocrystals hybridized with functional ligands represent an important new class of composite nanomaterials. The development of these new nanoscale building blocks has intensified over the past few years and offer significant advantages in a wide array of applications. Functional ligands allow for incorporation of nanocrystals into areas where their unique photophysics can be exploited. Energy and charge transfer between the ligands and the nanocrystal also result in enhanced physical properties that can be tuned by the choice of ligand architecture. Here, progress in the development and applications involving this new class of composite materials will be discussed.
New Applications for Phage Integrases (2014)

Within the last 25 years, bacteriophage integrases have rapidly risen to prominence as genetic tools for a wide range of applications from basic cloning to genome engineering. Serine integrases such as that from ϕC31 and its relatives have found an especially wide range of applications within diverse micro-organisms right through to multi-cellular eukaryotes. Here, we review the mechanisms of the two major families of integrases, the tyrosine and serine integrases, and the advantages and disadvantages of each type as they are applied in genome engineering and synthetic biology. In particular, we focus on the new areas of metabolic pathway construction and optimization, biocomputing, heterologous expression and multiplexed assembly techniques. Integrases are versatile and efficient tools that can be used in conjunction with the various extant molecular biology tools to streamline the synthetic biology production line.