gebhart/patrepeval huggingface dataset:
Structural Requirements for the Activation of Rat Anterior Pituitary Adenylate Cyclase by Growth Hormone–Releasing Factor (GRF): Discovery of (<i>N</i>–Ac–Tyr<sup>1</sup>,<scp>d</scp>–Arg<sup>2</sup>)–GRF(l–29)–NH<sub>2</sub>as a GRF Antagonist on Membranes* (1985)

The efficacy and potency of 14 GH-releasing factor (GRF) analogs, substituted in position 1 to 7, on adenylate cyclase activation in crude homogenates from rat anterior pituitary were related to those of human pancreatic GRF(1-29)-amide and vasoactive intestinal peptide. Among several D-amino acid substitutions, that in position 2 was the only one to yield a super-agonist [with a Kact (concentration required for half-maximal adenylate cyclase activation) 2 times lower than that of GRF(1-29)-NH2]. By contrast, D-isomer substitution in position 1 and 3 was without effect and D-isomer substitution in position 4, 6, or 7 decreased the affinity of the analog. The N-acetylated analog of GRF was as potent and active as the parent peptide, and the identity of the amino acid in position 2 of (N-Ac-Tyr1)-GRF(1-29)-NH2 proved to be determining for enzyme activation, with D-Phe2 and D-Trp2 derivatives acting as partial agonists and the (N-Ac-Tyr1,D-Arg2) analog being an efficient competitive antagonist of GRF(1-29)-NH2. With use of this antagonist, it was possible to demonstrate that GRF and vasoactive intestinal peptide receptors represent distinct entities in the rat anterior pituitary.
Use of oligonucleotide probes to study the relatedness of delta-endotoxin genes among Bacillus thuringiensis subspecies and strains (1987)

Fifteen Bacillus thuringiensis strains representing 13 serotypes were screened with five oligodeoxyribonucleotide probes specific for certain regions of two published sequences and one unpublished sequence of B. thuringiensis delta-endotoxin genes. Of the 15 cultures, 14 hybridized with at least one probe; the B. thuringiensis subsp. thompsoni strain alone did not hybridize. Two B. thuringiensis subsp. kurstaki strains of commercial interest, HD-1 and NRD-12, were found to be so closely related as to be indistinguishable with this technique; the same situation was found with strains from B. thuringiensis subspp. dendrolimus and sotto. Five strains were identified as probably containing only one endotoxin gene. A probe specific for the gene from the B. thuringiensis subsp. kurstaki HD-73 strain hybridized to only 3 of the 15 cultures tested. The hybridization data suggest that the DNA sequences coding for the C-terminal region of the endotoxin protein are as well conserved as those coding for the N-terminal toxic portion.
Recovery of Mycobacteria from Patients with Cystic Fibrosis (1999)

Despite decontamination, overgrowth by pseudomonads renders cultural isolation of mycobacteria from respiratory specimens of patients with cystic fibrosis (CF) difficult or impossible. We performed a prospective study by comparing levels of reduction of overgrowth and recovery of mycobacteria using either pretreatment with N-acetyl-L-cysteine (NALC)-NaOH alone or pretreatment with NALC-NaOH and then with oxalic acid. From 406 specimens of 148 CF patients, 11 specimens were positive for mycobacteria, 5 of which grew mycobacteria after decontamination by either procedure. Three specimens grew mycobacteria only after decontamination with NALC-NaOH, whereas three specimens grew mycobacteria only after treatment with NALC-NaOH followed by oxalic acid but were overgrown after decontamination with NALC-NaOH. Thus, inactivation of mycobacteria by the more aggressive oxalic acid treatment offsets its beneficial effect of reducing the proportion of cultures overgrown with microorganisms other than mycobacteria.
The NADH oxidase of <i>Streptococcus pneumoniae</i> : its involvement in competence and virulence (1999)

A soluble flavoprotein that reoxidizes NADH and reduces molecular oxygen to water was purified from the facultative anaerobic human pathogen Streptococcus pneumoniae. The nucleotide sequence of nox, the gene which encodes it, has been determined and was characterized at the functional and physiological level. Several nox mutants were obtained by insertion, nonsense or missense mutation. In extracts from these strains, no NADH oxidase activity could be measured, suggesting that a single enzyme encoded by nox, having a C44 in its active site, was utilizing O2 to oxidize NADH in S. pneumoniae. The growth rate and yield of the NADH oxidase-deficient strains were not changed under aerobic or anaerobic conditions, but the efficiency of development of competence for genetic transformation during growth was markedly altered. Conditions that triggered competence induction did not affect the amount of Nox, as measured using Western blotting, indicating that nox does not belong to the competence-regulated genetic network. The decrease in competence efficiency due to the nox mutations was similar to that due to the absence of oxygen in the nox+ strain, suggesting that input of oxygen into the metabolism via NADH oxidase was important for controlling competence development throughout growth. This was not related to regulation of nox expression by O2. Interestingly, the virulence and persistence in mice of a blood isolate was attenuated by a nox insertion mutation. Global cellular responses of S. pneumoniae, such as competence for genetic exchange or virulence in a mammalian host, could thus be modulated by oxygen via the NADH oxidase activity of the bacteria, although the bacterial energetic metabolism is essentially anaerobic. The enzymatic activity of the NADH oxidase coded by nox was probably involved in transducing the external signal, corresponding to O2 availability, to the cell metabolism and physiology; thus, this enzyme may function as an oxygen sensor. This work establishes, for the first time, the role of O2 in the regulation of pneumococcal transformability and virulence.
The Effect of Engine Misfire on Exhaust Emission Levels in Spark Ignition Engines (1995)

&lt;div class="htmlview paragraph"&gt;One of the gray areas in the implementation of regulations limiting the generation of pollutants from mobile sources is the actual effectiveness of the exhaust gas emissions control strategy in vehicles that have been in use for some time. While it is possible today to conduct limited diagnostics with the on-board engine computer by performing periodic checks to verify the validity of the signals measured by the on-board sensors, and to measure tailpipe emissions during routine inspection and maintenance, the task of correlating these measurements with each other to provide an on-line, accurate diagnosis of critical malfunctions has thus far proven to be a very challenging task, especially in the case of misfire.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;A typical automotive emission control system relies on the measurements provided by various sensors, including for example air charge temperature, intake manifold pressure, exhaust gas oxygen concentration, and engine speed, to adjust the air and fuel mixture as closely as possible to the stoichiometric air-to-fuel ratio (AFR). Maintaining the AFR close to stoichiometry allows the catalytic converter to operate in a high conversion efficiency region, and to significantly reduce the emission of the three major pollutants (for gasoline engines), that is, CO, HC, and NOx. Improper operation of any of the sensors, as well as actual component malfunctions (e.g., a fouled spark plug or fuel injector, or a vacuum or compression leak), may sufficiently upset the delicate balance sought by the electronic controller to cause the mixture to significantly deviate from the desired set point. Such a condition results not only in increased emissions, but possibly in further damage to components (e.g., the catalytic converter), with significant cost to the consumer or to the manufacturer.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;It is clearly important to diagnose malfunctions in the emission control system at the incipient stage. Since in practice the first visible “symptom” of a problem with the emission control system may be the measurement of excessive tailpipe emissions during an inspection and maintenance test, it is very important that the exhaust gas measurements be somehow correlated with the health of the emission control system. This is a particularly challenging problem, because the chemistry of exhaust gas production is very complex, and not easily modeled by conventional dynamic system modeling methods. One approach to understanding the correlation between emission control system malfunctions and measured tailpipe emissions is to generate an extensive data base, and to analyze the data to uncover characteristic patterns that may assist in the diagnosis of specific faults. The ultimate aim of the project is to provide a methodology for the development of diagnostic tools that can integrate the information supplied by conventional tailpipe inspection programs with on-board diagnostics to provide fast and reliable diagnosis of misfire.&lt;/div&gt;
The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling (2005)

Mice deficient for cathepsin L (CTSL) show epidermal hyperplasia due to a hyperproliferation of basal keratinocytes. Here we show that the critical function of CTSL in the skin is keratinocyte specific. This is revealed by transgenic re-expression of CTSL in the keratinocytes of ctsl-/- mice, resulting in a rescue of the ctsl-/- skin phenotype. Cultivation of primary mouse keratinocytes with fibroblast- and keratinocyte-conditioned media, as well as heterologous organotypic co-cultures of mouse fibroblasts and human keratinocytes, showed that the altered keratinocyte proliferation is caused primarily by CTSL-deficiency in keratinocytes. In the absence of EGF, wild type and CTSL-knockout keratinocytes proliferate with the same rates, while in presence of EGF, ctsl-/- keratinocytes showed enhanced proliferation compared with controls. Internalization and degradation of radioactively labeled EGF was identical in both ctsl-/- and ctsl+/+ keratinocytes. However, ctsl-/- keratinocytes recycled more EGF to the cell surface, where it is bound to the EGF-receptor, which is also more abundant in ctsl-/- cells. We conclude that the hyperproliferation of keratinocytes in CTSL-knockout mice is caused by an enhanced recycling of growth factors and growth factor receptors from the endosomes to the keratinocyte plasma membrane, which result in sustained growth stimulation.
FPX is a Novel Chemical Inducer that Promotes Callus Formation and Shoot Regeneration in Plants (2018)

Auxin and cytokinin control callus formation from developed plant organs as well as shoot regeneration from callus. Dedifferentiation and regeneration of plant cells by auxin and cytokinin stimulation are considered to be caused by the reprogramming of callus cells, but this hypothesis is still argued to this day. Although an elucidation of the regulatory mechanisms of callus formation and shoot regeneration has helped advance plant biotechnology research, many plant species are intractable to transformation because of difficulties with callus formation. In this study, we identified fipexide (FPX) as a useful regulatory compound through a chemical biology-based screening. FPX was shown to act as a chemical inducer in callus formation, shoot regeneration and Agrobacterium infection. With regards to morphology, the cellular organization of FPX-induced calli differed from those produced under auxin/cytokinin conditions. Microarray analysis revealed that the expression of approximately 971 genes was up-regulated 2-fold after a 2 d FPX treatment compared with non-treated plants. Among these 971 genes, 598 genes were also induced by auxin/cytokinin, whereas 373 genes were specifically expressed upon FPX treatment only. FPX can promote callus formations in rice, poplar, soybean, tomato and cucumber, and thus can be considered a useful tool for revealing the mechanisms of plant development and for use in plant transformation technologies.
Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1–4 (2018)

Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. To obtain a vaccine effective against all four PIV types, we engineered mutations in each of the four PIV fusion (F) glycoproteins to stabilize their metastable prefusion states, as such stabilization had previously enabled the elicitation of high-titer neutralizing antibodies against the related respiratory syncytial virus. A cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, bound to the prefusion-specific antibody PIA174, revealed atomic-level details for how introduced mutations improved stability as well as how a single PIA174 antibody recognized the trimeric apex of prefusion PIV3 F. Nine combinations of six newly identified disulfides and two cavity-filling mutations stabilized the prefusion PIV3 F immunogens and induced 200- to 500-fold higher neutralizing titers in mice than were elicited by PIV3 F in the postfusion conformation. For PIV1, PIV2, and PIV4, we also obtained stabilized prefusion Fs, for which prefusion versus postfusion titers were 2- to 20-fold higher. Elicited murine responses were PIV type-specific, with little cross-neutralization of other PIVs. In nonhuman primates (NHPs), quadrivalent immunization with prefusion-stabilized Fs from PIV1-4 consistently induced potent neutralizing responses against all four PIVs. For PIV3, the average elicited NHP titer from the quadrivalent immunization was more than fivefold higher than any titer observed in a cohort of over 100 human adults, highlighting the ability of a prefusion-stabilized immunogen to elicit especially potent neutralization.
A finite-state morphological processor for Spanish (1990)

A finite transducer that processes Spanish inflectional amt derivational morphology is presented. The system handles both generation astd analysis of tens of millions inflected ibrms. Lexical and surface (orthographic) representations of the words are linked by a program that interprets a finite directed graph whose arcs are labelled by n-tuples of strings. Each of about 55,000 base forms requires at le~t one arc in the graph. Representing the inflectional and derivational possibilities for these forms imposed an overhead of only about 3000 additional arcs, of which about 2500 represent (phonologicallypredictable) stem allomorphy, so that we pay a storage price of about 5% for compiling these form~ offline. A simple interpreter for the resulting automaton processes several hundred words per second on a Sun4.
Are recommended doses of acetaminophen hepatotoxic for recently abstinent alcoholics? A randomized trial (2008)

Although acetaminophen overdose is a leading cause of fulminant hepatic failure, it is controversial whether therapeutic doses of acetaminophen can cause hepatotoxicity in alcoholics, especially those rendered most vulnerable by recent abstinence. We performed a randomized, triple-blind, parallel-group trial comparing sustained-release acetaminophen, 1300 mg orally q8h for 11 doses, against placebo. We enrolled chronic alcohol abusers (defined as >or= 6 drinks daily for >or= 6 weeks) who had discontinued alcohol consumption 12 to 72 hours prior to enrollment. Individuals with self-reported viral hepatitis, HIV or intravenous drug use, baseline AST or ALT >120 IU/L, or INR >1.5 were excluded. Hepatic function tests were drawn daily for 5 days. The primary outcome was change in serum alpha-GST, a sensitive experimental biomarker of hepatocellular injury; secondary outcomes were changes in serum AST, ALT, INR, and study withdrawal for a doubling of aminotransferases to >120 IU/L. Of 52 subjects randomized, 40 completed at least four days of intervention. Subjects receiving acetaminophen had 32% [95% CI 7%, 50%] and 29% [6%, 46%] lower serum alpha-GST concentrations on days 2 and 3, respectively, compared to placebo, but these differences disappeared by day 4. No subjects were withdrawn for safety reasons. In conclusion, therapeutic doses of sustained-release acetaminophen cause a measurable decrease in serum alpha-GST during the first days of abstinence from chronic alcohol use. While the mechanism is unclear, these observations do provide some reassurance that short courses of acetaminophen are unlikely to cause subclinical hepatocellular injury in recently abstinent alcoholics.
Quantitative T2 Mapping of Matrix-Associated Autologous Chondrocyte Transplantation at 3 Tesla (2007)

T2 mapping allows visualization of cartilage repair tissue maturation. Global T2 repair tissue values approach that of control sites after more than 1.5 years, similar behavior is seen in the zonal organization.
O2 metabolites and neutrophil elastase synergistically cause edematous injury in isolated rat lungs (1986)

Addition of glucose oxidase (GO) increased H2O2 concentrations and decreased antielastolytic activities of beta-D-glucose containing perfusates of isolated rat lungs. Pretreatment with GO also caused acute edematous injury (increased lung weight gains, increased recovery of Ficoll in lung lavages, and increased pulmonary arterial pressures) in isolated lungs perfused with purified human neutrophil elastase (NE). Acute edematous injury in isolated lungs pretreated with GO and then NE exceeded levels found in lungs following addition of GO or NE alone or NE before GO. Simultaneous addition of catalase (an H2O2 scavenger) or methoxy-succinyl-L-alanyl-L-alanyl-prolyl-L-valine-chloromethyl ketone (an NE inhibitor, but not aminotriazole-inactivated catalase, N-tosyl-L-phenyl-alanine chloromethyl ketone (a chymotrypsin inhibitor) or N-alpha-p-tosyl-L-lysine chloromethyl ketone (a trypsin inhibitor), prevented acute edematous injury in isolated lungs perfused with both GO and NE. This observation indicated that injury was dependent on both H2O2 and NE, especially since the relative inactivating specificities of the inhibitors for H2O2 or NE, respectively, were confirmed under similar conditions in vitro. The synergistic nature of the interaction between H2O2 and NE-mediated injury was further clarified when GO- and NE-induced lung injury was prevented by addition of an oxidant-resistant NE inhibitor (Eglin-C), but not an oxidant-sensitive NE inhibitor (human alpha 1-protease inhibitor, alpha 1PI). Moreover, treatment with H2O2 also decreased the ability of alpha 1PI but not Eglin-C to decrease NE activity in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Noggin-Mediated Retinal Induction Reveals a Novel Interplay Between Bone Morphogenetic Protein Inhibition, Transforming Growth Factor β, and Sonic Hedgehog Signaling (2015)

It has long been known that the depletion of bone morphogenetic protein (BMP) is one of the key factors necessary for the development of anterior neuroectodermal structures. However, the precise molecular mechanisms that underlie forebrain regionalization are still not completely understood. Here, we show that Noggin1 is involved in the regionalization of anterior neural structures in a dose-dependent manner. Low doses of Noggin1 expand prosencephalic territories, while higher doses specify diencephalic and retinal regions at the expense of telencephalic areas. A similar dose-dependent mechanism determines the ability of Noggin1 to convert pluripotent cells in prosencephalic or diencephalic/retinal precursors, as shown by transplant experiments and molecular analyses. At a molecular level, the strong inhibition of BMP signaling exerted by high doses of Noggin1 reinforces the Nodal/transforming growth factor (TGF)β signaling pathway, leading to activation of Gli1 and Gli2 and subsequent activation of Sonic Hedgehog (SHH) signaling. We propose a new role for Noggin1 in determining specific anterior neural structures by the modulation of TGFβ and SHH signaling.
Synthesis of FeCo nanocrystals encapsulated in nitrogen-doped graphene layers for use as highly efficient catalysts for reduction reactions (2014)

A facile strategy to fabricate FeCo nanocrystals with nitrogen-doped graphene shells has been designed, which involves one-step thermal decomposition of Prussian blue analogue (PBA) Fe3[Co(CN)6]2 spheres. The as-prepared product can be used as a non-precious-metal catalyst with a highly efficient catalytic activity and a magnetically separable capability in the reduction of 4-nitrophenol.
Breast Cancer Histopathology Image Analysis: A Review (2014)

This paper presents an overview of methods that have been proposed for the analysis of breast cancer histopathology images. This research area has become particularly relevant with the advent of whole slide imaging (WSI) scanners, which can perform cost-effective and high-throughput histopathology slide digitization, and which aim at replacing the optical microscope as the primary tool used by pathologist. Breast cancer is the most prevalent form of cancers among women, and image analysis methods that target this disease have a huge potential to reduce the workload in a typical pathology lab and to improve the quality of the interpretation. This paper is meant as an introduction for nonexperts. It starts with an overview of the tissue preparation, staining and slide digitization processes followed by a discussion of the different image processing techniques and applications, ranging from analysis of tissue staining to computer-aided diagnosis, and prognosis of breast cancer patients.
Substance (2002)

Substance has been a leading idea in the history of Western philosophy. Joshua Hoffman and Gary S. Rosenkrantz explain the nature and existence of individual substances, including both living things and inanimate objects. Specifically written for students new to this important and often complex subject, Substance provides both the historical and contemporary overview of the debate.Great Philosophers of the past, such as Aristotle, Descartes, Spinoza, Leibnitz, Locke, and Berkeley were profoundly interested in the concept of substance. And, the authors argue, a belief in the existence of substances is an integral part of our everyday world view. But what constitutes substance? Was Aristotle right to suggest that artefacts like tables and ships don't really exist?Substance: Its Nature and Existence is one of the first non-technical, accessible guides to this central problem and will be of great use to students of metaphysics and philosophy.