gebhart/patrepeval huggingface dataset:
Length-Dependent Aggregation of Uninterrupted Polyalanine Peptides (2011)

Polyalanine (polyA) is the third-most prevalent homopeptide repeat in eukaryotes, behind polyglutamine and polyasparagine. Abnormal expansion of the polyA repeat is linked to at least nine human diseases, and the disease mechanism likely involves enhanced length-dependent aggregation. Because of the simplicity of its side chain, polyA has been a favorite target of computational studies, and because of their tendency to fold into α-helix, peptides containing polyA-rich domains have been a popular experimental subject. However, experimental studies on uninterrupted polyA are very limited. We synthesized polyA peptides containing uninterrupted sequences of 7 to 25 alanines (A7 to A25) and characterized their length-dependent conformation and aggregation properties. The peptides were primarily disordered, with a modest component of α-helix that increased with increasing length. From measurements of mean distance spanned by the polyA segment, we concluded that physiological buffers are neutral solvents for shorter polyA peptides and poor solvents for longer peptides. At moderate concentration and near-physiological temperature, polyA assembled into soluble oligomers, with a sharp transition in oligomer physical properties between A19 and A25. With A19, oligomers were large, contained only a small fraction of the total peptide mass, and slowly grew into loose clusters, while A25 rapidly and completely assembled into small stable oligomers of ~7 nm radius. At high temperatures, A19 assembled into fibrils, but A25 precipitated as dense, micrometer-sized particles. A comparison of these results to those obtained with polyglutamine peptides of similar design sheds light on the role of the side chain in regulating conformation and aggregation.
Removal of lactoferrin from plasma is mediated by binding to low density lipoprotein receptor‐related protein/α2‐macroglobulin receptor and transport to endosomes (1995)

LDL receptor related protein (LRP) is a ubiquitously expressed cell surface receptor that binds, at least in vitro, a plethora of ligands among them alpha 2-macroglobulin and lactoferrin (Lf). The function of LRP in internalisation and distribution of ligands within cellular metabolism is still unclear. We here investigated by combined ligand- and immunoblotting the participation of LRP/alpha 2MR and its associated protein (RAP) in receptor mediated endocytosis of Lf into rat liver. We found LRP highly enriched in sucrose density gradient fractions around density 1.10 g/ml, previously characterised as endosomal fractions. RAP was concentrated in distinct fractions around density 1.14 g/ml. This separation of RAP from LRP/alpha 2MR is physiologically meaningful as RAP avidly binds to LRP/alpha 2MR and by that shuts off all ligand binding function. In endosomal fractions we found one single binding protein for 125I-labelled Lf. With a specific anti LRP/alpha 2MR antibody and ligand blotting with 125I-labelled RAP this endosomal Lf binding site was verified to be LRP/alpha 2MR. Endosomes did not bind labelled Lf when prepared from rats that received an intravenous injection of Lf (20 mg per animal) 20 min prior to preparation. Surprisingly we immunodetected Lf in these endosomes at a position around 600 kDa, comigrating with LRP/alpha 2MR. We determined Lf binding to be optimal at pH 5.8, what led us to suggest the existence of a very stable LF-LRP/alpha 2MR complex in endosomes. These data support the idea of effective binding of Lf at pH as found in inflamed tissue environment where Lf is reported to be involved in leukocyte mediated inflammation regulation.
Endothelin-1 Promotes Ca 2+ Antagonist-Insensitive Coronary Smooth Muscle Contraction Via Activation of ε-Protein Kinase C (2004)

Certain forms of coronary artery disease do not respond to treatment with Ca2+ channel blockers, and a role for endothelin-1 (ET-1) in Ca2+ antagonist-insensitive forms of coronary vasospasm has been suggested; however, the signaling mechanisms involved are unclear. We tested the hypothesis that a component of ET-1-induced coronary smooth muscle contraction is Ca2+ antagonist-insensitive and involves activation of protein kinase C (PKC). Cell contraction was measured in smooth muscle cells isolated from porcine coronary artery, [Ca2+]i was measured in fura-2 loaded cells, and the cytosolic and particulate fractions were examined for PKC activity and reactivity with isoform-specific PKC antibodies using Western blot analysis. In Hank's solution (1 mmol/L Ca2+), ET-1 (10(-7) mol/L) caused a transient increase in [Ca2+]i (236+/-14 nmol/L) followed by a maintained increase in [Ca2+]i (184+/-8 nmol/L) and 35% cell contraction. The Ca2+ channel blockers verapamil and diltiazem (10(-6) mol/L) abolished the maintained ET-1-induced [Ca2+]i, but only partially inhibited ET-1-induced cell contraction to 18%. The verapamil-insensitive component of ET-1 contraction was inhibited by the PKC inhibitors calphostin C and epsilon-PKCV1-2. ET-1 caused translocation of Ca2+-dependent alpha-PKC and Ca2+-independent epsilon-PKC from the cytosolic to the particulate fraction that was inhibited by calphostin C. Verapamil abolished ET-1-induced translocation of alpha-PKC, but not that of epsilon-PKC. Phorbol 12-myristate 13-acetate (10(-6) mol/L), a direct activator of PKC, caused 22% cell contraction, with no increase in [Ca2+]i, and translocation of epsilon-PKC that was inhibited by calphostin C, but not by verapamil. KCl (51 mmol/L), which stimulates Ca2+ influx, caused 35% cell contraction and increase in [Ca2+]i (291+/-11 nmol/L) that were inhibited by verapamil, but not by calphostin C, and did not cause translocation of alpha- or epsilon-PKC. In Ca2+-free (2 mmol/L EGTA) Hank's solution, ET-1 caused 15% cell contraction, with no increase in [Ca2+]i, and translocation of epsilon-PKC that were inhibited by epsilon-PKC V1-2 inhibitory peptide. Thus, a significant component of ET-1-induced contraction of coronary smooth muscle is Ca2+ antagonist-insensitive and involves activation and translocation of Ca2+-independent epsilon-PKC, and may represent a signaling mechanism of Ca2+ antagonist-resistant forms of coronary vasospasm.
Effects of salmon calcitonin on patients with atypical (idiopathic) facial pain: a randomized controlled trial. (1996)

The analgesic properties of salmon calcitonin for the treatment of atypical facial pain (AFP) were investigated. An initial open-label trial of salmon calcitonin in subjects with refractory AFP was followed with a randomized, double-blind, placebo-controlled crossover trial of salmon calcitonin in the management of AFP. Salmon calcitonin (100 IU in 1 mL saline) was administered in an open-label fashion to 13 subjects with refractory AFP five times per week for 6 weeks. In the subsequent randomized investigation, salmon calcitonin (100 IU in 1 mL saline) or placebo (1 mL saline) was delivered three times per week for 3 weeks, with a 1-week washout prior to crossover. The percentage of subjects dropping out (57%) exceeded that reported in other pain studies using calcitonin. Therefore, it was imperative to halt the study for ethical reasons. There was no difference in outcome measures (P > .05) in subjects administered either active drug or placebo, and a high incidence of side effects led to dropout in subjects taking salmon calcitonin. Although salmon calcitonin may have analgesic properties, it is not efficacious for AFP, largely because of the side effects.
Ovarian cancer: natural history and metastatic pattern. (1997)

Ovarian cancer begins at a molecular level, however to date, our knowledge of genetic changes and mechanisms of ovarian tumorigenesis is limited. The natural history of ovarian cancer may depend on different anatomo-clinical and biological factors. In the life history of ovarian cancers the stage, histology, tumor grade, age of the patient and gene abnormalities, both oncogenes (c-myc, H-ra, new) and oncosuppressor genes (p53, in particular), DNA ploidy and steroid receptor status have important prognostic significance. Residual disease, when less than 1 cm, is another important prognostic factor, being significantly associated to the survival and, progression free, improvement in the survival. In the low stage ovarian cancer (Stage IA, IB, IAII,IBII,IC,IIA,IIB,IIC), adjuvant treatment seems not to influence Disease Free Survival (DFS) or Overall Survival (OS) The exception to this rule is when cisplatin regimen is assessed, as it can highly reduce the relapse rate while the survival is not significantly influenced. Ovarian cancers disseminate, primarily by continuity. Lymphatic dissemination to the pelvic and para-aortic lymph nodes (40% of patients at stage III-IV disease) as well as to the peritoneum is common. At the time of diagnosis, bone or brain metastases are rarely present and their presence is not related to the histology or grading of the tumor.
An improved long-acting delivery system for narcotic antagonists. (1981)

The feasibility of using cholesterol-glyceryltristearate matrix for prolonged release of naltrexone was evaluated in rats. Implantable cylindrical pellets (cholesterol 105 mg, glyceryl tristearate 15 mg and naltrexone 30 mg), diameter 4.5 mm, length 9 mm, blocked the antinociceptive action (hot plate 55 degrees C) of 10 mg/kg s.c. challenge dose of morphine in rats for 3 months. The release rate of naltrexone from 10 or 50 mg pellets approximated first-order kinetics with t1/2 alpha of 20-26 days and t1/2 beta 40-60 days. The factors affecting the release of drug from the delivery system were the ratio of cholesterol to naltrexone, drug loading level and surface area to unit volume of dosage form. The minimum release rate of naltrexone to block the effect of 10 mg/kg s.c. dose of morphine in rats was about 4 to 5 microgram/kg/hr. The cumulative urinary excretion of radioactivity from 10 mg [3H] naltrexone pellets implanted s.c. in rats after 30, 60, and 90 days was 17.7, 23.7, and 25.7% of dose respectively and the percent dose released from pellets at these times was 55.8, 68.8, and 78.2 respectively. The devices possess the desirable characteristics of simplicity, nontoxicity, nonirritability, ease of sterilization with ethylene oxide, small size for easy insertion and removal, absence of encapsulation by surrounding tissue, and an extended period of drug release unaffected by body metabolism. Neither deterioration of implant nor gross anatomic or histological changes at the site of implant occurred 6 months to 1 year after implantation and aside from some enhanced sexual activity (e.g., spontaneous penile erections) no side effects were observed in rats, which fed well and gained weight during the entire treatment. The concentrations of free morphine in brains of 30 mg naltrexone pellet-implanted rats were significantly lower (24 and 15%) as compared to the placebo controls 0.5 and 1.0 hr after a 10 mg/kg s.c. dose of [6-3H] morphine. We are currently evaluating these long-acting devices for the duration of effective antagonism to morphine in rhesus monkeys.
Potential applications of fish oils rich in n-3 fatty acids in the palliative treatment of advanced pancreatic cancer (2011)

The palliative treatment of patients with advanced pancreatic cancer (APC) has undergone little advancement in the last 15 years. Novel therapies that have been investigated to extend survival have shown little benefit over existing chemotherapy regimens. Patients with APC often experience significant weight loss, which is one of the primary factors involved in declining quality of life. Recently, the ability of n-3 fatty acid rich oral preparations to attenuate or reverse tumour-related weight loss has been investigated in this patient group with encouraging results. Laboratory investigation has also yielded promising results suggesting a potential direct tumouricidal effect of n-3 fatty acids as well as the putative potentiation of existing chemotherapy regimes. The present review aims to examine the potential applications of fish oils rich in n-3 fatty acids in patients with APC, present a selection of the studies carried out to date and outline avenues of possible further clinical investigation.
Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains (1996)

Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficiency, the choice of the vaccine strain may play an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used for BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated that a great difference exists between the capacity of various BCG strains to multiply and persist in target organs. A much lower recovery of BCG could be shown in mice immunized with Prague and Japanese BCG strains. T-cell responses of BCG-immunized mice were also examined by analyzing T-cell proliferative responses, cytokine production, delayed-type hypersensitivity responses, and cytotoxic activity. All these assays demonstrated that BCG immunization induced strong CD4+ T-cell responses, mostly of the Th1 type, as demonstrated by interleukin-2 and gamma interferon production. These studies also demonstrated that there are differences between BCG strains in stimulating these T-cell responses. A lack of induction of cytotoxic activity was observed following immunization with the Japanese strain. Lower anti-purified protein derivative antibody responses were also observed after intravenous or oral immunization with this BCG strain. Finally, the protective activity of these BCG strains was tested by measuring the capacity of immunized mice to eliminate recombinant Pasteur and Japanese BCG strains which expressed beta-galactosidase. The results of these experiments clearly demonstrated that the Prague and Japanese strains were unable to protect mice against a second mycobacterial challenge whereas mice immunized with the Glaxo, Pasteur, or Russian strain eliminated the recombinant BCG very efficiently. Altogether, the results of the present study strongly support the view that there are considerable differences in the immunogenicity of various BCG vaccine strains and that these differences may play a major role in BCG vaccination efficiency.
Prediction of difficult sequences in solid-phase peptide synthesis (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrediction of difficult sequences in solid-phase peptide synthesisR. C. de L. Milton, Saskia C. F. Milton, and Paul A. AdamsCite this: J. Am. Chem. Soc. 1990, 112, 16, 6039–6046Publication Date (Print):August 1, 1990Publication History Published online1 May 2002Published inissue 1 August 1990https://pubs.acs.org/doi/10.1021/ja00172a020https://doi.org/10.1021/ja00172a020research-articleACS PublicationsRequest reuse permissionsArticle Views1998Altmetric-Citations112LEARN 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 Get e-Alerts
Asymmetric deprotonations: enantioselective syntheses of 2-substituted tert-(butoxycarbonyl)pyrrolidines (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric deprotonations: enantioselective syntheses of 2-substituted tert-(butoxycarbonyl)pyrrolidinesShawn T. Kerrick and Peter BeakCite this: J. Am. Chem. Soc. 1991, 113, 25, 9708–9710Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://pubs.acs.org/doi/10.1021/ja00025a066https://doi.org/10.1021/ja00025a066research-articleACS PublicationsRequest reuse permissionsArticle Views2569Altmetric-Citations259LEARN 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 Get e-Alerts
The Kinetics and Extent of Engraftment of Chronic Myelogenous Leukemia Cells in Non-Obese Diabetic/Severe Combined Immunodeficiency Mice Reflect the Phase of the Donor’s Disease: An In Vivo Model of Chronic Myelogenous Leukemia Biology (1998)

In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using51Cr-labeled cells. The first signs of engraftment for BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0.5%/week). FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor’s disease, thus providing an in vivo model of CML biology. © 1998 by The American Society of Hematology.
Reference Norms For Data Backup And Information Security (2007)

The present article shows that by keeping adherence to the NBR ISO/IEC 17799 ABNT guidelines one canwrite efficient data backup rules, to be inserted into a given Information Security Policy proposal. The importance of following the NBR ISO/IEC 17799 has come to light through a research including internet documents from secure sources, books and other references on the importance of data backup to Information Security, Security Policies and their relation with the NBR ISO/IEC 17799 regarding the best practices for protecting data. The main rules for data backup as stated in the NBR ISO/IEC 17799 have been studied, which has lead to demonstrating how they can be rendered into practices by the actual Information Technology administrator when devising secure data backup procedures. Also, the analysis of the answers of a selected group of Information Security professionals to a questionnaire elaborated to reveal if the respondent would keep adherence to the NBR ISO/IEC 17799 has shown that the vast majority does so, confirming the importance of the ISO document as a main guide to data backup procedures.
Growth-inhibitory effects of the ketone body, monoacetoacetin, on human gastric cancer cells with succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency. (2004)

Parenteral nutrition with MAA may provide preferential energy for patients with some types of gastric cancer with SCOT deficiency.
PET imaging of colorectal cancer in xenograft-bearing mice by use of an 18F-labeled T84.66 anti-carcinoembryonic antigen diabody. (2007)

The 18F-labeled diabody represents a new class of tumor-specific probes for PET that are based on targeting cell surface antigen expression. The 18F-FB-T84.66 diabody can be used for high-contrast small-animal PET imaging of CEA-positive tumor xenografts. It may be translated to the clinic for PET of CEA-positive malignancies.
Performance and reliability analysis of new fault-tolerant advance omega network (2008)

The performance and fault tolerance are two very crucial factors in designing interconnection networks for a multiprocessor system. A new type of MIN, Fault Tolerant Advanced Omega network, which using 4×4. switches, is proposed on the basis of the idea of the Delta network and the Omega network. In this paper, it is proved that 4×4. switches have the better performance/cost ratios than 2×2. switches based on the current level of the VLSI technology. This paper expounds its topological properties and routing algorithm and makes performance/cost ratios comparisons. The mathematical analysis approach is used here to find the probability of acceptance and bandwidth with change in traffic. Furthermore reliability analysis of Fault-Tolerant Advanced Omega Network (FTAON) is discussed in detail, It is seen that FTAON is more reliable and cost effective than other previously proposed MINs of similar class. It has been also observed that it has fault tolerant and nonblocking capability in complex parallel systems.