gebhart/patrepeval huggingface dataset:
Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference (1999)

Decreased triacylglycerol synthesis within hepatocytes due to decreased diacylglycerol acyltransferase (DGAT) activity has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. New findings suggest that eicosapentaenoic acid (EPA), and not docosahexaenoic acid (DHA), lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation and decreased availability of fatty acids for triacylglycerol synthesis. To contribute to the understanding of the triacylglycerol-lowering mechanism of fish oil, the different metabolic properties of EPA and DHA were studied in rat liver parenchymal cells and isolated rat liver organelles. EPA-CoA was a poorer substrate than DHA-CoA for DGAT in isolated rat liver microsomes, and in the presence of EPA, a markedly lower value for the triacyl[3H]glycerol/diacyl[3H]glycerol ratio was observed. The distribution of [1-14C]palmitic acid was shifted from incorporation into secreted glycerolipids toward oxidation in the presence of EPA (but not DHA) in rat liver parenchymal cells. [1-14C]EPA was oxidized to a much greater extent than [1-14C]DHA in rat liver parenchymal cells, isolated peroxisomes, and especially in purified mitochondria. As the oxidation of EPA was more effective and sensitive to the CPT-I inhibitor, etomoxir, when measured in a combination of both mitochondria and peroxisomes, we hypothesized that both are involved in EPA oxidation, whereas DHA mainly is oxidized in peroxisomes. In rats, EPA treatment lowered plasma triacylglycerol and increased hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase (CPT)-I activity in both the presence and absence of malonyl-CoA. Whereas only EPA treatment increased the mRNA levels of CPT-I, DHA treatment increased the mRNA levels of peroxisomal fatty acyl-CoA oxidase and fatty acid binding protein more effectively than EPA treatment. In conclusion, EPA and DHA affect cellular organelles in relation to their substrate preference. The present study strongly supports the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by increased mitochondrial fatty acid oxidation.
Data prefetch mechanisms (2000)

The expanding gap between microprocessor and DRAM performance has necessitated the use of increasingly aggressive techniques designed to reduce or hide the latency of main memory access. Although large cache hierarchies have proven to be effective in reducing this latency for the most frequently used data, it is still not uncommon for many programs to spend more than half their run times stalled on memory requests. Data prefetching has been proposed as a technique for hiding the access latency of data referencing patterns that defeat caching strategies. Rather than waiting for a cache miss to initiate a memory fetch, data prefetching anticipates such misses and issues a fetch to the memory system in advance of the actual memory reference. To be effective, prefetching must be implemented in such a way that prefetches are timely, useful, and introduce little overhead. Secondary effects such as cache pollution and increased memory bandwidth requirements must also be taken into consideration. Despite these obstacles, prefetching has the potential to significantly improve overall program execution time by overlapping computation with memory accesses. Prefetching strategies are diverse, and no single strategy has yet been proposed that provides optimal performance. The following survey examines several alternative approaches, and discusses the design tradeoffs involved when implementing a data prefetch strategy.
The Role of Configurational Entropy in Amorphous Systems (2010)

Configurational entropy is an important parameter in amorphous systems. It is involved in the thermodynamic considerations, plays an important role in the molecular mobility calculations through its appearance in the Adam-Gibbs equation and provides information on the solubility increase of an amorphous form compared to its crystalline counterpart. This paper presents a calorimetric method which enables the scientist to quickly determine the values for the configurational entropy at any temperature and obtain the maximum of information from these measurements.
Analysis of growth : the responses of cells and tissues in culture (1969)

Plant Physiology: A Treatise, Volume VB: Analysis of Growth: The Responses of Cells and Tissues in Culture deals with the innate capacities for growth that reside in mature organs, tissues, and cells of higher plants. The book examines the various ways, normal and abnormal, in which surviving organs, tissues, or cells from plants may grow, metabolize, and develop. The text will be of value to botanists, horticulturists, and biologists.
Adriamycin-Induced DNA Damage Mediated by Mammalian DNA Topoisomerase II (1984)

Adriamycin (doxorubicin), a potent antitumor drug in clinical use, interacts with nucleic acids and cell membranes, but the molecular basis for its antitumor activity is unknown. Similar to a number of intercalative antitumor drugs and nonintercalative epipodophyllotoxins (VP-16 and VM-26), adriamycin has been shown to induce single- and double-strand breaks in DNA. These strand breaks are unusual because a covalently bound protein appears to be associated with each broken phosphodiester bond. In studies in vitro, mammalian DNA topoisomerase II mediates DNA damage by adriamycin and other related antitumor drugs.
Efficacy and Safety of Prolonged-Release Lanreotide in Patients With Gastrointestinal Neuroendocrine Tumors and Hormone-Related Symptoms (1999)

Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.
A Robust Reputation System for Mobile Ad-hoc Networks (2003)

Reputation systems in mobile ad-hoc networks can be tricked by the spreading of false reputation ratings, be it false accusations or false praise. Simple solutions such as exclusively relying on one's own direct observations have drawbacks, as they do not make use of all the information available. We propose a fully distributed reputation system that can cope with false disseminated information. In our approach, everyone maintains a reputation rating and a trust rating about everyone else that they care about. From time to time first-hand reputation information is exchanged with others; using a modified Bayesian approach we designed and present in this paper, only second-hand reputation information that is not incompatible with the current reputation rating is accepted. Thus, reputation ratings are slightly modified by accepted information. Trust ratings are updated based on the compatibility of second-hand reputation information with prior reputation ratings. Data is entirely distributed: someone's reputation and trust is the collection of ratings maintained by others. We enable node redemption and prevent the sudden exploitation of good reputation built over time by introducing re-evaluation and reputation fading. We present the application of our generic reputation system to the context of neighborhood watch in mobile ad-hoc networks, specifically to the CONFIDANT protocol for the detection and isolation of nodes exhibiting routing or forwarding misbehavior. We evaluate the performance by simulation.
Identification of Potent, Selective Non-peptide CC Chemokine Receptor-3 Antagonist That Inhibits Eotaxin-, Eotaxin-2-, and Monocyte Chemotactic Protein-4-induced Eosinophil Migration (2000)

Eosinophils have been implicated in the pathogenesis of asthma and other allergic diseases. Several CC chemokines including eotaxin (CCL-11), eotaxin-2 (CCL-24), RANTES (CCL-5), and monocyte chemotactic protein-3 (MCP-3, CCL-7) and 4 (MCP-4, CCL-13) are potent eosinophil chemotactic and activating peptides acting through CC chemokine receptor-3 (CCR3). Thus, antagonism of CCR3 could have a therapeutic role in asthma and other eosinophil-mediated diseases. A high throughput, cellular functional screen was configured using RBL-2H3 cells stably expressing CCR3 (RBL-2H3-CCR3) to identify non-peptide receptor antagonists. A small molecule CCR3 antagonist was identified, SK&F 45523, and chemical optimization led to the generation of a number of highly potent, selective CCR3 antagonists including SB-297006 and SB-328437. These compounds were further characterized in vitro and demonstrated high affinity, competitive inhibition of (125)I-eotaxin and (125)I-MCP-4 binding to human eosinophils. The compounds were potent inhibitors of eotaxin- and MCP-4-induced Ca(2+) mobilization in RBL-2H3-CCR3 cells and eosinophils. Additionally, SB-328437 inhibited eosinophil chemotaxis induced by three ligands that activate CCR3 with similar potencies. Selectivity was affirmed using a panel of 10 seven-transmembrane receptors. This is the first description of a non-peptide CCR3 antagonist, which should be useful in further elucidating the pathophysiological role of CCR3 in allergic inflammatory diseases.
Ocular blood flow assessment using continuous laser Doppler flowmetry (2009)

This article describes the technique of continuous laser Doppler flowmetry (LDF) as applied to the measurement of the flux of red blood cells in the optic nerve head, iris and subfoveal choroid. Starting with the exposition of the physical principles underlying LDF, we first describe the various devices developed to perform LDF in these vascular beds. We then discuss the clinical protocols, blood flow parameters, calibration procedures, reproducibility and limitations of the LDF technique. Various problems still need to be solved in order to bring to light the full potential of LDF in the assessment of microcirculatory haemodynamics.
Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma. (1999)

A high-affinity IgG1 kappa murine monoclonal anti-CD20 antibody (IDEC-2B8) was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. A stable immunoconjugate (Zevalintrade mark) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a chelator exhibiting high affinity and retention for 90Y. Zevalin exhibited antigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (90Y-Zevalin) or 111In (111In-Zevalin) exhibited excellent retention of immunoreactivity with radioincorporations >95%. The radiolabeled conjugates formulated in PBS containing human serum albumin were stable in vitro at 4 degrees C for 48 h as indicated by negligible loss of radioisotope and retention of binding to CD20+ cells. In vitro human serum stability studies at 37 degrees C with 90Y-Zevalin indicated that loss of 90Y from the conjugate was minimal, averaging 1% per day. Biodistribution studies in BALB/c mice confirmed the in vitro stability of 90Y-Zevalin and 111In-Zevalin. In particular, excellent in vivo retention of 90Y by the conjugate was demonstrated by minimal bone accumulation (</=3% of the injected dose over three days). Radiation dose estimates to normal organs calculated from mouse biodistribution studies with 90Y-Zevalin were comparable to those determined in a phase I/II clinical trial and below generally accepted safe radiation levels. Studies in athymic mice bearing CD20+ tumors demonstrated that 111In-Zevalin accumulated in the tumors preferentially compared with normal organs. 90Y-Zevalin is currently being evaluated in phase III clinical trials for treatment of relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma.
Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength (1992)

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.
Compositional dynamic test generation (2007)

Dynamic test generation is a form of dynamic program analysis that attempts to compute test inputs to drive a program along a specific program path. Directed Automated Random Testing, or DART for short, blends dynamic test generation with model checking techniques with the goal of systematically executing all feasible program paths of a program while detecting various types of errors using run-time checking tools (like Purify, for instance). Unfortunately, systematically executing all feasible program paths does not scale to large, realistic programs.This paper addresses this major limitation and proposes to perform dynamic test generation compositionally, by adapting known techniques for interprocedural static analysis. Specifically, we introduce a new algorithm, dubbed SMART for Systematic Modular Automated Random Testing, that extends DART by testing functions in isolation, encoding test results as function summaries expressed using input preconditions and output postconditions, and then re-using those summaries when testing higher-level functions. We show that, for a fixed reasoning capability, our compositional approach to dynamic test generation (SMART) is both sound and complete compared to monolithic dynamic test generation (DART). In other words, SMART can perform dynamic test generation compositionally without any reduction in program path coverage. We also show that, given a bound on the maximum number of feasible paths in individual program functions, the number of program executions explored by SMART is linear in that bound, while the number of program executions explored by DART can be exponential in that bound. We present examples of C programs and preliminary experimental results that illustrate and validate empirically these properties.
Photoreceptor signals and vision. Proctor lecture. (1987)

In recent years, there has been rapid progress in understanding the properties and mechanism of generation of the light-evoked electrical signals of vertebrate rods and cones. The graded hyperpolarization that carries information over the length of the cell is generated by closure of cation-selective aqueous pores in the surface membrane of the outer segment. These pores are controlled cooperatively by cyclic GMP, which acts continuously in darkness to keep the pores open. Photoisomerization of rhodopsin or cone pigment produces the rapid amplified activation of phosphodiesterase, which lowers the concentration of cGMP, thereby lowering the conductance of the surface membrane. Calcium ions, once thought to relay excitation to the light-sensitive channels, do not play this role. Instead, they appear to participate in a feedback control mechanism that regulates the nucleotide cascade. Although some general features of the transduction mechanism are now understood, a number of important questions remain. How is the nucleotide cascade shut off? Where does Ca act? What is the structure of the light-sensitive channel? How are stereotyped single photon responses produced? Primate photoreceptors are no longer off limits to single cell electrophysiology. Analysis of the response properties and dark noise of primate rods gives a physiological basis for several fundamental features of human rod vision: single photon detection, poor temporal resolution, the "dark light," rod saturation, scotopic spectral sensitivity, and, perhaps, after-image signals. Primate cones show less sensitive but faster responses shaped by a resonance which may figure in the flicker sensitivity of human cone vision. The spectral sensitivity of the three types of primate cones has been determined over the entire visible region. These sensitivities satisfactorily predict human color matching. The spectral sensitivity curves indicate that the pigment in a given cone is very pure, and that individual cones of a given type normally contain pigments with very similar or identical spectral properties.
Compact helical antenna for smart implant applications (2015)

Smart implants are envisioned to revolutionize personal health care by assessing physiological processes, for example, upon wound healing, and communicating these data to a patient or medical doctor. The compactness of the implants is crucial to minimize discomfort during and after implantation. The key challenge in realizing small-sized smart implants is high-volume cost- and time-efficient fabrication of a compact but efficient antenna, which is impedance matched to 50 Ω, as imposed by the requirements of modern electronics. Here, we propose a novel route to realize arrays of 5.5-mm-long normal mode helical antennas operating in the industry-scientific-medical radio bands at 5.8 and 2.4 GHz, relying on a self-assembly process that enables large-scale high-yield fabrication of devices. We demonstrate the transmission and receiving signals between helical antennas and the communication between an antenna and a smartphone. Furthermore, we successfully access the response of an antenna embedded in a tooth, mimicking a dental implant. With a diameter of ~0.2 mm, these antennas are readily implantable using standard medical syringes, highlighting their suitability for in-body implant applications. Helical antennas that are just 5.5 millimetres long have been developed for use in smart medical implants by scientists in Germany. Smart implants are set to transform personal health care by monitoring physiological processes and relaying data to medical workers. It is critical for such implants to be compact, but miniaturizing antenna has proved challenging. Now, researchers based in Dresden have applied strain engineering to polymer–metal heterostructures to achieve large scale high yield fabrication of compact helical antennas that are about five times smaller than conventional two-dimensional dipole antennas. They demonstrate transmission and reception of signals between a pair of antennas as well as between an antenna and smartphone. They also show that the antenna can be addressed when embedded in a tooth model. The small size of the antennas permits them to be implanted using standard medical syringes. We fabricated compact helical antenna operating in the industry-scientific-medical radio band. With a total length of only 5.5 mm, it is about five times smaller compared with the conventional dipole antenna. The transmission and receiving signals between helical antennas and the communication between a helical antenna and a smartphone is reported. Owing to the shape and dimensions, we successfully demonstrate the possibility to address the antenna, when embedded in a tooth, as well as to implant the antenna using standard medical syringes. These demonstrations highlight the potential of helical antennas for medical applications as components of smart system implants.
Improved coagulation in bleeding disorders by Non-Anticoagulant Sulfated Polysaccharides (NASP) (2005)

Additional therapeutic options are needed for patients with bleeding disorders such as hemophilia A, hemophilia B, severe von Willebrand disease, and other rare factor deficiencies. A novel approach to improve coagulation in such clotting disorders has been identified that, parodoxically, involves heparinlike sulfated polysaccharides. Select molecules of this broad class are largely devoid of anticoagulant activity and are here denoted Non-Anticoagulant Sulfated Polysaccharides (NASPs). A mechanism involving blockade of the extrinsic pathway downregulator, Tissue Factor Pathway Inhibitor (TFPI) by NASPs, was conceived as an approach for improving procoagulant behavior in hemophilic settings. A subset of NASPs, including pentosan polysulfate (PPS) and fucoidan inhibited both full-length and Kunitz 1 and 2 (K1K2) TFPI and, at concentrations from 4-500 nM, improved (i.e. accelerated) the clotting time of human hemophilia A and hemophilia B plasmas or plasma with reduced factor VII levels when tested in dilute prothrombin time (dPT) assays. Fucoidan did not reduce normal plasma APTT times implying specificity for extrinsic pathway control. Improved hemostasis in vivo was observed in mice with hemophilias A or B following low dose subcutaneous administration of PPS or fucoidan, or a combination of NASP plus factor supplement. Increased survival of factor deficient mice following a bleeding challenge was observed. Accordingly, administration of select NASP(s), via mechanism(s) not fully understood, represents a unique means of improving coagulation in bleeding disorders.
BCL2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia (2009)

A number of single nucleotide polymorphisms (SNP) have been implicated to impact upon the disease course of chronic lymphocytic leukemia (CLL). However, few of these association studies could be confirmed in independent studies in the past. Recently, three independent studies did not confirm the prognostic impact of a new functional SNP in the BCL2 gene (-938C>A) described by Nückel et al. For this reason we genotyped an independent group of patients with CLL (n = 271) with mature follow up and detailed analysis of molecular genetics. The genotype distribution of this BCL2 polymorphism did not differ from that described in the original work. However, genotypes were not associated with time to first treatment (TFT) and overall survival (OS) in univariate or multivariate analysis in the current cohort. Comparing the characteristics of the two study cohorts in more detail we found differences between the two cohorts demonstrating a potentially more aggressive second study cohort. However, TFT and OS in patients with CLL according to Binet A did not differ significantly depending on the genotype. Our findings underscore the need for optimally matched patient cohorts in replication studies. The study re-emphasizes the need for large cohorts and validation in independent data sets before firm conclusions can be made about genotype-phenotype associations.