gebhart/patrepeval huggingface dataset:
Ballistocardiogram: Mechanism and Potential for Unobtrusive Cardiovascular Health Monitoring (2016)

For more than a century, it has been known that the body recoils each time the heart ejects blood into the arteries. These subtle cardiogenic body movements have been measured with increasingly convenient ballistocardiography (BCG) instruments over the years. A typical BCG measurement shows several waves, most notably the "I", "J", and "K" waves. However, the mechanism for the genesis of these waves has remained elusive. We formulated a simple mathematical model of the BCG waveform. We showed that the model could predict the BCG waves as well as physiologic timings and amplitudes of the major waves. The validated model reveals that the principal mechanism for the genesis of the BCG waves is blood pressure gradients in the ascending and descending aorta. This new mechanistic insight may be exploited to allow BCG to realize its potential for unobtrusive monitoring and diagnosis of cardiovascular health and disease.
Histone deacetylase inhibitors: novel anticancer agents (1999)

Previous studies have established that the regulation of gene expression is dependent upon the nucleosomal integrity of nuclear DNA. To a large extent, this integrity is dictated by the acetylation status of the core histone particles. The acetylation of histones is, in turn, controlled by the combined activity of specific acetylases and deacetylases. Moreover, disruption of histone acetylases and deacetylases has been linked to a wide variety of human cancers. For this reason, the recent availability of potent and specific histone deacetylase inhibitors has provoked a great deal of interest amongst cancer biologists, oncologists and pharmacologists. Within the past 2- 3 years, several novel histone deacetylase inhibitors have been reported, many of which have already been tested in vivo in mouse models of cancer. In this review we focus on the rationale behind the use of histone deacetylase inhibitors as anticancer agents. Moreover, we review some of the recent findings pertaining to the use of these compounds as anticancer agents.
Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia (2011)

Minor histocompatibility (H) antigens are major targets of a graft-versus-leukemia (GVL) effect mediated by donor CD8(+) and CD4(+) T cells following allogeneic hematopoietic cell transplantation (HCT) between human leukocyte antigen identical individuals. In the 15 years since the first molecular characterization of human minor H antigens, significant strides in minor H antigen discovery have been made as a consequence of advances in cellular, genetic and molecular techniques. Much has been learned about the mechanisms of minor H antigen immunogenicity, their expression on normal and malignant cells, and their role in GVL responses. T cells specific for minor H antigens expressed on leukemic cells, including leukemic stem cells, can be isolated and expanded in vitro and infused into allogeneic HCT recipients to augment the GVL effect to prevent and treat relapse. The first report of the adoptive transfer of minor H antigen-specific T-cell clones to patients with leukemic relapse in 2010 illustrates the potential for the manipulation of alloreactivity for therapeutic benefit. This review describes the recent developments in T-cell recognition of human minor H antigens, and efforts to translate these discoveries to reduce leukemia relapse after allogeneic HCT.
High power density supercapacitor electrodes of carbon nanotube films by electrophoretic deposition (2006)

Carbon nanotube thin films have been successfully fabricated by the electrophoretic deposition technique. The supercapacitors built from such thin film electrodes have a very small equivalent series resistance, and a high specific power density over 20 kW kg−1 was thus obtained. More importantly, the supercapacitors showed superior frequency response. Our study also demonstrated that these carbon nanotube thin films can serve as coating layers over ordinary current collectors to drastically enhance the electrode performance, indicating a huge potential in supercapacitor and battery manufacturing.
Underwater Gliders for Ocean Research (2004)

Underwater gliders are autonomous vehicles that profile vertically by controlling buoyancy and move horizontally on wings. Gliders are reviewed, from their conception by Henry Stommel as an extension of autonomous profiling floats, through their development in three models, and including their first deployments singly and in numbers. The basics of glider function are discussed as implemented by University of Washington in Seaglider, Scripps Institution of Oceanography in Spray, and Webb Research in Slocum. Gliders sample in the archetypical modes of sections and of "virtual moorings." Preliminary results are presented from a recent demonstration project that used a network of gliders off Monterey. A wide range of sensors has already been deployed on gliders, with many under current development, and an even wider range of future possibilities. Glider networks appear to be one of the best approaches to achieving subsurface spatial resolution necessary for ocean research.
Automated test data generation using an iterative relaxation method (1998)

An important problem that arises in path oriented testing is the generation of test data that causes a program to follow a given path. In this paper, we present a novel program execution based approach using an iterative relaxation method to address the above problem. In this method, test data generation is initiated with an arbitrarily chosen input from a given domain. This input is then iteratively refined to obtain an input on which all the branch predicates on the given path evaluate to the desired outcome. In each iteration the program statements relevant to the evaluation of each branch predicate on the path are executed, and a set of linear constraints is derived. The constraints are then solved to obtain the increments for the input. These increments are added to the current input to obtain the input for the next iteration. The relaxation technique used in deriving the constraints provides feedback on the amount by which each input variable should be adjusted for the branches on the path to evaluate to the desired outcome.When the branch conditions on a path are linear functions of input variables, our technique either finds a solution for such paths in one iteration or it guarantees that the path is infeasible. In contrast, existing execution based approaches may require an unacceptably large number of iterations for relatively long paths because they consider only one input variable and one branch predicate at a time and use backtracking. When the branch conditions on a path are nonlinear functions of input variables, though it may take more then one iteration to derive a desired input, the set of constraints to be solved in each iteration is linear and is solved using Gaussian elimination. This makes our technique practical and suitable for automation.
Three-dimensional subband scalable video coding embedded with H.264/AVC codec (2005)

This paper presents a new Base Layer coding scheme which introduces the rate-distortion optimization mode decision into hierarchical-fashion B-picture coding with open-loop structure. It can not only achieve high coding performance for Base Layer bit-rate point and meanwhile, but the scheme also keep the strong correlation between Base Layer and Enhancement Layer implemented by 3D subband scalable video codec, because they share the similar lifting based Motion-Compensated Temporal Filtering (MCTF) decomposition structure. In addition, how to exploit the correlation between Base Layer and Enhancement Layer is also investigated. Experimental results show this method improves the coding performance and visual quality at both low and high bit-rate points.
Synthesis of (2'-5')oligoadenylate and activation of an endoribonuclease in interferon-treated HeLa cells infected with reovirus (1982)

Treatment with interferon protected HeLa cells from infection with reovirus. This virus apparently activated an antiviral mechanism that was detected by the presence of (2'-5')oligoadenylate [(2'-5')An] in intact cells. The (2'-5')An was previously shown to activate an endoribonuclease, RNase L. We measured (2'-5')An by a sensitive competition-binding assay in cells infected at different multiplicities and for different lengths of time. Nanomolar concentrations of (2'-5')An were detected in cells infected at a multiplicity of greater than 5 after 2 h of infection, the time at which the infecting virions were uncoated. The level of (2'-5')An increased up to 6 h postinfection but declined afterward. To establish whether viral mRNAs were cleaved by RNase L, we analyzed the RNA extracted from infected cells by a highly specific hybridization assay on Northern blots. Full-sized reovirus mRNAs were detected in control infected cells, but not in interferon-treated infected cells, at 6 h postinfection. At this time, a nuclease activity could be detected in these cells by demonstration of cleavage of rRNA, degradation of cellular mRNA, and polysome breakdown in the presence of emetine. Since this inhibitor freezes ribosomes, cleavage of mRNA between ribosomes could only be accounted for by an endonuclease, presumably RNase L.
Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014)

Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE<3.2); and III) "normal aging" (N)--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.
Purinoceptors on blood platelets: further pharmacological and clinical evidence to suggest the presence of two ADP receptors (1995)

Platelet aggregation by ADP plays a major role in the development and extension of arterial thrombosis. The antithrombotic thienopyridine compounds ticlopidine and clopidogrel have proved useful tools to investigate the mechanisms of ADP-induced platelet activation. In essence, although clopidogrel has been shown to completely and selectively block ADP-induced platelet aggregation, G protein activation and inhibition of adenylyl cyclase, this drug does not affect shape change and Ca2+ influx. Binding studies, using the non-hydrolysable ligand [33P]2MeSADP, have shown that human platelets contain about 600 high-affinity binding sites for 2MeSADP (Kd approximately 5 nM). These sites present pharmacological characteristics of a P2T receptor. Clopidogrel treatment reduces the number of sites by 70% on rat platelets (from 1200 to 450) and leaves the residual binding sites resistant to clopidogrel. Moreover, patients with congenital impairment of ADP-induced platelet aggregation but normal shape change display very low levels of [33P]2MeSADP binding sites. The current data thus strongly suggest the presence of two ADP receptors, one responsible for shape change and rapid Ca2+ influx and the other a Gi protein-coupled receptor responsible for Ca2+ mobilization from internal stores, inhibition of adenylyl cyclase and platelet aggregation.
Synthesis and Biological Activity of Some New Pyrazolo[3,4-b]Pyrazines (2006)

New derivatives of pyrazolo[3,4-b]pyrazine and related heterocycles were prepared starting from 6-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile (2) and using the key intermediates 4, 5, 6, 14, 15 and 16. Some of the prepared compounds were evaluated for their antifungal and antibacterial activities.
Reproductive Hormones in Aging Men. II. Basal Pituitary Gonadotropins and Gonadotropin Responses to Luteinizing Hormone-Releasing Hormone (1982)

Although basal serum LH and FSH levels have been shown to increase with age in men, there is evidence that aging may impair pituitary gonadotropin secretion to some extent. We have measured serum LH and FSH before and after the iv injection of 100 micrograms LRH in 69 healthy men, divided into 3 age groups: A (25-49 yr; n = 24), B (50-69 yr; n = 23), and C (70-89 yr; n = 22). We have previously demonstrated these men to have unaltered serum androgens and estrogens over the entire age range. Only log-transformed measures were analyzed in order to equalize variance among groups. Because we found increasing age to be associated with significant rises in basal levels of LH and FSH, and because the basal level affects the magnitude of response, we used repeated measures analysis of variance to compare LRH peak responses with basal gonadotropin levels. The presence of a significant interaction term would indicate an effect of age on response beyond that expected from the effect of basal level alone. The mean LRH responses (log peak--log basal) decreased, with significant interaction terms for both LH (P = 0.001) and FSH (P less than 0.0001) responses. This means that the function relating basal to peak gonadotropin concentrations changed significantly with age. Peak LH responses in the youngest group (A) occurred equally as often 15 and 30 min after LRH injection, but in the oldest group (C) there were no 15 min peaks, and 40% of the peak values occurred at 60 min (P less than 0.01). FSH peaks were equally distributed at 30, 60, and 120 min in all 3 groups. Total testicular volumes did not decrease significantly with age. We conclude that there is a small but statistically significant tendency for LH and FSH responses to LRH to be both diminished and delayed in healthy aging men. The mechanisms responsible for this apparent pituitary gonadotropic hypofunction remain to be clarified.
11 MW peak-power, 7 W average-power, high-spectral-brightness, diffraction-limited pulses from a photonic crystal fiber amplifier (2005)

We report a large-core, Yb-doped photonic crystal fiber amplifier generating diffraction-limited (M2 = 1.04), approximately 0.45 ns, approximately 8 GHz linewidth pulses with energies of 540 microJ, peak power in excess of 1.1 MW, and average power of approximately 7.2 W at a repetition rate of 13.4 kHz. The pulse peak spectral brightness exceeds 10 kW/(sr Hz cm2) and is the highest generated by a fiber source, to our knowledge.
Charge transfer complexes and hyperpolarizabilities (1977)

We have measured the second order β and third order γ hyperpolarizabilities of the three charge transfer complexes pyridine+I2, pyridine+ICl, and 4-aminopyridine+I2. Using Mulliken’s charge transfer theory we have been able to understand theoretically the large magnitude and absolute sign of these hyperpolarizabilities as well as their interesting and surprising dependence on the strength of the charge transfer interaction.
A single‐use purification process for the production of a monoclonal antibody produced in a PER.C6 human cell line (2010)

Advances in single-use technologies can enable greater speed, flexibility, and a smaller footprint for multi-product production facilities, such as at a contract manufacturer. Recent efforts in the area of cell line and media optimization have resulted in bioreactor productivities that exceed 8 g/L in fed-batch processes or 25 g/L in high-density cell culture processes. In combination with the development of single-use stirred tank bioreactors with larger working volumes, these intensified upstream processes can now be fit into a single-use manufacturing setting. Contrary to these upstream advances, downstream single-use technologies have been slower to follow, mostly limited by low capacity, high cost, and poor scalability. In this study we describe a downstream process based solely on single-use technologies that meets the challenges posed by expression of a mAb (IgG(1)) in a high-density suspension culture of PER.C6 cells. The cell culture harvest was clarified by enhanced cell settling (ECS) and depth filtration. Precipitation was used for crude purification of the mAb. A high capacity chromatographic membrane was then used in bind/elute mode, followed by two membranes in flow-through (FT) mode for polishing. A proof of concept of the entire disposable process was completed for two different scales of the purification train.
Characterization of wild type and mutant glucocorticoid receptors from rat hepatoma and mouse lymphoma cells. (1985)

Using a combination of immunological blotting techniques and hormone affinity labeling, we have characterized the glucocorticoid receptors present in wild type and mutant rat hepatoma (HTC) and mouse thymoma (S49 and WEHI7) cells. Mutant HTC and WEHI7 cells of the receptorless phenotype, which contain greatly reduced amounts of glucocorticoid hormone binding activity, show parallel decreases in immunoreactive material using a monoclonal antibody raised against the rat liver glucocorticoid receptor. This indicates that these receptorless mutant cells harbor defects in either the production or accumulation of receptor protein. Quantitation of immunoreactivity and hormone binding activity present in wild type and mutant S49 cells indicates that these cells contain significantly more immunoreactive material than hormone binding activity. We conclude that S49 cells produce, in addition to their well characterized wild type or mutant receptors, a mutant receptor from a second allele which is of wild type size, is immunologically reactive, but is unable to bind hormone. The S49 mutant cell line nti (nuclear transfer increase) contains a glucocorticoid receptor which has a molecular weight of 40,000, while the wild type receptor has a molecular weight of 94,000. Affinity labeling of glucocorticoid receptors in nti cells with [3H]dexamethasone mesylate indicates that nti cells do not contain wild type sized precursor molecules which bind hormone, nor do they contain immunoreactive fragments of a molecular mass smaller than 94 kDa. It is proposed that the 40-kDa nti receptor is produced as a truncated protein most likely resulting from a nonsense mutation or from a truncated messenger RNA.
Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia (2012)

This study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.
Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival (2011)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder with increased mortality and morbidity resulting from intravascular hemolysis. Eculizumab, a monoclonal antibody against the complement protein 5, stops the intravascular hemolysis in PNH. We evaluated 79 consecutive patients treated with eculizumab in Leeds between May 2002 and July 2010. The survival of patients treated with eculizumab was not different from age- and sex-matched normal controls (P = .46) but was significantly better than 30 similar patients managed before eculizumab (P = .030). Three patients on eculizumab, all over 50 years old, died of causes unrelated to PNH. Twenty-one patients (27%) had a thrombosis before starting eculizumab (5.6 events per 100 patient-years) compared with 2 thromboses on eculizumab (0.8 events per 100 patient-years; P < .001). Twenty-one patients with no previous thrombosis discontinued warfarin on eculizumab with no thrombotic sequelae. Forty of 61 (66%) patients on eculizumab for more than 12 months achieved transfusion independence. The 12-month mean transfusion requirement reduced from 19.3 units before eculizumab to 5.0 units in the most recent 12 months on eculizumab (P < .001). Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to a similar level to that of the general population.
A task-parameterized probabilistic model with minimal intervention control (2014)

We present a task-parameterized probabilistic model encoding movements in the form of virtual spring-damper systems acting in multiple frames of reference. Each candidate coordinate system observes a set of demonstrations from its own perspective, by extracting an attractor path whose variations depend on the relevance of the frame at each step of the task. This information is exploited to generate new attractor paths in new situations (new position and orientation of the frames), with the predicted covariances used to estimate the varying stiffness and damping of the spring-damper systems, resulting in a minimal intervention control strategy. The approach is tested with a 7-DOFs Barrett WAM manipulator whose movement and impedance behavior need to be modulated in regard to the position and orientation of two external objects varying during demonstration and reproduction.
Eletriptan in acute migraine (2000)

In this placebo-controlled trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of action and patient acceptability in the acute treatment of migraine when compared with oral sumatriptan and placebo.