gebhart/patrepeval huggingface dataset:
Endothelial dysfunction : the early predictor of atherosclerosis (2012)

Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body's vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.
3-D Sound for Virtual Reality and Multimedia (1995)

Technology and applications for the rendering of virtual acoustic spaces are reviewed. Chapter 1 deals with acoustics and psychoacoustics. Chapters 2 and 3 cover cues to spatial hearing and review psychoacoustic literature. Chapter 4 covers signal processing and systems overviews of 3-D sound systems. Chapter 5 covers applications to computer workstations, communication systems, aeronautics and space, and sonic arts. Chapter 6 lists resources. This TM is a reprint of the 1994 book from Academic Press.
Prevention of Early-Onset Neonatal Group B Streptococcal Disease with Selective Intrapartum Chemoprophylaxis (1986)

Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease.
Frequent c-myc oncogene activation and infrequent presence of Epstein- Barr virus genome in AIDS-associated lymphoma (1988)

Sixteen cases of histologic intermediate-grade and high-grade AIDS-associated non-Hodgkin's lymphoma (NHL) were studied for the presence and patterns of c-myc gene and bcl-2 locus rearrangements. The presence of Epstein-Barr virus (EBV) sequences and proteins and HTLV-I sequences were also investigated. c-myc gene rearrangements analogous to those observed in sporadic Burkitt lymphomas were detected in 12 of 16 cases. Six of 16 cases had detectable EBV sequences and proteins. None of the cases displayed bcl-2 rearrangements or contained HTLV-I sequences. These data suggest a frequent role for c-myc activation in the pathogenesis of AIDS-associated NHL, independent of histologic type. Conversely, EBV does not appear to be directly involved in lymphomagenesis in the majority of AIDS-associated NHLs.
Interleukin-1 and Occlusive Arterial Diseases (2006)

Interleukin (IL)-1 is a pro-inflammatory cytokine and a central mediator in the cytokine network, and is known to control important functions both in the immune system and inflammation. The activity of IL-1 is counter-regulated by its endogenous inhibitor, IL-1 receptor antagonist (IL-1Ra). IL-1 and IL-1Ra are produced and secreted by a variety of cells including those responsible for controlling immunity. A recent study indicated that IL-1 and IL-1Ra transcripts were expressed in the vessel wall, suggesting that these cytokines contribute to the development and progression of vascular diseases. In this review, we will discuss the recent advances in our understanding of the mechanism of action of IL-1 in occlusive arterial diseases such as neointimal hyperplasia and atherosclerosis, specifically in a mouse model.
CD19: a biomarker for B cell development, lymphoma diagnosis and therapy (2012)

The human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD19 is classified as a type I transmembrane protein, with a single transmembrane domain, a cytoplasmic C-terminus, and extracellular N-terminus. CD19 is a biomarker for normal and neoplastic B cells, as well as follicular dendritic cells. CD19 is critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor-dependent and independent signaling. CD19 functions as the dominant signaling component of a multimolecular complex on the surface of mature B cells, alongside complement receptor CD21, and the tetraspanin membrane protein CD81 (TAPA-1), as well as CD225. Through study of CD19 transgenic and knockout mouse models, it becomes clear that CD19 plays a critical role in maintaining the balance between humoral, antigen-induced response and tolerance induction. This review also summarized latest clinical development of CD19 antibodies, anti-B4-bR (an immunotoxin conjugate), blinatumomab (BiTE), and SAR3419 (huB4-DM4), a novel antibody-drug conjugate.
Reconstitution and Further Characterization of the Cholesterol Transport Activity of the Small-Intestinal Brush Border Membrane (1997)

The sterol (free and esterified cholesterol) transport activity of the small-intestinal brush border membrane was solubilized with the short-chain detergent diheptanoylphosphatidylcholine and reconstituted to an artificial membrane system (proteoliposomes). The resulting proteoliposomes were identified as unilamellar membrane vesicles ranging in size between 50 and 200 nm with a broad maximum at 70-110 nm. That the sterol transport protein was indeed incorporated into the lipid bilayer was shown by density gradient centrifugation on a Ficoll gradient: the proteoliposomes yielded a single band with an apparent density of 1.035 g/mL. By subjecting solubilized brush border membrane vesicles (BBMV) to gel filtration on Sephadex G-200 prior to reconstitution, a 7-fold enrichment of the sterol transport activity was achieved relative to the original BBMV. The experimental evidence presented lends strong support to the notion that the sterol transport protein is an integral protein of the brush border membrane which is anchored in the lipid bilayer by at least one hydrophobic domain. The active center(s) is (are) exposed to the external side of the membrane. Anchoring of this protein to the lipid bilayer by a glycosylphosphatidylinositol moiety is unlikely. The reconstituted proteoliposomes behaved very similarly to the original BBMV in terms of facilitated sterol uptake. Using these proteoliposomes, a hitherto unknown activity of the brush border membrane was discovered. Long-chain triacylglycerols can be taken up by this membrane as such and need not be hydrolyzed prior to absorption.
A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles (2015)

Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled 'detection and perturbation' strategy.
Synthesis and Metabotropic Glutamate Receptor Activity of S-Oxidized Variants of (−)-4-Amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate:  Identification of Potent, Selective, and Orally Bioavailable Agonists for mGlu2/3 Receptors (2006)

(-)-4-Amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate (LY389795, (-)-3) is a highly potent and selective agonist of metabotropic glutamate receptors 2 (mGlu2) and 3 (mGlu3). As part of our ongoing research program, we have prepared S-oxidized variants of (-)-3, compounds (-)-10, (+)-11 (LY404040), and (-)-12 (LY404039). Each of these chiral heterobicyclic amino acids displaced specific binding of the mGlu2/3 receptor antagonist 3H-2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid (3H-LY341495) from membranes expressing recombinant human mGlu2 or mGlu3 and acted as potent agonists in cells expressing these receptor subtypes. Docking of the most potent of these derivatives, (+)-11, to mGlu2 revealed the possibility of an additional H-bond interaction between the sulfoxide oxygen of (+)-11 with tyrosine residue Y236. Pharmacokinetic analysis of mGlu active enantiomers (+)-11 and (-)-12 in rats showed each to be well absorbed following oral administration. Consistent with their mGlu2/3 agonist potency and pharmacokinetic properties, both (+)-11 and (-)-12 blocked phencyclidine-evoked ambulations in a dose-dependent manner, indicating their potential as nonclassical antipsychotic agents.
Chimeric Constructs between Human and Rat Equilibrative Nucleoside Transporters (hENT1 and rENT1) Reveal hENT1 Structural Domains Interacting with Coronary Vasoactive Drugs (1998)

We have recently isolated cDNAs from human placenta and rat jejunum encoding the prototypic human and rat equilibrative nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporters hENT1 and rENT1. The two proteins (456 and 457 residues, Mr 50,000) are 78% identical in amino acid sequence and contain 11 potential transmembrane segments (TMs) with a large putative extracellular loop between TMs 1 and 2 and a large cytoplasmic loop between TMs 6 and 7. When expressed in Xenopus oocytes, recombinant hENT1 and rENT1 transport both purine and pyrimidine nucleosides, including adenosine, and are inhibited by nanomolar concentrations of NBMPR. hENT1 is also potently inhibited by coronary vasodilator drugs (dipyridamole, dilazep, and draflazine), whereas rENT1 is insensitive to inhibition by these compounds (dipyridamole IC50 values 190 nM (hENT1) and >/=10 microM (rENT1) at 10 microM uridine). In the present study, we have generated reciprocal chimeras between hENT1 and rENT1, using splice sites at residues 99 (end of TM 2) and 231 (end of TM 6), to identify structural domains of hENT1 responsible for transport inhibition by vasoactive compounds. Transplanting the amino-terminal half of hENT1 into rENT1 converted rENT1 into a dipyridamole/dilazep-sensitive transporter, whereas the amino-terminal half of rENT1 rendered hENT1 dipyridamole/dilazep-insensitive. Domain swaps within the amino-terminal halves of hENT1 and rENT1 identified residues 100-231 (incorporating TMs 3-6) of hENT1 as the major site of vasodilator interaction. Since these drugs function as competitive inhibitors of nucleoside transport and NBMPR binding, TMs 3-6 are likely to form part of the substrate-binding site.
Evaluation of Cardiovascular Stents as Antennas for Implantable Wireless Applications (2009)

In this study, we explore the use of stents as radiating structures to support transcutaneous wireless telemetry for data transfer of internal measurements from within the circulatory system. The implant location is chosen for the specific application of heart failure detection by monitoring internal pressure measurements of the pulmonary artery. The radiative properties of the single stent are quantified in free space within an anechoic chamber and compared with measurements taken while implanted in a live porcine subject. The <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> studies of our 2.4-GHz stent-based transmitter, implanted at a depth of 3.5 cm within the chest, showed a 32-35-dB power reduction at a receive distance of 10 cm for both co- and cross-polarizations. The approximate far-field <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</i> -plane antenna pattern is quantified at a distance of 50 cm both in free space within an anechoic chamber and while implanted within a porcine chest. These results are used to explore the accuracy of a high-fidelity simulation model developed using Ansoft's High Frequency Structural Simulator and components of their Human Body Model to provide a model that is validated with empirical data. This study provides insight into the effects of tissue on high-frequency electromagnetic transcutaneous transmission and develops a high-fidelity model that can be used for further design and optimization.
Residual macrovascular risk in 2013: what have we learned? (2014)

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.
Grid-Filter Design for a Multimegawatt Medium-Voltage Voltage-Source Inverter (2010)

This paper describes the design procedure and performance of an <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">LCL</i> grid filter for a medium-voltage neutral-point clamped converter to be adopted for a multimegawatt (multi-MW) wind turbine. The unique filter design challenges in this application are driven by a combination of the medium-voltage converter, a limited allowable switching frequency, component physical size and weight concerns, and the stringent limits for allowable injected current harmonics. Traditional design procedures of grid filters for lower power and higher switching frequency converters are not valid for a multi-MW filter connecting a medium-voltage converter switching at low frequency to the electric grid. This paper demonstrates a frequency-domain-model-based approach to determine the optimum filter parameters that provide the necessary performance under all operating conditions given the necessary design constraints. To achieve this goal, new concepts, such as virtual-harmonic content and virtual filter losses are introduced. Moreover, a new passive-damping technique that provides the necessary damping with low losses and very little degradation of the high-frequency attenuation is proposed.
Role of platelets in thrombosis and hemostasis (1994)

Platelet aggregates, stabilized by fibrin, rapidly form hemostatic plugs when blood vessels are severed or arterial thrombi at sites of vessel injury, such as ruptured atherosclerotic plaques, or regions where blood flow is disturbed, such as at stenoses. These thrombi cause the thromboembolic complications of atherosclerosis: heart attacks, strokes, and peripheral vascular disease. Platelet adhesion to subendothelial components such as collagen activates signalling pathways that lead to thromboxane A2 formation and secretion of platelet granule contents, including ADP. Both these substances cause platelet aggregation, a process in which the integrin, glycoprotein IIb/IIIa, becomes a receptor for fibrinogen, which forms bridges between adjacent platelets. On the surface of stimulated platelets, coagulation is accelerated and thrombin is generated; it is a potent inducer of platelet aggregation and secretion and also causes fibrin to form around the aggregates, stabilizing them. There are receptors on the platelet surface for thrombin, thromboxane A2, collagen, ADP, platelet-activating factor, fibrinogen, von Willebrand factor, and other ligands. Agents that inhibit platelet aggregation and the signalling pathways that are activated by the various aggregating agents are under intensive investigation in many laboratories.
The nucleotide sequence of a human immnnoglobulin C-gamma-1 gene (1982)

We report the nucleotide sequence of a gene encoding the constant region of a human immnnoglobulin γ1 heavy chain (Cγ1). A comparison of this sequence with those of the Cγ2 and Cγ4 genes reveals that these three human Cγ genes share considerable homology in both coding and noncoding regions. The nucleotide sequence differences indicate that these genes diverged from one another approximately 6–8 million years ago. An examination of hinge exons shows that these coding regions have evolved more rapidly than any other areas of the Cγ genes in terms of both base substitution and deletion–insertion events. Coding sequence diversity also is observed in areas of CH domains which border the hinge.
COMPOSITION OF VOLATILE ORGANIC COMPOUNDS IN DIATHERMY PLUME AS DETECTED BY SELECTED ION FLOW TUBE MASS SPECTROMETRY (2007)

Although there is no evidence of adverse health effects from the volatile organic compound in diathermy plume, the evidence that it is safe to breathe this plume is lacking. Therefore, we would recommend the use of smoke evacuators where practical.
GERM-LINE TRANSFORMATION OF MICE (1986)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More
Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina (2017)

There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and the route of surgical delivery-intravitreal or subretinal. This study compared three of the most efficacious AAV vectors known to date in a mouse model of retinal degeneration (rd1 mouse) and macaque and human retinal explants. Green fluorescent protein (GFP) driven by a ubiquitous promoter was packaged into three AAV capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) and AAV2/2(7m8). Overall, AAV2/2(7m8) transduced the largest area of retina and resulted in the highest level of GFP expression, followed by AAV2/2(quad Y-F) and AAV2/8(Y733F). AAV2/2(7m8) and AAV2/2(quad Y-F) both resulted in similar patterns of transduction whether they were injected intravitreally or subretinally. AAV2/8(Y733F) transduced a significantly smaller area of retina when injected intravitreally compared with subretinally. Retinal ganglion cells, horizontal cells and retinal pigment epithelium expressed relatively high levels of GFP in the mouse retina, whereas amacrine cells expressed low levels of GFP and bipolar cells were infrequently transduced. Cone cells were the most frequently transduced cell type in macaque retina explants, whereas Müller cells were the predominant transduced cell type in human retinal explants. Of the AAV serotypes tested, AAV2/2(7m8) was the most effective at transducing a range of cell types in degenerate mouse retina and macaque and human retinal explants.
Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone (2003)

Water-soluble phosphate prodrugs of buparvaquone (1), containing a hydroxynaphthoquinone structure, were synthesized and evaluated in vitro for improved topical and oral drug delivery against cutaneous and visceral leishmaniasis. The successful prodrug synthesis involved a strong base; e.g., sodium hydride. Buparvaquone-3-phosphate (4a) and 3-phosphonooxymethyl-buparvaquone (4b) prodrugs possessed significantly higher aqueous solubilities (>3.5 mg/mL) than the parent drug (</=0.03 microg/mL) over a pH range of 3.0-7.4. Moreover, 4a and 4b maintained adequate lipophilicity as indicated by distribution coefficients (log D) between 0.5 and 3.0 over this pH range. Both 4a and 4b were also shown to be substrates for alkaline phosphatase in vitro and thus are promising bioreversible prodrugs for the improved topical and oral bioavailability of 1. Buparvaquone and its prodrugs showed nanomolar or low-micromolar ED(50) activity values against species that cause cutaneous leishmaniasis, e.g., L. major, L. amazonensis, L. aethiopica, L. mexicana, and L. panamensis and also L. donovani, which is the causative agent of visceral leishmaniasis. From these results, the human skin permeation of the prodrugs 4a and 4b were studied in vitro. While no buparvaquone permeated across post mortem skin in vitro during 72 h of experiments, both prodrugs 4a and 4b permeated readily through the skin. In addition, 4b easily released the parent drug in human skin homogenate and, therefore, is a promising prodrug candidate to deliver buparvaquone through the skin for the treatment of cutaneous leishmaniasis.