gebhart/patrepeval huggingface dataset:
Secretion of Ipa proteins by Shigella flexneri: inducer molecules and kinetics of activation (1997)

The type III Mxi-Spa secretion machinery of Shigella flexneri is responsible for secretion of Ipa proteins, which are involved in the entry of bacteria into epithelial cells. Ipa proteins accumulate within bacteria growing in laboratory media, and their secretion is activated upon contact of bacteria with eukaryotic cells. In this study, we have identified a group of chemical compounds, including Congo red, Evans blue, and direct orange, which are able to induce secretion of Ipa proteins by bacteria suspended in phosphate-buffered saline. Parameters of kinetics of activation of Ipa secretion by Congo red were determined by measuring by enzyme-linked immunosorbent assay the amount of IpaC secreted and by investigating the increase in susceptibility of Ipa proteins to proteinase K degradation. Ipa secretion occurred at 37 degrees C, was obtained with 5 to 10 microM Congo red, and was complete within 30 min. In addition, activation of Ipa secretion by Congo red was observed with bacteria harvested throughout the exponential phase of growth but not with bacteria in the stationary phase. The interactions of Congo red and Congo red-related compounds with the Mxi-Spa secretion apparatus might be specific hydrophobic interactions similar to those involved in binding of Congo red to amyloid proteins.
An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries (2017)

An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting as an Aurora kinase A inhibitor was discovered with a combination of rational design, parallel synthesis using the procedures developed, in silico and in vitro screenings.
Scuba (2013)

Facebook takes performance monitoring seriously. Performance issues can impact over one billion users so we track thousands of servers, hundreds of PB of daily network traffic, hundreds of daily code changes, and many other metrics. We require latencies of under a minute from events occuring (a client request on a phone, a bug report filed, a code change checked in) to graphs showing those events on developers' monitors. Scuba is the data management system Facebook uses for most real-time analysis. Scuba is a fast, scalable, distributed, in-memory database built at Facebook. It currently ingests millions of rows (events) per second and expires data at the same rate. Scuba stores data completely in memory on hundreds of servers each with 144 GB RAM. To process each query, Scuba aggregates data from all servers. Scuba processes almost a million queries per day. Scuba is used extensively for interactive, ad hoc, analysis queries that run in under a second over live data. In addition, Scuba is the workhorse behind Facebook's code regression analysis, bug report monitoring, ads revenue monitoring, and performance debugging.
Residual stress measurement in steel plates and welds using critically refracted longitudinal (LCR) waves (1996)

Abstract The application of acoustoelasticity using critically refracted longitudinal (LCR) waves is described for measuring residual stress in welded steel plates. Residual stresses are self-equilibrating and may exist in a material that has been deformed in a nonhomogeneous manner. When unknown residual stress is present in a structure, the true stress may become significantly greater than the working stress. In a corrosive environment, highly stressed areas that have not been properly stress relieved are prone to stress corrosion cracking. Areas near welds are particularly susceptible to stress corrosion cracking. Two welded plates were investigated for the present work: one hot-rolled and the other cold-rolled. Residual stresses are usually greatest after welding. Further, longitudinal stress (i.e., stress parallel to the weld bead) is typically greater than the component transverse to the weld bead. Since the acoustoelastic behavior of the LCR wave is largest when propagated parallel to a uniaxial st...
Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle (1988)

We have assessed the effects of glutamine (Gln) availability on protein breakdown in perfused rat hindlimb by measuring net phenylalanine (Phe) production (an index of protein balance), the dilution of [15N]Phe labelling (an index of mixed protein breakdown) and rate of production of 3-methylhistidine (3-MeH) (an index of myofibrillar breakdown). 15 mM Gln significantly inhibited net protein loss and protein breakdown compared to rates obtained in its absence (net protein loss, 200 +/- 230 vs 2080 +/- 200 nmol Phe/hindlimb per h; protein breakdown, 4566 +/- 480 vs 1614 +/- 180 nmol Phe/hindlimb per h; both p less than 0.01). Insulin (100 microU/ml) inhibited protein breakdown but less than Gln. The effects on protein breakdown of Gln and insulin together were not additive, suggesting a common mode of action. Production of 3-MeH (mean 20.3 +/- 2.8 nmol/hindlimb per h) was unaffected by Gln or insulin. Gln appears to inhibit protein breakdown of soluble rather than myofibrillar protein in muscle.
Selected Murine Residues Endow Human TCR with Enhanced Tumor Recognition (2010)

TCR-gene transfer can mediate tumor regression in terminally ill melanoma patients. However, the formation of mix dimers between endogenous and transduced TCR chains may result in the surface dilution of the introduced TCR, which translates in poorer cellular avidity. Recently, we reported that murinization of human TCRs (i.e., the replacement of human C regions by murine ones) can improve TCR function. However, because xenogenic sequences may trigger immunogenicity, we sought to identify the essential murine residues that mediate this enhanced functional effect. We constructed murine/human chimeras of alpha- and beta-chains and assessed for their surface expression and function. We identified an evolutionary-unique lysine residue in Cbeta, central to murine TCR function. The mapping of Calpha revealed that a few short stretches of amino acids play a role in enhancing TCR function, one of the most important ones being the SDVP sequence. This information led us to design improved and minimally murinized human TCR C regions that mediate increased tumor recognition. This also enabled us to suggest a structural model that could explain the role of the aforementioned residues in promoting the preferential pairing and stability of murinized TCRs. Overall, these findings could have implications for the treatment of malignant diseases using TCR-gene transfer.
[Nurse and diabetic: many problems first crop up after returning home]. (1978)

Theodore Roosevelt agreed to a meeting with Major Belcher under the impression that Belcher was a British officer that wished to discuss the "Oriental question" after serving in New Zealand and East Asia. He made it clear to Belcher that their conversation wasn't for publication and Belcher agreed. Many of the statements Belcher attributed to Roosevelt are "absurd falsehoods" and Roosevelt doesn't want anything from Belcher to be published. H. A. Gwynne should have contacted Roosevelt to determine if the interview was genuine.
Vascular inflammation: a role in vascular disease in hypertension? (2003)

Inflammatory mechanisms are important participants in the pathophysiology of hypertension and cardiovascular disease. The identification of useful markers of inflammation, of new therapeutic targets to interfere with these mechanisms, and the evaluation of the efficacy of antiinflammatory treatments will allow progress in our ability to combat cardiovascular disease and the complications of hypertension.
Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials (2003)

Few controlled clinical trials have been published and most are methodologically weak. The clinical efficacy of none of the herbal medicines has so far been demonstrated beyond doubt. This area seems to merit further study through rigorous clinical trials.
Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity (1994)

We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5- to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta. Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 microM), methyl (3c, 0.10 microM), chloro (3d, 0.019 microM), thiomethyl (3f, 0.031 microM), and cyano (3p, 0.090 microM) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 microM), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE.
Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance (1999)

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452-reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin-deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance.
The Second and Fourth Cluster of Class A Cysteine-rich Repeats of the Low Density Lipoprotein Receptor-related Protein Share Ligand-binding Properties (1999)

The low density lipoprotein receptor-related protein (LRP) is a multifunctional endocytic cell-surface receptor that binds and internalizes a diverse array of ligands. The receptor contains four putative ligand-binding domains, generally referred to as clusters I, II, III, and IV. In this study, soluble recombinant receptor fragments, representing each of the four individual clusters, were used to map the binding sites of a set of structurally and functionally distinct ligands. Using surface plasmon resonance, we studied the binding of these fragments to methylamine-activated alpha(2)-macroglobulin, pro-urokinase-type plasminogen activator, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1, t-PA.plasminogen activator inhibitor-1 complexes, lipoprotein lipase, apolipoprotein E, tissue factor pathway inhibitor, lactoferrin, the light chain of blood coagulation factor VIII, and the intracellular chaperone receptor-associated protein (RAP). No binding of the cluster I fragment to any of the tested ligands was observed. The cluster III fragment only bound to the anti-LRP monoclonal antibody alpha(2)MRalpha3 and weakly to RAP. Except for t-PA, we found that each of the ligands tested binds both to cluster II and to cluster IV. The affinity rate constants of ligand binding to clusters II and IV and to LRP were measured, showing that clusters II and IV display only minor differences in ligand-binding kinetics. Furthermore, we demonstrate that the subdomains C3-C7 of cluster II are essential for binding of ligands and that this segment partially overlaps with a RAP-binding site on cluster II. Finally, we show that one RAP molecule can bind to different clusters simultaneously, supporting a model in which RAP binding to LRP induces a conformational change in the receptor that is incompatible with ligand binding.
Isolation and characterization of rat schwannoma neurite-promoting factor: evidence that the factor contains laminin (1985)

Rat RN22 schwannoma cells in vitro release into their growth medium a macromolecular factor that, when bound to polyornithine-coated culture substrata, will stimulate neuritic regeneration from axotomized peripheral and central neurons. During the purification of this factor, the neurite-promoting activity co-purifies with laminin immunoreactivity as measured by an enzyme-linked immunoadsorbent assay. The purified factor has an immunoreactivity per milligram of protein similar to that of purified rat yolk sac tumor laminin. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions, the purified factor exhibits a major band at 200 kilodaltons (kD) and two minor ones at about 130 and 35 kD. The 200-kD band comigrates with the 200-kD band of purified rat laminin. After SDS-PAGE under non-reducing conditions, the rat schwannoma factor and rat laminin both exhibit a band in the 900-kD range with the schwannoma factor band migrating slightly faster than the laminin one. The 200-kD (reducing conditions) and 900-kD (non-reducing conditions) bands of both the schwannoma factor and laminin are stained by immunoblotting with antisera raised against rat and human laminin and against a partially purified preparation of the schwannoma factor. On immunoblots the 400-kD band of laminin (a band not seen in the schwannoma factor preparation) also stains with all three antisera. When the antibodies from each of the three antisera are immobilized on protein A-agarose beads, the beads will completely remove from solution the neurite-promoting activities of both the schwannoma factor and laminin. Antibodies raised against rat laminin fail to block the neurite-promoting activity of the purified schwannoma factor but totally block that of rat laminin. In contrast, antibodies raised against the schwannoma factor will block the neurite-promoting activities of both the schwannoma factor and laminin. By rotary shadowing electron microscopy the schwannoma factor preparation exhibits cross-shaped images similar but not identical to those previously reported for rat and mouse laminin. In addition, the schwannoma factor preparation contains images resembling proteoglycans.
Differential Defense Reactions in Leaf Tissues of Barley in Response to Infection by Rhynchosporium secalis and to Treatment with a Fungal Avirulence Gene Product (2003)

Expression of defense-associated genes was analyzed in leaf tissues of near-isogenic resistant and susceptible barley cultivars upon infection by Rhynchosporium secalis. The genes encoding pathogenesis-related (PR) proteins PR-1, PR-5, and PR-9 are specifically expressed in the mesophyll of resistant plants, whereas a germin-like protein (OxOLP) is synthesized in the epidermis irrespective of the resistance genotype. Restriction-mediated differential display was employed to identify additional epidermis-specific genes. This resulted in the detection of another PR gene, PR-10, along with a lipoxygenase gene, LoxA, and a gene of unknown function, pI2-4, which are specifically induced in the epidermis of resistant plants. The gene encoding a putative protease inhibitor, SD10, is preferentially but not exclusively expressed in the epidermis. The fungal avirulence gene product NIP1 triggers the induction of the four PR genes only. At least two additional elicitors, therefore, must be postulated, one for the unspecific induction of OxOLP and one for the resistance-specific induction of LoxA, pI2-4, and SD10. PR-10 expression can be assumed to be the consequence of NIP1 perception by epidermis cells. In contrast, gene expression in the mesophyll is likely to be triggered by an as yet unknown signal that appears to originate in the epidermis and that is strongly amplified in the mesophyll.
Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. (2009)

No association was found between the expressions of Bcl-2, PCNA, Ki-67, MCM-2 and histological type of tumor, distant metastasis, gender or age of patients. However, we observed a correlation of PCNA, Ki-67 and MCM-2 expressions, but not of Bcl-2, in the main mass of tumor in patients with lymph node metastases. Moreover, a very strong relationship was noted between the expression of Bcl-2 and PCNA, Ki-67 and MCM-2 in the main mass of tumor. Conlusion: These investigations seem to suggest that the expression of proliferative proteins (PCNA, Ki-67, MCM-2) in pT3, G2 of colorectal cancer may indicate the development of lymph node metastases and that inhibited apoptosis by Bcl-2 protein can enhance the action of these proteins in tumor progression.
The Use of Image Blur as a Depth Cue (1997)

Images of three-dimensional scenes inevitably contain regions that are spatially blurred by differing amounts, owing to depth-of-focus limitations in the imaging apparatus. Recent perceptual data indicate that this blur variation acts as an effective cue to depth: if one image region contains sharply focused texture, and another contains blurred texture, then the two regions may be perceived at different depths, even in the absence of other depth cues. Calculations based on the optical properties of the human eye have shown that variation in blur as a function of depth follows the same course as variation in binocular disparity with depth. Computational modelling has shown that the effect of blur on single-step edges is very similar to its effect on random fractal patterns, because the two stimuli have similar Fourier amplitude spectra. Blur discrimination thresholds for the two stimuli were also very similar, and could be predicted by a model based on high-spatial-frequency discrimination. A comparison of blur discrimination thresholds with the range of binocular stereopsis indicates that blur and disparity cues cover different distance ranges: stereopsis is most effective for distances relatively close to fixation, while blur information should be more effective for larger distances.
Nervous control of the urogenital system (1993)

For many years the idea of antagonistic parasympathetic, cholinergic and sympathetic adrenergic control of most organs in visceral and cardiovascular systems formed the working basis for most studies. However, major advances since the 1960s have made it necessary to revise the thinking about mechanisms of autonomic transmission. These advances have significant implications for our understanding of diseases involving the autonomic nervous system and their treatment. In broad terms, these concepts shift the earlier emphasis on central control mechanisms towards greater consideration of the sophisticated local peripheral control mechanisms. Volume one of this series deals with the basic mechanisms of neuroeffector transmission which sets the stage for later volumes devoted to the autonomic nervous control of particular organ systems. Other volumes deal with the central nervous control of autonomic function, interaction of autonomic mechanisms with the endocrine system, development, regeneration and plasticity of the autonomic nervous system and comparative physiology and evolution. This second volume in the series deals with nervous control of the urogenital system. Coverage includes the neural control of renal function, neural regulation of ureteric mobility, synaptic transmission of pelvic ganglia, neural control of penile erection and pain arising from the urogenital tract.
Identification of the First Retinoid X Receptor Homodimer Antagonist (1996)

ADVERTISEMENT RETURN TO ISSUELetterNEXTIdentification of the First Retinoid X Receptor Homodimer AntagonistStacie S. Canan Koch, Laura J. Dardashti, Jonathan J. Hebert, Steven K. White, Glenn E. Croston, Karen S. Flatten, Richard A. Heyman, and Alex M. NadzanView Author Information Departments of Retinoid Chemistry Research, New Leads Discovery, Endocrine Research, and Retinoid Research, Ligand Pharmaceuticals, Inc., 10255 Science Center Drive, San Diego, California 92121 Cite this: J. Med. Chem. 1996, 39, 17, 3229–3234Publication Date (Web):August 16, 1996Publication History Received26 April 1996Published online16 August 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm960311dhttps://doi.org/10.1021/jm960311drapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1014Altmetric-Citations55LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Agonists,Antagonists,Hydrocarbons,Ligands,Receptors Get e-Alerts
XCERT Software, Inc. (1998)

Xcert's business is in developing Internet and Intranet security enhancement technology. Xcert was founded in April 1996 by Andrew Csinger and Pat Richard and was headquartered in Vancouver, Canada. Xcert's solution to Internet security was a public key infrastructure (PKI). PKI is a system of digital certificates, certificate authorities (CAs) and other registration authorities that verify and authenticate the validity of each party involved in an Internet transaction. Xcert's PKI technology allows organizations of any size to issue digital certificates to their members. These organizations become their own CA and are empowered to issue digital certificates to their individual client base. This case study is about a start-up company that is in transition from a dream stage to a reality stage. One of the issues that surfaces in the case study is intraindustry competition. Despite being an early entrant into the Internet security business, Xcert faced brutal competition from companies such as Entrust, Nortel, VeriSign and Netscape. The problems facing the company include (1) finances, (2) future direction and leadership, (3) structure, experience and size and (4) marketing. This is a very rich case study with a number of interrelated issues. The case serves two teaching aims. Firstly, this case allows students to confront and discuss real-life issues facing a start-up information technology (IT) company. The students analysing the case are asked to provide alternatives and solutions to the problems by putting themselves in the positions of the founders of the company. Students should come to understand the difficulty in managing a start-up company and the various trade-offs the management needs to make. Secondly, the case study introduces various Internet security concepts to students.