gebhart/patrepeval huggingface dataset:
CD8+ T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope. (1992)

Cytotoxic T lymphocytes (CTL) recognize short antigenic peptides associated with cell surface class I major histocompatibility complex (MHC) molecules. This association presumably occurs between newly synthesized class I MHC molecules and peptide fragments in a pre-Golgi compartment. Little is known about the factors that regulate the formation of these antigenic peptide fragments within the cell. To examine the role of residues within a core epitope and in the flanking sequences for the generation and presentation of the newly synthesized peptide fragment recognized by CD8+ CTL, we have mutagenized the coding sequence for the CTL epitope spanning residues 202-221 in the influenza A/Japan/57 hemagglutinin (HA). In this study over 60 substitution mutations in the epitope were tested for their effects on target cell sensitization using a cytoplasmic viral expression system. The HA202-221 site contains two overlapping subsites defined by CTL clones 11-1 and 40-2. Mutations in HA residues 204-213 or residues 210-219 often abolished target cell lysis by CTL clones 11-1 and 40-2, respectively. Although residues outside the core epitope did not usually affect the ability to be lysed by CTL clones, substitution of a Gly residue for Val-214 abolished lysis by clone 11-1. These data suggest that residues within a site that affect MHC binding and T cell receptor recognition appear to play the predominant role in dictating the formation of the antigenic complex recognized by CD8+ CTL, and therefore the antigenicity of the protein antigen presented to CD8+ T cells. Most alterations in residues flanking the endogenously expressed epitope do not appreciably affect the generation and recognition of the site.
Influence of physicochemical properties of polylactic acid on the characteristics and in vitro release patterns of polylactic acid microspheres containing local anesthetics. (1982)

DL-Polylactic acid (PLA) microspheres were prepared from three lots of PLA by a solvent-evaporation process and release patterns of butamben, tetracaine and dibucaine from these microspheres were examined. As a first step, the physicochemical characteristics of three lots of PLA were examined. The release mechanism was examined by scanning electron microscopy. Microsphere characteristics and release patterns from the microspheres were dependent on both PLA characteristics and the local anesthetics used for the preparation.
A peek at ice binding by antifreeze proteins (2011)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Impaired enteroendocrine development in intestinal-specificIslet1mouse mutants causes impaired glucose homeostasis (2014)

Enteroendocrine cells secrete over a dozen different hormones responsible for coordinating digestion, absorption, metabolism, and gut motility. Loss of enteroendocrine cells is a known cause of severe congenital diarrhea. Furthermore, enteroendocrine cells regulate glucose metabolism, with the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) playing critical roles in stimulating insulin release by pancreatic β-cells. Islet1 (Isl1) is a LIM-homeodomain transcription factor expressed specifically in an array of intestinal endocrine cells, including incretin-expressing cells. To examine the impact of intestinal Isl1 on glycemic control, we set out to explore the role of intestinal Isl1 in hormone cell specification and organismal physiology. Mice with intestinal epithelial-specific ablation of Isl1 were obtained by crossing Villin-Cre transgenic animals with mice harboring a Isl1(loxP) allele (Isl1(int) model). Gene ablation of Isl1 in the intestine results in loss of GLP-1, GIP, cholecystokinin (CCK), and somatostatin-expressing cells and an increase in 5-HT (serotonin)-producing cells, while the chromogranin A population was unchanged. This dramatic change in hormonal milieu results in animals with lipid malabsorption and females smaller than their littermate controls. Interestingly, when challenged with oral, not intraperitoneal glucose, the Isl-1 intestinal-deficient animals (Isl1(int)) display impaired glucose tolerance, indicating loss of the incretin effect. Thus the Isl1(int) model confirms that intestinal biology is essential for organism physiology in glycemic control and susceptibility to diabetes.
Comparison of the structural and chemical composition of two unique micro/nanostructures produced by femtosecond laser interactions on nickel (2013)

The structural and chemical composition of two unique microstructures formed on nickel, with nanoscale features, produced using femtosecond laser surface processing (FLSP) techniques is reported in this paper. These two surface morphologies, termed mounds and nanoparticle-covered pyramids, are part of a larger class of self-organized micro/nanostructured surfaces formed using FLSP. Cross-sections of the structures produced using focused ion beam milling techniques were analyzed with a transmission electron microscope. Both morphologies have a solid core with a layer of nanoparticles on the surface. Energy dispersive X-ray spectroscopy by scanning transmission electron microscopy studies reveal that the nanoparticles are a nickel oxide, while the core material is pure nickel.
Toward Tissue Engineering of the Knee Meniscus (2001)

This review details current efforts to tissue engineer the knee meniscus successfully. The meniscus is a fibrocartilaginous tissue found within the knee joint that is responsible for shock absorption, load transmission, and stability within the knee joint. If this tissue is damaged, either through tears or degenerative processes, then deterioration of the articular cartilage can occur. Unfortunately, there is a dearth in the amount of work done to tissue engineer the meniscus when compared to other musculoskeletal tissues, such as bone. This review gives a brief overview of meniscal anatomy, biochemical properties, biomechanical properties, and wound repair techniques. The discussion centers primarily on the different components of attempting to tissue engineer the meniscus, such as scaffold materials, growth factors, animal models, and culturing conditions. Our approach for tissue engineering the meniscus is also discussed.
Decision trees for inter-word context dependencies in Spanish continuous speech recognition tasks (1999)

This paper presents a new system for the continuous speech recognition of Spanish, integrating previous works in the fields of acoustic-phonetic decoding and language modelling. Acoustic and language models separately trained with speech and text samples, respectivelyare integrated into one single automaton, and their probabilities combined according to a standard beam search procedure. Two key issues were to adequately adjust the beam parameter and the weight affecting the language model probabilities. For the implementation, a client-server arquitecture was selected, due to the desirable working scene where one or more simple machines in the client side make the speech analysis task, and a more powerful workstation in the server side looks for the best sentence hypotheses. Preliminary experimentation gives promising results with around 90% word recognition rates in a medium size word speech recognition task.
R: A Language and Environment for Statistical Computing (2000)

Most R novices will start with Appendix A [A sample session], page 80.This should give some familiarity with the style of R sessions and more importantly some instant feedback on what actually happens.Many users will come to R mainly for its graphical facilities.
A comparison of two methods for choosing repeatable control strategies for kinematically redundant manipulators (2003)

A kinematically redundant manipulator is a robotic system that has more than the minimum number of degrees of freedom that are required for a specified task. Due to this additional freedom, control strategies may yield solutions which are not repeatable in the sense that the manipulator may not return to its initial joint configuration for closed end effector paths. The authors present two methods for choosing repeatable control strategies which minimize their distance from a non-repeatable inverse with desirable properties. The first method minimizes the integral norm of the difference of the desired inverse and a repeatable inverse. While this is the more appropriate criterion, it results in a difficult optimization. The second method, which minimizes the distance of the null vectors associated with the desired and the repeatable inverses, is somewhat easier to implement. As an illustrative example the pseudoinverse is approximated in a region of the joint space using both techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated with Mycobacterium avium-M. intracellulare: activation of bactericidal activity by GM-CSF (1991)

Treatment of monocytes with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to enhance their antimycobacterial activity in an in vitro assay. Furthermore, Mycobacterium avium-M. intracellulare was found to induce the production of this hemopoietic growth factor. Human peripheral blood mononuclear cells were fractionated by plastic adherence and Percoll density centrifugation, and each population of cells was stimulated with mycobacteria. GM-CSF was produced by both monocytes and large granular lymphocytes (LGL) but not T lymphocytes. The phenotype of the GM-CSF-producing LGL was found to be CD2+, CD16+, and HLA-DR+ but negative for T-cell and monocyte markers. Kinetic studies demonstrated that GM-CSF appeared in the supernatant fluids within 2 days of culture of either monocytes or LGL and continued to be produced up to 7 days of incubation. Northern (RNA) blot analysis of RNA from both cell types demonstrated the expression of GM-CSF message within 24 h of stimulation. From these studies, LGL and monocytes are capable of responding to M. avium-M. intracellulare by producing factors that augment normal immune functions, including the antibacterial capability of monocytes.
Overexpression of Lymphangiogenic Growth Factor VEGF-C in Human Pancreatic Cancer (2001)

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In this study, we characterized VEGF-C expression in cultured human pancreatic cancer cell lines and determined whether the presence of VEGF-C in human pancreatic cancers is associated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was associated with increased lymphatic vessels invasion and lymph node metastasis, but not with decreased patient survival. These findings indicate that VEGF-C and its receptor are commonly overexpressed in human pancreatic cancers and that this factor may contribute to the lymphangiogenic process and metastasis in this disorder.
Comparison of PCR, Culture, and Direct Fluorescent-Antibody Testing for Detection of Bordetella pertussis (1999)

ABSTRACT We prospectively compared the performance of culture, direct fluorescent-antibody testing (DFA), and an in-house-developed PCR test targeting the repeated insertion sequence IS 481 for the detection of Bordetella pertussis in nasopharyngeal swab specimens. We tested 319 consecutive paired specimens on which all three tests were performed. A total of 59 specimens were positive by one or more tests. Of these, 5 were positive by all three tests, 2 were positive by culture and PCR, 16 were positive by PCR and DFA, 28 were positive by PCR only, and 8 were positive by DFA only. Any specimen positive by culture was considered to be a true positive, as were specimens positive by both PCR and DFA. Specimens positive only by PCR or DFA were considered discrepant, and their status was resolved by review of patient histories. Patients with symptoms meeting the Centers for Disease Control and Prevention clinical case definition for pertussis and who had a specimen positive by PCR or DFA were considered to have true B. pertussis infections. Of the 28 patients positive by PCR only, 20 met the clinical case definition for pertussis, while 3 of the 8 patients positive by DFA only met the clinical case definition. After resolution of the status of discrepant specimens, the sensitivity, specificity, positive predictive value, and negative predictive value were 15.2, 100, 100, and 87.5%, respectively, for culture; 93.5, 97.1, 84.3, and 98.9%, respectively, for PCR; and 52.2, 98.2, 82.8, and 92.4%, respectively, for DFA. The actual positive predictive value of PCR was probably greater, as several PCR-positive patients who did not meet the clinical case definition had symptoms consistent with typical or atypical pertussis. PCR is a sensitive and specific method for the detection of B. pertussis.
Template Requirement and Initiation Site Selection by Hepatitis C Virus Polymerase on a Minimal Viral RNA Template (2000)

RNA-dependent RNA polymerase, NS5B protein, catalyzes replication of viral genomic RNA, which presumably initiates from the 3'-end. We have previously shown that NS5B can utilize the 3'-end 98-nucleotide (nt) X region of the hepatitis C virus (HCV) genome as a minimal authentic template. In this study, we used this RNA to characterize the mechanism of RNA synthesis by the recombinant NS5B. We first showed that NS5B formed a complex with the 3'-end of HCV RNA by binding to both the poly(U-U/C)-rich and X regions of the 3'-untranslated region as well as part of the NS5B-coding sequences. Within the X region, NS5B bound stem II and the single-stranded region connecting stem-loops I and II. Truncation of 40 nt or more from the 3'-end of the X region abolished its template activity, whereas X RNA lacking 35 nt or less from the 3'-end retained template activity, consistent with the NS5B-binding site mapped. Furthermore, NS5B initiated RNA synthesis from a specific site within the single-stranded loop I. All of the RNA templates that have a double-stranded stem at the 3'-end had the same RNA initiation site. However, the addition of single-stranded nucleotides to the 3'-end of X RNA or removal of double-stranded structure in stem I generated RNA products of template size. These results indicate that HCV NS5B initiates RNA synthesis from a single-stranded region closest to the 3'-end of the X region. These results have implications for the mechanism of HCV RNA replication and the nature of HCV RNA templates in the infected cells.
The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment (1999)

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g. , cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in clinical trials, the National MS Society's Clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg function/ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (1) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over 1- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.
The Reaction of Hydroxylamine with Activated Acyl Groups. I. Formation of O-Acylhydroxylamine1 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reaction of Hydroxylamine with Activated Acyl Groups. I. Formation of O-Acylhydroxylamine1William P. JencksCite this: J. Am. Chem. Soc. 1958, 80, 17, 4581–4584Publication Date (Print):September 1, 1958Publication History Published online1 May 2002Published inissue 1 September 1958https://doi.org/10.1021/ja01550a040RIGHTS & PERMISSIONSArticle Views1279Altmetric-Citations108LEARN 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 InReddit PDF (541 KB) Get e-Alerts Get e-Alerts
The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo (2015)

Despite recent advances in the development of novel therapies against castration-resistant prostate cancer, the advanced form of the disease remains a major treatment challenge. Aberrant sphingolipid signaling through sphingosine kinases and their product, sphingosine-1-phosphate, can promote proliferation, drug resistance, angiogenesis, and inflammation. The sphingosine kinase 2 inhibitor ABC294640 is undergoing clinical testing in cancer patients, and in this study we investigated the effects this first-in-class inhibitor in castration-resistant prostate cancer. In vitro, ABC294640 decreased prostate cancer cell viability as well as the expression of c-Myc and the androgen receptor, while lysosomal acidification increased. ABC294640 also induced a greater than 3-fold increase in dihydroceramides that inversely correlated with inhibition of dihydroceramide desaturase (DEGS) activity. Expression of sphingosine kinase 2 was dispensable for the ABC294640-mediated increase in dihydroceramides. In vivo, ABC294640 diminished the growth rate of TRAMP-C2 xenografts in syngeneic hosts and elevated dihydroceramides within tumors as visualized by MALDI imaging mass spectroscopy. The plasma of ABC294640-treated mice contained significantly higher levels of C16- and C24:1-ceramides (but not dihydro-C16-ceramide) compared with vehicle-treated mice. In summary, our results suggest that ABC294640 may reduce the proliferative capacity of castration-resistant prostate cancer cells through inhibition of both sphingosine kinase 2 and dihydroceramide desaturase, thereby providing a foundation for future exploration of this small-molecule inhibitor for the treatment of advanced disease.
The roles of amantadine, rimantadine, ursodeoxycholic acid, and NSAIDs, alone or in combination with alpha interferons, in the treatment of chronic hepatitis C. (1999)

Although alpha interferons are currently the standard treatments for chronic hepatitis C, they are effective in only 15% to 20% of patients. This low success rate has prompted research into new approaches for maximizing responses to alpha interferons. A variety of drugs have been investigated alone or in combination with alpha interferons. Of these agents, ribavirin is currently the most promising adjuvant, and the combination therapy of ribavirin plus recombinant interferon alfa-2b is reviewed in detail elsewhere in this issue (see Davis article, pp. 49-55; and McHutchison article, pp. 57-65). This article reviews the literature concerning studies of amantadine, rimantadine, ursodeoxycholic acid (UDCA), and nonsteroidal anti-inflammatory drugs (NSAIDs), which are the most commonly used alternatives to ribavirin. As of this writing, virologic response rates have been unsatisfactory when these agents are used as monotherapies. Furthermore, combining alpha interferons with either UDCA or NSAIDs does not appear to improve sustained virologic response rates. However, combination regimens composed of an alpha interferon plus amantadine, or an alpha interferon plus rimantadine, or triple therapy with either amantadine or rimantadine plus an alpha interferon and ribavirin, warrant further investigation.
Thiazolidenediones Mediate Apoptosis in Prostate Cancer Cells in Part through Inhibition of Bcl-xL/Bcl-2 Functions Independently of PPARγ (2005)

Certain members of the thiazolidenedione family of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as troglitazone and ciglitazone, exhibit antitumor effects; however, the underlying mechanism remains inconclusive. This study shows that the effect of these thiazolidenedione members on apoptosis in prostate cancer cells is independent of PPARgamma activation. First, close structural analogues of thiazolidenediones, whereas devoid of PPARgamma activity, retain the ability to induce apoptosis with equal potency. Second, both PC-3 (PPARgamma-expressing) and LNCaP (PPARgamma-deficient) cells are sensitive to apoptosis induction by troglitazone and its PPARgamma-inactive analogue irrespective of their PPARgamma expression status. Third, rosiglitazone and pioglitazone, potent PPARgamma agonists, show marginal effects on apoptosis even at high concentrations. Evidence indicates that the apoptotic effect of troglitazone, ciglitazone, and their PPARgamma-inactive analogues 5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-ylmethoxy)-benzylidene]-2,4-thiazolidine-dione (Delta2-TG) and 5-[4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione, respectively, is in part attributable to their ability to inhibit the anti-apoptotic functions of Bcl-xL and Bcl-2. Treatment of PC-3 cells with troglitazone or Delta2-TG led to reduced association of Bcl-2 and Bcl-xL with Bak, leading to caspase-dependent apoptosis. Bcl-xL overexpression protects LNCaP cells from apoptosis induction by troglitazone and Delta2-TG in an expression level-dependent manner. Considering the pivotal role of Bcl-xL/Bcl-2 in regulating mitochondrial integrity, this new mode of mechanism provides a framework to account for the PPARgamma-independent action of thiazolidenediones in inducing apoptosis in cancer cells. Moreover, dissociation of these two pharmacologic activities provides a molecular basis to develop novel Bcl-xL/Bcl-2 inhibitors, of which the proof of principle is illustrated by a Delta2-TG analogue with potent in vivo antitumor activities.