gebhart/patrepeval huggingface dataset:
Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll-like receptor 4 (2013)

The present study was designed to determine the renoprotective and hepatoprotective effect of lidocaine in septic rats through the Toll‑like receptor 4 (TLR4) signaling pathway. Adult male Sprague‑Dawley rats were randomly divided into the following three groups: control, sepsis model and 10% lidocaine. A model of sepsis was established by injection of lipopolysaccharide (LPS; 5 mg/kg) into the intraperitoneal cavity of rats. The same volume of saline was injected intraperitoneally into rats of the control group instead of LPS. Light microscopy was used to observe structural changes of the hepatic and nephridial tissues. qPCR was used to measure TLR4 mRNA expression levels and the protein expression was detected by flow cytometry. Western blotting was used to measure myocardial nuclear factor κB (NF‑κB) protein levels and ELISA was used to measure the levels of interleukin‑6 (IL‑6) in hepatic and nephridial tissues. The results demonstrated that 10% lidocaine treatment markedly decreased hepatic and nephridial injury in septic rats and inhibited the expression levels of TLR4, NF‑κB and IL‑6, which were upregulated in the sepsis model. In addition, the results indicated that lidocaine protects against renal and hepatic dysfunction in septic rats, which may be mediated by the downregulation of TLR4 and associated signaling molecules and inhibition of the inflammatory response.
Identifying almost identical files using context triggered piecewise hashing (2006)

Homologous files share identical sets of bits in the same order. Because such files are not completely identical, traditional techniques such as cryptographic hashing cannot be used to identify them. This paper introduces a new technique for constructing hash signatures by combining a number of traditional hashes whose boundaries are determined by the context of the input. These signatures can be used to identify modified versions of known files even if data has been inserted, modified, or deleted in the new files. The description of this method is followed by a brief analysis of its performance and some sample applications to computer forensics.
Thymic involution and rising disease incidence with age (2018)

For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation. In humans, the thymus atrophies from infancy, resulting in an exponential decline in T cell production with a half-life of ∼16 years, which we use as the basis for a minimal mathematical model of disease incidence. Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. This framework provides mechanistic insight into cancer emergence, suggesting that age-related decline in T cell output is a major risk factor.
Management of multidimensional aggregates for efficient online analytical processing (2003)

Proper management of multidimensional aggregates is a fundamental prerequisite for efficient OLAP. The experimental OLAP server CUBESTAR whose concepts are described, was designed exactly for that purpose. All logical query processing is based solely on a specific algebra for multidimensional data. However, a relational database system is used for the physical storage of the data. Therefore, in popular terms, CUBESTAR can be classified as a ROLAP system. In comparison to commercially available systems, CUBESTAR is superior in two aspects. First, the implemented multidimensional data model allows more adequate modeling of hierarchical dimensions, because properties which apply only to certain dimensional elements can be modeled context-sensitively. This fact is reflected by an extended star schema on the relational side. Second, CUBESTAR supports multidimensional query optimization by caching multidimensional aggregates. Since summary tables are not created in advance but as needed, hot spots can be adequately represented. The dynamic and partition-oriented caching method allows cost reductions of up to 60% with space requirements of less than 10% of the size of the fact table.
2'-Deoxy-2'-fluoro-beta-D-arabinonucleosides and oligonucleotides (2'F-ANA): synthesis and physicochemical studies (2000)

Recently, hybrids of RNA and D-arabinonucleic acids (ANA) as well as the 2'-deoxy-2'-fluoro-D-arabinonucleic acid analog (2'F-ANA) were shown to be substrates of RNase H. This enzyme is believed to be involved in the primary mechanism by which antisense oligonucleotides cause a reduction in target RNA levels in vivo. To gain a better understanding of the properties of arabinose based oligonucleotides, we have prepared a series of 2'F-ANA sequences of homopolymeric (A and T) and mixed base composition (A, T, G and C). UV thermal melting and circular dichroic (CD) studies were used to ascertain the thermodynamic stability and helical conformation of 2'F-ANA/RNA and 2'F-ANA/DNA hybrids. It is shown that 2'F-ANA has enhanced RNA affinity relative to that of DNA and phosphorothioate DNA. The 2'-fluoroarabino modification showed favorable pairing to single-stranded DNA also. This is in sharp contrast to ANA, which forms weak ANA/DNA hybrids at best. According to the measured thermodynamic parameters for duplex formation, the increased stability of hybrids formed by 2'F-ANA (e.g., 2'F-ANA/RNA) appears to originate from conformational pre-organization of the fluorinated sugars and a favorable enthalpy of hybridization. In addition, NMR spectroscopy revealed a five-bond coupling between the 2'F and the base protons (H6/H8) of 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides. This observation is suggestive of a through-space interaction between 2'F and H6/H8 atoms. CD experiments indicate that 2'F-ANA/RNA hybrids adopt an 'A-like' structure and show more resemblance to DNA/RNA hybrids than to the pure RNA/RNA duplex. This feature is believed to be an important factor in the mechanism that allows RNase H to discriminate between 2'F-ANA/RNA (or DNA/RNA) and RNA/RNA duplexes.
Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle (1992)

Plasmid DNA or artificial mRNA injected intramuscularly into skeletal muscle via a 27 g needle expressed transgenes at relatively efficient levels in skeletal myofibers and cardiac cells. In the present study, several approaches were used to determine the mechanism of cellular uptake. After exposure of naked plasmid DNA, primary rat muscle cells in vitro expressed transgenes to a much greater extent than other types of immortalized or primary cells. In vivo light microscope studies showed that intramuscularly injected plasmid DNA was distributed throughout the muscle and was able to diffuse through the extracellular matrix, cross the external lamina, and enter myofibers. Electron microscope studies showed that colloidal gold conjugated to plasmid DNA traversed the external lamina and entered T tubules and caveolae, while gold complexed with polylysine, polyethylene glycol or polyglutamate primarily remained outside of the myofibers. The results indicate that it is highly unlikely that the plasmid DNA enters the myofiber simply by the needle grossly disrupting the sarcolemma. In addition, transient membrane disruptions do not appear to be responsible for the uptake of DNA. Furthermore, no evidence for endocytosis could be found. The possible uptake of plasmid DNA by some type of cell membrane transporter, in particular via potocytosis, is discussed.
Mechanism of antibody-mediated viral clearance in immunotherapy of respiratory syncytial virus infection of cotton rats (1990)

Antibody-mediated clearance of respiratory syncytial virus from cotton rat pulmonary tissues occurs in the absence of complement and in the absence of the Fc portion of the immunoglobulin G molecule, suggesting that complement-independent, cell-independent neutralization is the major mechanism of clearance.
MRF Energy Minimization and Beyond via Dual Decomposition (2010)

This paper introduces a new rigorous theoretical framework to address discrete MRF-based optimization in computer vision. Such a framework exploits the powerful technique of Dual Decomposition. It is based on a projected subgradient scheme that attempts to solve an MRF optimization problem by first decomposing it into a set of appropriately chosen subproblems, and then combining their solutions in a principled way. In order to determine the limits of this method, we analyze the conditions that these subproblems have to satisfy and demonstrate the extreme generality and flexibility of such an approach. We thus show that by appropriately choosing what subproblems to use, one can design novel and very powerful MRF optimization algorithms. For instance, in this manner we are able to derive algorithms that: 1) generalize and extend state-of-the-art message-passing methods, 2) optimize very tight LP-relaxations to MRF optimization, and 3) take full advantage of the special structure that may exist in particular MRFs, allowing the use of efficient inference techniques such as, e.g., graph-cut-based methods. Theoretical analysis on the bounds related with the different algorithms derived from our framework and experimental results/comparisons using synthetic and real data for a variety of tasks in computer vision demonstrate the extreme potentials of our approach.
Plasma Norepinephrine Predicts Survival and Incident Cardiovascular Events in Patients With End-Stage Renal Disease (2002)

Sympathetic nerve overactivity is associated with mortality and cardiovascular outcomes in ESRD. Controlled trials with antiadrenergic drugs are needed to determine whether interference with the sympathetic system could reduce the high cardiovascular morbidity and mortality in dialysis patients.
Colonic Perforation at CT Colonography: Assessment of Risk in a Multicenter Large Cohort (2006)

Perforation of the colon and rectum is a rare complication of CT colonography. Older age and underlying concomitant colonic disease were present in patients with perforation.
Akt: Versatile Mediator of Cell Survival and Beyond (2002)

The serine/threonine kinase Akt has been intensely studied for its role in growth factor-mediated cell survival for the past 5 years. On the other hand, the ongoing research effort has recently uncovered novel regulatory mechanisms and downstream effectors of Akt that demonstrate the involvement of Akt in other cellular functions such as cell cycle progression, angiogenesis, and cancer cell invasion/metastasis. Furthermore, recent studies using whole model organisms suggest additional roles for Akt in important diseases such as aging and diabetes. The following review addresses these recent advances in the understanding of Akt function.
Effect of magnetic anisotropy on signal and noise of NiFe magnetoresistive sensor (1995)

The effect of magnetic anisotropy field (K/sub K/) on the signal and noise characteristics of NiFe magnetoresistive (MR) sensor has been studied. Lowering the anisotropy field of the thin NiFe films not only increases the sensitivity of the MR sensors but also induces higher noise. The experimental results show that the sensitivity is inversely proportional to the anisotropy field H/sub K/, while the noise is inversely proportional to the (H/sub K/)/sup 2/. The increased sensitivity of the MR sensor is attributed to the increased susceptibility of the sample films associated with lowering the anisotropy field. The noise level of the sensor is found to be increased with decreased anisotropy field, which can be explained by the induced instability of the magnetic domain structure of the NiFe films due to the anisotropy field decrease.
Use of Human Cancer Cell Lines Mitochondria to Explore the Mechanisms of BH3 Peptides and ABT-737-Induced Mitochondrial Membrane Permeabilization (2010)

Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance of malignant cells. A number of recent anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to purify functional mitochondria from various human cell lines to analyze the effect of peptidic and xenobiotic compounds described to harbour either Bcl-2 inhibition properties or toxic effects related to mitochondria. Mitochondrial inner and outer membrane permeabilization were systematically investigated in cancer cell mitochondria versus non-cancerous mitochondria. The truncated (t-) Bid protein, synthetic BH3 peptides from Bim and Bak, and the small molecule ABT-737 induced a tumor-specific and OMP-restricted mitochondrio-toxicity, while compounds like HA-14.1, YC-137, Chelerythrine, Gossypol, TW-37 or EM20-25 did not. We found that ABT-737 can induce the Bax-dependent release of apoptotic proteins (cytochrome c, Smac/Diablo and Omi/HtrA2 but not AIF) from various but not all cancer cell mitochondria. Furthermore, ABT-737 addition to isolated cancer cell mitochondria induced oligomerization of Bax and/or Bak monomers already inserted in the mitochondrial membrane. Finally immunoprecipatations indicated that ABT-737 induces Bax, Bak and Bim desequestration from Bcl-2 and Bcl-xL but not from Mcl-1L. This study investigates for the first time the mechanism of action of ABT-737 as a single agent on isolated cancer cell mitochondria. Hence, this method based on MOMP (mitochondrial outer membrane permeabilization) is an interesting screening tool, tailored for identifying Bcl-2 antagonists with selective toxicity profile against cancer cell mitochondria but devoid of toxicity against healthy mitochondria.
CD6 Ligation Modulates the Bcl-2/Bax Ratio and Protects Chronic Lymphocytic Leukemia B Cells From Apoptosis Induced by Anti-IgM (1997)

CD6 and CD5 belong to a scavenger-receptor cysteine-rich (SRCR) super family of membrane glycoproteins that are expressed on chronic lymphocytic leukemia B (B-CLL) cells, normal T cells, and a small subset of normal B cells. CD6 configures in the membrane in relation to the cellular activation level and can act as a coreceptor for T-cell activation. We have examined a group of progressive and nonprogressive B-CLL cells. Most B-CLL cells were positive for CD6 and the expression of CD6 was increased after activation with Staphylococcus aureus Cowan I plus interleukin-2 or 12-O-tetradecanoylphorbol 13-acetate, although anti-CD6 antibodies did not increase proliferative responses to these stimuli. However, anti-CD6 stimulation was found to protect against anti-IgM-induced apoptosis in B-CLL. bax(alpha) upregulation and bcl-2 downregulation were found in anti-IgM- and glucocorticoid (GCC)-induced apoptotic cells, respectively. Furthermore, CD6 cross-linking downregulated bax(alpha) mRNA levels in anti-IgM-treated cells, resulting in an increased bcl-2/bax(alpha) ratio. CD6 activation also prevented bcl-2 mRNA downregulation and apoptosis induced by GCC in one of six GCC-sensitive patients. These data suggest that an interaction between CD6 and its ligand might contribute to B-CLL survival through the modulation of the Bcl-2/Bax ratio.
CtpV: a putative copper exporter required for full virulence of Mycobacterium tuberculosis (2010)

Copper is a required micronutrient that is also toxic at excess concentrations. Currently, little is known about the role of copper in interactions between bacterial pathogens and their human hosts. In this study, we elucidate a mechanism for copper homeostasis in the human pathogen Mycobacterium tuberculosis via characterization of a putative copper exporter, CtpV. CtpV was shown to be required by M. tuberculosis to maintain resistance to copper toxicity. Furthermore, the deletion of ctpV resulted in a 98-gene transcriptional response, which elucidates the increased stress experienced by the bacteria in the absence of this detoxification mechanism. Interestingly, although the ΔctpV mutant survives close to the wild-type levels in both murine and guinea pig models of tuberculosis, animals infected with the ΔctpV mutant displayed decreased lung damage, and mutant-infected mice had a reduced immune response to the bacteria as well as a significant increase in survival time relative to mice infected with wild-type M. tuberculosis. Overall, our study provides the first evidence for a connection between bacterial copper response and the virulence of M. tuberculosis, supporting the hypothesis that copper response could be important to intracellular pathogens, in general.
Double-Blind Clinical Trials of Oral Triptans Vs Other Classes of Acute Migraine Medication — A Review (2004)

Although the migraine clinical trials literature is enormous, we identified only nine published double-blind studies which compare an oral triptan with a non-triptan acute treatment. Of the nine comparative trials that met inclusion criteria for this review, six compared sumatriptan with other drugs, zolmitriptan was studied in two trials and eletriptan in one trial. In seven of the nine studies reviewed herein, differences between active treatments on the primary endpoints were not dramatic. Experience in clinical practice suggests that, for many patients, oral triptans are superior to non-specific acute treatments, creating a discrepancy between clinical trials results and clinical practice experience. Four possible explanations for the disparities between clinical trials and clinical practice are likely: (i) statistically significant differences may not have emerged because the studies lack adequate statistical power; (ii) patients treated with triptans in clinical practice may be relatively more responsive to triptans and relatively less responsive to other agents than those who participate in clinical trials (patient selection); (iii) headache response at 2 h, as measured in clinical trials, may not fully capture the benefits of triptans relative to other therapies, as assessed in clinical practice; (iv) waiting until pain is moderate or severe, as required in clinical trials, may disadvantage triptans relative to comparators.
A Chemical Screen Identifies Anisomycin as an Anoikis Sensitizer That Functions by Decreasing FLIP Protein Synthesis (2007)

Malignant epithelial cells with metastatic potential resist apoptosis that normally occurs upon loss of anchorage from the extracellular matrix, a process termed "anoikis." Resistance to anoikis enables malignant cells to survive in an anchorage-independent manner, which leads to the formation of distant metastases. To understand the regulation of anoikis, we designed, automated, and conducted a high-throughput chemical screen for anoikis sensitizers. PPC-1 anoikis-resistant prostate cancer cells were seeded in hydrogel-coated ultralow binding plates for suspension conditions and standard tissue culture plates to promote adhesion. After seeding, cells were treated with aliquots from a library of previously characterized small molecules, and viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt, assay. From this chemical screen, we identified anisomycin that induced apoptosis in suspension conditions, but was not toxic to these cells grown under adherent conditions. Anisomycin sensitized cells to anoikis by decreasing levels of the caspase-8 inhibitor FLIP and subsequently activating the death receptor pathway of caspase activation. Although anisomycin activated c-Jun-NH(2)-kinase and p38, these kinases were not functionally important for the effect of anisomycin on anoikis and FLIP. Rather, anisomycin decreased FLIP and sensitized cells to anoikis by inhibiting its protein synthesis. Finally, we showed that anisomycin decreased distal tumor formation in a mouse model of prostate cancer metastases. Thus, a novel chemical screen identified anisomycin as an anoikis sensitizer that acts by decreasing FLIP protein synthesis. Our results suggest that FLIP is a suppressor of anoikis and inhibiting FLIP protein synthesis may be a useful antimetastatic strategy.
Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. (1996)

The uterine expression of leukemia inhibitory factor (LIF) is essential for embryo implantation in the mouse. Here, we describe the expression of LIF, related members of this group of cytokines, oncostatin M and ciliary neurotrophic factor, and the LIF receptor beta and glycoprotein gp130 in normal human tissues and in the endometrium of fertile women. Our results show that LIF is the only one of these factors expressed at detectable levels in the endometrium of women of proven fertility. LIF expression is restricted to the endometrial glands during the secretory/postovulatory phase but is not present in the endometrium during the proliferative/preovulatory phase. The LIF receptor beta is expressed during the proliferative and secretory phases of the cycle and is restricted to the luminal epithelium. The associated signal-transducing component of the LIF receptor, gp130, is also expressed in both the luminal and glandular epithelium throughout the cycle. These results suggest that uterine expression of LIF in humans, like mice, may have a role in regulating embryo implantation, possibly through an autocrine/paracrine interaction between LIF and its receptor at the luminal epithelium.
Contribution of Fructose-1,6-bisphosphatase and Sedoheptulose-1,7-bisphosphatase to the Photosynthetic Rate and Carbon Flow in the Calvin Cycle in Transgenic Plants (2006)

To clarify the contributions of fructose-1,6-bisphosphatase (FBPase) and sedoheptulose-1,7-bisphosphatase (SBPase) separately to the carbon flux in the Calvin cycle, we generated transgenic tobacco plants expressing cyanobacterial FBPase-II in chloroplasts (TpF) or Chlamydomonas SBPase in chloroplasts (TpS). In TpF-11 plants with 2.3-fold higher FBPase activity and in TpS-11 and TpS-10 plants with 1.6- and 4.3-fold higher SBPase activity in chloroplasts compared with the wild-type plants, the amount of final dry matter was approximately 1.3-, 1.5- and 1.5-fold higher, respectively, than that of the wild-type plants. At 1,500 micromol m(-2) s(-1), the photosynthetic activities of TpF-11, TpS-11 and TpS-10 were 1.15-, 1.27- and 1.23-fold higher, respectively, than that of the wild-type plants. The in vivo activation state of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and the level of ribulose-1,5-bisphosphate (RuBP) in TpF-11, TpS-10 and TpS-11 were significantly higher than those in the wild-type plants. However, the transgenic plant TpF-9 which had a 1.7-fold higher level of FBPase activity showed the same phenotype as the wild-type plant, except for the increase of starch content in the source leaves. TpS-11 and TpS-10 plants with 1.6- and 4.3-fold higher SBPase activity, respectively, showed an increase in the photosynthetic CO(2) fixation, growth rate, RuBP contents and Rubisco activation state, while TpS-2 plants with 1.3-fold higher SBPase showed the same phenotype as the wild-type plants. These data indicated that the enhancement of either a >1.7-fold increase of FBPase or a 1.3-fold increase of SBPase in the chloroplasts had a marked positive effect on photosynthesis, that SBPase is the most important factor for the RuBP regeneration in the Calvin cycle and that FBPase contributes to the partitioning of the fixed carbon for RuBP regeneration or starch synthesis.