gebhart/patrepeval huggingface dataset:
Fibrin-associated plasminogen activation in alpha 2-plasmin inhibitor deficiency (1983)

The clot formed from the plasma of a patient with congenital deficiency of alpha 2-plasmin inhibitor underwent a spontaneous extensive fibrinolysis. Radiolabeled fibrinogen was added to the plasma before clotting, and the whole process of the fibrinolysis was followed by measuring the release of radiolabels. Plasminogen activation was also followed by measuring the amidolytic activity that developed. There was an initial latent period, followed by an exponential increase of fibrinolytic activity. During the latent period, there was little or no release of radiolabels and no development of amidolytic activity. During the latent period, the clot was washed thoroughly to remove unbound proteins from fibrin and was incubated in buffered saline. The washed clot still underwent fibrinolysis, similar to the original plasma clot, suggesting that the plasminogen/plasminogen activators bound to fibrin during the initial latent period are responsible for fibrinolysis. The amount of plasminogen bound to fibrin during the latent period was close to the amount of plasminogen activated during the whole process of fibrinolysis. When the amount of plasminogen bound to fibrin was decreased by epsilon aminocaproic acid, the extent of fibrinolysis was decreased in parallel with the decrease of the amount of the bound plasminogen. This suggests that the amount of plasminogen bound to fibrin is one of the determinants of the rate of the fibrinolytic process.
Identification and selection of cardiomyocytes during human embryonic stem cell differentiation (2007)

Human embryonic stem cells (hESC) are pluripotent lines that can differentiate in vitro into cell derivatives of all three germ layers, including cardiomyocytes. Successful application of these unique cells in the areas of cardiovascular research and regenerative medicine has been hampered by difficulties in identifying and selecting specific cardiac progenitor cells from the mixed population of differentiating cells. We report the generation of stable transgenic hESC lines, using lentiviral vectors, and single-cell clones that express a reporter gene (eGFP) under the transcriptional control of a cardiac-specific promoter (the human myosin light chain-2V promoter). Our results demonstrate the appearance of eGFP-expressing cells during the differentiation of the hESC as embryoid bodies (EBs) that can be identified and sorted using FACS (purity>95%, viability>85%). The eGFP-expressing cells were stained positively for cardiac-specific proteins (>93%), expressed cardiac-specific genes, displayed cardiac-specific action-potentials, and could form stable myocardial cell grafts following in vivo cell transplantation. The generation of these transgenic hESC lines may be used to identify and study early cardiac precursors for developmental studies, to robustly quantify the extent of cardiomyocyte differentiation, to label the cells for in vivo grafting, and to allow derivation of purified cell populations of cardiomyocytes for future myocardial cell therapy strategies.
High Resistance of Escherichia coli Ribonuclease HI Variant with Quintuple Thermostabilizing Mutations to Thermal Denaturation, Acid Denaturation, and Proteolytic Degradation (1995)

To test whether the combination of multiple thermostabilizing mutations is a useful strategy to generate a hyperstable mutant protein, five mutations, Gly23-->Ala, His62-->Pro, Val74-->Leu, Lys95-->Gly, and Asp134-->His or Asn, were simultaneously introduced into Escherichia coli ribonuclease HI. The enzymatic activities of the resultant quintuple mutant proteins, 5H- and 5N-RNases HI, which have His and Asn at position 134, respectively, were 35 and 55% of that of the wild-type protein. The far-UV and near-UV CD spectra of these mutant proteins were similar to those of the wild-type protein, suggesting that the mutations did not seriously affect the tertiary structure of the protein. The differences in the free energy change of unfolding between the wild-type and mutant proteins, delta delta G, were estimated by analyzing the thermal denaturation of the proteins by CD. The 5H-RNase HI protein, which was slightly more stable than the 5N-RNase HI, was more stable than the wild-type protein by 20.2 degrees C in Tm and 5.6 kcal/mol in delta G at pH 5.5. In addition, the 5H-RNase HI was highly resistant to proteolysis and acid denaturation. The effects of each mutation on the thermal stability and the susceptibility to chymotryptic digestion were nearly cumulative, and the 5H-RNase HI undergoes chymotryptic digestion at a rate that is 41 times slower than that of the wild-type protein. Good correlation was observed between the thermal stability and the resistance to chymotryptic digestion for all proteins examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Self-starting of passively mode-locked lasers (1991)

The self-starting condition of passively mode-locked lasers, including those locked by additive-pulse mode locking, is reexamined. A quantitative model is developed for a threshold intensity for self-starting based on the hypothesis that spurious reflections have to be overcome by coherent injection signals of sufficient amplitude.
Interferon γ, interleukin 4 and transforming growth factor β in experimental autoimmune encephalomyelitis in lewis rats: Dynamics of cellular mrna expression in the central nervous system and lymphoid cells (1995)

The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.
Sphere and distance models for binary disordered systems (1990)

Abstract First-neighbour geometrical models are presented and shown to provide a good approximation for the structural description of binary disordered systems with metallic, covalent or ionic bonding. Sphere mixture models taking into account atomic size and chemical order effects are first studied and analytical expressions for the partial coordination numbers are derived which only involve packing fraction, diameter ratio, concentration and chemical order parameter. Relations between the concentration thresholds separating different chemical order regimes and site percolation theory are established. Close-packed sphere mixtures are finally shown to be a good representation of liquid or glassy alloys. Hole sphere models are then introduced and shown to provide a satisfactory approximation to the structure of loose-packed covalent glasses of silicon and germanium. Finally, first-neighbour distance models are presented and the variations of their partial structure factors with non-additivity parameter are studied. These models provide a satisfactory approximation to the structure of ionic molten salts.
Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment (2013)

Acromegaly is a rare disease most often caused by the prolonged secretion of excess growth hormone from a pituitary adenoma. The disease is associated with multiple significant comorbidities and increased mortality. The delay to diagnosis is often long. This may be because of low disease awareness among health care professionals, the insidious onset of differentiating features, and because patients are likely to present with complaints typical of other conditions more frequently seen in primary care. Early identification of acromegaly facilitates prompt treatment initiation and may minimize the permanent effects of excess growth hormone. The primary treatment for many patients will be pituitary surgery, although not all patients will be eligible for surgery or achieve a surgical cure. If biochemical control is not achieved following surgery, other treatment options include medical therapy and radiation therapy. Improved biochemical control may only alleviate rather than reverse the associated comorbidities. Thus, lifelong monitoring of patient health is needed, with particular attention to the management of cardiovascular risk factors. It is additionally important to consider the impact of both disease and treatment on patients' quality of life and minimize that impact where possible, but particularly for chronic therapies. For the majority of patients, chronic therapy is likely to include somatostatin analog injections. In some circumstances, it may be possible to extend the dosing interval of the analog once good biochemical control is achieved. Additional convenience may be gained from the possibility of self-/partner administration of treatment or administration of treatment by a health care professional at home. Overall, it is clear that the care of patients with acromegaly requires a highly coordinated approach involving numerous specialties (eg, endocrinology, surgery, cardiology). Further, patients' needs must be at the core of management and every effort must be made to improve health care experiences and minimize treatment burdens.
The Relationship between Team Risk Factors and IT Governance under ERP Environment (2011)

The implementation team problem is one of the critical elements lead to ERP project failure. The purpose of thisresearch is to explore the relationship between team risk factors and IT governance. The IT governance includesfive important domains, that is, IT strategic alignment, IT value delivery, IT resource management, IT riskmanagement, and IT performance management. Our research results indicate that, among five domains of ITgovernance, strategic alignment is the most important area. As for the team risk factors, two main team riskfactors are “Lack of cross-functional team members” and “IT members’ lack of specialized knowledge requiredby the ERP project”. Companies that encountered these team risk factors during ERP project implementationhave lower IT governance achievement level than those that did not. It is suggested that Corporations shouldtrain their IT members in specialized ERP knowledge and set up a cross-functional team for ERP implementationin order to achieve effective IT governance.
Women's studies, gender studies. Le contexte américain (2002)

Résumé Aux États-Unis, l’histoire des femmes et du genre a suivi un itinéraire parallèle à celui du champ pluridisciplinaire dont elle fait partie intégrante, les women’s and gender studies . Bien que ce type de recherche n’ait pas toujours été accueilli à bras ouverts, son implantation au sein du paysage universitaire américain a commencé dès les années 1970, si bien que l’on peut aujourd’hui parler d’un véritable univers professionnel ayant ses programmes d’études, ses publications, ses associations. Le développement inégal de ce domaine en France et aux États-Unis provient des différences à la fois structurelles, idéologiques, et culturelles des deux pays. Les particularités de son système éducatif, le rôle prépondérant du privé, la prééminence d’un féminisme libéral pour n’en citer que quelques-unes, ont rendu l’université américaine moins résistante que son homologue française à l’intégration, même imparfaite, de ces nouvelles approches et méthodes.
Computational design of small transcription activating RNAs for versatile and dynamic gene regulation (2017)

A longstanding goal of synthetic biology has been the programmable control of cellular functions. Central to this is the creation of versatile regulatory toolsets that allow for programmable control of gene expression. Of the many regulatory molecules available, RNA regulators offer the intriguing possibility of de novo design-allowing for the bottom-up molecular-level design of genetic control systems. Here we present a computational design approach for the creation of a bacterial regulator called Small Transcription Activating RNAs (STARs) and create a library of high-performing and orthogonal STARs that achieve up to ~ 9000-fold gene activation. We demonstrate the versatility of these STARs-from acting synergistically with existing constitutive and inducible regulators, to reprogramming cellular phenotypes and controlling multigene metabolic pathway expression. Finally, we combine these new STARs with themselves and CRISPRi transcriptional repressors to deliver new types of RNA-based genetic circuitry that allow for sophisticated and temporal control of gene expression.
Epidermal growth factor receptor synthesis is stimulated by phorbol ester and epidermal growth factor. Evidence for a common mechanism. (1987)

Previously, we and others have shown that epidermal growth factor (EGF) stimulates the synthesis of its own receptor and the accumulation of EGF receptor mRNA. Here, we demonstrate that the tumor promotor, 12-O-tetradecanoylphorbol-13-acetate (TPA), like EGF, also stimulates receptor synthesis in the human breast carcinoma cell line, MDA468 cells. The receptor synthesis rate increased 5-fold with a peak at 8 h after exposure to TPA with half-maximal stimulation at a dose of 5 ng/ml TPA. This stimulation of receptor synthesis occurred despite a 30% decrease in general cellular protein synthesis. The increased receptor synthesis rate resulted in the accumulation of 60% more receptor protein as determined by quantitative immunoblotting using a newly developed monoclonal antibody, H9B4. Although TPA treatment resulted in an immediate loss of high affinity EGF-binding sites, the long-term effect was an increase in both the low and high affinity binding sites. The effects of EGF and TPA on receptor synthesis were not additive. Furthermore, down-regulation of protein kinase C (the Ca2+/phospholipid-dependent enzyme) by long-term TPA treatment resulted in cells unable to respond to the stimulatory effects of both TPA and EGF on receptor synthesis. Nevertheless, the TPA-pretreated cells were still growth-inhibited by EGF. These results suggest that the stimulatory effect of EGF on receptor synthesis requires protein kinase C, whereas the inhibitory effect of EGF on the proliferation of these cells does not. Although we confirmed that EGF stimulated the incorporation of phosphate into phosphatidylinositol in A431 cells, it failed to do so in the MDA468 cells. Thus, in MDA468 cells, EGF may require protein kinase C for part of its action, but we could not demonstrate an associated activation of phosphatidylinositol turnover by EGF. The exact mechanism of involvement of protein kinase C in EGF action is still not clear.
RECODING: Dynamic Reprogramming of Translation (1996)

A minority of genes in probably all organisms rely on "recoding" for translation of their mRNAs. In these cases, the rules for decoding are temporarily altered through the action of specific signals built into the mRNA sequences. Three classes are described. 1. Frameshifting at a particular site allows expression of a protein from an mRNA with overlapping open reading frames, often giving two protein products from one mRNA. 2. The meanings of code words are altered: specific stop codons can be redirected to encode selenocysteine, tryptophan, or glutamine. 3. Ribosomes can translate over coding gaps in mRNA. These novel mechanisms expand the repertoire of the genetic code and are at the heart of several regulatory schemes.
Adjuvants for Enhancing the Immunogenicity of Whole Tumor Cell Vaccines (2011)

Whole tumor cell lysates can serve as excellent multivalent vaccines for priming tumor-specific CD8(+) and CD4(+) T cells. Whole cell vaccines can be prepared with hypochlorous acid oxidation, UVB-irradiation and repeat cycles of freeze and thaw. One major obstacle to successful immunotherapy is breaking self-tolerance to tumor antigens. Clinically approved adjuvants, including Montanide™ ISA-51 and 720, and keyhole-limpet proteins can be used to enhance tumor cell immunogenicity by stimulating both humoral and cellular anti-tumor responses. Other potential adjuvants, such as Toll-like receptor agonists (e.g., CpG, MPLA and PolyI:C), and cytokines (e.g., granulocyte-macrophage colony stimulating factor), have also been investigated.
CXCR4 Function Requires Membrane Cholesterol: Implications for HIV Infection (2002)

HIV requires cholesterol and lipid rafts on target cell membranes for infection. To elucidate a possible mechanism, we determined that cholesterol extraction by hydroxypropyl-beta-cyclodextrin (BCD) inhibits stromal cell-derived factor 1alpha (SDF-1alpha) binding to CXCR4 on T cell lines and PBMCs. Intracellular calcium responses to SDF-1alpha, as well as receptor internalization, were impaired in treated T cells. Loss in ligand binding is likely due to conformational changes in CXCR4 and not increased sensitivity to internalization. SDF-1alpha binding and calcium responses were effectively restored by reloading cholesterol. Immunofluorescence microscopy revealed that SDF-1alpha binding occurred in lipid raft microdomains that contained GM1. CXCR4 surface expression, on the other hand, only partially colocalized with GM1. HIV-1(IIIB) infection assays confirmed the functional loss of CXCR4 in the cell lines tested, Sup-T1 and CEM-NKR-CCR5. These data suggest that cholesterol is essential for CXCR4 conformation and function and that lipid rafts may play a regulatory role in SDF-1alpha signaling.
Enhancing the Critical Heat Flux Using Microchanneled Surfaces (1998)

Flow boiling critical heat flux was studied experimentally for liquid flowing over a heated surface with longitudinal microchannels machined into the surface. The experiments investigated the effect of the microchannel structure on the critical heat flux and the transition boiling heat transfer. A physical model of the enhancement mechanism for the microchanneled surface was proposed to theoretically describe the enhanced effects. The numerical predictions show quite similar enhancement behavior with the experimental measurements. These confirm that the microchannel structure can obviously increase the critical heat flux of a heated plate and augment the transition boiling heat transfer for the cases of low flow velocity.
Marked Inflammatory Sequelae to Implantation of Biodegradable and Nonbiodegradable Polymers in Porcine Coronary Arteries (1996)

An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.
Heterodimeric Bispecific Single-Chain Variable-Fragment Antibodies Against EpCAM and CD16 Induce Effective Antibody-Dependent Cellular Cytotoxicity Against Human Carcinoma Cells (2013)

A heterodimeric bispecific biological recombinant drug was synthesized by splicing DNA fragments from two fully humanized single-chain variable-fragment (scFV) antibody fragments forming a novel drug simultaneously recognizing the CD16 natural killer (NK) cell marker and the cancer marker epithelial cell adhesion molecule (EpCAM). The drug precipitously enhanced the killing of human carcinomas of the prostate, breast, colon, head, and neck even at very low effector:target ratios. The drug EpCAM16 rendered even nonactivated NK cell-proficient killers and activated them to kill via degranulation and cytokine production. Studies show that bispecific antibodies can be used to induce proficient killing of the carcinoma targets that ordinarily are resistant to NK-mediated killing. Apparently, the innate immune system can be effectively recruited to kill cancer cells using the bispecific antibody platform and EpCAM targeting.
Solid freeform fabrication of ceramics (1998)

In the past five years solid freeform fabrication of ceramics has generated a great deal of interest as it offers fully automated, rapid, mouldless desktop forming of small ceramic parts. In solid freeform fabrication, 3D computer images of parts generated with CAD software is sliced to produce 2D images and then used to control a fabrication unit which manufactures it layer by layer. In this paper the focus of attention will be continuous ink-jet printing which is a novel solid freeform fabrication method where a ceramic suspension is pressurized and delivered through a fine nozzle and deposited on a substrate according to a pattern generated by a computer. Research into this technique carried out recently is discussed in detail. The development of ceramic suspensions for this process, i.e. materials and properties required, will be analysed. The process, i.e. the use of these suspensions to print monolayers and multilayers of ceramic will be illustrated with several examples. The future potential of the process to micro-engineer components while tailoring the microstructure will be elucidated.
Synthesis of novel pyrimidines thiazolopyrimidines, triazolopyrimidines and pyrimidotriazines as potent antimicrobial agent (2014)

A new seriesof 4-aryl-5-cyano thiouracilderivatives 4(a-c)was synthesized by reacting ethyl cyanoacetate, thiourea or substituted thiourea and aromatic aldehyde in presence of anhydrous potassium carbonate. The main target compound 4-(p-chlorophyll) -2- mercapto -6 -oxo-1,6- dihydropyrimidine-5- carbonitriles ( 4a) were reacted with chloroacetyl chloride , chloroacetonitrile or oxalyl chloride to give 2,5-dioxothiazolopyrimidines, 3-amino-5- oxothiazolopyrimidines and 2,3,5-trioxothiazolopyrimidines 5,6,7 respectively . Derivatives of 2-substituted benzylidne 3, 5-dioxothiazolopyrimidines 8a, b were prepared via reacting 4a with chloroacetic acid, aromatic aldehyde and anhydrous sodium acetate in presence of a mixture of acetic acid and acetic anhydride. Reacting compound 9 which was obtained by refluxing compound 4a with hydrazine hydrate , with formic acid or acetic anhydride give the respective triazolopyrimidines 10,11 .On the other handthe pyrimidotriazines 12,13 were obtained by the action of compound 9 with diethyl oxalate and ethyl bromoacetate in sodium ethoxide respectively. Reacting compound 9 with different aromatic aldehyde in glacial acetic acid gave a series of azomethene compounds 14(a-d). All the newly formed compounds are evaluated for their antimicrobial activity .It was found that some of the tested compoundshas variable activity against the selected strain.