gebhart/patrepeval huggingface dataset:
Synthesis and Biochemical Characterization of a Series of 17α-Perfluoroalkylated Estradiols as Selective Ligands for Estrogen Receptor α (2010)

Despite intensive research efforts, the distinct biological roles of two closely related estrogen receptors, ERα and ERβ, are only partially understood. Therefore, ligands selective for either of two isotypes are useful research tools because they allow for exerting a desired subset of biological effects mediated by only one of the receptors. Here we report on the synthesis of a new class of potent and selective ligands for ERα represented by a series of 17α-substituted estradiols bearing lipophilic perfluoroalkyl chains. These 17α-perfluoroalkylated estradiols were synthesized by Ru-catalyzed cross metathesis reactions of 17α-allyl- or 17α-vinylestradiols with perfluoroalkylpropenes. Compounds were tested in both agonistic and antagonistic modes using a panel of stable steroid receptor reporter cell lines established in U2OS cells and consisting of ERα-LBD, ERβ-LBD, GR-LBD, and MR-LBD reporters. Some of the compounds are potent and selective agonists of ERα, exhibiting weak partial to no detectable agonistic activity on ERβ. Notably, 11c is the most ERα selective ligand of the prepared compounds because it activates ERα but inhibits ERβ. In addition, some compounds are pure agonists on ERα but show mixed agonistic/antagonistic profile on ERβ which is a typical pattern observed for selective estrogen receptor modulators (SERMs).
[Time trends on the prevalence of cancer during 1970-2005 in Shandong province]. (2009)

In Shandong province, a marked increase was seen in the mortality rate of tumors in the past 35 years. Evidence showed that the spectrum of death among main malignant tumors had changed which might provide a scientific basis for the development of a community-based prevention and control program on cancer.
Development of magnetic particle techniques for long-term culture of bone cells with intermittent mechanical activation (2002)

Magnetic particles were coated with RGD and adhered to primary human osteoblasts. During a 21-day culture, the osteoblasts plus adhered magnetic particles underwent a daily exposure to a time-varying magnetic field via a permanent NdFeB magnet, thus applying a direct mechanical stress to the cells (Bmax approximately 60 mT). After 21 days, preliminary results show that the cells plus magnetic particles were viable and had proliferated. A von-kossa stain showed mineralized bone matrix produced at 21 days in the experimental group whereas the control groups showed no mineralized matrix production. Real-time reverse transcription-polymerase chain reaction at 21 days showed an upregulation of osteopontin from the experimental group in comparison to the control group of cells with adhered particles and no magnet applied. These preliminary results indicate that adherence of RGD-coated 4.5 microm ferromagnetic particles to primary human osteoblasts does not initiate cell necrosis up to 21 days in vitro. Also, mechanical stimulation of human osteoblasts by magnetic particle technology appears to have an influence on osteoblastic activity.
Valproic Acid Increases the In Vitro Effects of Nitrosureas on Human Glioma Cell Lines (2007)

Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.
Prostaglandins in reproductive physiology (1975)

Summary The role of prostaglandins in reproductive physiology is reviewed with particular emphasis on their possible importance in ovulation in humans. A possible interaction between gonadal steroids, biogenic amines and prostaglandins at hypothalamic-pituitary level, in relation to the release of luteinizing hormone releasing factor, and LH, is discussed. Anomalies regarding the role of oestrogens in LH release are noted, and it is suggested that high oestrogen levels may release prostaglandins from the uterus and/or centrally in humans, in connection with the mid-cycle LH surge and ovulation. A hypothetical role for prostaglandins in sexual behaviour and premenstrual changes is discussed. The hypotheses open up new areas for clinical research to establish the role of prostaglandins in human endocrinology. The need for measurement of prostaglandin metabolites in blood and urine is emphasized.
Selective Estrogen Receptor Modulator Raloxifene-Associated Aggravation of Nonalcoholic Steatohepatitis (2007)

A 53-year-old postmenopausal woman, who had a family history of cryptogenic liver cirrhosis, was diagnosed with osteoporosis, and started on the selective estrogen receptor modulator (SERM) raloxifene 60 mg/day orally. She developed marked liver dysfunction. Her body mass index (BMI) was 26.5. Her blood chemistry indicated AST 342 IU/L, ALT 356 IU/L, and hyaluronic acid 255 ng/mL. An oral glucose tolerance test showed impaired glucose tolerance with marked insulin resistance. Histologically, we diagnosed this case as having pre-cirrhotic nonalcoholic steatohepatitis (NASH). This is the first histologically confirmed case of NASH that was aggravated by raloxifene.
Bromination of 10-phenylphenothiazine and 10-phenylphenoxazine (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBromination of 10-phenylphenothiazine and 10-phenylphenoxazineMisa V. Jovanovic and Edward R. BiehlCite this: J. Org. Chem. 1984, 49, 11, 1905–1908Publication Date (Print):June 1, 1984Publication History Published online1 May 2002Published inissue 1 June 1984https://pubs.acs.org/doi/10.1021/jo00185a011https://doi.org/10.1021/jo00185a011research-articleACS PublicationsRequest reuse permissionsArticle Views1618Altmetric-Citations22LEARN 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 Get e-Alerts
MicroRNA-146a Feedback Suppresses T Cell Immune Function by Targeting Stat1 in Patients with Chronic Hepatitis B (2013)

More than 350 million people are chronically infected with hepatitis B virus, and dysfunctional T cell responses contribute to persistent viral infection and immunopathogenesis in chronic hepatitis B (CHB). However, the underlying mechanisms of T cell hyporesponsiveness remain largely undefined. Given the important role of microRNA-146a (miR-146a) in diverse aspects of lymphocyte function, we investigated the potential role and mechanism of miR-146a in regulating T cell immune responses in CHB. We found that miR-146a expression in T cells is significantly upregulated in CHB compared with healthy controls, and miR-146a levels were correlated with serum alanine aminotransaminase levels. Both inflammatory cytokines and viral factors led to miR-146a upregulation in T cells. Stat1 was identified as a miR-146a target that is involved in antiviral cytokine production and the cytotoxicity of CD4(+) and CD8(+) T cells. In vitro blockage of miR-146a in T cells in CHB greatly enhanced virus-specific T cell activity. Therefore, our work demonstrates that miR-146a upregulation in CHB causes impaired T cell function, which may contribute to immune defects and immunopathogenesis during chronic viral infection.
Elucidation of the Electrochemical Oxidation Pathway of Ammonia in Dimethylformamide and the Room Temperature Ionic Liquid, 1‐Ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (2004)

Abstract The direct electrochemical oxidation of ammonia has been examined in both the organic solvent dimethylformamide (DMF) and the room temperature ionic liquid 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][N(Tf) 2 ]. The corresponding voltammetric responses have been shown to be similar in each solvent with a broad oxidative wave occurring upon the introduction of ammonia to the solution and the appearance of a new reductive wave following the oxidation. The oxidative reaction process has been examined and a suitable reaction pathway has been deduced, corresponding to the formation of ammonium cations after oxidation of the ammonia. A linear response of limiting current against vol% ammonia was observed in both DMF and [EMIM][N(Tf) 2 ], suggesting potential application for analytical methods.
A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate (1983)

Seven mutants of Escherichia coli were isolated that are sensitive to methyl methane sulfonate but not to UV light. They exhibited decreased host cell reactivation capacity for methyl methane sulfonate-treated phage lambda. Five of the mutations were mapped in the same region as alkA (previously called alk) and may indeed be identical to known mutations. Another mutation was found near nalA, and the gene responsible was named alkB. Its phenotype was different from that of ada, since the alkB mutant exhibited a normal adaptive response to N-methyl-N'-nitro-N-nitrosoguanidine. A third type of mutation was mapped near polA, but this mutant contained an almost normal level of DNA polymerase I activity.
Quasiphase-matched second harmonic generation of blue light in electrically periodically-poled lithium tantalate waveguides (1991)

Blue light was generated at room temperature by quasiphase matched second harmonic generation in planar and channel lithium tantalate (LiTaO3) annealed proton exchange waveguides using the d33 nonlinear coefficient. Alternating ferro-electric domains for third order quasiphase matching were created by poling the substrates with a periodic electric field.
Single-Molecule Electronic Measurements with Metal Electrodes (2005)

The process of transferring electrons from one metal electrode to another via an intervening molecule differs from electrochemically or optically-induced electron transfer in important ways. The simplest process of ballistic electron transport with no charge localization on the molecule (tunneling) should be easy to understand quantitatively, yet experimental reports and theoretical calculations can differ by orders of magnitude. Here, we show how many of the discrepancies are resolved with measurements carefully constructed to provide data on single molecules connected to electrodes in well-defined ways. Furthermore, a number of these results are in good agreement with first-principles calculations (no adjustable parameters). The more interesting (and theoretically challenging) process of charge transport with intermediate localization by redox states can be measured in the same ways, but present theories do not yet describe these processes fully.
Sequencing-Grade <i>De novo</i> Analysis of MS/MS Triplets (CID/HCD/ETD) From Overlapping Peptides (2013)

Full-length de novo sequencing of unknown proteins remains a challenging open problem. Traditional methods that sequence spectra individually are limited by short peptide length, incomplete peptide fragmentation, and ambiguous de novo interpretations. We address these issues by determining consensus sequences for assembled tandem mass (MS/MS) spectra from overlapping peptides (e.g., by using multiple enzymatic digests). We have combined electron-transfer dissociation (ETD) with collision-induced dissociation (CID) and higher-energy collision-induced dissociation (HCD) fragmentation methods to boost interpretation of long, highly charged peptides and take advantage of corroborating b/y/c/z ions in CID/HCD/ETD. Using these strategies, we show that triplet CID/HCD/ETD MS/MS spectra from overlapping peptides yield de novo sequences of average length 70 AA and as long as 200 AA at up to 99% sequencing accuracy.
Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure (2011)

Incidence of whooping cough, unlike many other childhood diseases for which there is an efficacious vaccine, has been increasing over the past twenty years despite high levels of vaccine coverage. Its reemergence has been particularly noticeable among teenagers and adults. Many hypotheses have been put forward to explain these two patterns, but parsimonious reconciliation of clinical data on the limited duration of immunity with both pre- and postvaccine era age-specific incidence remains a challenge. We consider the immunologically relevant, yet epidemiologically largely neglected, possibility that a primed immune system can respond to a lower dose of antigen than a naive one. We hypothesize that during the prevaccine era teenagers' and adults' primed immunity was frequently boosted by reexposure, so maintaining herd immunity in the face of potentially eroding individual immunity. In contrast, low pathogen circulation in the current era, except during epidemic outbreaks, allows immunity to be lost before reexposure occurs. We develop and analyze an age-structured model that encapsulates this hypothesis. We find that immune boosting must be more easily triggered than primary infection to account for age-incidence data. We make age-specific and dynamical predictions through bifurcation analysis and simulation. The boosting model proposed here parsimoniously captures four key features of pertussis data from highly vaccinated countries: (i) the shift in age-specific incidence, (ii) reemergence with high vaccine coverage, (iii) the possibility for cyclic dynamics in the pre- and postvaccine eras, and (iv) the apparent shift from susceptible-infectious-recovered (SIR)-like to susceptible-infectious-recovered-susceptible (SIRS)-like phenomenology of infection and immunity to Bordetella pertussis.
Excellent silicon nitride films made by hybrid process and their application to a-Si TFTs (2002)

From a discovery of ammonia plasma effect, we have developed "hybrid-process" where plasma and light are complementally used to make excellent silicon nitride films at low temperatures. The films made by the hybrid process have excellent interfaces as well as high dense film properties. High electron mobility a-Si TFTs were made by using the films as gate insulators.
Viscous Flow Deformation in Supercooled Liquid State of Bulk Amorphous Zr&lt;SUB&gt;55&lt;/SUB&gt;Al&lt;SUB&gt;10&lt;/SUB&gt;Ni&lt;SUB&gt;5&lt;/SUB&gt;Cu&lt;SUB&gt;30&lt;/SUB&gt; Alloy (1996)

The deformation behavior in the supercooled liquid region for the amorphous Zr55Al10Ni5Cu30 alloy was examined as a function of temperature, applied stress and deformation rate. The deformation occurs through the Newtonian viscous flow with the strain rate sensitivity (m value) of approximately 1.0. By utilizing the ideal superplastic flow, the extrusion with an extrusion ratio of 3.6 for the cast amorphous Zr–Al–Ni–Cu cylinder was easily made in the condition where the extrusion temperature was in the range of 703 to 743 K and the extrusion velocity was 0.67 to 22 μm/s. The extruded alloy also keeps an amorphous phase and no appreciable difference in the mechanical properties is seen between the cast and extruded amorphous alloys. However, a distinct endothermic reaction is observed around the extrusion temperature on the differential scanning calorimetric curve of the extruded alloy. The endothermic reaction is due to the structural change from the relaxed disordered atomic configurations developed by extrusion to internally equilibrium disordered atomic configurations. The evidence on the modification in the disordered structure during the severe deformation of the supercooled liquid is important for future development of basic science and engineering utilization of the supercooled liquid.
Supporting asynchronous telemedicine: multimedia mail vs. the World Wide Web vs. replicated databases (2002)

This paper investigates the development and implementation of an asynchronous telemedicine application for the purposes of tele-consultation in remote regions. Three applications were developed: MailTeleMed, WebTeleMed and MCLTeleMed utilizing various communication and database models.
Appearance-space texture synthesis (2006)

The traditional approach in texture synthesis is to compare color neighborhoods with those of an exemplar. We show that quality is greatly improved if pointwise colors are replaced by appearance vectors that incorporate nonlocal information such as feature and radiance-transfer data. We perform dimensionality reduction on these vectors prior to synthesis, to create a new appearance-space exemplar. Unlike a texton space, our appearance space is low-dimensional and Euclidean. Synthesis in this information-rich space lets us reduce runtime neighborhood vectors from 5x5 grids to just 4 locations. Building on this unifying framework, we introduce novel techniques for coherent anisometric synthesis, surface texture synthesis directly in an ordinary atlas, and texture advection. Remarkably, we achieve all these functionalities in real-time, or 3 to 4 orders of magnitude faster than prior work.
Local anaesthetics have different mechanisms and sites of action at the recombinant N‐methyl‐D‐aspartate (NMDA) receptors (2003)

(1) Although the principal pharmacological targets of local anaesthetics (LAs) are voltage-gated Na(+) channels, other targets have also been suggested. Here we examined the effects of LAs on the N-methyl-D-aspartate (NMDA) receptor, a receptor involved in the process of nociception. (2) LAs (bupivacaine, lidocaine, procaine, and tetracaine) reversibly and concentration-dependently inhibited recombinant epsilon1/zeta1 and epsilon2/zeta1 NMDA receptors expressed in Xenopus oocytes (IC(50)s for bupivacaine, lidocaine, procaine, and tetracaine were 1032.0, 1174.1, 642.1 and 653.8 micro M at the epsilon1/zeta1 receptor; and 1090.8, 1821.3, 683.0 and 662.5 micro M respectively (at the epsilon2/zeta1 receptor). Bupivacaine and procaine were non-competitive antagonists; bupivacaine possesses non-competitive and competitive actions when interacting with glycine, whereas procaine has only non-competitive action. (3) Mutation of asparagine residue at position 598 (Asp(598)) in the zeta1 subunit, a residue associated with the blockade site for Mg(2+) and ketamine, to glutamine or arginine reduced the sensitivity to procaine but not to bupivacaine. Thus, procaine may interact with sites of action that are closely related to those of Mg(2+) and ketamine blockade. (4) These results suggest that LAs inhibit the NMDA receptor by various mechanisms.
Characterization of the interaction of polyomavirus middle T antigen with type 2A protein phosphatase (1992)

Two cellular proteins of 36 and 63 kDa which bind the small T and middle T antigens of polyomavirus recently have been identified as the catalytic and regulatory subunits of the phosphoserine/threonine-specific type 2A protein phosphatase (PP2A). We report here the presence of phosphoseryl phosphatase activity associated with polyomavirus small T and middle T antigens in immunoprecipitates prepared from virus-infected and transformed cells. Phosphatase activity was also found associated with middle T-antigen mutants, some of which had been defined previously to associate with 36- and 63-kDa cellular proteins. Middle T-antigen-associated phosphatase activity was sensitive to okadaic acid and microcystin-LR, inhibitors of PP2A, and insensitive to inhibitor 1 or 2, orthovanadate, or EDTA. Using antiserum specific for the catalytic subunit of PP2A, we found that unlike the majority of PP2A, middle T-antigen-bound PP2A was membrane associated. However, no gross change in the amount, activity, or localization of PP2A could be attributed to middle T-antigen expression in transformed cells. Anti-PP2A antibodies coprecipitated a 63-kDa protein from normal cells and in addition coprecipitated middle T antigen, 60- and 61-kDa proteins (identified as src family members), and an 81-kDa protein from middle T-antigen-transformed cells. Furthermore, we detected protein kinase activity in PP2A immunoprecipitates and protein phosphatase activity in src immune complexes from extracts of middle T-antigen-transformed, but not normal, cells. These results reinforce the notion that at least a portion of middle T antigen bridges a protein kinase with a protein phosphatase.
Molecular engineering of antibodies for therapeutic and diagnostic purposes (2012)

During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications.
Superhard and Elastic Carbon Nitride Thin Films Having Fullerenelike Microstructure (1995)

${\mathrm{CN}}_{x}$ films were found to have a distorted graphitelike microstructure consisting of buckled and curved basal planes using high-resolution electron microscopy. Nanoindentation showed an elastic recovery of 85%, and a hardness of $\ensuremath{\sim}60$ GPa. Based on detailed quantum chemical calculations and photoelectron spectroscopy, the observed structure is proposed to consist of a network of buckled ${\mathrm{sp}}^{2}$-hybridized ${\mathrm{CN}}_{x}$ planes, cross-linked by ${\mathrm{sp}}^{3}$-hybridized bonds. The buckling is shown to be due to the incorporation of pentagons in the basal planes, giving rise to a fullerenelike microstructure.