gebhart/patrepeval huggingface dataset:
Induction of Aggregation of Human Blood Platelets by Ultraviolet Light: Action Spectrum and Structural Changes (1973)

Abstract Exposure of washed human platelets to ultraviolet light is followed by platelet aggregation. The effect occurs at wavelengths between 302 and 225 mµ with a maximal response at 248 mµ, and the effect is greatly enhanced by the addition of fibrinogen. Platelets exposed to ultraviolet light show ultrastructural changes which can be induced independently of aggregation if the addition of fibrinogen is omitted.
Inhibition of Polysome Assembly Enhances Imatinib Activity against Chronic Myelogenous Leukemia and Overcomes Imatinib Resistance (2008)

Dysregulated mRNA translation is implicated in the pathogenesis of many human cancers including chronic myelogenous leukemia (CML). Because our prior work has specifically implicated translation initiation in CML, we tested compounds that could modulate translation initiation and polysomal mRNA assembly. Here, we evaluated the activity of one such compound, CGP57380, against CML cells and explored its mechanisms of action. First, using polysomal mRNA profiles, we found that imatinib and CGP57380 could independently, and cooperatively, impair polysomal mRNA loading. Imatinib and CGP57380 also synergistically inhibited the growth of Ba/F3-Bcr-Abl and K562 cells via impaired cell cycle entry and increased apoptosis. Mechanistically, CGP57380 inhibited efficient polysomal assembly via two processes. First, it enhanced imatinib-mediated inhibition of eukaryotic initiation factor 4F induction, and second, it independently impaired phosphorylation of ribosomal protein S6 on the preinitiation complex. We also identified multiple substrates of the mTOR, Rsk, and Mnk kinases as targets of CGP57380. Finally, we found a novel negative-feedback loop to the mitogen-activated protein kinase/Mnk pathway that is triggered by CGP57380 and demonstrated that an interruption of the loop further increased the activity of the combination against imatinib-sensitive and -resistant CML cells. Together, this work supports the inhibition of translation initiation as a therapeutic strategy for treating cancers fueled by dysregulated translation.
Encapsulation of Sn@carbon Nanoparticles in Bamboo‐like Hollow Carbon Nanofibers as an Anode Material in Lithium‐Based Batteries (2009)

Carbon-coated Sn nanoparticles in carbon nanofibers (see image) were fabricated by pyrolysis of coaxially electrospun nanofibers as an anode material for Li-ion batteries. The significantly improved electrochemical performance of such an electrode is believed to result from the unique nanostructure consisting of a thin carbon shell around tin nanoparticles, which are further encapsulated in hollow carbon nanofibers. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Maternal hyperoxygenation test in fetuses undergoing FETO for severe isolated congenital diaphragmatic hernia (2010)

In fetuses undergoing FETO, pulmonary vascular reactivity in relation to oxygen and lung size are independent predictors of neonatal survival and pulmonary hypertension. The hyperoxygenation test merits further study in expectantly managed cases.
CD1d is expressed on B‐chronic lymphocytic leukemia cells and mediates α‐galactosylceramide presentation to natural killer T lymphocytes (2004)

Generation of immune responses against B cell chronic lymphocytic leukemia (B-CLL) has been the aim of several studies that have demonstrated a poor antigen presenting ability of B-CLL cells and an inconsistent emergence of T cells capable of killing efficiently the leukemic cells. CD1d is a restriction element structurally related to the major histocompatibility complex (MHC) and capable of presenting lipid antigens to CD1d-restricted T cells (also defined as natural killer-T [NKT] cells). The synthetic lipid alpha-galactosylceramide (alpha-GalCer) has been characterized as a potent stimulator of CD1d-restricted T cells. We have investigated the expression of CD1d on B-CLL cells. CD1d was detected by flow cytometric analyses on leukemic cells of all B-CLL cases studied (n = 38) and was expressed at higher density on cells carrying unmutated immunoglobulin variable region (IgV) genes. In addition, CD1d on B-CLL cells mediated the presentation of alpha-GalCer to CD1d-restricted T cells, which in turn induced B-CLL cell death. At variance with another study (Metelitsa et al., Leukemia 2003;17:1068-77), no correlation between expression levels of CD1d and susceptibility to NKT cell lysis was observed. Proliferation and production of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) by CD1d-restricted T cells, in the presence of B-CLL cells loaded with alpha-GalCer, were also observed. Our study demonstrates that B-CLL cells express a monomorphic restriction element that is functionally capable of antigen presentation and can be useful to design novel B-CLL immunotherapies.
Specification of <i>Drosophila</i> Hematopoietic Lineage by Conserved Transcription Factors (2000)

Two major classes of cells observed within the Drosophila hematopoietic repertoire are plasmatocytes/macrophages and crystal cells. The transcription factor Lz (Lozenge), which resembles human AML1 (acute myeloid leukemia- 1) protein, is necessary for the development of crystal cells during embryonic and larval hematopoiesis. Another transcription factor, Gcm (glial cells missing), has previously been shown to be required for plasmatocyte development. Misexpression of Gcm causes crystal cells to be transformed into plasmatocytes. The Drosophila GATA protein Srp (Serpent) is required for both Lz and Gcm expression and is necessary for the development of both classes of hemocytes, whereas Lz and Gcm are required in a lineage-specific manner. Given the similarities of Srp and Lz to mammalian GATA and AML1 proteins, observations in Drosophila are likely to have broad implications for understanding mammalian hematopoiesis and leukemias.
THE POLYPHENOL CHLOROGENIC ACID INHIBITS STAPHYLOCOCCAL EXOTOXIN-INDUCED INFLAMMATORY CYTOKINES AND CHEMOKINES (2002)

Proinflammatory cytokines mediate the toxic effect of staphylococcal exotoxins (SE). Chlorogenic acid, a plant polyphenol, inhibited SE-induced T-cell proliferation (by 98%) and production of interleukin 1beta, tumor necrosis factor, interleukin 6, interferon gamma, monocyte chemotactic protein I (MCP-l), macrophage inflammatory protein (MIP)-lalpha, and MIP-lbeta by human peripheral blood mononuclear cells. These data indicate that chlorogenic acid may be therapeutically useful for mitigating the pathogenic effects of SE. Naturally occurring polyphenolic compounds such as chlorogenic acid may serve as a potent anti-inflammatory agent alternative to conventional chemotherapeutics.
Partial lobectomy via a ligature fracture technique: a method for multiple hepatic biopsies in nonhuman primates. (1991)

A ligature fracture technique was used to obtain multiple large (2 to 4 g) liver biopsy samples in both African green and cynomolgus monkeys. The technique was performed 195 times in 84 animals using three different surgical approaches, with no associated illness or mortality. In a subset of 18 animals, a slight decline in hematocrit percentage was noted during 14 days postsurgery (44.6 to 39.4%), but total plasma protein remained unchanged (5.98 to 5.95 g/dl). Serum alanine aminotransferase concentrations rose to 178.11 U/l at day 1 postoperatively, from a baseline value of 93.61 U/l. This elevation was transient, however, and declined to 49.65 U/l by day 14. Our experience has shown that the partial lobectomy via the ligature fracture technique is a safe and effective means to obtain multiple large samples of liver in nonhuman primates.
Regulation of gene expression by TBP-associated proteins (1998)

Transcription of rRNA, mRNA, and small RNAs in eukaryotes is accomplished by RNA polymerases I, II, and III. Much of the control of transcription occurs at the promoters, where transcriptional regulators can affect the recruitment of polymerases and their accessory factors, the rate at which the polymerases leave the promoter and the rate of transcriptional elongation. At least three levels of control must operate to ensure that regulation of the entire genome is efficiently coordinated in response to the extracellular environment and the cell cycle. There must be mechanisms that permit cells to rapidly increase or reduce the transcription of specific protein-coding genes. There must be an ability to modulate global transcription to adjust for changing levels of nutrients or growth factors, and to accommodate the demands of the cell cycle. Finally, there must be a system to coordinate the relative amounts of rRNA, mRNA, and small RNAs. One factor that is present at promoters used by all three RNA polymerases, and is thus a likely target for all three types of control, is TATA-binding protein (TBP). TBP is associated with a variety of factors that play important roles in both general and gene-specific regulation of gene expression. Early biochemical studies in mammalian, fly, and yeast systems identified three distinct complexes containing TBP, each of which directs transcription at class I, II, or III promoters. The TBP-associated factors that bind to class I, II, and III promoters are called TAFIs, TAFIIs, and TAFIIIs, respectively. There is now evidence that at least five additional factors interact with TBP. Among the eight factors that interact with TBP, four (TAFI, TAFIIs, TAFIIIs, and PTF/SNAPc) function in promoter selection (Fig. 1). The other four (SAGA, Mot1, NC2, and Nots) function together with TAFIIs to regulate expression of protein-coding genes (Fig. 2). All but one of these factors (PTF/SNAPc) is highly conserved among eukaryotes. The factors that interact with TBP in yeast are summarized in Table 1. Here we review our current understanding of the eukaryotic TBP-associated proteins and their roles in regulation of gene expression. We describe evidence that relatively small pools of each of the TBP-associated proteins interact with and regulate a large cellular pool of TBP in yeast, and discuss its implications for genome-wide regulation. The conservation of the TBP-associated proteins suggests that the regulatory mechanisms described here apply to eukaryotes in general. Among the concepts that emerge in this discussion, we note that the TBP-associated regulatory apparatus is more complex than is typically modeled for protein-coding genes, that the means by which TBP is recruited to promoters is not yet well understood, and that there are a surprising number and variety of regulatory factors devoted to repressing TBP function.
Lazy garbage collection of recovery state for fault-tolerant distributed shared memory (2002)

We address the problem of garbage collection in a single-failure fault-tolerant home-based lazy release consistency (HLRC) distributed shared-memory (DSM) system based on independent checkpointing and logging. Our solution uses laziness in garbage collection and exploits consistency constraints of the HLRC memory model for low overhead and scalability. We prove safe bounds on the state that must be retained in the system to guarantee correct recovery after a failure. We devise two algorithms for garbage collection of checkpoints and logs, checkpoint garbage collection (CGC), and lazy log trimming (LLT). The proposed approach targets large-scale distributed shared-memory computing on local-area clusters of computers. The challenge lies in controlling the size of the logs and the number of checkpoints without global synchronization while tolerating transient disruptions in communication. Evaluation results for real applications show that it effectively bounds the number of past checkpoints to be retained and the size of the logs in stable storage.
In silico mechanistic analysis of IRF3 inactivation and high-risk HPV E6 species-dependent drug response (2015)

The high-risk human papillomavirus E6 (hrHPV E6) protein has been widely studied due to its implication in cervical cancer. In response to viral threat, activated kinases phosphorylate the IRF3 autoinhibitory domain, inducing type1 interferon production. HPV circumvents the antiviral response through the possible E6 interaction with IRF3 and abrogates p53's apoptotic activity by recruiting E6-associated protein. However, the molecular mechanism of IRF3 inactivation by hrHPV E6 has not yet been delineated. Therefore, we explored this mechanism through in silico examination of protein-protein and protein-ligand docking, binding energy differences, and computational alanine mutagenesis. Our results suggested that the LxxLL motifs of IRF3 binds within the hydrophobic pocket of E6, precluding Ser-patch phosphorylation, necessary for IRF3 activation and interferon induction. This model was further supported by molecular dynamics simulation. Furthermore, protein-ligand docking and drug resistance modeling revealed that the polar patches in the pocket of E6, which are crucial for complex stability and ligand binding, are inconsistent among hrHPV species. Such variabilities pose a risk of treatment failure owing to point mutations that might render drugs ineffective, and allude to multi-drug therapy. Overall, this study reveals a novel perspective of innate immune suppression in HPV infections and suggests a plausible therapeutic intervention.
A Profit-Aware Virtual Machine Deployment Optimization Framework for Cloud Platform Providers (2012)

As a rising application paradigm, cloud computing enables the resources to be virtualized and shared among applications. In a typical cloud computing scenario, customers, Service Providers (SP), and Platform Providers (PP) are independent participants, and they have their own objectives with different revenues and costs. From PPs' viewpoints, much research work reduced the costs by optimizing VM placement and deciding when and how to perform the VM migrations. However, some work ignored the fact that the balanced use of the multi-dimensional resources can affect overall resource utilization significantly. Furthermore, some work focuses on the selection of the VMs and the target servers without considering how to perform the reconfigurations. In this paper, with a comprehensive consideration of PPs' interests, we propose a framework to improve their profits by maximizing the resource utilization and reducing the reconfiguration costs. Firstly, we use the vector arithmetic to model the objective of balancing the multi-dimensional resources use and propose a VM deployment optimization method to maximize the resource utilization. Then a two-level runtime reconfiguration strategy, including local adjustment and VM parallel migration, is presented to reduce the VM migration and shorten the total migration time. Finally, we conduct some preliminary experiments, and the results show that our framework is effective in maximizing the resource utilization and reducing the costs of the runtime reconfiguration.
Design And Evaluation Of Ethylene Vinyl Acetate Sintered Matrix Tablets (2003)

A new method of preparation of sintered matrix tablets of rifampicin with ethylene-vinyl acetate copolymer is developed for controlling its release rate. This method is very simple. Drug and polymer powder (ethylene-vinyl acetate copolymer) were mixed and compressed at room ternperature. The compressed fluffy matrices were kept at 60o, 70o and 80o for 1.5,3 and 4.5 h for sintering. The sintered tablets were characterized for their physical characteristics and evaluated for in vitro dissolution studies. The sintering time markedly affected the drug release properties from the matrices. The release rate of rifampicin from EVA 1408 matrices was inversely related to the time of sintering due to the increase in the extent and firmness of sintering which compacts the mass further so that the drug release is affected. The drug release followed diffusive mechanism with first-order release kinetics.
A Cognitive Radio Approach for Usage of Virtual Unlicensed Spectrum (2005)

While essentially all of the frequency spectrum is allocated to different applications, observations provide evidence that usage of the spectrum is actually quite limited, particularly in above 3 GHz. In this paper we present a Cognitive Radio approach for usage of Virtual Unlicensed Spectrum (CORVUS), a vision of a Cognitive Radio (CR) based approach that uses allocated spectrum in a opportunistic manner to create virtual unlicensed bands i.e. that are shared with the primary (often licensed) users on a non-interfering basis. Dynamic spectrum management techniques are used to adapt to immediate local spectrum availability. We define the system requirements for this approach, as well as the general architecture and basic physical and link layer functions of CORVUS.
Hard X-ray phase-contrast imaging with the Compact Light Source based on inverse Compton X-rays (2008)

The first imaging results obtained from a small-size synchrotron are reported. The newly developed Compact Light Source produces inverse Compton X-rays at the intersection point of the counter propagating laser and electron beam. The small size of the intersection point gives a highly coherent cone beam with a few milliradian angular divergence and a few percent energy spread. These specifications make the Compact Light Source ideal for a recently developed grating-based differential phase-contrast imaging method.
Transglutaminase Type II Is Involved in the Pathogenesis of Endotoxic Shock (2008)

The pathogenesis of sepsis is characterized by the inability of the host to regulate the inflammatory response, and as a consequence, dysregulated inflammatory processes induce organ dysfunctions and death. Altered transglutaminase type II (TG2) expression is associated with the development of many inflammatory diseases. Therefore, in this study, we questioned whether TG2 could also contribute to the pathological inflammatory dysregulation occurring in septic shock in vivo. To this aim, we used as an experimental model the TG2 knockout mice, in which the process of septic shock was elicited by treatment with LPS. Interestingly, our results demonstrated that TG2 ablation leads to partial resistance to experimental sepsis. The increased survival of TG2(-/-) mice was reflected in a drastic reduction of organ injury, highlighted by a limited infiltration of neutrophils in kidney and peritoneum and by a better homeostasis of the proinflammatory mediators as well as mitochondrial function. We also showed that in wild-type mice, the TG2 expression is increased during endotoxemia and, being directly involved in the mechanisms of NF-kappaB activation, it may cause a continuous activation cycle in the inflammatory process, thus contributing to development of sepsis pathogenesis. We propose that the inhibition of TG2 could represent a novel approach in the treatment of inflammatory processes associated with sepsis.
Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41) (2000)

Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.
Repurposing avermectins as new potential TB therapies (2014)

Background: Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. Co-infection with HIV and the emergence of drug-resistant Mycobacterium tuberculosis strains (MDR-and XDR-TB) has reaffirmed TB as a global public health threat. New therapies are urgently needed. An alternative approach to generate new TB treatment options in a timely and cost-effective manner is “repurposing” clinically used drugs with known pharmaceutical properties. In the course of a screening program [PMID: 21576426], we identified the in vitro anti-tuberculosis activity of the anthelmintic avermectins (ivermectin, selamectin, moxidectin and doramectin) [PMID: 23165468]. Methods & Materials: We performed a literature search on the pharmacological properties of the avermectins. We integrated this information with our in vitro data and calculated a theoretical pharmacodynamic value (AUC/MIC; a measure of drug exposure) to define potential in vivo efficacy. We validated our analysis by evaluating avermectins in an in vivo model of M. tuberculosis infection. Results: An AUC/MIC ratio of 10 to 15 was calculated for bactericidal activity of the avermectins. Due to tolerability and pharmacokinetic issues the low maximal plasma concentrations of ivermectin (ng/mL range) resulted in a low calculated exposure (AUC/MIC < 1). Moxidectin had a longer half-life than ivermectin and, therefore, the calculated AUC/MIC ratios increased. However, this was still not enough to provide theoretical in vivo activity. In contrast, selamectin's pharmacokinetic properties suggest that it might be effective in vivo against M. tuberculosis; high plasma concentrations (μg/mL range), low toxicity (LD50 >1,600 mg/kg bw), and theoretical AUC/MIC ratios are consistent with potential in vivo activity. Interestingly, reported concentrations of selamectin in the lungs (the main site where M. tuberculosis resides) were ca. 2-fold higher than in plasma, suggesting even higher AUC/MIC ratios at the site of infection. We therefore tested ivermectin and selamectin for in vivo activity against M. tuberculosis. Our predictions were consistent with the in vivo data; while ivermectin at the highest possible safe dose did not have anti-mycobacterial activity in vivo, selamectin was active. Conclusion: This theoretical data analysis supports the potential of selamectin for TB therapy, including MDR- and XDR-TB, and warrant further in vivo testing in mouse infection models.
Ultrasonic vehicle detector for side-fire implementation and extensive results including harsh conditions (2001)

Concerns vehicle detectors, which collect passing vehicle information and traffic condition in real time. This paper develops an ultrasonic vehicle detector (UVD) system that can be implemented in a side-fire configuration. Conventionally, UVD systems are installed in overhead configurations. If these sensors can be mounted from the side of a road, the installation cost can be reduced. In addition, the aesthetic integrity of roadways will not be affected very much. However, this side-fire configuration has not been used, because of the fact that vehicles generally do not have sufficiently large oblique-angled surfaces to reflect the emitted ultrasonic wave back to the sensor for detection. This paper reports on the feasibility of a side-fire UVD system. A new low-cost instrumentation and control system for side-fire implementation was developed, and comprehensive experiments were performed at highway and downtown test sites. Experimental conditions included various traffic conditions as well as various weather conditions, including daylight, dusk, night, heavy rain, and heavy snow. Traffic data were generated for every five minutes. For the highway location, the vehicle counting error was less than 1%. For the downtown location, the error was approximately 3% during normal weather conditions and approximately 5% during a snow storm. The larger error in downtown is mainly attributed to vehicles changing lane. We believe that these side-fire implementation results are adequate for implementing advanced traveler information systems (ATIS).