gebhart/patrepeval huggingface dataset:
Deficits in social behavior and sensorimotor gating in mice lacking phospholipase Cβ1 (2007)

Abnormal phospholipid metabolism has been implicated in the pathogenesis of schizophrenia, and it was reported that phospholipase C (PLC) beta1 is reduced in specific brain areas of patients with schizophrenia. However, the causal relationship of the PLCbeta1 gene with behavioral symptoms of schizophrenia remains unclear. To address this issue, we have examined the mutant mice lacking PLCbeta1 for schizophrenia-related phenotypes by performing various behavioral tests, including general locomotor activity, sensorimotor gating, social behaviors, and learning and memory. Phospholipase C beta1 knockout mice showed hyperactivities in an open field. They showed impaired prepulse inhibition of acoustic startle response, which was ameliorated by a systemic administration of an antipsychotic D2-receptor antagonist, haloperidol. In addition, they showed abnormal social behaviors, such as lack of barbering behavior, socially recessive trait and lack of nesting behavior. Furthermore, they showed impaired performance in the delayed-non-match-to-sample T-maze test. The present results show that the PLCbeta1 mutant mice share some of the behavioral abnormalities that have been reported in patients with schizophrenia. Thus, the PLCbeta1-linked signaling pathways may be involved in the neural system whose function is disrupted in the pathogenesis of schizophrenia.
The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination (2002)

The mismatch-repair (MMR) system plays a central role in maintaining genetic stability and requires evolutionarily conserved protein factors, including MutS and MutL homologs. Since the discovery of a link between the malfunction of post-replicative MMR and human cancers, a number of works have focused on the function of MutS and MutL homologs in the correction of replication errors. However, several MutS-like and MutL-like proteins also participate in meiotic recombination. The MutL homolog MLH3 has been recently identified in mammals. Several pieces of evidence support a role for this protein in post-replicative MMR. To investigate whether MLH3 also acts during meiotic recombination, we analyzed its expression in mammalian germ cells. The MLH3 gene is expressed in mouse meiotic cells and in human testis, and, as revealed by immunoprecipitation assays, the MLH3 protein is found in mouse spermatocytes. We further demonstrate that the meiosis-specific MSH4 protein, known to participate to meiotic recombination, is co-immunoprecipitated with MLH3 from mouse meiotic cell extracts. In addition, the two MLH3 protein isoforms potentially expressed in human testis (hMLH3 and hMLH3 Delta 7) interact in vitro with the hMSH4 protein. These interaction data suggest that MLH3 is associated with MSH4 in mammalian meiotic cells, and strongly support the possibility that MLH3 plays a role in mammalian meiotic recombination.
Calcitonin induction of a persistent activated state of adenylate cyclase in human breast cancer cells (T 47D). (1981)

In a calcitonin-responsive human breast cancer cell line (T 47D), specific receptors exist for calcitonin in intact cells, which show saturable binding which is only slowly and incompletely reversible.Full stimulation of cyclic AMP production in the cells was achieved with less than 50% receptor occupancy.Pretreatment of cells in culture with calcitonin, followed by washing, led to loss of adenylate cyclase response to calcitonin in homogenates.This took place rapidly, reaching a maximum after 15 min of preincubation with 3 r m salmon calcitonin, and was associated with a substantial increase in basal adenylate cyclase activity, which was dose-dependent and agonist-specific, in that it did not occur upon treatment of the cells with prostaglandin Ez.Receptor loss, as measured by decrement in specific binding of ["'T]calcitonin to intact cells, took place more slowly, requiring at least 1 h for completion.Recovery of adenylate cyclase responsiveness and return of basal activity to normal was a relatively slow process, always requiring more than 24 h for completion.Neither the desensitization nor the persistent basal activity could be transferred in the cytosol compartment of calcitonin-preincubated cells.When calcitonin-preincubated cells were washed, and at intervals thereafter, the production of cyclic AMP was measured in the presence of a phosphodiesterase inhibitor, a 120fold rise in basal cyclic AMP production was observed, and the response to added calcitonin was lost.Return of basal activity and of calcitonin responsiveness followed a time course similar to that seen in recovery of adenylate cyclase response.The results indicate the ability of calcitonin to induce rapidly a persistent state of adenylate cyclase activation which remains stable for several hours.This may be due to persistent tight binding of calcitonin but may also be related to changes induced by calcitonin in availability or function of nucleotide regulatory units.Calcitonin receptors and calcitonin-responsive adenylate cyclase in cancer cell lines show the same structural specificities that would be expected of a physiological calcitonin receptor (1-3).In a human lung cancer cell line (BEN cells), calcitonin induces subsensitivity to itself (1, 2, 4) in a manner similar to that found in organ culture of bone (5) and in lymphoid cells (6).This phenomenon may be related to that
A Novel Agarose Acrobeads Protein A Column for Selective Immunoadsorbance of Whole Blood: Performance, Specificity and Safety (1992)

The present study describes the performance and safety parameters of a novel column composed of protein A linked to acrobeads. Hemoperfusion of anticoagulated whole human blood was carried out in a closed system. Specific adsorption of IgG was documented in whole blood, plasma and IgG diluted in saline. Specific activity of the column was 3.52 mg/ml beads. These studies revealed slight changes in platelet counts and minor hemolysis. The relatively short period needed for maximal hemoperfusion effect and safety may enable the use of this novel therapeutic approach in clinical practice.
Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus (2000)

The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model. Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus, there is significant association between repeated failure times for individual patients.
Nanomedicines for Cancer Therapy: An Update of FDA Approved and Those under Various Stages of Development (2014)

Nanomaterials, with their size range (1-100 nm) that corresponds to basic biological materials such as DNA, vastly increased surface area (1000 m 2 /g) and unique mechanical, electronic, photonic and magnetic properties are projected to have a wide range of applications from drug and gene delivery to biomedical imaging and more recently to personalized medicine. The major advantages of using nanomaterials as a carrier for anticancer agents are the possibility of targeted delivery to the tumor, tumor imaging, their ability to hold thousands of molecules of a drug and also their ability to overcome solubility, stability and resistance issues. Currently, there are several nanotechnology-enabled diagnostic and therapeutic agents undergoing clinical trials and a few are already approved by the FDA. Targeted delivery of anticancer agents is achieved by exploiting a unique characteristic of the tumor cells called "the Enhanced Permeation and Retention Effect (EPR effect). In addition to this passive targeting based mainly on size, the nanoparticle surface may be modified with a variety of ligands that would interact with specific receptors over-expressed on the surface of the tumor cells, thus imparting specificity for active targeting. Site-specific release of a drug contained in a nanoparticulate system by the application of external stimuli such as hyperthermia to a thermosensitive device is another innovative strategy for targeted delivery. This review provides an update on the FDA approved cancer nanomedicines such as Abraxane, Doxil, daunoxome, Oncaspar, DepoCyt and those in nanoplatforms that have reached an advanced stage of clinical development utilizing liposomes, lipid nanoparticles, lipoplexes, albumin nanospheres, thermosensitive devices, micelles and gold nanoparticles.
Employing Blockchain Technology for Decentralized Crowdsourced Data Access and Management (2019)

In recent years, the crowdsourced data analytics have gained an unprecedented interest and adoption from the research communities. In data crowdsourcing, large scientific problems can be solved by utilizing collective human intelligence, where various researchers or groups work on solving various sub-problems. However, the main challenges that encompasses a crowdsourcing system are data access, management, and analysis along with user privacy and trust preservation. In this paper, we present a decentralized data access and control framework to handle data crowdsourcing using blockchain technology. Leveraging on blockchain, our permissioned system enables confidentiality, accountability and traceability of the Crowdsourced data while maintaining control of it via Proof of Stake consensus algorithm. The proposed framework will be employed to crowdsource operational data to the National Energy Research Scientific Computing Center (NERSC) users at Lawrence Berkeley National Laboratory.
Mechanisms that determine plasma cell lifespan and the duration of humoral immunity (2010)

Humoral immunity following vaccination or infection is mainly derived from two types of cells: memory B cells and plasma cells. Memory B cells do not actively secrete antibody but instead maintain their immunoglobulin in the membrane-bound form that serves as the antigen-specific B-cell receptor. In contrast, plasma cells are terminally differentiated cells that no longer express surface-bound immunoglobulin but continuously secrete antibody without requiring further antigenic stimulation. Pre-existing serum or mucosal antibody elicited by plasma cells (or other intermediate antibody-secreting cells) represents the first line of defense against reinfection and is critical for protection against many microbial diseases. However, the mechanisms involved with maintaining long-term antibody production are not fully understood. Here, we examine several models of long-term humoral immunity and present a new model, described as the 'Imprinted Lifespan' model of plasma cell longevity. The foundation of this model is that plasma cells are imprinted with a predetermined lifespan based on the magnitude of B-cell signaling that occurs during the induction of an antigen-specific humoral immune response. This represents a testable hypothesis and may explain why some antigen-specific antibody responses fade over time whereas others are maintained essentially for life.
Expression of the bcl‐2 gene family in normal and malignant breast tissue: Low bax‐α expression in tumor cells correlates with resistance towards apoptosis (1995)

We have studied the expression of the apoptosis-regulating genes bcl-2, bcl-x, bax and APO-1/fas (CD95) in human breast cancer. The expression pattern of these genes in human breast-cancer tissues and breast-cancer-derived cell lines was compared to that seen in normal breast epithelium and breast epithelial cell lines. No difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and tumor tissue or breast cancer and non-malignant epithelial cell lines. In contrast, bax-alpha, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal cell lines and breast tissue, whereas only weak or no expression could be detected in cancer-cell lines and malignant tissue. In contrast to malignant cell lines, which express low levels of bax-alpha, non-malignant epithelial cell lines displaying high amounts of bax-alpha were highly sensitive to induction of programmed cell death by both serum starvation and APO-1/fas (CD95) triggering. We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti-apoptosis genes (such as bcl-2/bcl-x) and apoptosis-promoting genes (bax).
Synthesis and biological activity of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine: water-soluble and peripherally selective adenosine agonists. (1992)

A series of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine was synthesized, revealing that N6-(p-sulfophenyl)adenosine (10b) is a moderately potent (Ki vs [3H]PIA in rat cortical membranes was 74nM) and A1-selective (120-fold) adenosine agonist, of exceptional aqueous solubility of > 1.5 g/mL (approximately 3 M). Compound 10b was very potent in inhibiting synaptic potentials in gerbil hippocampal slices with an IC50 of 63 nM. At a dose of 0.1 mg/kg ip in rats, 10b inhibited lipolysis (a peripheral A1 effect) by 85% after 1 h. This in vivo effect was reversed using the peripherally selective A1-antagonist 1,3-dipropyl-8-[p-(carboxyethynyl)phenyl]xanthine (BW1433). The same dose of 10b in NIH Swiss mice (ip) was nearly inactive in locomotor depression, an effect that has been shown to be centrally mediated when elicited by lower doses of other potent adenosine agonists, such as N6-cyclohexyladenosine (CHA) (Nikodijevic et al. FEBS Lett. 1990, 261, 67). HPLC studies of biodistribution of a closely related and less potent homologue, N6-[4-(p-sulfophenyl)butyl]adenosine indicated that a 25 mg/kg ip dose in mice resulted in a plasma concentration after 30 min of 0.46 micrograms/mL and no detectable drug in the brain (detection limit < 0.1% of plasma level). Although 10b at doses > 0.1 mg/kg in mice depressed locomotor activity, this depression was unlike the effects of CHA and was reversible by BW1433. These data suggest that 10b is a potent adenosine agonist in vivo and shows poor CNS penetration.
Role of adhesion molecules in synovial inflammation (2006)

Cell-cell and cell-ECM interactions through CAMs play an important role in synovial inflammation. Future studies of CAMs are needed to define more thoroughly their role in synovial inflammation and their potential as therapeutic targets in the treatment of rheumatoid arthritis and related inflammatory arthritic conditions.
Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection (2002)

In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D(b)/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL(-/-) mice show a decrease in D(b)/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL(-/-) mice show a decrease in the number of D(b)/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.
Drug survival of biologic therapy in a large, disease‐based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) (2016)

Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.
When Good Randomness Goes Bad: Virtual Machine Reset Vulnerabilities and Hedging Deployed Cryptography. (2010)

Random number generators (RNGs) are consistently a weak link in the secure use of cryptography. Routine cryptographic operations such as encryption and signing can fail spectacularly given predictable or repeated randomness, even when using good long-lived key material. This has proved problematic in prior settings when RNG implementation bugs, poor design, or low-entropy sources have resulted in predictable randomness. We investigate a new way in which RNGs fail due to reuse of virtual machine (VM) snapshots. We exhibit such VM reset vulnerabilities in widely-used TLS clients and servers: the attacker takes advantage of (or forces) snapshot replay to compromise sessions or even expose a serverâs DSA signing key. Our next contribution is a backwards-compatible framework for hedging routine cryptographic operations against bad randomness, thereby mitigating the damage due to randomness failures. We apply our framework to the OpenSSL library and experimentally confirm that it has little overhead.
Postischemic Stunning (1992)

Journal of Cardiovascular Pharmacology™ is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, clinical results with new and established agents and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases.
A review of bone pain relief with ibandronate and other bisphosphonates in disorders of increased bone turnover. (2008)

Several disorders of increased bone turnover and low bone mineral density (BMD) are associated with severe pain that is refractory to treatment with conventional and even opioid analgesics. Because of their ability to effectively improve the underlying pathogenesis of these disorders (i.e., reduce bone resorption and increase BMD), bisphosphonates are considered part of the palliative care of malignant bone-related pain and also appear to have some analgesic efficacy in other, non-malignant conditions. Ibandronate, a potent, nitrogen-containing bisphosphonate that can be given orally and intravenously, has demonstrated robust effects in relieving the pain associated with several malignant disorders. Unlike other available intravenous (i.v.) bisphosphonates, i.v. ibandronate is not associated with renal side effects, even at high doses such as 6 mg every 3 weeks. In addition, oral ibandronate (50 mg daily) is currently the only oral bisphosphonate proven to reduce and maintain bone pain scores below baseline for 2 years in patients with metastatic bone disease. Lower dose, less intense dosing regimens of ibandronate relieve bone pain in non-malignant conditions: i.v. ibandronate (2 mg every 3 months with or without an initial 4 mg injection) provides pain relief for patients with corticosteroid-induced osteoporosis, localised transient osteoporosis (bone marrow oedema) and sternocostoclavicular hyperostosis. Both oral and i.v. ibandronate are well tolerated. In conclusion, ibandronate offers an effective and convenient choice for the relief of bone pain in a wide variety of underlying bone conditions.
Proposed Mechanisms for the Translocation of Intestinal Bacteria (1988)

Members of the endogenous flora have become recognized as major pathogens in nosocomial infections, and the intestinal tract has become recognized as a major portal of entry for these pathogens. The English-language literature on this topic has been summarized and a working hypothesis devised describing a mechanism whereby intestinal bacteria can escape and cause systemic disease. It is postulated that the motile phagocyte ingests intestinal bacteria, transports them to extraintestinal sites, fails to accomplish intracellular killing, and then liberates the bacteria in the extraintestinal site. This hypothesis is consistent with many observations found in the literature: (1) The intestinal bacteria that most readily translocate out of the intestinal tract are classified as facultative intracellular pathogens. (2) Intestinal particles with no intrinsic motility (e.g., yeast, ferritin, starch) can translocate out of the intestinal lumen within hours after their ingestion. (3) The rate of translocation of intestinal bacteria can be altered with agents that modulate immune (including phagocytic) function. In the context of the mechanisms involved in intestinal immune responses, bacterial translocation appears to be a part of the normal antigen-sampling process of gut-associated lymphoid tissue. Systemic disease caused by translocating intestinal bacteria could be due to a maladaptation of the antigen-sampling process that has been designed to regulate the immune response to intestinal antigens.
Activation and Entrainment Mapping Defines the Tricuspid Annulus as the Anterior Barrier in Typical Atrial Flutter (1996)

Closely spaced sites around the tricuspid annulus are activated sequentially, and are all within the flutter circuit according to entrainment criteria. This demonstrates that the tricuspid annulus constitutes a continuous anterior barrier constraining the reentrant wave front of human counterclockwise atrial flutter.
Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner (2011)

These results establish that transfer of in vivo primed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is essential for AAM protein expression, lung inflammation and eosinophilia are only partially dependent on this pathway. Further studies are required to identify other proteins and signaling pathways involved in airway inflammation.
Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the ${\hbox{ pre-tRNA }}_{\left(\hbox{ CAA }\right)}^{\hbox{ Leu }}$ (2006)

We identified a human orthologue of tRNA:m5C methyltransferase from Saccharomyces cerevisiae, which has been previously shown to catalyse the specific modification of C34 in the intron-containing yeast pre-tRNA Leu (CAA). Using transcripts of intron-less and intron-containing human pre-tRNA Leu (CAA) genes as substrates, we have shown that m5C34 is introduced only in the intron-containing tRNA precursors when the substrates were incubated in the HeLa extract. m5C34 formation depends on the nucleotide sequence surrounding the wobble cytidine and on the structure of the prolongated anticodon stem. Expression of the human Trm4 (hTrm4) cDNA in yeast partially complements the lack of the endogenous Trm4p enzyme. The yeast extract prepared from the strain deprived of the endogenous TRM4 gene and transformed with hTrm4 cDNA exhibits the same activity and substrate specificity toward human pre-tRNALeu transcripts as the HeLa extract. The hTrm4 MTase has a much narrower specificity against the yeast substrates than its yeast orthologue: human enzyme is not able to form m5C at positions 48 and 49 of human and yeast tRNA precursors. To our knowledge, this is the first report showing intron-dependent methylation of humanpre-tRNA Leu (CAA) and identification of human gene encoding tRNA methylase responsible for this reaction.