gebhart/patrepeval huggingface dataset:
The CsrR/CsrS two-component system of group A Streptococcus responds to environmental Mg 2+ (2003)

Group A streptococci control expression of key virulence determinants via the two-component sensorregulator system CsrRCsrS. The membrane-bound sensor CsrS is thought to respond to previously unknown environmental signal(s) by controlling phosphorylation of its cognate regulator component CsrR. Phosphorylation of CsrR increases its affinity for binding to the promoter regions of Csr-regulated genes to repress transcription. Here we show that environmental Mg(2+) concentration is a potent and specific stimulus for CsrRCsrS-mediated regulation. We studied the effect of divalent cations on expression of the Csr-regulated hyaluronic acid capsule genes (hasABC) by measuring chloramphenicol acetyltransferase (CAT) activity in a reporter strain of group A Streptococcus carrying a has operon promoter-cat fusion. Addition of Mg(2+), but not of Ca(2+), Mn(2+), or Zn(2+), repressed capsule gene expression by up to 80% in a dose-dependent fashion. The decrease in capsule gene transcription was associated with a marked reduction in cell-associated capsular polysaccharide. RNA hybridization analysis demonstrated reduced expression of the Csr-regulated hasABC operon, streptokinase (ska), and streptolysin S (sagA) during growth in the presence of 15 mM Mg(2+) for the wild-type strain 003CAT but not for an isogenic csrS mutant. We propose that Mg(2+) binds to CsrS to induce phosphorylation of CsrR and subsequent repression of virulence gene expression. The low concentration of Mg(2+) in extracellular body fluids predicts that the CsrRCsrS system is maintained in the inactive state during infection, thereby allowing maximal expression of critical virulence determinants in the human host.
The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival (2018)

Metastatic castration resistant prostate cancer is one of the main causes of male cancer associated deaths worldwide. Development of resistance is inevitable in patients treated with anti-androgen therapies. This highlights a need for novel therapeutic strategies that would be aimed upstream of the androgen receptor (AR). Here we report that the novel small molecule anti-androgen, galeterone targets USP12 and USP46, two highly homologous deubiquitinating enzymes that control the AR-AKT-MDM2-P53 signalling pathway. Consequently, galeterone is effective in multiple models of prostate cancer including both castrate resistant and AR-negative prostate cancer. However, we have observed that USP12 and USP46 selectively regulate full length AR protein but not the AR variants. This is the first report of deubiquitinating enzyme targeting as a strategy in prostate cancer treatment which we show to be effective in multiple, currently incurable models of this disease.
Biochemical markers of basement membrane disturbances and occupational exposure to hydrocarbons and mixed solvents (1995)

To investigate possible mechanisms of hydrocarbon or solvent-induced renal damage, we studied three groups of healthy men employed in a UK manufacturing plant. Group 1 (n = 111) were occupationally exposed to hydrocarbon-based paints, Group 2 (n = 100) were occupationally exposed to petroleum-based mineral oils, and Group 3 (n = 92) had low background occupational exposure to hydrocarbons. Occupational atmospheric exposure levels for toluene, xylene, butanol and oil mist around the time of this study were within UK permissible limits. Group 4 (controls) were males with no known occupational hydrocarbon or solvent exposure (n = 108). Circulating laminin antibodies and the auto-antibody implicated in Goodpasture's syndrome (anti-GBM) were measured, as were serum laminin, a basement membrane turnover marker, and soluble E-selectin, an endothelial activation marker. Group 1 had a significantly greater proportion of subjects with high levels of both anti-laminin antibodies and soluble E-selectin; Group 2 had significantly more subjects with raised anti-GBM antibodies, laminin and soluble E-selectin. Mean levels of soluble E-selectin were increased in Groups 1 and 2. In a small but significant proportion of these workers exposed to hydrocarbons/mixed solvents there are alterations both to basement membranes, resulting in auto-antibody production, and to overlying vascular endothelial cells.
Regional Variation in Percutaneous Penetration in Man (1971)

Pesticides labeled with radioactive carbon (14C) (parathion, malathion, and carbaryl) were applied on the skin of volunteers. The experimental variable studied was the effect of anatomic site; all other factors (dose, solvent, and analytic method) remained constant. Quantitation was based on urinary recovery of the 14C. The forearm was used as the frame reference. The palm, of which the thick stratum corneum is allegedly almost impenetrable, allowed approximately the same penetration as the forearm. The abdomen and dorsum of the hand had twice the penetration of the forearm, whereas folliclerich sites, including the scalp, angle of the jaw, postauricular area, and forehead, had fourfold greater penetration. The intertriginous axilla had a fourfold to sevenfold increase; the scrotum allowed almost total absorption.
Prostaglandin E receptors and the kidney (2000)

Prostaglandin E(2) is a major renal cyclooxygenase metabolite of arachidonate and interacts with four G protein-coupled E-prostanoid receptors designated EP(1), EP(2), EP(3), and EP(4). Through these receptors, PGE(2) modulates renal hemodynamics and salt and water excretion. The intrarenal distribution and function of EP receptors have been partially characterized, and each receptor has a distinct role. EP(1) expression predominates in the collecting duct where it inhibits Na(+) absorption, contributing to natriuresis. The EP(2) receptor regulates vascular reactivity, and EP(2) receptor-knockout mice have salt-sensitive hypertension. The EP(3) receptor is also expressed in vessels as well as in the thick ascending limb and collecting duct, where it antagonizes vasopressin-stimulated salt and water transport. EP(4) mRNA is expressed in the glomerulus and collecting duct and may regulate glomerular tone and renal renin release. The capacity of PGE(2) to bidirectionally modulate vascular tone and epithelial transport via constrictor EP(1) and EP(3) receptors vs. dilator EP(2) and EP(4) receptors allows PGE(2) to serve as a buffer, preventing excessive responses to physiological perturbations.
Gene expression and protein purification (2000)

The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today--truly an essential publication for researchers in all fields of life sciences.
Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes (2014)

Our results underscore the need to sample multiple regions in GBM and other glial tumors when devising personalized treatments based on genomic information, and furthermore demonstrate the importance of measuring both point mutation and copy number alteration while investigating genetic heterogeneity within cancer samples.
Gain of Function Mutagenesis of the Erythromycin Polyketide Synthase. 2. Engineered Biosynthesis of an Eight-Membered Ring Tetraketide Lactone (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTGain of Function Mutagenesis of the Erythromycin Polyketide Synthase. 2. Engineered Biosynthesis of an Eight-Membered Ring Tetraketide LactoneCamilla M. Kao, Michael McPherson, Robert N. McDaniel, Hong Fu, David E. Cane, and Chaitan KhoslaView Author Information Departments of Chemical Engineering, Chemistry and Biochemistry, Stanford University Stanford, California 94305-5025 Department of Chemistry, Box H, Brown University Providence, Rhode Island 02912 KOSAN Biosciences, Inc., 1450 Rollins Road Burlingame, California 94010 Cite this: J. Am. Chem. Soc. 1997, 119, 46, 11339–11340Publication Date (Web):November 19, 1997Publication History Received31 July 1997Published online19 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/ja972609ehttps://doi.org/10.1021/ja972609erapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views608Altmetric-Citations74LEARN 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-Alertsclose SUBJECTS:Lactones,Metabolism,Peptides and proteins,Pharmaceuticals,Reaction products Get e-Alerts
Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2. (1986)

In this study we used human monoclonal antibody (Hu-mAb) L72 as an intratumoral injection of cutaneous metastasis of melanoma to study its anti-tumor effects in human patients. Hu-mAb L72 was developed by transforming peripheral blood lymphocytes from a melanoma patient in vitro with the Epstein-Barr virus, forming a human lymphoblastoid cell line that produces 2-5 micrograms of IgM per ml. This IgM Hu-mAb was shown to react specifically with ganglioside GD2 and have a strong cytotoxic effect on human melanoma cells in the presence of complement. Patients with cutaneous metastatic melanoma were given intralesional injections on a daily or weekly injection schedule. Regression was seen in all tumors except in those of two patients whose tumors were shown to have low antigenicity. Histopathological data showed tumor degeneration, fibrosis, free melanin, and some degree of lymphocyte or macrophage infiltration. One patient with melanoma satellitosis treated with Hu-mAb showed complete regression with no sign of recurrence 20 months after the initial treatment. With the exception of mild erythema, no side effects were observed in any patient.
The STE20 Kinase HGK Is Broadly Expressed in Human Tumor Cells and Can Modulate Cellular Transformation, Invasion, and Adhesion (2003)

HGK (hepatocyte progenitor kinase-like/germinal center kinase-like kinase) is a member of the human STE20/mitogen-activated protein kinase kinase kinase kinase family of serine/threonine kinases and is the ortholog of mouse NIK (Nck-interacting kinase). We have cloned a novel splice variant of HGK from a human tumor line and have further identified a complex family of HGK splice variants. We showed HGK to be highly expressed in most tumor cell lines relative to normal tissue. An active role for this kinase in transformation was suggested by an inhibition of H-Ras(V12)-induced focus formation by expression of inactive, dominant-negative mutants of HGK in both fibroblast and epithelial cell lines. Expression of an inactive mutant of HGK also inhibited the anchorage-independent growth of cells yet had no effect on proliferation in monolayer culture. Expression of HGK mutants modulated integrin receptor expression and had a striking effect on hepatocyte growth factor-stimulated epithelial cell invasion. Together, these results suggest an important role for HGK in cell transformation and invasiveness.
Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. (2000)

Difficulties in the detection, diagnosis, and treatment of ovarian cancer result in an overall low survival rate of women with this disease. A better understanding of the pathways involved in ovarian tumorigenesis will likely provide new targets for early and effective intervention. Here, we have used serial analysis of gene expression (SAGE) to generate global gene expression profiles from various ovarian cell lines and tissues, including primary cancers, ovarian surface epithelia cells, and cystadenoma cells. The profiles were used to compare overall patterns of gene expression and to identify differentially expressed genes. We have sequenced a total of 385,000 tags, yielding >56,000 genes expressed in 10 different libraries derived from ovarian tissues. In general, ovarian cancer cell lines showed relatively high levels of similarity to libraries from other cancer cell lines, regardless of the tissue of origin (ovarian or colon), indicating that these lines had lost many of their tissue-specific expression patterns. In contrast, immortalized ovarian surface epithelia and ovarian cystadenoma cells showed much higher similarity to primary ovarian carcinomas than to primary colon carcinomas. Primary tissue specimens therefore appeared to be a better model for gene expression analyses. Using the expression profiles described above and stringent selection criteria, we have identified a number of genes highly differentially expressed between nontransformed ovarian epithelia and ovarian carcinomas. Some of the genes identified are already known to be overexpressed in ovarian cancer, but several represent novel candidates. Many of the genes up-regulated in ovarian cancer represent surface or secreted proteins such as claudin-3 and -4, HE4, mucin-1, epithelial cellular adhesion molecule, and mesothelin. Interestingly, both apolipoprotein E (ApoE) and ApoJ, two proteins involved in lipid homeostasis, are among the genes highly up-regulated in ovarian cancer. Selected serial analysis of gene expression results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in archival material. These experiments provided additional evidence of the relevance of our findings in vivo. The publicly available expression data reported here should stimulate and aid further research in the field of ovarian cancer.
ProteinO-Glycosylation in Fungi: Diverse Structures and Multiple Functions (2007)

Protein glycosylation is essential for eukaryotic cells from yeasts to humans. When compared to N-glycosylation, O-glycosylation is variable in sugar components and the mode of linkages connecting the sugars. In fungi, secretory proteins are commonly mannosylated by protein O-mannosyltransferase (PMT) in the endoplasmic reticulum, and subsequently glycosylated by several glycosyltransferases in the Golgi apparatus to form glycoproteins with diverse O-glycan structures. Protein O-glycosylation has roles in modulating the function of secretory proteins by enhancing the stability and solubility of the proteins, by affording protection from protease degradation, and by acting as a sorting determinant in yeasts. In filamentous fungi, protein O-glycosylation contributes to proper maintenance of fungal morphology, hyphal development, and differentiation. This review describes recent studies of the structure and function of protein O-glycosylation in industrially and medically important fungi.
Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation (2003)

Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer.
Design and synthesis of boronic-acid-labeled thymidine triphosphate for incorporation into DNA (2007)

The boronic acid moiety is a versatile functional group useful in carbohydrate recognition, glycoprotein pull-down, inhibition of hydrolytic enzymes and boron neutron capture therapy. The incorporation of the boronic-acid group into DNA could lead to molecules of various biological functions. We have successfully synthesized a boronic acid-labeled thymidine triphosphate (B-TTP) linked through a 14-atom tether and effectively incorporated it into DNA by enzymatic polymerization. The synthesis was achieved using the Huisgen cycloaddition as the key reaction. We have demonstrated that DNA polymerase can effectively recognize the boronic acid-labeled DNA as the template for DNA polymerization, that allows PCR amplification of boronic acid-labeled DNA. DNA polymerase recognitions of the B-TTP as a substrate and the boronic acid-labeled DNA as a template are critical issues for the development of DNA-based lectin mimics via in vitro selection.
Clinical Uses of Gut Peptides (1997)

Gut peptides have been used successfully in an increasing variety of clinical conditions. Further refinements in analogue and antagonist design are likely to lead to even more selective agents that may have important clinical applications. Further studies are needed to identity and evaluate these new agents.
Assisted Multi-view Stereo Reconstruction (2013)

Multiview stereo reconstruction methods can provide impressive results in a number of applications. Nevertheless, when trying to apply the state-of-the-art methods in the case of a more structured 3D acquisition, the lack of feedback on the quality of the reconstruction during the photo shooting can be problematic. In this paper we present a framework for the assisted reconstruction from images of real objects. The framework is able to provide, in quasi-real time, a sparse reconstruction of the scene, so that the user is able to spot the missing or problematic parts. Moreover, the framework is able to separate the object of interest from the background and suggests missing points of view to the user, without any previous knowledge of the shape of the scene and the acquisition path. This is obtained by analyzing the sparse reconstruction and the connection between the reconstructed points and the input images. The framework has been tested on a variety of practical cases, and it has proved to be effective not only to obtain more complete reconstructions, but also to reduce the number of images needed and the processing time for dense reconstruction.
Analysis of the Relationship between Bus Board Customers' Purchasing Behavior and Business Decision Making (2010)

The paper establishes an Analytic Hierarchy model by applying the basic decision theory of AHP and carefully analyzing consideration factors of bus board customers. Regarding the scientificalness, feasibility, stability and efficiency as evaluation criterions, the model structures judgment matrixes and determines the important degree of each influencing factor with the help of hierarchical single arrangement. The paper provides a reference for the bus board enterprise's decision-making by making clear of main factors affecting its customers’ purchasing behavior.
Polymeric tunable optical attenuator with an optical monitoring tap for WDM transmission network (1999)

A polymeric tunable optical attenuator has been fabricated using asymmetric Y-branch waveguides integrated with an optical monitoring tap. One arm of the branch serves as the main output port, while the other arm helps remove the residual optical power resulting from attenuation. An optical power tap used for the monitoring port is introduced to take a fraction of the main port power. This monitoring port is useful for observing the main output continuously. Furthermore, it can be fed back to the electrical driver to maintain the attenuated output regardless of variations in input light polarization and power. By utilizing the modal evolution effect in asymmetric branches, the attenuator has enhanced fabrication tolerance and reduced wavelength sensitivity. Also, no electrical bias is needed to achieve maximum optical transmission. The attenuator exhibited a dynamic range of more than 20 dB at 1550 nm and a response time of about 1 ms. The polarization dependent loss was about 0.9 dB, and the wavelength uniformity was less than 1.2 dB over the range of 1530-1560 mm.
A 13.56 MHz Wireless Power Transfer System With Reconfigurable Resonant Regulating Rectifier and Wireless Power Control for Implantable Medical Devices (2015)

A 13.56 MHz wireless power transfer system with a 1X/2X reconfigurable resonant regulating (R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) rectifier and wireless power control for biomedical implants is presented. Output voltage regulation is achieved through two mechanisms: (1) a local PWM loop at the secondary side controls the duty cycle of mode-switching of the rectifier between the 1X and 2X modes; and (2) a global control loop obtains the mode-switching information from the secondary side and send it back to the primary side through the wireless channel and adjusts the transmitter power of the primary coil to adapt to load and coupling variations. Two novel backscattering uplink techniques are proposed for fast and energy-efficient data feedback. The first is for general data transmission using Manchester code; and the second is for fast duty cycle feedback to cater for fast load-transient responses. Stability analysis of the entire system with the two control loops is also presented. The primary transmitter and the secondary R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> rectifier are fabricated in 0.35 μm CMOS process with the digital control circuits implemented using FPGA. The measured maximum received power and receiver efficiency are 102 mW and 92.6%, respectively. For load transients, the overshoot and the undershoot are approximately 110 mV and the settling times are less than 130 μs.
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study (2016)

This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.
Targeted toxins. (2000)

Targeted toxins, consisting of tumor-selective ligands coupled to polypeptide toxins, represent a new class of cancer therapeutics that kills malignant cells by inactivating cytosolic protein synthesis and inducing apoptosis. A number of these molecules have been produced under good manufacturing practice conditions and given systemically to patients with a variety of neoplasms. The promising results to date and the remaining pharmacological hurdles are discussed.