gebhart/patrepeval huggingface dataset:
A Missense LAMB2 Mutation Causes Congenital Nephrotic Syndrome by Impairing Laminin Secretion (2011)

Laminin β2 is a component of laminin-521, which is an important constituent of the glomerular basement membrane (GBM). Null mutations in laminin β2 (LAMB2) cause Pierson syndrome, a severe congenital nephrotic syndrome with ocular and neurologic defects. In contrast, patients with LAMB2 missense mutations, such as R246Q, can have less severe extrarenal defects but still exhibit congenital nephrotic syndrome. To investigate how such missense mutations in LAMB2 cause proteinuria, we generated three transgenic lines of mice in which R246Q-mutant rat laminin β2 replaced the wild-type mouse laminin β2 in the GBM. These transgenic mice developed much less severe proteinuria than their nontransgenic Lamb2-deficient littermates; the level of proteinuria correlated inversely with R246Q-LAMB2 expression. At the onset of proteinuria, expression and localization of proteins associated with the slit diaphragm and foot processes were normal, and there were no obvious ultrastructural abnormalities. Low transgene expressors developed heavy proteinuria, foot process effacement, GBM thickening, and renal failure by 3 months, but high expressors developed only mild proteinuria by 9 months. In vitro studies demonstrated that the R246Q mutation results in impaired secretion of laminin. Taken together, these results suggest that the R246Q mutation causes nephrotic syndrome by impairing secretion of laminin-521 from podocytes into the GBM; however, increased expression of the mutant protein is able to overcome this secretion defect and improve glomerular permselectivity.
The metabolic syndrome: targeting dyslipidaemia to reduce coronary risk. (2003)

The metabolic syndrome is a complex constellation of disorders, each one a significant risk factor for the development of cardiovascular disease (CVD). The increasing prevalence of this condition is a major concern for healthcare providers both in Europe and North America. The concern surrounding the prevalence of the metabolic syndrome is reflected in the recently published National Cholesterol Education Program Adult Treatment Panel III guidelines. Although complex in nature, the individual components of the metabolic syndrome appear to be linked by the presence of insulin resistance. Concurrently treating the underlying insulin resistance along with the complex array of other disorders should form the core of any management strategy. Treatment of atherogenic dyslipidaemia should be a major aim, since it is associated with a significant risk of CVD. While lifestyle modifications form the cornerstone of any dyslipidaemia management strategy, many patients require the addition of lipid-modifying drugs. Several agents are available for the treatment of lipid abnormalities, including fibrates, bile acid sequestrants, niacin and hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins). Of these, statins should be used as the first treatment option in the majority of patients because they are efficacious for reducing low-density lipoprotein cholesterol, are effective across the lipid profile and are well tolerated in the majority of cases. Furthermore, the American Diabetes Association (ADA) recommends statins as first-line pharmacological treatment of dyslipidaemia in patients with diabetes mellitus. This review discusses the diagnosis and management of the metabolic syndrome and examines the potential of future treatment options.
Modulation of Induction Properties of Glucocorticoid Receptor-Agonist and -Antagonist Complexes by Coactivators Involves Binding to Receptors but Is Independent of Ability of Coactivators to Augment Transactivation (2002)

Coactivators such as TIF2 and SRC-1 modulate the positioning of the dose-response curve for agonist-bound glucocorticoid receptors (GRs) and the partial agonist activity of antiglucocorticoid complexes. These properties of coactivators differ from their initially defined activities of binding to, and increasing the total levels of transactivation by, agonist-bound steroid receptors. We now report that constructs of TIF2 and SRC-1 lacking the two activation domains (AD1 and AD2) have significantly less ability to increase transactivation but retain most of the activity for modulating the dose-response curve and partial agonist activity. Mammalian two-hybrid experiments show that the minimum TIF2 segment with modulatory activity (TIF2.4) does not interact with p300, CREB-binding protein, or PCAF, which also modulates GR activities. DRIP150 and DRIP205 have been implicated in coactivator actions but are unable to modulate GR activities. The absence of synergism by PCAF or DRIP150 with SRC-1 or TIF2, respectively, further suggests that these other factors are not involved. The ability of a TIF2.4 fragment (i.e. TIF2.37), which is not known to interact with proteins, to block the actions of TIF2.4 suggests that an unidentified binder mediates the modulatory activity of TIF2. Pull-down experiments with GST/TIF2.4 demonstrate a direct interaction of TIF2 with GR in a hormone-dependent fashion that requires the receptor interaction domains of TIF2 and is equally robust with agonists and most antiglucocorticoids. These observations, which are confirmed in mammalian two-hybrid assays, suggest that the capacity of coactivators such as TIF2 to modulate the partial agonist activity of antisteroids is mediated by the binding of coactivators to GR-antagonist complexes. In conclusion, the modulatory activity of coactivators with GR-agonist and -antagonist complexes is mechanistically distinct from the ability of coactivators to augment the total levels of transactivation and appears to involve the binding to both GR-steroid complexes and an unidentified TIF2-associated factor(s).
Ejercicio de la acción de reducción de donaciones inoficiosas (2011)

El proposito de este trabajo es el de ayudar a dar luz sobre las numerosas cuestiones que plantea el ejercicio de la accion de reduccion de las donaciones inoficiosas, concretamente si ese plazo es de caducidad o de prescripcion, cuando se inicia su computo, que duracion tiene, cual es el procedimiento adecuado, o quien esta legitimado. He indagado en la doctrina y en la jurisprudencia, con especial atencion a la de los Tribunales extremenos, por ser este el ambito habitual de mi actuacion profesional, y he encontrando, a veces, soluciones contradictorias.
Wavelength routing for long haul networks (2003)

Networks employing wavelength routing, optical amplifiers, and flexible access techniques offer the potential of high reliability and high capacity for telecommunications core network systems. The requirements of these long-haul networks will place high demands on the optical bandwidth and noise performance of optical amplifiers. Network models based on both optical broadband and wavelength selective principles are compared, and a method of equalizing the useful optical bandwidth of amplified routes in wavelength selective networks is presented. Experimental work using commercially available wavelength-division in multiplexing technology, distributed-feedback lasers, and optical amplifiers is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Highly reliable wave-guide photodiode with wide bandwidth of 50 GHz at the low operation voltage of -1.5 V (2004)

Wave-guide photodiodes with 50 GHz bandwidth at the low operation bias voltage of -1.5 V are realized, which have life time over 8/spl times/10/sup 7/ h at 25 /sup /spl deg//C by adopting buried structure with semiinsulating InP.
Methods and related drawbacks in the estimation of surgical risks in cirrhotic patients undergoing hepatectomy. (2002)

There has been a dramatic improvement in recent results of hepatectomy for hepatocellular carcinoma in cirrhotic patients. Hospital mortality rates of less than 5% are frequently reported. The improvement is largely a result of better techniques and performance of surgeons in hepatectomy, and reduction in blood loss and transfusion requirement. Better selection of patients is perhaps a more significant contributory factor. Careful identification of risk factors related to the medical condition of the patient, functional reserve of the liver and volume of the remnant liver is essential for the prevention of postoperative liver failure. Indocyanine green clearance test is the most accurate test for assessment of liver function reserve. An indocyanine green retention rate of 14% at 15 minutes is the safety limit for major hepatectomy for cirrhotic patients. A maximum of 60% of the nontumorous liver can be resected safely. Computed tomography is therefore an important assessment parameter. The liver function reserve also reveals the suitability for hepatectomy. Liver enzymes, alanine aminotransferase or aspartate aminotransferase can reflect the hepatic activity, which could be responsible for the impaired liver function. Steatosis is another factor that influences hepatic function reserve. Age is also an important risk factor in hepatectomy because elderly patients may harbor occult heart disease, reduced respiratory and liver function reserves. After recognizing the risk factors, surgeons should eliminate operative morbidity and mortality by making appropriate decisions based on the assessments. In conclusion, preoperative risk assessment involves evaluation of hepatic function reserve, remnant liver volume, liver status, age and the medical condition of the patient. A 0% hospital mortality rate is considered the objective.
Single‐ and Multiple‐dose Pharmacokinetics of Clarithromycin, a New Macrolide Antimicrobial (1993)

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.
The <i>Xenopus</i> XIHbox 6 homeo protein, a marker of posterior neural induction, is expressed in proliferating neurons (1990)

XIHbox 6 is an early spatially restricted marker for molecular studies of neural induction. The sequence of the full-length XIHbox 6 protein is reported. An antibody raised against a beta-galactosidase/XIHbox 6 fusion protein was used to analyze the expression of XIHbox 6 proteins during frog embryogenesis. The anterior border of XIHbox 6 expression lies just posterior of the hindbrain/spinal cord junction. Immunostaining extends the entire length of the spinal cord. A much weaker transient expression with a similar anterior border is observed in mesoderm. Almost all nuclei in the newly closed spinal cord contain XIHbox 6. The number of positive nuclei decreases over the next stages of development, until in later embryos XIHbox 6 is restricted to nuclei of the dividing neuroepithelium, and not the mantle or marginal zones of the spinal cord. When the limb buds begin to grow, there is a second burst of XIHbox 6 expression in proliferating neurons of the cervical and lumbar enlargements, where nerves arise that supply the limbs. The data suggest that XIHbox 6 expression is spatially and temporally restricted to immature neurons of the spinal cord, before their differentiation into mature neurons.
A Novel Ubiquitously Expressed α-Latrotoxin Receptor Is a Member of the CIRL Family of G-protein-coupled Receptors (1999)

Poisoning with alpha-latrotoxin, a neurotoxic protein from black widow spider venom, results in a robust increase of spontaneous synaptic transmission and subsequent degeneration of affected nerve terminals. The neurotoxic action of alpha-latrotoxin involves extracellular binding to its high affinity receptors as a first step. One of these proteins, CIRL, is a neuronal G-protein-coupled receptor implicated in the regulation of secretion. We now demonstrate that CIRL has two close homologs with a similar domain structure and high degree of overall identity. These novel receptors, which we propose to name CIRL-2 and CIRL-3, together with CIRL (CIRL-1) belong to a recently identified subfamily of large orphan receptors with structural features typical of both G-protein-coupled receptors and cell adhesion proteins. Northern blotting experiments indicate that CIRL-2 is expressed ubiquitously with highest concentrations found in placenta, kidney, spleen, ovary, heart, and lung, whereas CIRL-3 is expressed predominantly in brain similarly to CIRL-1. It appears that CIRL-2 can also bind alpha-latrotoxin, although its affinity to the toxin is about 14 times less than that of CIRL-1. When overexpressed in chromaffin cells, CIRL-2 increases their sensitivity to alpha-latrotoxin stimulation but also inhibits Ca2+-regulated secretion. Thus, CIRL-2 is a functionally competent receptor of alpha-latrotoxin. Our findings suggest that although the nervous system is the primary target of low doses of alpha-latrotoxin, cells of other tissues are also susceptible to the toxic effects of alpha-latrotoxin because of the presence of CIRL-2, a low affinity receptor of the toxin.
Efficient ablation of an organic polymer by a laser driven shock wave (1993)

A new method for the efficient removal of an organic polymer is described. Fragments on the order of 1 mm diam are produced when a 0.02 J, 5 ns pulse of 532 nm light is focused into a red organic polymer that is coated on the front side of a transparent window. Quantities as large as 200 μg and craters as deep as 200 μm have been ablated in a single laser pulse. The large mass particles resulting from the ablation generate high transient pressures on the order of 100 kbar.
Left ventricular volume estimation for real-time three-dimensional echocardiography (2002)

The application of level set techniques to echocardiographic data is presented. This method allows semiautomatic segmentation of heart chambers, which regularizes the shapes and improves edge fidelity, especially in the presence of gaps, as is common in ultrasound data. The task of the study was to reconstruct left ventricular shape and to evaluate left ventricular volume. Data were acquired with a real-time three-dimensional (3-D) echocardiographic system. The method was applied directly in the three-dimensional domain and was based on a geometric-driven scheme. The numerical scheme for solving the proposed partial differential equation is borrowed from numerical methods for conservation law. Results refer to in vitro and human in vivo acquired 3-D + time echocardiographic data. Quantitative validation was performed on in vitro balloon phantoms. Clinical application of this segmentation technique is reported for 20 patient cases providing measures of left ventricular volumes and ejection fraction.
Gigabit Ethernet Networking (1999)

From the Publisher:
Beginning with an historical context that brings an understanding of the constraints under which Gigabit was designed, the authors will then discuss the standard reference model in some detail. They will then segue into a discussion of the Media Access Control for Gigabit Ethernet. From here, the authors will discuss repeaters and switches in the Gigabit architecture. Switching is critical for any bandwidth as large as one billion bits per second. The authors then begin a discussion of baseband transmission from which they move on to an explanation of the various physical sub-layers including copper and optical media. For long distances, Gigabit transmission will depend heavily on fiber optic media to deliver the necessary signal quality. The authors are experts in this area and will discuss optical transmission issues in some detail. Finally, the authors will discuss various application examples for the Gigabit technology including Gigabit in a hybrid network that includes 10 Mbps, 100 Mbps (Fast Ethernet), ATM, and Fiber Channel. The examples also consider Gigabit Ethernet and Quality of Service, plus cabling for Gigabit LANs and other installation issues. 
Gigabit Ethernet is a rapidly advancing technology that will increase network traffic speeds by a factor of 10. It is of critical importance to the vast majority of corporate network engineers and administrators Gigabit Ethernet is the definitive work from the authors of the specification Gigabit Ethernet will give the reader an unparalleled depth of understanding for this technology
Thymus‐derived lymphocytes: their distribution and role in the development of peripheral lymphoid tissues of the mouse (1971)

Abstract Using the theta (Θ) alloantigen of mice as a marker of thymus‐derived cells, we have studied the distribution of these lymphocytes in adult and developing lymphoid tissues of CBA and Balb/c mice. In adult mice, lymphoid tissues can be arranged in the following order according to the approximate proportions of Θ‐bearing (thymus‐derived) lymphocytes they contain: thymus (100%), thoracic duct lymphocytes (80–85%), blood lymphocytes (70%), lymph nodes (65–70%), spleen (30–35%), peritoneal lymphocytes (30–35%) and Peyer's patches (20–25%). Results obtained in newborn mice show that the development of peripheral lymphoid tissues is largely dependent on the inflow (and possibly the proliferation) of thymus‐derived lymphocytes. The presence of Θ‐bearing lymphocytes in developing Peyer's patches indicates that lymphoid differentiation in these organs is, in part at least, thymus‐dependent.
Probing the birth of the first quasars with the future far infrared mission (2005)

It is now widely recognised that massive black holes must have had a fundamental influence on the formation of galaxies and vice versa. With current and imminent missions we aim to unravel much of this relationship for the last 10 Gyr of cosmic history, while the quasar population waned and star formation died down. The picture at earlier times will be more difficult to reconstruct, but will likely be even more exciting: when the first stars shone, the first dust was formed, and quasars were a vigorously rising population. One of the primary goals of XEUS is to allow us to find and study the earliest quasars, however deeply buried in gas and dust they may be. But to understand fully the astrophysical context of these objects, their significance in the grand picture, we must learn how they relate to their environments and their host galaxies. The ESA future Far-InfraRed Mission (FIRM) will provide much of the data we require, revealing the dust heated by star formation in the host galaxy, the relative evolutionary stages of spheroid and black hole, and the total energy budgets posessed by these first quasars. FIRM will reveal star formation in the immediate proto-cluster environment of the quasar and so tell us how the formation of the first galaxies and quasars coupled to the earliest large scale structures.
Practical Enhanced Reservoir Engineering: Assisted With Simulation Software (2008)

This book is intended to be a reservoir engineering book for college students, but its not the usual college text book. It is a modern and very practical guide offering reservoir engineering fundamentals, advanced reservoir related topics, reservoir simulation fundamentals, and problems and case studies from around the world. It is designed to aid students and professionals alike in their active and important roles throughout the reservoir life cycle (discovery, delineation, development, production, and abandonment), and in the various phases of the reservoir management process (setting strategy, developing plan, implementing, monitoring, evaluating, and completing). Benefits & Features:The authors bring to this book their life-long experience and expertise in reservoir engineering and simulation techniques and practice. The goal is to present a comprehensive book, starting from basic principles and leading to real-life reservoir management aided by simulation. This practical book explores the functions of reservoir engineers, and how they analyze, think and work in real life situations. It presents: Rock and fluid properties, fluid flow principles, well test analysis, and reservoir performance analysis techniques. New topics such as reserves, reservoir economics, risk and uncertainties, probabilistic methods, and recovery processes. Role of reservoir simulation models in enhancing basic reservoir engineering concepts and practice. Computer-based tools, including reservoir simulation, are used extensively in this book to illustrate various concepts related to reservoir engineering. Finally, the book offers class projects where the students can apply what they have learned to treat their problems. This book will serve the students and the industry well.
Apatinib inhibits VEGFR-2 and angiogenesis in an<i>in vivo</i>murine model of nasopharyngeal carcinoma (2017)

Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP). The impact of treatment regimens on the growth, microvascularization, apoptosis, and metabolic response of tumors, as well as mouse survival was determined by histopathology, immunohistochemistry (VEGFR-2 and CD31), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), micro 18F-FDG PET/CT imaging and survival curves. Administration of apatinib alone inhibited tumor growth, reduced microvascular density, and facilitated the apoptosis of tumors. Tumors treated simultaneously with apatinib and cisplatin exhibited significantly-increased inhibition of tumor growth, prolonged survival time, decreased expression of VEGFR-2, reduced microvascular density, and frequency of apoptosis over standalone and sequential administration therapy. Tumors treated simultaneously with apatinib and cisplatin had the lowest uptake of FDG. Taken together, the simultaneous administration of apatinib and cisplatin improves the therapeutic efficacy over standalone treatments, which also led to improved efficacy over sequential administration regimens. VEGFR-2 is an important predictive marker for efficacy of apatinib treatment of NPC.