gebhart/patrepeval huggingface dataset:
Thrombin Responses in Human Endothelial Cells (2000)

The recent identification of two new thrombin receptors, PAR3 and PAR4, led us to re-examine the basis for endothelial cell responses to thrombin. Human umbilical vein endothelial cells (HUVEC) are known to express PAR1 and the trypsin/tryptase receptor, PAR2. Northern blots detected both of those receptors and, to a lesser extent, PAR3, but PAR4 message was undetectable and there was no response to PAR4 agonist peptides. To determine whether PAR3 or any other receptor contributes to thrombin signaling in HUVEC, PAR1 cleavage was blocked with two selective antibodies and PAR1 activation was inhibited with the antagonist, BMS200261. The antibodies completely inhibited HUVEC responses to thrombin, but BMS200261 was only partly effective, even though separate studies established that the antagonist completely inhibits PAR1 signaling at the concentrations used. Since peptides mimicking the PAR1 tethered ligand domain can also activate PAR2, we asked whether the remaining thrombin response in the presence of the antagonist could be due in part to the intermolecular transactivation of PAR2 by cleaved PAR1. Evidence that transactivation can occur was obtained in COS-7 cells co-expressing PAR2 and a variant of PAR1 that can be cleaved, but not signal. There was a substantial response to thrombin only in cells expressing both receptors. Conversely, in HUVEC, complete blockade of the thrombin response by the PAR1 antagonist occurred only when signaling through PAR2 was also blocked. From these observations we conclude that 1) PAR1 is the predominant thrombin receptor expressed in HUVEC and cleavage of PAR1 is required for endothelial cell responses to thrombin; 2) although PAR3 may be expressed, there is still no evidence that it mediates thrombin responses; 3) PAR4 is not expressed on HUVEC; and 4) transactivation of PAR2 by cleaved PAR1 can contribute to endothelial cell responses to thrombin, particularly when signaling through PAR1 is blocked. Such transactivation may limit the effectiveness of PAR1 antagonists, which compete with the tethered ligand domain rather than preventing PAR1 cleavage.
Department of Error (2009)

1330 www.thelancet.com Vol 374 October 17, 2009 There have been some positive outcomes to this competition. Without NGOs rallying public opinion and encouraging countries to issue compulsory licences, industry would probably never have started its current drug donation programmes. Without industry supporting changes at the World Trade Organization that facilitate access in least developing countries, NGOs would not have had a platform for promoting alternative mechanisms such as a prize system and patent pools. Whatever the successes, however, they have been more on paper than in lives saved. Although it has advanced policy debates, competition has not led to the concrete solutions needed to create, manufacture, and deliver medicines to the world’s poor. NGOs and industry need to work together to achieve success. We support The Lancet’s call for government leadership, but would go further. Not only should the government push pharmaceutical companies to license their HIV/AIDS patents to the UNITAID patent pool, the UK should also use its UNITAID board seat to encourage the organisation to invite industry to play a greater part in the design and management of the pool to avoid the perception that only NGOs have a say.
Microinjection of Zebrafish Embryos to Analyze Gene Function (2009)

One of the advantages of studying zebrafish is the ease and speed of manipulating protein levels in the embryo. Morpholinos, which are synthetic oligonucleotides with antisense complementarity to target RNAs, can be added to the embryo to reduce the expression of a particular gene product. Conversely, processed mRNA can be added to the embryo to increase levels of a gene product. The vehicle for adding either mRNA or morpholino to an embryo is microinjection. Microinjection is efficient and rapid, allowing for the injection of hundreds of embryos per hour. This video shows all the steps involved in microinjection. Briefly, eggs are collected immediately after being laid and lined up against a microscope slide in a Petri dish. Next, a fine-tipped needle loaded with injection material is connected to a microinjector and an air source, and the microinjector controls are adjusted to produce a desirable injection volume. Finally, the needle is plunged into the embryo's yolk and the morpholino or mRNA is expelled.
Salivary α‐Amylase in Biobehavioral Research (2007)

In the history of science, technical advances often precede periods of rapid accumulation of knowledge. Within the past three decades, discoveries that enabled the noninvasive measurement of the psychobiology of stress (in saliva) have added new dimensions to the study of health and human development. This widespread enthusiasm has led to somewhat of a renaissance in behavioral science. At the cutting edge, the focus is on testing innovative theoretical models of individual differences in behavior as a function of multilevel biosocial processes in the context of everyday life. Several new studies have generated renewed interest in salivary alpha-amylase (sAA) as a surrogate marker of the autonomic/sympathetic nervous system component of the psychobiology of stress. This article reviews sAA's properties and functions; presents illustrative findings relating sAA to stress and the physiology of stress, behavior, cognitive function, and health; and provides practical information regarding specimen collection and assay. The overarching intent is to accelerate the learning curve such that investigators avoid potential pitfalls associated with integrating this unique salivary analyte into the next generation of biobehavioral research.
Dietary Phosphorus Acutely Impairs Endothelial Function (2009)

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.
Intravascular Ultrasound (2001)

Intravascular ultrasound (IVUS) is a valuable adjunct to angiography, providing new insights in the diagnosis of and therapy for coronary disease. Angiography depicts only a 2D silhouette of the lumen, whereas IVUS allows tomographic assessment of lumen area, plaque size, distribution, and composition. The safety of IVUS is well documented, and the assessment of luminal dimensions represents an important application of this modality. Comparative studies show the greatest disparities between angiography and ultrasound after mechanical interventions. In young subjects, normal intimal thickness is typically approximately 0.15 mm. With IVUS, lipid-laden lesions appear hypoechoic, fibromuscular lesions generate low-intensity echoes, and fibrous or calcified tissues are echogenic. Calcium obscures the underlying wall (acoustic shadowing). The extent and severity of disease by angiography and ultrasound are frequently discrepant. Arterial remodeling refers to changes in vascular dimensions during the development of atherosclerosis. At diseased sites, the external elastic membrane may actually shrink in size, contributing to luminal stenosis. The interpretation of IVUS relies on simple visual inspection of acoustic reflections to determine plaque composition. However, different tissue components may look quite similar, and artifacts may adversely affect ultrasound images. IVUS commonly detects occult disease in angiographically "normal" sites. In ambiguous lesions, ultrasound permits lesion quantification, particularly for left main coronary disease. IVUS has emerged as the optimal method for the detection of transplant vasculopathy. An important potential application of ultrasound is the identification of atheromas at risk of rupture. The mechanisms of action of interventional devices have been elucidated using IVUS, and ultrasound is used by some operators to select the most suitable interventional device. IVUS-derived residual plaque burden is the most useful predictor of clinical outcome. In restenosis after balloon angioplasty, negative remodeling is a major mechanism of late lumen loss. IVUS is not routinely used for stent optimization, and there is no consensus regarding optimal procedural end points. Ultrasound has proven useful in evaluating brachytherapy. New and emerging applications for IVUS are continuing to evolve, particularly in atherosclerosis regression-progression trials.
Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. (1995)

A metastatic human melanoma cell line that produces urokinase-type plasminogen activator was stably transfected with cDNA encoding human plasminogen activator inhibitor 2 (PAI-2). Transfected clones expressed PAI-2 at levels two to nine times higher than both the parental cell line and mock transfectants, as detected by ELISA of cell lysates and conditioned medium. The clone with the highest PAI-2 expression exhibited complete inhibition of soluble and cell-surface-bound plasminogen activator activity. The level of PAI-2 overexpression in these clonal cell lines correlated positively with the inhibition of their ability to degrade extracellular matrix in vitro. Parental, mock-transfected, and PAI-2-transfected cell lines produced rapidly growing tumors when injected s.c. into the skin of mice with severe combined immunodeficiency. The tumors producing the highest levels of PAI-2 were surrounded by a dense tumor capsule. Both parental cells and mock-transfected cells invariably metastasized from s.c. tumors to lymph nodes and lungs of mice. PAI-2-transfected cell lines produced significantly less or no metastases. Taken together, these data indicate a critical role for plasminogen activator activity in melanoma invasion and metastasis.
[Guillain-Barré syndrome and pregnancy]. (1993)

Guillain-Barré syndrome is a rare occurrence in pregnant women. We describe the case of a 21-year old woman, seen at "Nuevo Hospital Civil de Guadalajara" with a term pregnancy, who presented with limbs weakness and paresthesias, drowsiness and malaise. Her vital signs were normal but she was quadriparetic, there was muscular atrophy in the extremities and deep tendon reflexes were decreased. Spinal fluid analysis revealed a protein of 71.2 mg/dl, glucosa 48 mg/dl and no white cells and both Gram stain and routine cultures were negative. EMG studies reported poliradiculoneuritis; a C-section was done, and both the mother and a newborn girl did very well. Guillain-Barré syndrome should be suspected in similar cases in order to offer prompt intervention.
Dengue and Dengue Hemorrhagic Fever (1998)

Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to develop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.
Immunopharmacology (1992)

IMMUNOPHARMACOLOGY involves the study of the regulation of the immune system by pharmacological agents and the development of methods to selectively modify immune function to treat human disease. The delineation of the cellular immune system and the mechanisms of allograft reaction discovered in the early 1960s brought immunosuppression for transplantation and for selected use in autoimmune disease. In the last 15 years, the demonstration of the prevalence of cellular immune defects in cancer, aging, autoimmunity, and infectious diseases has generated interest in the development of immunotherapeutic agents. This chapter provides a brief introduction to immunosuppression and immunotoxicology with emphasis on recent developments in preclinical immunopharmacology and experimental immunotherapeutics. <h3>IMMUNOSUPPRESSIVE THERAPY</h3> A variety of immunosuppressive agents and procedures have been found to be useful in the treatment of autoimmune disease<sup>1</sup>as well as organ transplantation<sup>2</sup>(Table 24-1). These agents are extensively used in cancer therapy primarily because of their
Minireview: Basal-Like Breast Cancer: From Molecular Profiles to Targeted Therapies (2010)

The classification of breast cancer into molecular subtypes with distinctive gene expression signatures that predict treatment response and prognosis has ushered in a new era of personalized medicine for this remarkably heterogeneous and deadly disease. Basal-like breast cancer (BLBC) is a particularly aggressive molecular subtype defined by a robust cluster of genes expressed by epithelial cells in the basal or outer layer of the adult mammary gland. BLBC is a major clinical challenge because these tumors are prevalent in young woman, often relapsing rapidly. Additionally, most (but not all) basal-like tumors lack expression of steroid hormone receptors (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2, limiting targeted therapeutic options for these predominantly triple-negative breast cancers. This minireview will focus on new insights into the molecular etiology of these poor-prognosis tumors that underlie their intrinsic genomic instability, deregulated cell proliferation and apoptosis, and invasive tumor biology. We will also review ongoing efforts to translate these fundamental insights into improved therapies for women with BLBC.
Coherent Optical OFDM Transmission Up to 1 Tb/s per Channel (2009)

Coherent optical frequency-division multiplexing (CO-OFDM) is one of the promising pathways toward future ultrahigh capacity transparent optical networks. In this paper, numerical simulation is carried out to investigate the feasibility of 1 Tb/s per channel CO-OFDM transmission. We find that, for 1 Tb/s CO-OFDM signal, the performance difference between single channel and wavelength division multiplexing (WDM) transmission is small. The maximum Q is 13.8 and 13.2 dB respectively for single channel and WDM transmission. We also investigate the CO-OFDM performance on the upgrade of 10-Gb/s to 100-Gb/s based DWDM systems with 50-GHz channel spacing to 100-Gb/s systems. It is shown that due to the high spectral efficiency and resilience to dispersion, for 100-Gb/s CO-OFDM signals, only 1.3 dB Q penalty is observed for 10 GHz laser frequency detuning. A comparison of CO-OFDM system performance under different data rate of 10.7 Gb/s, 42.8 Gb/s, 107 Gb/s and 1.07 Tb/s with and without the impact of dispersion compensation fiber is also presented. We find that the optimum fiber launch power increases almost linearly with the increase of data rate. 7 dB optimum launch power difference is observed between 107 Gb/s and 1.07 Tb/s CO-OFDM systems.
Efficiency of cache mechanism for network processors (2009)

With the explosion of network bandwidth and the ever-changing requirements for diverse network-based applications, the traditional processing architectures, i.e., general purpose processor (GPP) and application specific integrated circuits (ASIC) cannot provide sufficient flexibility and high performance at the same time. Thus, the network processor (NP) has emerged as an alternative to meet these dual demands for today's network processing. The NP combines embedded multi-threaded cores with a rich memory hierarchy that can adapt to different networking circumstances when customized by the application developers. In today's NP architectures, multithreading prevails over cache mechanism, which has achieved great success in GPP to hide memory access latencies. This paper focuses on the efficiency of the cache mechanism in an NP. Theoretical timing models of packet processing are established for evaluating cache efficiency and experiments are performed based on real-life network backbone traces. Testing results show that an improvement of nearly 70% can be gained in throughput with assistance from the cache mechanism. Accordingly, the cache mechanism is still efficient and irreplaceable in network processing, despite the existing of multithreading.
Nucleotide sequence of htpB, the Legionella pneumophila gene encoding the 58-kilodalton (kDa) common antigen, formerly designated the 60-kDa common antigen (1990)

Gene htpB, which encodes the 58-kilodalton protein of Legionella pneumophila, was cloned in Escherichia coli and its complete nucleotide sequence was determined. Analysis of this sequence revealed an open reading frame of 1,644 nucleotides encoding a protein with a predicted molecular mass of 57,952 daltons. Data obtained by amino-terminal sequencing of the purified 58-kilodalton protein agreed, except for one amino acid residue, with the predicted amino acid sequence, identifying this open reading frame as htpB. A comparison of the primary structure of this protein to other proteins of similar molecular weights from E. coli, Mycobacterium leprae, M. tuberculosis, and Coxiella burnetii revealed significant regions of sequence similarity, which are discussed.
Human monoclonal antibody reactive to stomach cancer produced by mouse-human hybridoma technique. (1986)

Production of human monoclonal antibodies reactive to stomach cancer was attempted by the hybridoma technique using splenic lymphocytes from stomach cancer patients. The parental cells used were NS-1 mouse myeloma line and three human lines including RPMI-1788 6TGR, which was established in our laboratories. Ten mouse-human and two human-human (from the fusion with RPMI-1788 6TGR) hybridomas have been producing IgM antibody for over 18 months, and all the heterohybridomas yielded ascites when transplanted into nude mice. Four antibodies produced by the heterohybridomas were selected and analyzed. These 4 antibodies, 3F6, 4A10, 3H5 and 1F9, reacted predominantly to cytoplasmic antigens of stomach and other epithelial cancer lines. The reactivity against human tumors transplantable in nude mice showed that all antibodies but 3F6 were reactive with stomach and lung cancers. Smears prepared from normal and cancer tissues were also tested, and these 4 antibodies showed positive reactions not only to stomach cancer, but also to normal stomach and colon. The reactivity against fetal tissues demonstrated that 3H5 antibody was reactive with epithelium of the stomach, and 1F9 antibody was positive with epithelium of the respiratory tract and bile duct, but the other two were negative. Thus, the serological analysis showed that the antigens detected are not tumor-specific, but are differentiation antigens. Chromosome analysis of these 4 mouse-human hybridomas and another one, which seems to produce an antibody against keratin, showed that three retained human chromosome 14 on which immunoglobulin heavy chain (Ig H) gene is located, but two did not. Southern blot analysis, however, revealed that all 5 hybridomas had a human Ig H gene.
Lack of antibodies to porcine circovirus type 2 virus in beef and dairy cattle and horses in western Canada. (2001)

Porcine circovirus type 2 (PCV2) is a recently recognized agent that is consistently associated with postweaning multisystemic wasting disease in swine. There are conflicting data concerning the ability of this virus to infect and cause disease in other species. To determine if normal cattle, cattle affected with various illnesses, and normal horses in endemic areas of PCV2 infection in swine have had PCV2 infections, 100 randomly selected bovine sera, 100 equine sera, and 100 colostrum samples from clinically normal dairy cattle were examined for the presence of antibodies to porcine circoviruses by using ELISAs. All samples tested were negative for antibodies to porcine circoviruses. As well, a seronegative neonatal Holstein calf and 6 seronegative, 6-month-old beef calves that were experimentally infected with PCV2 failed to develop antibodies to the virus. These results suggest that natural infection of cattle and horses with PCV2 does not occur, or is a rare event, in western Canada.