gebhart/patrepeval huggingface dataset:
Animal Models of Medulloblastomas and Related Primitive Neuroectodermal Tumors. A Review (1995)

Primitive neuroectodermal tumors (PNET) belong to a family of pediatric neoplasms of the central nervous system (CNS) that are composed predominantly of primitive neuroepithelial cells. Among the different CNS PNET, those arising in the posterior fossa (i.e. medulloblastomas) are prototypical of this group of brain tumors. The basic cell biology of PNET is incompletely understood, but recent studies of human PNET biopsies and cell lines derived therefrom demonstrate that neoplastic cells in human PNET recapitulate many of the phenotypic properties of immature CNS neurons or their progenitors. Based on these findings, it has been possible to develop several animal models of human PNET that will enhance efforts to gain fundamental insights into the induction and progression of PNET. In addition, these model systems will enable emerging gene therapies to be targeted specifically for human PNET. Accordingly, this review summarizes current understanding of the cell biology of human PNET, particularly medulloblastomas, and it highlights the most salient features of representative in vivo model systems of human PNET that are relevant to future studies of these tumors.
MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space (2012)

Since its introduction in 2001, MrBayes has grown in popularity as a software package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) methods. With this note, we announce the release of version 3.2, a major upgrade to the latest official release presented in 2003. The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly. The introduction of new proposals and automatic optimization of tuning parameters has improved convergence for many problems. The new version also sports significantly faster likelihood calculations through streaming single-instruction-multiple-data extensions (SSE) and support of the BEAGLE library, allowing likelihood calculations to be delegated to graphics processing units (GPUs) on compatible hardware. Speedup factors range from around 2 with SSE code to more than 50 with BEAGLE for codon problems. Checkpointing across all models allows long runs to be completed even when an analysis is prematurely terminated. New models include relaxed clocks, dating, model averaging across time-reversible substitution models, and support for hard, negative, and partial (backbone) tree constraints. Inference of species trees from gene trees is supported by full incorporation of the Bayesian estimation of species trees (BEST) algorithms. Marginal model likelihoods for Bayes factor tests can be estimated accurately across the entire model space using the stepping stone method. The new version provides more output options than previously, including samples of ancestral states, site rates, site d(N)/d(S) rations, branch rates, and node dates. A wide range of statistics on tree parameters can also be output for visualization in FigTree and compatible software.
Dimerization of Human Growth Hormone in the Presence of Metal Ions (2000)

Zn(2+) and Co(2+) ions are known to promote human growth hormone reversible dimerization. In these studies, dimerization was also shown to be initiated by nine other metal ions: Cd(2+), Hg(2+), Cu(2+), Ag+, Au(3+), Au+, Pd(2+), Ni(2+), and Pt(4+). In some cases (Hg(2+), Ag(+), Au(3+), and Ni(2+)) formation of higher oligomers also took place. In addition further detailed investigation of dimerization in the presence of Zn(2+) ions was carried out.
Inhibition of γ-Glutamylcysteine Synthetase by l-Methionine-S-sulfoximine (1973)

Abstract Methionine sulfoximine was found to be an effective inhibitor of γ-glutamylcysteine synthetase. The data indicate that methionine sulfoximine binds to the glutamate site of the enzyme and that, in the presence of ATP and metal ions (Mg2+ or Mn2+), it is converted to methionine sulfoximine phosphate. Of the four stereoisomers of methionine sulfoximine, only l-methionine-S-sulfoximine inhibits the enzyme; this is the same stereoisomer which inhibits glutamine synthetase and which causes convulsions in mice. Chemically synthesized l-methionine sulfoximine phosphate inhibits the enzyme in the presence of Mg2+ or Mn2+. These findings indicate that the mechanism of inhibition of γ-glutamylcysteine synthetase by methionine sulfoximine is similar to that by which this compound was previously shown to inhibit glutamine synthetase. However, methionine sulfoximine phosphate is less tightly bound to γ-glutamylcysteine synthetase than to glutamine synthetase; thus, under certain conditions methionine sulfoximine phosphate can be released from inhibited γ-glutamylcysteine synthetase with restoration of catalytic activity. The findings are in accord with the view that enzyme-bound γ-glutamyl phosphate is an intermediate in the reaction catalyzed by γ-glutamylcysteine synthetase, and that phosphorylation of methionine sulfoximine by the enzyme reflects the phosphorylation step of the normal catalytic reaction.
Effect of Lactobacillus GG and Breast-feeding in the Prevention of Rotavirus Nosocomial Infection (2002)

In our study, GG was ineffective in preventing nosocomial rotavirus infections, whereas breast-feeding was effective.
An Erythromycin Derivative Produced by Targeted Gene Disruption in Saccharopolyspora erythraea (1991)

Derivatives of erythromycin with modifications at their C-6 position are generally sought for their increased stability at acid pH, which in turn may confer improved pharmacological properties. A recombinant mutant of the erythromycin-producing bacterium, Saccharopolyspora erythraea, produced an erythromycin derivative, 6-deoxyerythromycin A, that could not be obtained readily by chemical synthesis. This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB). Enzymes normally acting on EB can process the alternative substrate DEB to form the biologically active erythromycin derivative lacking the C-6 hydroxyl group.
Mechanism-based selection of pharmacologic agents for rosacea. (2004)

All effective agents used to treat rosacea have a common mechanism of action: anti-inflammatory effects. Concomitant with this, many of these agents also show antioxidant effects. Both anti-inflammatory and antioxidant effects may address the proposed underlying pathophysiology of rosacea. Future topical formulations may involve the combination of active pharmacologic agents and sunscreens or sun blocks to address the proposed etiologic role played by UV radiation in the pathophysiology of rosacea.
APC gene: database of germline and somatic mutations in human tumors and cell lines (1996)

A database is described in which over 700 mutations in the human APC gene of tumors (colon cancer predominantly) are compiled from the literature. It includes both molecular informations about the mutations and also clinical data about the patients. A software have been designed in order to analyse all these informations in the database.
A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo (2010)

Argonaute/Piwi proteins associate with small RNAs that typically provide sequence specificity for RNP function in gene and genome regulation. Here we show that Twi12, a Tetrahymena Piwi protein essential for growth, is loaded with mature tRNA fragments. The tightly bound ~18- to 22-nucleotide tRNA 3' fragments are biochemically distinct from the tRNA halves produced transiently in response to stress. Notably, the end positions of Twi12-bound tRNA 3' fragments precisely match RNAs detected in total small RNA of mouse embryonic stem cells and human cancer cells. Our studies demonstrate unanticipated evolutionary conservation of mature tRNA processing to tRNA fragment small RNAs.
Shades of grey: On the effectiveness of reputation-based &#x201C;blacklists&#x201D; (2008)

Malicious code, or malware, executed on compromised hosts provides a platform for a wide variety of attacks against the availability of the network and the privacy and confidentiality of its users. Unfortunately, the most popular techniques for detecting and preventing malware have been shown to be significantly flawed, and it is widely believed that a significant fraction of the Internet consists of malware infected machines. In response, defenders have turned to coarse-grained, reputation-based techniques, such as real time blackhole lists, for blocking large numbers of potentially malicious hosts and network blocks. In this paper, we perform a preliminary study of a type of reputation-based blacklist, namely those used to block unsolicited email, or spam. We show that, for the network studied, these blacklists exhibit non-trivial false positives and false negatives. We investigate a number of possible causes for this low accuracy and discuss the implications for other types of reputation-based blacklists.
Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the micro(3) opiate receptor subtype: a hormonal role for endogenous morphine. (2004)

Studies from our laboratory have revealed a novel micro opiate receptor, micro(3), which is expressed in both human vascular tissues and leukocytes. The micro(3) receptor is selective for opiate alkaloids, insensitive to opioid peptides and is coupled to constitutive nitric oxide (cNO) release. We now identify the micro(3) receptor characteristics in mammalian gut tissues. It appears that the various regions of the mouse gut release low levels of NO (0.02 to 4.6 nM ) in a pulsatile manner. We demonstrate that morphine stimulates cNO release (peak level 17 nM) in the mouse stomach, small intestine and large intestine in a naloxone and L-NAME antagonizable manner. Opioid peptides do not exhibit cNO-stimulating capabilities in these tissues. Taken together, we surmise morphine acts as a hormone to limit gut activity via micro(3) coupled to NO release since micro opiate receptors are found in the gut and endogenous morphine is not but is found in blood.
More powerful procedures for multiple significance testing (1990)

The problem of multiple comparisons is discussed in the context of medical research. The need for more powerful procedures than classical multiple comparison procedures is indicated. To this end some new, general and simple procedures are discussed and demonstrated by two examples from the medical literature: the neuropsychologic effects of unidentified childhood exposure to lead, and the sleep patterns of sober chronic alcoholics.
Operator controlled device-to-device communications in LTE-advanced networks (2012)

This article studies direct communications between user equipments in the LTE-advanced cellular networks. Different from traditional device-to-device communication technologies such as Bluetooth and WiFi-direct, the operator controls the communication process to provide better user experience and make profit accordingly. The related usage cases and business models are analyzed. Some technical considerations are discussed, and a resource allocation and data transmission procedure is provided.
Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity (2002)

The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells.Studies described here examine the functional significance of cathepsin S inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for Sjgren syndrome.Specific inhibitor of cathepsin S (Clik60) in vitro markedly impaired presentation of an organ-specific autoantigen, 120-kDa -fodrin, by interfering with MHC class II-peptide binding.Autoantigen-specific T cell responses were significantly and dose-dependently inhibited by incubation with Clik60, but not with inhibitor s of cathepsin B or L. Clik60 treatment of mouse salivary gland cells selectively inhibited autopeptide-bound class II molecules.Moreover, the treatment with Clik60 in vivo profoundly blocked lymphocytic infiltration into the salivary and lacrimal glands, abrogated a rise in serum autoantibody production, and led to recovery from autoimmune manifestations.Thus, inhibition of cathepsin S in vivo alters autoantigen presentation and development of organ-specific autoimmunity.These data identify selective inhibition of cysteine protease cathepsin S as a potential therapeutic strategy for autoimmune disease processes.
Differentiation of Effector CD4 T Cell Populations (2010)

CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics (2014)

The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent binding to DNA. In recent years, this picture has increased in complexity, based on studies indicating that cellular molecules other than DNA may potentially act as targets, and that part of the antitumor effects of platinum drugs occurs through modulation of the immune system. These immunogenic effects include modulation of STAT signaling; induction of an immunogenic type of cancer cell death through exposure of calreticulin and release of ATP and high-mobility group protein box-1 (HMGB-1); and enhancement of the effector immune response through modulation of programmed death receptor 1-ligand and mannose-6-phosphate receptor expression. Both basic and clinical studies indicate that at least part of the antitumor efficacy of platinum chemotherapeutics may be due to immune potentiating mechanisms. Clinical studies exploiting this novel mechanism of action of these old cancer drugs have been initiated. Here, we review the literature on the immunogenic effects of platinum, summarize the clinical advances using platinum as a cytotoxic compound with immune adjuvant properties, and discuss the limitations to these studies and the gaps in our understanding of the immunologic effects of these drugs. Clin Cancer Res; 20(11); 2831-7. ©2014 AACR.
Leveraging Identity-Based Cryptography for Node ID Assignment in Structured P2P Systems (2008)

Structured peer-to-peer (P2P) systems have grown enormously because of their scalability, efficiency, and reliability. These systems assign a unique identifier to each user and object. However, current assignment schemes allow an adversary to carefully select user IDs and/or simultaneously obtain many pseudo-identities-ultimately leading to an ability to disrupt the P2P system in very targeted and dangerous ways. In this paper, we propose novel ID assignment protocols based on identity-based cryptography. This approach permits the acquisition of node IDs to be tightly regulated without many of the complexities and costs associated with traditional certificate solutions. We broadly consider the security requirements of ID assignment and present three protocols representing distinct threat and trust models. A detailed empirical study of the protocols is given. Our analysis shows that the cost of our identity-based protocols is nominal, and that the associated identity services can scale to millions of users using a limited number of servers.
Translocation t(2;5) is not a primary event in Hodgkin's disease. Simultaneous immunophenotyping and interphase cytogenetics. (1996)

A number of neoplastic disorders are characterized by recurrent chromosome aberrations. One of these is the translocation t(2;5), which is found in a considerable percentage of large-cell anaplastic lymphomas. This translocation results in the fusion of two genes, alk and npm. The recent discovery of alk/npm mRNA in 11 of 13 cases of Hodgkin's disease has caused a controversial discussion concerning the question of whether t(2;5) is also present in Hodgkin and Reed-Sternberg cells. We tackled this problem on the molecular cytogenetic level by combined CD30 immunophenotyping and interphase cytogenetics. Using a pair of DNA probes flanking both sides of the npm gene breakpoint at 5q35 we were able to prove, at least in 12 of 13 cases of Hodgkin's disease, that all CD30-positive Hodgkin and Reed-Sternberg cells lacked the translocation t(2;5). Fifteen to forty-five Hodgkin/Reed-Sternberg cells were analyzed per case (mean, 27). Our findings indicate that this translocation is not a primary event in the development of Hodgkin's disease.
Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors (2007)

An involvement of the transient receptor potential vanilloid (TRPV) 1 channel in the regulation of body temperature (T(b)) has not been established decisively. To provide decisive evidence for such an involvement and determine its mechanisms were the aims of the present study. We synthesized a new TRPV1 antagonist, AMG0347 [(E)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide], and characterized it in vitro. We then found that this drug is the most potent TRPV1 antagonist known to increase T(b) of rats and mice and showed (by using knock-out mice) that the entire hyperthermic effect of AMG0347 is TRPV1 dependent. AMG0347-induced hyperthermia was brought about by one or both of the two major autonomic cold-defense effector mechanisms (tail-skin vasoconstriction and/or thermogenesis), but it did not involve warmth-seeking behavior. The magnitude of the hyperthermic response depended on neither T(b) nor tail-skin temperature at the time of AMG0347 administration, thus indicating that AMG0347-induced hyperthermia results from blockade of tonic TRPV1 activation by nonthermal factors. AMG0347 was no more effective in causing hyperthermia when administered into the brain (intracerebroventricularly) or spinal cord (intrathecally) than when given systemically (intravenously), which indicates a peripheral site of action. We then established that localized intra-abdominal desensitization of TRPV1 channels with intraperitoneal resiniferatoxin blocks the T(b) response to systemic AMG0347; the extent of desensitization was determined by using a comprehensive battery of functional tests. We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T(b).
The IL-15/IL-15Rα on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells (2007)

We previously described unique features of the IL-15 receptor (IL-15R)alpha. IL-15Ralpha by itself forms stable complexes with IL-15 on cell surfaces and presents IL-15 in trans to neighboring natural killer/T cells. Moreover, the membrane IL-15/IL-15Ralpha complexes (membIL-15) undergo endosomal internalization but survive lysosomal degradation, allowing the complexes to recycle back to the cell surface. Here, we show that membIL-15+ cells act as a persistent source of IL-15 for the surrounding microenvironment (intercellular reservoir effect). Additionally, membIL-15+ cells give rise to augmented retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15 retention was particularly associated with lungs, rather than with lymph nodes, in normal unstimulated mice, which correlated with the preferential homing of antigen-specific CD8 T cells to lungs during their contraction phase in an IL-15Ralpha-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused sustained IL-15 signal transduction in the target cells. Collectively, these characteristics define IL-15 as a unique cytokine with prolonged in vivo survival and sustained biological action on the target cells, which may account for the proposed persistent action of IL-15 that helps the long-term survival of functional CD8 memory T cells in vivo.
Specificity and affinity of monoclonal antibodies against carcinoembryonic antigen. (1992)

The binding specificities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen (CEA) from 12 different research groups were studied by immunohistochemistry and immuno flow cytometry. In addition, the binding constant for the interaction between Mab and CEA was determined by a solution-phase assay. Cryostat sections of colon carcinoma and normal colon, stomach, liver, pancreas, and spleen were studied by immunohistochemistry. Peripheral blood granulocytes, monocytes, and lymphocytes were assayed by immuno flow cytometry. The Mabs used here have previously been classified into five essentially nonoverlapping epitope groups (GOLD 1-5) (Cancer Res., 49: 4852-4858, 1989). Most Mabs cross-reacted with different normal tissues, ranging from highly cross-reactive Mabs (positive reaction with 8 of 9 discriminating tissues) to relatively specific Mabs (positive reaction with 1 of 9 discriminating tissues). Five Mabs (10%) were specific, reacting only with colon carcinoma, normal colon mucosa, and normal gastric foveola. There was a correlation between epitope group and binding specificity. Mabs with a high degree of CEA specificity almost exclusively belonged to epitope groups 1, 2, and 3, while highly cross-reactive Mabs belonged to epitope groups 4 and 5. There was no correlation between antibody specificity and affinity for CEA. Specific Mabs with high as well as low affinity were found.
Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice (2000)

The dose- and time-dependent changes of in vivo radioligand binding to the neuronal membrane dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were examined in mouse brain after MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administrations. Regional brain distribution studies were done in male C57BL/6 mice using simultaneous injections of d-threo-[(3)H]methylphenidate (DAT) and (+)-alpha-[(11)C]dihydrotetrabenazine (VMAT2). Single (55 mg/kg i.p. ) or multiple (4 x 10 mg/kg i.p., 1-hour intervals) administration of MPTP caused significant reductions in [(3)H]methylphenidate and [(11)C]dihydrotetrabenazine specific striatal binding, measured 14 days later. The single high dose of MPTP produced greater losses of [(11)C]dihydrotetrabenazine binding than did the multiple MPTP dosing regimen. Using the single high dose of MPTP, changes of in vivo binding of the two radioligands were determined at 1, 3, and 14 days after neurotoxin injection. At 1 day, there are large losses of [(3)H]methylphenidate binding (DAT) but no changes in [(11)C]dihydrotetrabenazine binding to the VMAT2 site in the striatum. At 3 and 14 days, there were >50% losses of binding of both bot radioligands, but significantly (P < 0.001) greater losses of VMAT2 binding of [(11)C]dihydrotetrabenazine. These studies indicate that the losses of the neuronal membrane and vesicular transporters are not always equal, and do not occur in the same time frame, after administration of the neurotoxin MPTP.