gebhart/patrepeval huggingface dataset:
SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor–Naïve Patients With Myelofibrosis (2017)

Purpose We evaluated the efficacy and safety of momelotinib, a potent and selective Janus kinase 1 and 2 inhibitor (JAKi), compared with ruxolitinib, in JAKi-naïve patients with myelofibrosis. Patients and Methods Patients (N = 432) with high risk or intermediate-2 risk or symptomatic intermediate-1 risk myelofibrosis were randomly assigned to receive 24 weeks of treatment with momelotinib 200 mg once daily or ruxolitinib 20 mg twice a day (or per label), after which all patients could receive open-label momelotinib. The primary end point was a ≥ 35% reduction in spleen volume at 24 weeks of therapy. Secondary end points were rates of symptom response and effects on RBC transfusion requirements. Results A ≥ 35% reduction in spleen volume at week 24 was achieved by a similar proportion of patients in both treatment arms: 26.5% of the momelotinib group and 29% of the ruxolitinib group (noninferior; P = .011). A ≥ 50% reduction in the total symptom score was observed in 28.4% and 42.2% of patients who received momelotinib and ruxolitinib, respectively, indicating that noninferiority was not met ( P = .98). Transfusion rate, transfusion independence, and transfusion dependence were improved with momelotinib (all with nominal P ≤ .019). The most common grade ≥ 3 hematologic abnormalities in either group were thrombocytopenia and anemia. Grade ≥ 3 infections occurred in 7% of patients who received momelotinib and 3% of patients who received ruxolitinib. Treatment-emergent peripheral neuropathy occurred in 10% of patients who received momelotinib (all grade ≤ 2) and 5% of patients who received ruxolitinib (all grade ≤ 3). Conclusion In JAKi-naïve patients with myelofibrosis, 24 weeks of momelotinib treatment was noninferior to ruxolitinib for spleen response but not for symptom response. Momelotinib treatment was associated with a reduced transfusion requirement.
A Gas Lift Bioreactor for Removal of Contaminants from the Vapor Phase (1994)

The cometabolic degradation of trichloroethylene (TCE) as a vapor by two aromatic-metabolizing pseudomonads was evaluated in an airlift reactor. These microorganisms were able to degrade 90 to 95% of TCE in air at concentrations at the reactor inlet of 300 to 4,000 mug/liter. Although exposure of the cells to high inlet concentrations of TCE (4 mg/liter) caused a decline in enzyme-specific activity and TCE removal efficiency, this loss in activity could be prevented or delayed by increasing the rate of cosubstrate addition. Under the appropriate operating conditions, the microorganisms were able to degrade even high concentrations of TCE and activity of the cells in the reactor could be maintained for periods of at least 2 weeks.
Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome (2015)

Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS ex vivo to probe for stress-induced sensitization of proinflammatory responses. Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to LPS, that is, microglia were sensitized. Treatment with BoxA abolished this effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was replaced with intracerebral administration of disulfide or fully reduced HMGB-1. Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and proinflammatory cytokine expression after LPS treatment, whereas fully reduced HMGB-1 had no effect. The present results suggest that the CNS innate immune system can respond to an acute stressor as if it were cellular damage, thereby releasing the danger signal HMGB-1 in the brain to prime microglia by acting on the NLRP3 inflammasome, in preparation for a later immune challenge.
A Novel Molecular Diagnostic of Glioblastomas: Detection of an Extracellular Fragment of Protein Tyrosine Phosphatase μ (2010)

We recently found that normal human brain and low-grade astrocytomas express the receptor protein tyrosine phosphatase mu (PTPmu) and that the more invasive astrocytomas, glioblastoma multiforme (GBM), downregulate full-length PTPmu expression. Loss of PTPmu expression in GBMs is due to proteolytic cleavage that generates an intracellular and potentially a cleaved and released extracellular fragment of PTPmicro. Here, we identify that a cleaved extracellular fragment containing the domains required for PTPmicro-mediated adhesion remains associated with GBM tumor tissue. We hypothesized that detection of this fragment would make an excellent diagnostic tool for the localization of tumor tissue within the brain. To this end, we generated a series of fluorescently tagged peptide probes that bind the PTPmu fragment. The peptide probes specifically recognize GBM cells in tissue sections of surgically resected human tumors. To test whether the peptide probes are able to detect GBM tumors in vivo, the PTPmu peptide probes were tested in both mouse flank and intracranial xenograft human glioblastoma tumor model systems. The glial tumors were molecularly labeled with the PTPmu peptide probes within minutes of tail vein injection using the Maestro FLEX In Vivo Imaging System. The label was stable for at least 3 hours. Together, these results indicate that peptide recognition of the PTPmu extracellular fragment provides a novel molecular diagnostic tool for detection of human glioblastomas. Such a tool has clear translational applications and may lead to improved surgical resections and prognosis for patients with this devastating disease.
An Updated Review: Newer Quinazoline Derivatives Under Clinical Trial (2011)

ABSTRACT
Quinazoline derivatives occupy a distinct and unique place in the medicinal chemistry as they possess diverse biological activities. As on date, about 25 clinically used drugs are quinazoline derivatives. This review has presented a comprehensive detail of quinazoline derivatives which are under clinical trial.
Digital Signal Processing Options in Long Haul Transmission (2008)

Digital signal processing (DSP) combined with spectrally efficient modulation has redefined the limits for long-haul transmission. We survey the options currently under consideration, including the impact of technology and discuss future directions for DSP research.
Network-Based Logistic Classification with an Enhanced<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mi>L</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn><mml:mo>/</mml:mo><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>Solver Reveals Biomarker and Subnetwork Signatures for Diagnosing Lung Cancer (2015)

Identifying biomarker and signaling pathway is a critical step in genomic studies, in which the regularization method is a widely used feature extraction approach. However, most of the regularizers are based on L 1-norm and their results are not good enough for sparsity and interpretation and are asymptotically biased, especially in genomic research. Recently, we gained a large amount of molecular interaction information about the disease-related biological processes and gathered them through various databases, which focused on many aspects of biological systems. In this paper, we use an enhanced L 1/2 penalized solver to penalize network-constrained logistic regression model called an enhanced L 1/2 net, where the predictors are based on gene-expression data with biologic network knowledge. Extensive simulation studies showed that our proposed approach outperforms L 1 regularization, the old L 1/2 penalized solver, and the Elastic net approaches in terms of classification accuracy and stability. Furthermore, we applied our method for lung cancer data analysis and found that our method achieves higher predictive accuracy than L 1 regularization, the old L 1/2 penalized solver, and the Elastic net approaches, while fewer but informative biomarkers and pathways are selected.
Evaluating the energy-awareness of future Internet devices (2011)

Advanced power management capabilities have been proposed to be included into next-generation green network devices in order to modulate their energy requirements according to the workload. The clear side effect of enabling these new capabilities consists in a performance level reduction of network devices. Starting from some existing benchmarking standards for evaluating energy-efficiency, namely ECR and ATIS-060015, this contribution is devoted to determining a set of parameters, and methodologies that can be applied to correctly and precisely evaluate the tradeoff between energy consumption and network performance. Some experimental results obtained with the proposed indexes and methodologies, as well as a green SW router prototype have been provided.
Proportional load sharing method for parallel connected inverters (2010)

In this paper, a control technique is proposed for parallel connected inverters to share linear and nonlinear loads in proportional to their capacities. Using locally measurable feedback voltages and currents without an external communication mechanism, this technique considerably reduces the sharing error of reactive power, output voltage drop and output voltage distortion, which are inherent drawbacks in the conventional control method. Simulation results are presented to verify the proposed technique.
Understanding Tuberculosis - Deciphering the Secret Life of the Bacilli (2012)

Mycobacterium tuberculosis, as recent investigations demonstrate, has a complex signaling expression, which allows its close interaction with the environment and one of its most renowned properties: the ability to persist for long periods of time under a non-replicative status. Although this skill is well characterized in other bacteria, the intrinsically very slow growth rate of Mycobium tuberculosis, together with a very thick and complex cell wall, makes this pathogen specially adapted to the stress that could be generated by the host against them. In this book, different aspects of these properties are displayed by specialists in the field.
Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. (1975)

The factors influencing the development of impaired sciatic motor nerve conduction velocity (MNCV) in acute experimental diabetes were examined. Decreased MNCV developed by the 14th day after streptozotocin administration but only in rats which became hyperglycemic. Insulin treatment, begun on day 3, failed to prevent imparied MNCV in diabetic rats in which improved or normal weight gain and a decreased degree of hyperglycemia was induced. However, insulin treatment prevented the development of impaired MNCV in a group of diabetic rats in which the tail vein plasma glucose concentration was never found to exceed 160 mg/dl during days 6 through 14, andin which the mean plus or minus SEM of the average plasma glucose concentration for each animal during the same period was 75 plus or minus 18 mg/dl. In normal rats fed diets containing 0.011% or 0.069% free myoinositol (a presumably normal range), sciatic nerve free myoinositol concentrations were 90- and 60-fold higher than those in plasma. On these diets the development of impaired MNCV in the diabetics was associated with a decrease in nerve free myoinositol as compared with nerves from normals fed the same diet, despite similar plasma levels in the normals and diabetics. Plasma and nerve free myoinositol increased with increasing dietary myoinositol content in both normals and diabetics, and nerve myoinositol content could be acutely increased by an i.p. myoinositol load. By supplementing the diets with 1.0% myoinositol, the difference in nerve myoinositol in normal and diabetic rats on day 14 was abolished; on this diet the development of impaired MNCV in the diabetics was moderated or totally prevented, despite persistent hyperglycemia and elevated nerve sorbitol and fructose concentrations. Insulin treatment that prevented impaired MNCV prevented a decrease in nerve myoinositol in diabetics. These studies suggest that insulin deficiency, and possibly hyperglycemia, are primary factors in the development of imparied MNCV in acute experimental diabetes. However, the development of impaired MNCV appears to be related in some manner to a derangement in the regulation of nerve free myoinositol content, which appears to be subject to modification by increases in plasma myoinositol concentration over a critical range.
Comparison of energy metabolism in human normal and neoplastic (Burkitt's lymphoma) lymphoid cells. (1983)

In order to detect possible differences in the energy metabolism between normal and neoplastic lymphoid cells, we studied purified normal human lymphocytes (FL) and transformed lymphoblastoid cell lines derived from umbilical cord blood (CL) and compared them to cell lines derived from American Burkitt's lymphoma (BL). The total adenosine triphosphate production rate by these cells was estimated by measuring O2 consumption and lactic acid production rates. O2 consumption (nmol/min/mg protein) was 4.9 +/- 0.3 (S.D.) in CL, 4.4 +/- 0.3 in FL, and 4.9 +/- 0.3 in BL. Lactic acid production (nmol/min/mg protein) was 30.9 +/- 3.0 in CL, 29.9 +/- 3.0 in FL, and 23.4 +/- 4.0 in BL. Using these values of O2 consumption and lactic acid production, the average adenosine triphosphate production rates (nmol/min/mg protein) were calculated to be 60 in CL, 56 in FL, and 53 in BL. We conclude that the BL do not have more aerobic glycolysis than do normal lymphoid cells, suggesting that the lactic acidosis seen in American Burkitt's lymphoma is not due to a preferential glycolytic metabolism of the tumor. More likely, the lactic acidosis is simply due to the large total mass of these neoplastic cells and not due to a modification of their energy metabolism.
[Effect of antisense oligonucleotides on myo-intimal hyperplasia in a model of abdominal aortic injury in the rat]. (1995)

Restenosis at a rate > 30% at 6 months is the major complication of both coronary and peripheral arterial angioplasty. Restenosis is mainly due to proliferation of smooth muscle cells, extracellular matrix and collagen which form a neointima. The proto-oncogene c-myb is a gene with an immediate response which has been implicated in the proliferation and alteration of the phenotype of smooth muscle cells. The antisenses are molecules of single-helix DNA the sequence of which is inverse to that of messenger RNA of the target proto-oncogene. They therefore have the possibility of forming a double helix with the messenger RNA and of preventing its translation. The antisenses of c-myb have already been successfully tested in in vitro and in vivo models of neointimal proliferation. The aim of this study was to demonstrate the efficacy of c-myb antisenses on the proliferation of smooth muscle cells in a model of abdominal aortic injury in the rat. Thirty-five male Wistar rats with an average weight of 350 grams were operated. Smooth muscle cell proliferation was obtained by desendothelialisation of the abdominal aorta from the level of the left renal vein to the aortic bifurcation. Using a randomised, double-blind protocol, 17 rats were given 500 microliters of pluronic gel (control group), 9 a sense oligonucleotide of c-myb in 500 microliters of pluronic gel (sense group) and 9 a c-myb antisense oligonucleide in 500 microliters of pluronic gel (antisense group). Two rats were given fluorescinlabelled antisenses; one was sacrificed 4 hours and the other 24 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)
Performance comparison of fundamental anisotropic diffusion algorithms (2004)

Anisotropic diffusion (AD), first introduced by Perona and Malik (PM), provides image enhancement a strong benefit as it favors intra-region over inter-region smoothing. Early updates on the original PM algorithm focused on the cures for its drawbacks. Later some authors provided their own versions of AD techniques with a wide variety of applications. We surveyed the pros and cons of many fundamental AD techniques. To put our purpose into perspective, we compared the performances of fundamental AD algorithms to simple traditional filters and to more sophisticated tools such as wavelets. Visual inspection and two mathematical criteria are used for performance comparison: Signal-to-noise ratio (SNR) and universal image quality index (UIQI). We believe that a good overview of its simplicity and power will show the rightful reason of so much interest in anisotropic diffusion since its introduction.
Deformable structure registration of bladder through surface mapping (2006)

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.
Role of <scp>F</scp>c‐mediated antibody function in protective immunity against <scp>HIV</scp>‐1 (2013)

The importance of Fc-mediated effector function in protective immunity to HIV-1 (hereafter referred to simply as HIV) is becoming increasingly apparent. A large of number of studies in natural infection cohorts, spanning the last 26 years, have associated Fc-mediated effector function, particularly antibody-dependent cellular cytotoxicity, with a favourable clinical course. These studies strongly suggest a role for Fc-mediated effector function in the post-infection control of viraemia. More recently, studies in both humans and non-human primates (NHPs) also implicate Fc-mediated effector function in blocking HIV acquisition. Accordingly, this review will discuss the results supporting a role of Fc-mediated effector function in both blocking acquisition and post-infection control of viraemia. Parallel studies in NHPs and humans will be compared for common themes. Context for this discussion will be provided by summarizing the temporal emergence of key host and virological events over the course of an untreated HIV infection framing where, when and how Fc-mediated effector function might be protective. A hypothesis that Fc-mediated effector function protects primarily in the early stages of both acquisition and post-infection control of viraemia will be developed.
Characterizing the sparseness of neural codes (2001)

It is often suggested that efficient neural codes for natural visual information should be `sparse'. However, the term `sparse' has been used in two different ways - firstly to describe codes in which few neurons are active at any time (`population sparseness'), and secondly to describe codes in which each neuron's lifetime response distribution has high kurtosis (`lifetime sparseness'). Although these ideas are related, they are not identical, and the most common measure of lifetime sparseness - the kurtosis of the lifetime response distributions of the neurons - provides no information about population sparseness. We have measured the population sparseness and lifetime kurtosis of several biologically inspired coding schemes. We used three measures of population sparseness (population kurtosis, Treves-Rolls sparseness and `activity sparseness'), and found them to be in close agreement with one another. However, we also measured the lifetime kurtosis of the cells in each code. We found that lifetime kurtosis is uncorrelated with population sparseness for the codes we used. Lifetime kurtosis is not, therefore, a useful measure of the population sparseness of a code. Moreover, the Gabor-like codes, which are often assumed to have high population sparseness (since they have high lifetime kurtosis), actually turned out to have rather low population sparseness. Surprisingly, principal components filters produced the codes with the highest population sparseness.