gebhart/patrepeval huggingface dataset:
Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure (2005)

In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.
Microfluidic tools for biological sample preparation (2003)

Researchers at Lawrence Livermore National Laboratory are developing means to collect and identify fluid-based biological pathogens in the forms of proteins, viruses, and bacteria. To support detection instruments, we are developing a flexible fluidic sample preparation unit. The overall goal of this Microfluidic Module is to input a fluid sample, containing background particulates and potentially target compounds, and deliver a processed sample for detection. We are developing techniques for sample purification, mixing, and filtration that would be useful to many applications including immunologic and nucleic acid assays. Sample preparation functions are accomplished with acoustic radiation pressure, dielectrophoresis, and solid phase extraction. We are integrating these technologies into packaged systems with pumps and valves to control fluid flow and investigating small-scale detection methods.
Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases (2010)

The importance of histone methylation in gene regulation was suggested over 40 years ago. Yet, the dynamic nature of this histone modification was recognized only recently, with the discovery of the first histone demethylase nearly five years ago. Since then, our insight into the mechanisms, structures, and macromolecular complexes of these enzymes has grown exponentially. Overall, the evidence strongly supports a key role for histone demethylases in eukaryotic transcription and other chromatin-dependent processes. Here, we examine these and related facets of histone demethylases discovered to date, focusing on their biochemistry, structure, and enzymology.
Bazedoxifene Exhibits Antiestrogenic Activity in Animal Models of Tamoxifen-Resistant Breast Cancer: Implications for Treatment of Advanced Disease (2013)

Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer.
Sequence and expression pattern ofpax-6are highly conserved between zebrafish and mice (1992)

Despite obvious differences in the patterns of early embryonic development, vertebrates share a number of developmental mechanisms and control genes, suggesting that they use similar genetic programs at some stages of development. To examine this idea, we isolated and characterized one such gene, pax-6, a member of the pax gene family, from the zebrafish Brachydanio rerio and determined the evolutionary conservation in the structure and expression of this gene by comparison to its homolog in mice. We found two alternatively spliced forms of the zebrafish pax-6 message. Sequence and expression pattern of the zebrafish pax-6 gene are remarkably similar to its murine homolog. pax-6 expression begins during early neurulation. A stripe of cells in the neuroectoderm, including the prospective diencephalon and a part of the telencephalon, expresses pax-6 as well as the hindbrain and the ventral spinal cord extending from the level of the first rhombomere to the posterior end of the CNS. During later development more limited regions of the brain including the eye, the olfactory bulb and the pituitary gland express pax-6. Cells at the midbrain-hindbrain junction express eng genes and are separated from the neighboring pax-6 regions by several cells that express neither gene, indicating a complex subdivision of this region. pax-6 expression appears during processes when cell-to-cell signalling is thought to be important, for example during induction of the eye and regionalization of the spinal cord and brain, suggesting that it may be one component mediating the response to inductive interactions.
High-dose intravenously administered iron versus orally administered iron in blood donors with iron deficiency: study protocol for a randomised, controlled trial (2016)

EudraCT: 2013-000327-14, Clinical Trials Identifier: NCT01787526 . Registered on 6 February 2013.
Traps and Pitfalls: Practical Problems in System Call Interposition Based Security Tools. (2003)

System call interposition is a powerful method for reg-ulating and monitoring application behavior. In recent years, a wide variety of security tools have been developed that use this technique. This approach brings with it a host of pitfalls for the unwary implementer that if overlooked can allow his tool to be easily circumvented. To shed light on these problems, we present the lessons we learned in the course of several design and implementation cycles with our own system call interposition-based sandboxing tool. We first present some of the problems and pitfalls we encountered, including incorrectly replicating OS seman-tics, overlooking indirect paths to resources, race condi-tions, incorrectly subsetting a complex interface, and side effects of denying system calls. We then present some practical solutions to these problems, and provide general principles for avoiding the difficulties we encountered. 1
The Changes in MGMT Promoter Methylation Status in Initial and Recurrent Glioblastomas (2012)

To evaluate the mechanism of the development of therapeutic resistance after temozolomide treatment, we focused on changes in O(6)-methylguanine DNA methyltransferase (MGMT) and mismatch repair (MMR) between initial and recurrent glioblastomas. Tissue samples obtained from 24 paired histologically confirmed initial and recurrent adult glioblastoma patients who were initially treated with temozolomide were used for MGMT and MMR gene promoter methylation status and protein expression analysis using methylation-specific multiplex ligation probe amplification (MS-MLPA), methylation-specific polymerase chain reaction (MSP), and immunohistochemical staining. There was a significant decrease in the methylation ratio of the MGMT promoter determined by MS-MLPA, which was not detectable with MSP, and MGMT protein expression changes were not remarkable. However, there was no epigenetic variability in MMR genes, and a relatively homogeneous expression of MMR proteins was observed in initial and recurrent tumors. We conclude that the development of reduced methylation in the MGMT promoter is one of the mechanisms for acquiring therapeutic resistance after temozolomide treatment in glioblastomas.
Lysozyme regulates LPS-induced interleukin-6 release in mice. (1994)

Bacterial lipopolysaccharide (LPS) stimulates the production and release of endogenous mediators [e.g., tumor necrosis factor (TNF), interleukins-1 and -6 (IL-1 and IL-6), and Platelet Activating Factor [PAF] responsible for the pathophysiologic changes and the mortality associated with sepsis. We recently demonstrated that lysozyme (LZM) bound to LPS (LZM-LPS complex) suppresses LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in vivo. In the present study, we investigated the effect of LZM-LPS complex formation on LPS-induced IL-6 production, both in vitro and in vivo. With the addition of LZM-LPS complex, TNF-alpha and IL-6 release was significantly reduced compared with that by LPS in a dose-dependent manner in mouse macrophage-like cells, RAW264.7. IL-6 production in serum by LPS in carrageenan (CAR)-primed mice peaked at 2 hr following injection. LZM-LPS and LZM-Escherichia coli cell complex (as 1 microgram of LPS per mouse) released significantly reduced concentrations of IL-6 in serum (P < 0.01 and P < 0.001 versus CAR-pretreated LPS- or cell-injected mice). These results emphasize the important role of LZM in vivo in the neutralization of endotoxin. However, in the case of IL-6, by administration of a lethal dose of LPS (as 100 micrograms of LPS per mouse), the IL-6 level was reduced by LZM, but a significant concentration of IL-6 was still released; although the TNF- alpha concentration was negligible in this experimental condition. Thus, it is suggested that LZM might regulate the systemic inflammation induced during Gram-negative bacterial infections by inhibiting the release of cytokines in serum.
Using redundancies to find errors (2002)

This paper explores the idea that redundant operations, like type errors, commonly flag correctness errors. We experimentally test this idea by writing and applying four redundancy checkers to the Linux operating system, finding many errors. We then use these errors to demonstrate that redundancies, even when harmless, strongly correlate with the presence of traditional hard errors (e.g., null pointer dereferences, unreleased locks). Finally we show that how flagging redundant operations gives a way to make specifications "fail stop" bydetecting dangerous omissions.
SUICIDAL GENETIC ELEMENTS AND THEIR USE IN BIOLOGICAL CONTAINMENT OF BACTERIA (1993)

The potential risks of unintentional releases of genetically modified organisms, and the lack of predictable behavior of these in the environment, are the subject of considerable concern. This concern is accentuated in connection with the next phase of gene technology comprising deliberate releases. The possibilities of reducing such potential risks and increasing the predictability of the organisms are discussed for genetically engineered bacteria. Different approaches towards designing disabled strains without seriously reducing their beneficial effects are presented. Principally two types of strain design are discussed: actively contained bacteria based on the introduction of controlled suicide systems, and passively contained strains based on genetic interference with their survival under environmental-stress conditions.
Intravenous Lignocaine (Lidocaine) Infusion for the Treatment of Chronic Daily Headache with Substantial Medication Overuse (2003)

Patients with chronic daily headache with medication overuse are difficult to treat, especially when the doses of analgesia are substantial. We have previously shown that intravenous lignocaine (lidocaine) infusion is useful in maintaining pain control while the offending analgesic agent is withdrawn in these patients. The published data on long-term efficacy of this treatment is limited. We undertook a retrospective survey of 71 consecutive patients admitted for lignocaine infusion (mean 8.7 days) for treatment of chronic daily headache, with substantial analgesic abuse. Ninety percent of patients had a history of migraine headaches. In 80% of patients codeine was the predominant agent implicated in the analgesic rebound headaches (mean 1053 mg/week) and 24% used ergotamine-containing medications (mean 16 mg/week). Thirty-one percent frequently used injected narcotics. At completion 90% reported that their daily headache was absent or improved, and the analgesic agent was withdrawn successfully in 97%. At six month follow-up, 70% of patients reported that their daily headache was absent or improved and 72% of patients remained free of the offending analgesic agent. Intravenous lignocaine is a useful treatment in the management of chronic daily headache with substantial medication overuse. The benefits of the program last for at least six months.
Many Robots Make Short Work (1997)

Keywords: OAA ; mobile robots ; [VRAI] Note: Paper decribing the AAAI competition Reference LSRO2-ARTICLE-1997-003 Record created on 2005-02-04, modified on 2017-05-10
Enhanced Microchannel Heat Sinks Using Oblique Fins (2009)

Oblique fins created in a microchannel heat sink can serve to modulate the flow, resulting in local and global heat transfer enhancement. Numerical analysis of laminar flow and heat transfer in such modified microchannel heat sink showed that significant enhancement of heat transfer can be achieved with negligible pressure drop penalty. The breakage of continuous fin into oblique sections causes the thermal boundary layers to be re-initialized at the leading edge of each oblique fin and reduces the boundary-layer thickness. This regeneration of the entrance effect causes the flow to be always in a developing state thus resulting in better heat transfer. In addition, the presence of the smaller oblique channels causes a fraction of the flow to branch into the adjacent main channels. The secondary flows thus created improve fluid mixing which serves to further enhance the heat transfer. The combination of the entrance and secondary flow effect results in a much improved heat transfer performance (the average and local heat transfer coefficients are enhanced by as much as 80%). Both the maximum wall temperature and temperature gradient are substantially decreased as a result.
The minimal essential sequence for a major cell type-specific adhesion site (CS1) within the alternatively spliced type III connecting segment domain of fibronectin is leucine-aspartic acid-valine (1991)

Fibronectin contains at least two major domains that support cell adhesion. One is the central cell-binding domain that is recognized by a variety of cell types via the integrin alpha 5 beta 1. The second, originally identified by its ability to support melanoma cell adhesion, is located in the alternatively spliced type III connecting segment (IIICS). A dominant cell type-specific adhesion site within the IIICS has been localized to a peptide designated as CS1 comprising its amino-terminal 25 residues. The receptor for CS1 is the integrin alpha 4 beta 1. We have synthesized a variety of peptides with overlapping sequences in order to identify the minimum active amino acid sequence of this major cell adhesion site. A peptide comprising the carboxyl-terminal 8 amino acids of CS1, EILDVPST, was found to support melanoma cell spreading, while all peptides without this sequence had little or no activity. Two smaller overlapping pentapeptides, EILDV and LDVPS, were also active, whereas EILEV, containing a conservative substitution of Glu for Asp, was inactive. These data suggested that the minimum sequence for cell adhesion activity is Leu-Asp-Val, the tripeptide sequence common to both active peptides. This prediction was confirmed by the observed ability of the Leu-Asp-Val peptide itself to block spreading on fibronectin, whereas Leu-Glu-Val was inactive. Interspecies amino acid sequence comparison also supports the importance of the LDV sequence, since it is completely conserved in the IIICS regions of human, rat, bovine, and avian fibronectins.
Rapid Detection and Molecular Serotyping of Adenovirus by Use of PCR Followed by Electrospray Ionization Mass Spectrometry (2007)

We have developed a PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) assay for the rapid detection, identification, and serotyping of human adenoviruses. The assay employs a high-performance mass spectrometer to "weigh" the amplicons obtained from PCR using primers designed to amplify known human adenoviruses. Masses are converted to base compositions and, by comparison against a database of the genetic sequences, the serotype present in a sample is determined. The performance of the assay was demonstrated with quantified viral standards and environmental and human clinical samples collected from a military training facility. Over 500 samples per day can be analyzed with sensitivities greater than 100 genomes per reaction. This approach can be applied to many other families of infectious agents for rapid and sensitive analysis.
Small Molecule-Mediated Directed Differentiation of Human Embryonic Stem Cells Toward Ventricular Cardiomyocytes (2013)

The generation of human ventricular cardiomyocytes from human embryonic stem cells and/or induced pluripotent stem cells could fulfill the demand for therapeutic applications and in vitro pharmacological research; however, the production of a homogeneous population of ventricular cardiomyocytes remains a major limitation. By combining small molecules and growth factors, we developed a fully chemically defined, directed differentiation system to generate ventricular-like cardiomyocytes (VCMs) from human embryonic stem cells and induced pluripotent stem cells with high efficiency and reproducibility. Molecular characterization revealed that the differentiation recapitulated the developmental steps of cardiovascular fate specification. Electrophysiological analyses further illustrated the generation of a highly enriched population of VCMs. These chemically induced VCMs exhibited the expected cardiac electrophysiological and calcium handling properties as well as the appropriate chronotropic responses to cardioactive compounds. In addition, using an integrated computational and experimental systems biology approach, we demonstrated that the modulation of the canonical Wnt pathway by the small molecule IWR-1 plays a key role in cardiomyocyte subtype specification. In summary, we developed a reproducible and efficient experimental platform that facilitates a chemical genetics-based interrogation of signaling pathways during cardiogenesis that bypasses the limitations of genetic approaches and provides a valuable source of ventricular cardiomyocytes for pharmacological screenings as well as cell replacement therapies.
Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery (1999)

Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.
Encapsulation of Superparamagnetic Nanoparticles Into Red Blood Cells as New Carriers of MRI Contrast Agents (2011)

A careful consideration of magnetic nanoparticles parameters, such as size, synthesis protocols, coating and/or dispersant agents, is required in order to obtain efficient loading through the cell membrane pores.
Engagement of immune effector cells by trastuzumab induces HER2/ERBB2 downregulation in cancer cells through STAT1 activation (2014)

This study reveals that engagement of immune effector cells by trastuzumab induces HER2 downregulation in HER2-expressing cancer cells, which represents a new function of immune cells in trastuzumab-mediated antitumor efficacy and serves as a novel mechanism of action for trastuzumab. Our results imply that HER2 downregulation in cancer cells treated by trastuzumab may predict active engagement of immune effector cells in tumor microenvironment.
Use of oral corticosteroids in the United Kingdom (2000)

Administration of oral corticosteroids is associated with the development of osteoporosis and an increased risk of fractures. However, the size of the treated sub-population who would benefit from preventive therapy remains uncertain. The objective of this study was to investigate the usage pattern of oral corticosteroids in a large sample representative of the general population in England and Wales. Information was obtained from the General Practice Research Database (GPRD) which contains medical records of general practitioners. Oral corticosteroid users were patients aged 18 years or older who received one or more prescriptions for oral corticosteroids. Over 1.6 million oral corticosteroid prescriptions were issued to the cohort of 244 235 oral corticosteroid users. At any point in time, oral corticosteroids were being used by 0.9% of the total adult GPRD population. The highest use (2.5%) was by people between 70 and 79 years of age. Respiratory disease was the most frequently recorded indication for oral corticosteroid treatment (40%). Patients with arthropathies were most likely to use long-term, continuous treatment, and patients with chronic obstructive pulmonary disease least likely (19.3% and 6.1%, respectively, used oral corticosteroids for more than 2 years). The overall use of bone-active medication (oestrogens, bisphosphonates, vitamin D, and calcitonin) during oral corticosteroid treatment was low (between 4.0% and 5.5%). The current population in the UK at risk of developing corticosteroid-induced fractures might be as large as 350 000. Identification of these patients will be important for implementing preventive strategies in a cost-effective manner.
Successful treatment of murine melanoma with bryostatin 1. (1991)

Bryostatins are a novel class of protein kinase C activators which were isolated from the marine bryozoan Bugula neritina and found to possess both antineoplastic and immunoenhancing properties. In this report, we examined the relationship between the in vivo and in vitro antineoplastic effects of bryostatin 1. The in vivo antitumor activity of bryostatin 1 was demonstrated in a B16 melanoma pulmonary metastases model, in which treatment of tumor-bearing C57BL/6 mice with 5 days of bryostatin 1 resulted in a significant reduction in of the number of lung nodules (control, 87; bryostatin, 7). There was a clear dose-response effect, with the optimal antimelanoma dose being 100 micrograms/kg/day, but even low doses of bryostatin 1 of 1 micrograms/kg/day resulted in a 53% reduction in the number of metastases. Although bryostatin 1 shares many biological properties with the phorbol esters, parallel treatment with 12-O-tetradecanoyl 13-phorbol acetate was ineffective against B16 melanoma in vivo. Using a clonogenic assay, bryostatin 1 was found to have a direct antiproliferative effect against B16 melanoma. This inhibition occurred at relatively high bryostatin 1 concentrations (10(-6) M), in comparison with a sensitive cell line REH (10(-10) M). Treatment of mice with bryostatin 1 or preincubation of normal spleen cells with bryostatin 1 failed to enhance nonspecific cell-mediated cytotoxicity against B16 melanoma in vitro. Moreover, bryostatin 1 was found to inhibit both natural killer cell activity and interleukin 2 generation of lymphokine-activated killer cells. Thus, a role for an in vivo immune enhancement mechanism as the basis for the antimelanoma activity observed with bryostatin 1 cannot be invoked from these experiments. These findings indicate that bryostatin 1 may act directly on the B16 melanoma pulmonary metastases. The precise mechanism whereby bryostatin exerts its antimelanoma effects remains unclear.