gebhart/patrepeval huggingface dataset:
The COOH-terminal domain of hirudin. An exosite-directed competitive inhibitor of the action of alpha-thrombin on fibrinogen. (1990)

Hirudin, a potent 65-residue polypeptide inhibitor of alpha-thrombin found in the saliva of the leech Hirudo medicinalis, and fragments thereof are potentially useful as antithrombotic agents. Hirugen, the synthetic N-acetylated COOH-terminal dodecapeptide (Ac-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr(SO3)-Leu) of hirudin was shown in the present study to behave as a pure competitive inhibitor (Ki = 0.54 microM) of human alpha-thrombin-catalyzed release of fibrinopeptide A from human fibrinogen. In contrast to this inhibitory activity, hirugen slightly enhanced (increased kcat/Km 1.6-fold) alpha-thrombin-catalyzed hydrolysis of the fluorogenic tripeptide substrate N-p-Tosyl-Gly-Pro-Arg-7-amino-4-methylcoumarin. These observations indicate that hirugen binds to alpha-thrombin at an exosite distinct from the active site, and that interaction with this exosite is a major determinant of the competence of alpha-thrombin to bind fibrinogen. Consistent with this view, hirugen blocked binding of fibrin II to alpha-thrombin. Studies of the effect of hirugen on the rate of inactivation of alpha-thrombin by antithrombin III (AT), the major plasma inhibitor of alpha-thrombin, indicated that binding of hirugen to alpha-thrombin results in less than a 2.5-fold decrease in the rate of inactivation of alpha-thrombin by AT, both in the absence and presence of heparin. This behavior is distinct from that of active site-directed competitive inhibitors of alpha-thrombin which bind to alpha-thrombin and block both conversion of fibrinogen to fibrin and inactivation of alpha-thrombin by AT. Hirugen, an exosite-directed competitive inhibitor, blocks the interaction of alpha-thrombin with fibrinogen while leaving alpha-thrombin competent to react with AT. Thus, unlike active site-directed competitive inhibitors, hirugen should act in concert with AT and heparin to reduce the amount of fibrinogen that is processed during the lifetime of alpha-thrombin in plasma.
The Evolution of the Kerberos Authentication Service (1992)

Two experimental models suitable for the screening of volatile compounds were set up. The first consisted of a glass-chamber slide with eight wells, one carrying the test compound, and the others carrying cells in monolayers. In the second model, the cells were cultured in a glass Petri dish, and the test compound was poured onto a filter lying on a glass cover-slip, supported by a metal ring. Four plant volatiles [carvacrol, S-(+)- carvone, thymol and decanal] and one essential oil (caraway oil) were chosen as test compounds. The toxicity rankings obtained with the two models were compared with that obtained in a previous study performed with the same compounds under conventional culture conditions. Differences in the toxicity ranking were observed between the conventional culture conditions and the gas-phase models, confirming the importance of correct exposure conditions for the evaluation of toxicity. Both models have advantages that make them suitable as a preliminary step in the toxicity screening of volatile compounds, or for use in a test battery when combined with conventional approaches.
Removal of polymerase-produced mutant sequences from PCR products (1997)

Heteroduplex DNA lacking d(GATC) methylation is subject to mismatch-provoked double-strand cleavage at d(GATC) sites in a reaction dependent on MutH, MutL, MutS, and ATP. We have exploited this reaction to develop a method for removal of polymerase-produced mutant sequences that arise during sequence amplification by PCR. After denaturation and reannealing, the PCR product pool is subjected to MutH, MutL, and MutS mismatch repair proteins under double-strand cleavage conditions, followed by isolation of uncleaved product by size selection. Use of an Escherichia coli lac forward mutation assay has shown that this procedure reduces the incidence of polymerase-induced mutant sequences by an order of magnitude. Twenty mutants that originated from three independent PCR amplification reactions and survived MutHLS treatment all were found to contain an infrequently occurring A.T --> T.A transversion mutation at a unique position within the product. By contrast, the majority of mutations in untreated PCR products were transitions occurring throughout the amplified region, although frameshifts and transversions also were observed. The MutHLS method thus can be used to effectively remove the majority of mutant sequences produced by polymerase errors during PCR amplification.
Vaccination with embryonic stem cells generates effective antitumor immunity against ovarian cancer (2012)

To date, only a few studies have suggested that human embryonic stem cells (hESCs) might effectively immunize against colon and lung cancer. The purpose of this study was to investigate the therapeutic potential of hESCs as a vaccine to induce widespread antitumor effects in different animal models and various types of cancer. C57BL/6 mice with ID8 ovarian cancer cell and Fischer 344 rats with NuTu-19 ovarian cancer cell models were used. Fifty-four mice were divided into six groups with nine mice in each group. Each mouse was immunized with pre-inactivated hESCs (H9) or mouse embryonic stem cells (mESCs; IVP-ES1) or ID8 or phosphate-buffered saline (PBS). Twenty-four rats were divided into four groups with six rats in each group, each rat immunized with pre-inactivated hESCs (H9) or NuTu-19 or PBS. After the vaccination, each mouse was challenged with live ID8 cells subcutaneously, and each rat was challenged with live NuTu-19 cells intraperitoneally. We discovered that vaccination of mice with the hESC line H9 and the mESC line IVP-ES1 generated consistent cellular and humoral immune responses against ID8 ovarian cancer. H9 and IVP-ES1 vaccinated mice obtained antitumor immune protection, and H9 vaccinated rats had the longest survival time and least distant metastases. No evidence of side-effects was observed. We also compared the immunogenicity against ovarian cancer between the hESC line, H9, and the mESC line, IVP-ES1, that derived from the inner cell mass in different species. We found that there were no significant differences between them. Furthermore, immunohistochemical staining revealed that several oncogenes and tumor suppressor genes, such as HER-2, C-myc, p53, and nm23, were expressed in H9, many of which were also shared by ovarian cancer. hESC vaccines can induce antitumor effects in two animal models and in ovarian cancer, indicating that the activity of the vaccine is universal, and, more importantly, it is safe.
Leptin Reduces Ovariectomy-Induced Bone Loss in Rats (2001)

Bone mineral density increases with fat body mass, and obesity has a protective effect against osteoporosis. However, the relationship between fat body mass and bone mineral density is only partially explained by a combination of hormonal and mechanical factors. Serum leptin levels are strongly and directly related to fat body mass. We report here the effects of leptin administration compared with estrogen therapy on ovariectomy-induced bone loss in rats. Leptin was effective at reducing trabecular bone loss, trabecular architectural changes, and periosteal bone formation. Interestingly, the combination of estrogen and leptin further decreased bone turnover compared with that in estrogen-treated ovariectomized rats. Leptin also significantly increased osteoprotegerin mRNA steady state levels and protein secretion and decreased RANK ligand mRNA levels in human marrow stromal cells in vitro. Our findings suggest that leptin could modulate bone remodeling in favor of a better bone balance in rats. This study is the first evidence that leptin therapy has a significant effect in preventing ovariectomy-induced bone loss, and this effect may at least in part be mediated by the osteoprotegerin/RANK ligand pathway.
Cause-Specific Excess Deaths Associated With Underweight, Overweight, and Obesity (2007)

The BMI-mortality association varies by cause of death. These results help to clarify the associations of BMI with all-cause mortality.
Monitoring Apoptosis in Real Time (2002)

Many therapeutically active anticancer treatments exert their effect by the induction of apoptosis and necrosis. Serial biopsies in breast cancer patients have suggested that response to therapy correlates with early posttreatment increases in tumor apoptotic index. Radiolabeled technetium Tc 99m-recombinant human (rh) annexin V provides a noninvasive technique for imaging treatment-induced cell death. Annexin V is a naturally occurring human protein that binds avidly to membrane-associated phosphatidylserine (PS). PS is normally found only on the inner leaflet of the cell membrane double layer, but it is actively transported to the outer layer as an early event in apoptosis and becomes available for annexin binding. Annexin also gains access to PS as a result of the membrane fragmentation associated with necrosis. In vitro studies of apoptosis using fluorescein annexin have shown good correlation with assessments of apoptosis documented by nuclear DNA degradation and caspase activation. In vivo localization of intravenously administered Tc 99m-annexin V has been demonstrated in numerous preclinical models of apoptosis, including anti-Fas-mediated hepatic apoptosis, rejection of allogeneic heterotopic cardiac allografts, cyclophosphamide treatment of murine lymphoma, cyclophosphamide-induced apoptosis in bone marrow, and leukocyte apoptosis associated with abscess formation. Scintigraphic studies in humans using Tc 99m-rh annexin V have demonstrated the feasibility of imaging cell death in acute myocardial infarction, in tumors with a high apoptotic index, and in response to anti-tumor chemotherapy of non-small cell lung cancer, small-cell lung cancer, breast cancer, lymphoma, and sarcoma. Increased localization of Tc 99m-rh annexin V within 1 to 3 days of chemotherapy has been noted in some, but not all, subjects with these tumors. To date, most subjects showing increased Tc 99m-rh annexin V uptake after the first course of chemotherapy have shown objective clinical responses. A single site study in 15 subjects with 1-year follow-up has suggested that increased posttreatment Tc 99m-rh annexin uptake is associated with improved time to progression of disease and survival time. In vivo imaging of cell death may have the potential to improve the treatment of cancer patients by allowing rapid, objective, patient-by-patient assessment of the efficacy of tumor cell killing.
Diabetes and oral oncogenesis. (2008)

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in humans including type I diabetic and normal rats. Tobacco and alcohol, as well as dysregulation of oncogenes and tumor suppressor genes, epigenetic changes and mitochondrial mutations have been implicated in OSCC development. Recent epidemiological studies have incriminated diabetes mellitus as a risk factor for the development of OSCC, as well as oral premalignant lesions. Recently, an animal model was employed to study the influence of diabetes on signal transduction pathways in every stage of oral cancer development, from normal mucosa to hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. Diabetes was induced by streptozotocin and chemical carcinogenesis was induced by the carcinogen 4-nitroquinoline N-oxide. The expression of EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, the tumor suppressor genes p53 and p16, apoptosis markers Bax and Bcl-2, and the cell proliferation marker Ki-67 in the sequential stages of rat oral oncogenesis was investigated. Diabetes seems to promote the activation of the Ras/Raf/MAPK signal transduction pathway mainly by induction of erbB2 and erbB3 receptors, leading to increased cell proliferation, while there was no difference in apoptosis levels during oncogenesis.
Milolides, New Briarane Diterpenoids from the Western Pacific Octocoral Briareum stechei (2001)

Eleven new briarane-type diterpene lactones, designated milolides (1--8, 10--12), together with four known diterpene lactones (9, 13--15), were isolated from the Micronesian octocoral Briareum stechei collected at Yap, Federated States of Micronesia. One aspect of the stereochemistry of one of the known compounds, solenolide C (9), is revised. Structures of the new compounds were determined from spectral data.
Accuracy of Clinical Diagnosis of Influenza in Outpatient Children (2005)

In a prospective study, children < or =13 years of age with respiratory infections were examined. At each visit, a nasal swab specimen was obtained for the detection of influenza, and the physician recorded his or her opinion on whether the child had influenza. Among 2288 infections, the overall sensitivity of the clinical diagnosis of influenza was 38% and the positive predictive value was 32%.
Influence of preparation method on the metal cluster size of platinum/ZSM-5 catalysts as studied with EXAFS (1990)

The size of Pt particles introduced into the channels of ZSM-5 zeolite by two different preparation methods has been studied\nwith EXAFS. ZSM-5 was loaded with 2 wt 5% Pt by ion exchange and by impregnation. By careful calcination of the catalysts\nthe dispersion was maintained. The EXAFS measurements were performed on the reduced system. Analysis of the data\nshowed that in the impregnated sample the platinum was present in particles which on average were smaller than the platinum\nparticles in the ion-exchanged sample. These results corroborate earlier high-resolution electron microscopy measurements\nperformed ex situ on the calcined catalysts. Moreover, the average particle size found from EXAFS analysis agrees well\nwith the HREM results, indicating that dispersion is maintained during reduction. Both techniques indicate particles that\nexceed the dimensions of a zeolite cage at the intersection of the channels. The fact that the impregnated system has smaller\nplatinum particles than the ion-exchanged catalyst can be explained by the presence of additional potassium species in the\npores of the impregnated zeolite. These species inevitably will hinder the migration of platinum to form larger particles.
Comparison of Amitriptyline, Cyclobenzaprine, and Placebo in the Treatment of Fibromyalgia (1994)

Abstract Objective . To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. Methods , Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6‐month prospective, double‐blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. Results . After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6‐month assessment ( P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1‐month evaluation (odds ratio 3.3, 95% confidence interval 1.2—9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long‐term response. Conclusion . Our data confirm the short‐term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long‐term efficacy could not be demonstrated because of a higher‐than‐expected placebo response. Predictors of response to these drugs could not be determined.
Structure of the gene for cartilage matrix protein, a modular protein of the extracellular matrix (1989)

The entire gene for chicken cartilage matrix protein (CMP) has been isolated and characterized by restriction mapping, electron microscopy, nuclease S1 mapping, and sequence analysis. The gene, which is present in a single copy in the chicken genome, is 18 kilobase pairs long and comprises eight exons and seven introns. It has two transcription initiation sites, 8 base pairs from each other. A sequence very homologous to the consensus nuclear factor III binding-site sequence, a CAT- and a TATA-like sequence are found in the promoter region and ATTAAA is used as a polyadenylation signal. The nucleotide sequence defines a primary translation product of 493 amino acids which consists of a 23-amino acid signal peptide and two large repeated domains connected by an epidermal growth factor module. Amino acid sequences homologous to those of the repeated domains are present in the type A repeats of von Willebrand factor, complement factors B and C2, and in the alpha chains of the integrins Mac-1, p150,95, and LFA-1. The exon-intron structure indicates that the CMP gene may have arisen by exon duplication and exon shuffling during evolution. The GT-AG splice rule cannot be applied for the excision of the last intron of the CMP pre-mRNA. The donor splice site of intron G is basically different from the consensus sequence indicating that a novel type of splicing mechanism might exist in cartilage.
Enhanced immunoregulation of mesenchymal stem cells by IL-10-producing type 1 regulatory T cells in collagen-induced arthritis (2016)

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA). A combination of MSCs and Tr1 cells prevented the development of destructive arthritis compared to single cell therapy. These therapeutic effects were associated with an increase in type II collagen (CII)-specific CD4+CD25+Foxp3+ Treg cells and inhibition of CII-specific CD4+IL-17+ T cells. We observed that Tr1 cells produce high levels of IL-10-dependent interferon (IFN)-β, which induces toll-like receptor (TLR) 3 expression in MSCs. Moreover, induction of indoleamine 2,3-dioxygenase (IDO) by TLR3 involved an autocrine IFN-β that was dependent on STAT1 signaling. Furthermore, we observed that production of IFN-β and IL-10 in Tr1 cells synergistically induces IDO in MSCs through the STAT1 pathway. These findings suggest co-administration of MSCs and Tr1 cells to be a novel therapeutic modality for clinical autoimmune diseases.
Attestation-based policy enforcement for remote access (2004)

Intranet access has become an essential function for corporate users. At the same time, corporation's security administrators have little ability to control access to corporate data once it is released to remote clients. At present, no confidentiality or integrity guarantees about the remote access clients are made, so it is possible that an attacker may have compromised a client process and is now downloading or modifying corporate data. Even though we have corporate-wide access control over remote users, the access control approach is currently insufficient to stop these malicious processes. We have designed and implemented a novel system that empowers corporations to verify client integrity properties and establish trust upon the client policy enforcement before allowing clients (remote) access to corporate Intranet services. Client integrity is measured using a Trusted Platform Module (TPM), a new security technology that is becoming broadly available on client systems, and our system uses these measurements for access policy decisions enforced upon the client's processes. We have implemented a Linux 2.6 prototype system that utilizes the TPM measurement and attestation, existing Linux network control (Netfilter), and existing corporate policy management tools in the Tivoli Access Manager to control remote client access to corporate data. This prototype illustrates that our solution integrates seamlessly into scalable corporate policy management and introduces only a minor performance overhead.
Phosphorylation of OmpR by the osmosensor EnvZ modulates expression of the ompF and ompC genes in Escherichia coli. (1989)

EnvZ and OmpR, the regulatory proteins for ompF and ompC expression in Escherichia coli, belong to a modulator-effector family of regulatory proteins which are essential for the response to environmental signals. We show that the soluble cytoplasmic domain of the transmembrane modulator protein EnvZ is phosphorylated in vitro by [gamma-32P]-ATP. We also demonstrate that the phosphate group can, in turn, be transferred to the transcription activator protein OmpR. The pH stability properties of the phosphate groups linked to EnvZ indicate that this molecule contains histidyl phosphate. The invariant His-243 of EnvZ corresponds to the phosphorylated His-48 of the chemotactic modulator protein CheA. Substitution of His-243 with valine produces an EnvZ that is refractory to phosphorylation and can no longer catalyze the transfer of phosphate to OmpR. Furthermore, in a delta envZ strain of E. coli, containing the envZ Val-243 plasmid, ompC expression is elevated 7-fold relative to that found in cells carrying the wild-type envZ plasmid. Based on these results we propose a model in which the phosphorylated state of OmpR modulates the expression of the ompF and ompC genes.
Bruton's tyrosine kinase is present in normal platelets and its absence identifies patients with X‐linked agammaglobulinaemia and carrier females (2001)

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk) and is characterized by an arrest of B-cell development. We analysed Btk protein expression in platelets using flow cytometry and found that normal platelets express large amounts of Btk. Assessment of affected males from 45 unrelated XLA families revealed that platelets of the majority of the patients (37 out of 45 families) had decreased or absent Btk expression, and that platelets from carrier females of these families had both normal and mutated Btk expression, indicating that megakaryocytes in XLA carriers undergo random X-chromosome inactivation. These observations demonstrate that Btk is not crucial for maturation of megakaryocytes and the production of platelets. No correlation between Btk expression in platelets and clinical phenotype was observed in this study. Flow cytometric evaluation using platelets is a simple and rapid method to test Btk expression. It may be used as a screening test for XLA and for carrier detection, followed, if necessary, by more expensive mutation analyses.