gebhart/patrepeval huggingface dataset:
Triggered aseismic fault slip from nearby earthquakes, static or dynamic effect? (2003)

Observations show that an earthquake can affect aseismic slip behavior of nearby faults and produce “triggered aseismic fault slip.” Two types of stress changes are often examined by researchers as possible triggering sources. One is the static stress change associated with the faulting process and the other is the dynamic stress change or transient deformation generated by the passage of seismic waves. No consensus has been reached, however, regarding the mechanism(s) of triggered aseismic fault slip. We evaluate the possible triggering role of static stress changes by examining observations made after 10 large earthquakes in California. Most of the nearby fault segments that slipped aseismically were encouraged to move by the imposed positive changes in static Coulomb Failure Stress (CFS). Nonetheless, three discrepancies or failures with this model exist, which implies that static stress triggering either is or is not the sole mechanism causing the observed triggered slip. We then use a spring‐slider system as a simplified fault model to study its slip behavior and the impact of transient (dynamic) loading on it. We show that a two‐state‐variable rate‐dependent and state‐dependent frictional law can generate creep events. Transient loads are then put into the system. Certain types of them can cause a large time advance of (or trigger) the next creep event. While our work examines triggered creep events near the surface, it may well have implications for the occurrence of similar events near the bottom of the seismogenic zone where a transition in frictional stability occurs.
Electric Vehicle Machines and Drives: Design, Analysis and Application (2015)

A timely comprehensive reference consolidates the research and development of electric vehicle machines and drives for electric and hybrid propulsions • Focuses on electric vehicle machines and drives • Covers the major technologies in the area including fundamental concepts and applications • Emphasis the design criteria, performance analyses and application examples or potentials of various motor drives and machine systems • Accompanying website includes the simulation models and outcomes as supplementary material
869. Pteridine studies. Part XIV. Methylation of 2-Amino-4-hydroxypteridine and related compounds (1961)

D. J. Brown and N. W. Jacobsen, J. Chem. Soc., 1961, 4413 DOI: 10.1039/JR9610004413
Enantioselective Formal Hydration of α,β-Unsaturated Imides by Al-Catalyzed Conjugate Addition of Oxime Nucleophiles (2004)

The (salen)Al-catalyzed asymmetric conjugate addition of salicylaldoxime to alpha,beta-unsaturated imides is the key step in an efficient and highly enantioselective two-step formal hydration of these electron-deficient olefins. This reaction constitutes the first example of an enantioselective conjugate addition of an oxygen-centered nucleophile to alpha,beta-unsaturated carboxylic acid derivatives. Application of this method to chiral, nonracemic substrates revealed a high level of catalyst-induced diastereoselectivity, underscoring its potential utility for polyketide natural product synthesis.
Irreversible electroporation for the ablation of pancreatic malignancies: A patient‐specific methodology (2017)

The proposed physics-based pre-treatment plan through finite element analysis and system for actively monitoring resistance changes can be paired to significantly reduce ablation times and risk of thermal effects during IRE procedures for LAPC.
Síndrome de Williams-Beuren. Estudio de un caso (2011)

espanolEl sindrome de Williams-Beuren que describiremos cursa con alteraciones del lenguaje y problemas auditivos, motivo por el que consideramos interesante el estudio del mismo basandonos en un caso valorado en la consulta de Foniatria. Se trata de un estudio prospectivo, la nina acudio por vez primera a dicha consulta cuando contaba 18 meses de edad, remitida por el Servicio de Neurologia Infantil de Salamanca para su evaluacion en la esfera del desarrollo del lenguaje, y hemos seguido su evolucion hasta el momento actual. Este Sindorme fue descrito por primera vez en el ano 1961 por un medico neozelandes, el Dr. Williams, quien informo de un cuadro clinico complejo en el que, los sintomas mas destacados consistian en una expresion caracteristica de la cara, existencia de discapacidad psiquica y un defecto cardiologico de nacimiento. Tres anos despues, el profesor Beuren, demostraria que estos cuadros clinicos suelen acompanarse de estenosis pulmonar. Esta afeccion tambien es conocida con el nombre de hipercalcemia idiopatica debido al aumento de las cifras de calcio en sangre, generalmente en los primeros anos de vida. La proporcion del numero de casos descritos se centra alrededor de uno por cada 20.000 nacidos vivos y se debe a una alteracion genetica �de novo� del cromosoma 7. EnglishThe Williams-Beuren syndrome,that we are going to describe, attends with language disorders and hearing problems, reason why we consider interesting study basing on a case rated at Phoniatrics area. This is a prospective study originated since a girl of 18 months arrived to us referred by the Child Neurology Service of Salamanca to her language and development and followed until today. This Syndrome was first described in 1961 by a New Zealand doctor called Dr. Williams, who reported a clinically complex report showing up the most marked symptoms consisted of a characteristic expression of the face, the existence of mental disabilities and a flaw cardiac since birth. Three years later, Professor Beuren, would demostrated that apart from the characteristics mentioned before , sometimes we could find pulmonary stenosis too. This affection is also known as idiopathic hypercalcemia due to increased blood calcium levels usually in the early years of life. The proportion of cases reported is around one by 20,000 births and is caused by a �de novo� genetic alteration in chromosome 7.
The cognitive NET is coming (2013)

The Internet will break down without new biologically inspired routing. The future Internet will need smarter routing algorithms to handle diverse data flows and prevent failures. Although there are no tried-and-true solutions yet, early designs might follow an architecture like this one.
A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary-Artery Stenting (1998)

As compared with aspirin alone and a combination of aspirin and warfarin, treatment with aspirin and ticlopidine resulted in a lower rate of stent thrombosis, although there were more hemorrhagic complications than with aspirin alone. After coronary stenting, aspirin and ticlopidine should be considered for the prevention of the serious complication of stent thrombosis.
The central structural feature of the membrane fusion protein subunit from the Ebola virus glycoprotein is a long triple-stranded coiled coil (1998)

The ectodomain of the Ebola virus Gp2 glycoprotein was solubilized with a trimeric, isoleucine zipper derived from GCN4 (pIIGCN4) in place of the hydrophobic fusion peptide at the N terminus. This chimeric molecule forms a trimeric, highly alpha-helical, and very thermostable molecule, as determined by chemical crosslinking and circular dichroism. Electron microscopy indicates that Gp2 folds into a rod-like structure like influenza HA2 and HIV-1 gp41, providing further evidence that viral fusion proteins from diverse families such as Orthomyxoviridae (Influenza), Retroviridae (HIV-1), and Filoviridae (Ebola) share common structural features, and suggesting a common membrane fusion mechanism.
Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and its possible mechanisms. (2005)

By interacting with mitochondria, preventing the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.
Inhibition of destructive autoimmune arthritis in FcγRIIa transgenic mice by small chemical entities (2008)

The interaction of immune complexes with the human Fc receptor, FcgammaRIIa, initiates the release of inflammatory mediators and is implicated in the pathogenesis of human autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, so this FcR is a potential target for therapy. We have used the three-dimensional structure of an FcgammaRIIa dimer to design small molecule inhibitors, modeled on a distinct groove and pocket created by receptor dimerization, adjacent to the ligand-binding sites. These small chemical entities (SCEs) blocked immune complex-induced platelet activation and aggregation and tumor necrosis factor secretion from macrophages in a human cell line and transgenic mouse macrophages. The SCE appeared specific for FcgammaRIIa, as they inhibited only immune complex-induced responses and had no effect on responses to stimuli unrelated to FcR, for example platelet stimulation with arachidonic acid. In vivo testing of the SCE in FcgammaRIIa transgenic mice showed that they inhibited the development and stopped the progression of collagen-induced arthritis (CIA). The SCEs were more potent than methotrexate and anti-CD3 in sustained suppression of CIA. Thus, in vitro and in vivo activity of these SCE FcgammaRIIa receptor antagonists demonstrated their potential as anti-inflammatory agents for autoimmune diseases involving immune complexes.
Transcriptional Origin of Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs (2006)

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 11 distinct microRNAs, all of which are found clustered within the major latency-associated region of the KSHV genome in the same transcriptional orientation. Because the KSHV microRNAs are all expressed in latently infected cells and are largely unaffected by induction of lytic replication, it appeared probable that they would be processed out of KSHV transcripts that are derived from a latent promoter(s) present in this region. Here, we define three latent transcripts, derived from two distinct KSHV latent promoters, that function as both KSHV primary microRNA precursors and as kaposin pre-mRNAs. These activities require the readthrough of a leaky viral polyadenylation signal located at nucleotide 122070 in the KSHV genome. In contrast, recognition of this polyadenylation signal gives rise to previously identified mRNAs that encode the KSHV open reading frames (ORFs) 71, 72 and 73 proteins as well as a novel unspliced KSHV mRNA that encodes only ORF72 and ORF71. Thus, transcripts initiating at the two latent promoters present in the KSHV latency-associated region can undergo two entirely distinct fates, i.e., processing to give a kaposin mRNA and viral microRNAs on the one hand or expression as KSHV ORF71, ORF72, or ORF73 mRNAs on the other, depending on whether the viral polyadenylation site located at position 122070 is ignored or recognized, respectively.
Two Domains within theMycoplasma hyopneumoniaeCilium Adhesin Bind Heparin (2005)

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia, a chronic and economically significant respiratory disease that affects swine production worldwide. M. hyopneumoniae adheres to and adversely affects the function of ciliated epithelial cells of the respiratory tract, and the cilium adhesin (Mhp183, P97) is intricately but not exclusively involved in this process. Although binding of pathogenic bacteria to glycosaminoglycans is a recognized step in pathogenesis, knowledge of glycosaminoglycan-binding proteins in M. hyopneumoniae is lacking. However, heparin and other sulfated polysaccharides are known to block the binding of M. hyopneumoniae to purified swine respiratory cilia. In this study, four regions within the cilium adhesin were examined for the ability to bind heparin. Cilium adhesin fragments comprising 653 amino acids of the N terminus and 301 amino acids of the C terminus (containing two repeat regions, R1 and R2) were cloned and expressed. These fragments bound heparin in a dose-dependent and saturable manner with physiologically significant binding affinities of 0.27 +/- 0.02 microM and 1.89 +/- 0.33 microM, respectively. Heparin binding of both fragments was strongly inhibited by the sulfated polysaccharides fucoidan and mucin but not by chondroitin sulfate B. When the C-terminal repeat regions R1 and R2 were cloned separately and expressed, heparin-binding activity was lost, suggesting that both regions are required for heparin binding. The ability of the cilium adhesin to bind heparin indicates that this molecule plays a multifunctional role in the adherence of M. hyopneumoniae to host respiratory surfaces and therefore has important implications with respect to the pathogenesis of this organism.
Lack of a Functional Alternative Complement Pathway Ameliorates Ischemic Acute Renal Failure in Mice (2003)

Ischemia/reperfusion (I/R) injury of the kidney is a common cause of acute renal failure (ARF) and is associated with high morbidity and mortality in the intensive care unit. The mechanisms underlying I/R injury are complex. Studies have shown that complement activation contributes to the pathogenesis of I/R injury in the kidney, but the exact mechanisms of complement activation have not been defined. We hypothesized that complement activation in this setting occurs via the alternative pathway and that mice deficient in complement factor B, an essential component of the alternative pathway, would be protected from ischemic ARF. Wild-type mice suffered from a decline in renal function and had significant tubular injury, particularly in the outer medulla, after I/R. We found that factor B-deficient mice (fB(-/-)) developed substantially less functional and morphologic renal injury after I/R. Furthermore, control wild-type mice had an increase in tubulointerstitial complement C3 deposition and neutrophil infiltration in the outer medulla after I/R, whereas fB(-/-) mice demonstrated virtually no C3 deposition or neutrophil infiltration. Our results demonstrate that complement activation in the kidney after I/R occurs exclusively via the alternative pathway, and that selective inhibition of this pathway provides protection to the kidneys from ischemic ARF.
CD44 expression in astrocytic tumors. (1997)

CD44 belongs to a family of adhesion molecules displayed by a wide range of normal and malignant cells. Several studies implicated its presence as a marker for poor prognosis or metastases, especially in breast and colon cancer. CD44 has been proposed as an invasion marker for glioblastoma. We studied 75 astrocytic tumors with different degrees of anaplasia including juvenile pilocytic astrocytoma (JPA), low-grade astrocytoma (LGA), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM) to determine whether standard CD44 (CD44s) can be used as a clinically useful marker distinguishing between low- and high-grade gliomas. Archival paraffin-embedded tissues from 19 JPAs, 20 LGAs, 17 AAs, and 19 GBMs were immunostained with standard CD44 monoclonal antibody and compared with glial fibrillary acidic protein, using the streptavidin-complex peroxidase technique. Immunostaining was rated on a three-tiered scale by two observers. The expression of variant-splice forms of CD44 (CD44v) have been variably reported in brain tumors; a subset of these gliomas were tested with anti-CD44v monoclonal antibodies. In the tumors studied, 89% of JPAs, 90% of LGAs, 76% of AAs, and 84% of GBMs have 2+ or 3+ intensity for CD44s. Low- and high-grade gliomas showed no significant difference in staining (P > .05). Therefore, CD44s does not seem to correlate with the grading range of astrocytomas. The overall intensity of CD44s immunostaining usually, but not always, showed concordance with glial fibrillary acidic protein immunostaining, but the distinctive membrane staining of CD44s surface staining revealed fine cytologic detail in tumor cell processes in diagnostic sections. Some very anaplastic tumors were negative for CD44s, and gliomas were immunonegative for CD44v6. If variant chains (CD44v) are not found in gliomas and if this large series of low- and high-grade gliomas show no difference in CD44 expression, other factors must be explored to understand the differential behavior of low- and high-grade astrocytomas.
Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase (1994)

Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras, src, raf, and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation.
A compact STED microscope providing 3D nanoscale resolution (2009)

The advent of supercontinuum laser sources has enabled the implementation of compact and tunable stimulated emission depletion fluorescence microscopes for imaging far below the diffraction barrier. Here we report on an enhanced version of this approach displaying an all-physics based resolution down to (19 +/- 3) nm in the focal plane. Alternatively, this single objective lens system can be configured for 3D imaging with resolution down to 45 x 45 x 108 nm in a cell. The obtained results can be further improved by mathematical restoration algorithms. The far-field optical nanoscale resolution is attained in a variety of biological samples featuring strong variations in the local density of features.
Expression of genes encoding xylose isomerases from and in the methylotrophic yeast (2005)

The thermotolerant methylotrophic yeast Hansenula polymorpha is able to ferment xylose to ethanol at high temperatures. H. polymorpha xylose reductase and xylitol dehydrogenase are involved during the first steps of this fermentation. In this article, expression of bacterial xylA genes coding for xylose isomerases from Escherichia coli or Streptomyces coelicolor in the yeast H. polymorpha was shown. The expression was achieved by integration of the xylA genes driven by the promoter of the H. polymorpha glyceraldehyde-3-phosphate dehydrogenase gene ( HpGAP) into the H. polymorpha genome. Expression of the bacterial xylose isomerase genes restored the ability of the H. polymorpha Deltaxyl1 mutant to grow in a medium with xylose as the sole carbon source. This mutant has a deletion of the XYL1 gene encoding xylose reductase and is not able to grow in the xylose medium. The H. polymorpha Deltaxyl1(xylA) transformants displayed xylose isomerase activities, which were near 20% of that of the bacterial host strain. The transformants did not differ from the yeast wild-type strain with respect to ethanol production in xylose medium.
Picture of a chelate in exchange: the crystal structure of NaHoDOTMA, a ‘semi’-hydrated chelate (2013)

Crystallography generally only provides static structural information. This can render it an ineffective technique for probing dynamic solution state processes. A crystal of HoDOTMA affords unique structures that effectively represent that of a lanthanide tetra-acetate chelate mid-way through the water exchange process.
Developing cell culture-derived pandemic vaccines. (2010)

The growing prospect of avian influenza viruses achieving sustained interhuman transmission, combined with the recent emergence of a novel swine-origin A/H1N1 influenza strain, has brought the issue of influenza vaccine production capacity into sharp focus. It is becoming increasingly clear that traditional egg-based manufacturing processes may be insufficient to meet global vaccine demands in a pandemic situation that is caused by a highly pathogenic influenza virus. This review introduces the concepts of modern, cell culture-derived influenza vaccines and their manufacture, and explains the advantages of these vaccines in terms of both speed and efficiency of production as well as immunogenic efficacy. Vaccine production technologies using the mammalian cell lines Vero, MDCK and PER.C6, as well as the baculovirus/insect cell platform, are described in detail. Clinical data are provided from cell culture-derived vaccines that are at an advanced stage of development, and insights are provided into recent developments in the preclinical evaluation of more experimental technologies.
Novel antagonists of the thioesterase domain of human fatty acid synthase (2007)

Fatty acid synthase (FAS) is up-regulated in a wide range of cancers and has been recently identified as a potential therapeutic target. Indeed, previous research has shown that inhibition of FAS with active site-modifying agents can block tumor cell proliferation, elicit tumor cell death, and prevent tumor growth in animal models. Here, we use a high-throughput fluorogenic screen and identify a novel pharmacophore, 5-(furan-2-ylmethylene) pyrimidine-2,4,6-trione, which inhibits the thioesterase domain of FAS. The novel antagonists are competitive inhibitors of the thioesterase domain, inhibit de novo fatty acid synthesis, and elicit FAS-dependent tumor cell death. This set of novel FAS antagonists provides an important pharmacologic lead for further development of anticancer therapeutics.
Suppression of Δ 5 -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells (1999)

Our earlier report suggested that androst-5-ene-3β,7β-diol (Δ 5 -androstenediol or Adiol) is a natural hormone with androgenic activity and that two potent antiandrogens, hydroxyflutamide (Eulexin) and bicalutamide (Casodex), fail to block completely the Adiol-induced androgen receptor (AR) transactivation in prostate cancer cells. Here, we report the development of a reporter assay to screen several selective steroids with anti-Adiol activity. Among 22 derivatives/metabolites of dehydroepiandrosterone, we found 4 steroids [no. 4, 1,3,5(10)-estratriene-17α-ethynyl-3,17β-diol; no. 6, 17α-ethynyl-androstene-diol; no. 8, 3β,17β-dihydroxy-androst-5-ene-16-one; and no. 10, 3β-methylcarbonate-androst-5-ene-7,17-dione] that have no androgenic activity and could also block the Adiol-induced AR transactivation in prostate cancer PC-3 cells. Interestingly, these compounds, in combination with hydroxyflutamide, further suppressed the Adiol-induced AR transactivation. Reporter assays further showed that these four anti-Adiol steroids have relatively lower glucocorticoid, progesterone, and estrogenic activity. Together, these data suggest some selective steroids might have anti-Adiol activity, which may have potential clinical application in the battle against the androgen-dependent prostate cancer growth.
Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis (2012)

Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention.