gebhart/patrepeval huggingface dataset:
Increased Plasma Concentrations of Soluble ST2 are Predictive for 1-Year Mortality in Patients with Acute Destabilized Heart Failure (2008)

Increased sST2 concentrations determined in plasma samples drawn from patients with acute destabilized heart failure at their initial presentation indicate increased risk of future mortality. Increased sST2 plasma concentrations are independently and strongly associated with one-year all-cause mortality in these patients.
Using large-scale RNAi screens to identify novel drug targets for cancer. (2010)

In recent years, the development and clinical implementation of targeted therapeutics have progressed significantly. The specific inhibition of components of signal transduction pathways controlling proliferation and survival has been a highly successful research strategy. However, cancer is a heterogeneous disease and, even within one type of cancer, different genetic alterations are associated with identical phenotypes. To advance the use of targeted therapeutics, it is not only essential to identify the crucial factors in the signal transduction networks that control cell proliferation and survival, but also to classify individual tumors according to genetic alterations that correlate with pathway activation. RNAi screening technologies have become established as an important strategy both to identify novel targets and to provide novel biomarkers that are crucial for the further development of personalized medicine. This feature review discusses different RNAi screening strategies and their contribution to the rapidly evolving field of targeted therapeutics.
The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications (2016)

PGC1α is a transcription factor coactivator that influences a majority of cellular metabolic pathways. Abnormal expression of PGC1α is associated with several chronic diseases and, in recent years, it has been shown to be a critical controller of cancer development. PGC1α acts as a stress sensor in cancer cells and can be activated by nutrient deprivation, oxidative damage, and chemotherapy. It influences mitochondria respiration, reactive oxygen species defense system, and fatty acid metabolism by interacting with specific transcription factors. The characteristic traits of PGC1α in maintaining metabolic homeostasis promote cancer cell survival and tumor metastasis in harsh microenvironments. Not only does PGC1α act as a coactivator, but is also itself controlled by oncogenes and transcription factors. PGC1α and these molecules can form signaling axes that include PML/PGC1α/PPARα, MITF/PGC1α, and PGC1α/ERRα, which are important in regulating metabolic adaptation in specific cancer types. Some of these PGC1α-associated pathways are inherently activated in cancer cells, and others are induced by stress, which enable cancer cells to acquire resistance against therapy. Notably, certain therapeutic-resistant cancer cells are addicted to PGC1α-dependent metabolic activities. Suppression of PGC1α expression resensitizes these cells to therapeutic treatments, which implicates PGC1α as a promising target in cancer molecular classification and therapy. Mol Cancer Ther; 15(5); 774-82. ©2016 AACR.
Did inappropriate delivery systems hamper therapeutic efficacy of di-sodium-cromo-glycate (DSCG)? Time for a reappraisal (2011)

Chymase-positive mast cells located in distal airways play a crucial role in asthma (Balzar 2005 & 2010). A review on inhaled DSCG by Keller & Schierholz (2011) provided evidence that poor efficacy of DSCG is most probably linked with sub-therapeutic lung doses. The hygroscopic nature of DSCG causes particle growth associated with reduced lung deposition (Hiller 1980) which may explain insufficient therapeutic efficacy. Significantly higher in-vitro respirable doses were found by aerodynamic particle size assessments in a next generation impactor operated at 50% and 95% rel. humid., respectively using small droplet nebulisers compared to Intal® MDI and DPI (Keller 2007). Nebulised isotonic solutions provided better tolerability and efficacy than hypotonic Intal solution (Weiner 1988, Soferman 1990). Higher Cmax and AUC values were obtained for nebulisers compared to MDIs and DPIs (Patel 1986 & Kato 1999). Above mentioned aspects and critisism on earlier meta-analyses by Stevens 2007 were still ignored in the latest Cochrane meta-analysis by van der Wouden 2009. Recent data from a clinical trial in 48 asthmatic children (10.3±2.8 yrs, 19 girls) inhaling for 6 months either 3× daily 20 mg isotonic DSCG via an investigational eFlow® electronic nebuliser or twice daily inhaled steroids via MDI with spacer showed comparable efficacy to inhaled steroids (Basek 2010). In conclusion, in-vivo data suggest that DSCG is a safe and effective asthma controller when a highly efficient, small droplet size generating nebuliser is used. Impactor data obtained at 50% and 95% rel. humidity show that therapeutic efficacy of DSCG is strongly affected by the delivery system.
Clostridial bacteremia in cancer patients. A 12-year experience (1991)

Over 12 years, 136 episodes of bacteremia caused by clostridial species were documented. Eighty-three were monomicrobial, and 53 were polymicrobial. Gastrointestinal, genitourinary carcinomas, and acute leukemia were the most common underlying malignancies. Septic shock occurred in 29% of monomicrobial bacteremias and 45% of polymicrobial bacteremias and was associated with a high mortality rate. Acute hemolysis, gas gangrene, and diffuse spreading cellulitis occurred infrequently but were associated with a 100% fatality rate. Many infections caused by Clostridium perfringens and C. septicum were associated with abdominal disease. The most commonly isolated organism was C. perfringens, followed by C. septicum and C. sporogenes. Overall survival was 58%, but it was 66% for monomicrobial episodes and 45% for polymicrobial infections. All of the patients with bacteremia due to an aerobic gram-negative bacillus in addition to the clostridial species died of their infection. The most effective antibiotics were clindamycin, penicillin, metronidazole, and moxalactam. Surgical drainage of abscesses was an important component of therapy.
Role of Dopamine Transporter in Methamphetamine-Induced Neurotoxicity: Evidence from Mice Lacking the Transporter (1998)

The role of the dopamine transporter (DAT) in mediating the neurotoxic effects of methamphetamine (METH) was tested in mice lacking DAT. Dopamine (DA) and serotonin (5-HT) content, glial fibrillary acidic protein (GFAP) expression, and free radical formation were assessed as markers of METH neurotoxicity in the striatum and/or hippocampus of wild-type, heterozygote, and homozygote (DAT -/-) mice. Four injections of METH (15 mg/kg, s.c.), each given 2 hr apart, produced 80 and 30% decreases in striatal DA and 5-HT levels, respectively, in wild-type animals 2 d after administration. In addition, GFAP mRNA and protein expression levels, extracellular DA levels, and free radical formation were increased markedly. Hippocampal 5-HT content was decreased significantly as well (43%). Conversely, no significant changes were observed in total DA content, GFAP expression, extracellular DA levels, or free radical formation in the striatum of DAT -/- mice after METH administration. However, modest decreases were observed in striatal and hippocampal 5-HT levels (10 and 17%, respectively). These observations demonstrate that DAT is required for, and DA is an essential mediator of, METH-induced striatal dopaminergic neurotoxicity, whereas serotonergic deficits are only partially dependent on DAT.
Ultrathin Cross-Linked Nanoparticle Membranes (2003)

The fabrication of functional nanostructured materials for sensing, encapsulation and delivery requires practical approaches to self-assembly on multiple length scales and the synthesis of tough yet permeable structures. Here, the self-assembly of functionalized, photoluminescent nanoparticles at liquid interfaces, followed by cross-linking of the associated ligands, affords robust membranes that maintain their integrity even when they are removed from the interface. These composite membranes, nanometers in thickness, are elastic yet permeable and have potential applications involving controlled permeability and diffusion. Cadmium selenide (CdSe) nanoparticles are used, since their inherent photoluminescence offers a direct way to probe the spatial organization of the particles. Functionalized ligands attached to the nanoparticles provide an effective means to stabilize the interfacial assembly by cross-linking. The concepts shown are adaptable to other type of nanoparticles, ligands, and solvent combinations.
Electronic discharge module for pump systems of solid-state lasers (2000)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text V. V. Togatov and P. A. Gnatyuk, "Electronic discharge module for pump systems of solid-state lasers," J. Opt. Technol. 67, 379- (2000) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. (1982)

Neonatal thymectomy during the critical period, 2-4 d after birth, can induce various organ-specific autoimmune diseases including oophoritis in A/J mice. The oophoritis thus induced was passively transferred into neonatal mice by injection of spleen cells obtained from syngeneic donors with the disease. Recipient ovaries were rapidly damaged with remarkable mononuclear cell infiltration and destruction of follicular structures. The phenotype of effector cells responsible for successful adoptive transfer was found to be Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, and was sensitive to antithymocyte serum treatment but resistant to cyclophosphamide treatment or in vitro X-ray irradiation. The compatibility between donor and recipient at the major histocompatibility complex was not required for the effector phase of transfer. The oophoritis induced in BALB/c (nu/+ or +/+) was also shown to be transferred into athymic BALB/c nude mice with resulting ovarian lesion and circulating autoantibodies against oocytes. In this transfer system, the effector cells were also demonstrated to be T cells with the Lyt-1+,23- phenotype. Adoptive transfer experiments in both systems revealed that the destruction of ovaries in postthymectomy autoimmune oophoritis was mediated by Lyt-1 T cells. Whether these T cells can be distinguished from other Lyt-1 cells, such as T helper cells and effector T cells in delayed-type hypersensitivity (DTH), is not clear at present, but the results suggest that the effector mechanisms may be closely related to a DTH reaction.
Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV (1993)

Hepatitis C virus (HCV) is a major cause of posttransfusion and community-acquired hepatitis, and a majority of individuals infected with this virus will subsequently develop chronic hepatitis. Characterization of the host immune response to this infection is an important first step that should facilitate the development of immunomodulatory agents and vaccines. Cellular immune responses, especially those mediated by cytotoxic T lymphocytes (CTL), are important in the control of many viral diseases. In this study, liver-infiltrating lymphocytes from persons with chronic HCV hepatitis were examined for evidence of HCV-specific CTL by using target cells infected with recombinant vaccinia viruses expressing the HCV core, E1, E2, and part of the NS2 proteins. Bulk expansion of liver-derived CD8+ lymphocytes resulted in the detection of HCV-specific CTL activity, whereas activity could not be found in CD8+ lymphocytes expanded from peripheral blood. Epitopes recognized by these CTL were defined by using CTL clones obtained by limiting dilution and target cells sensitized with synthetic HCV peptides. Four distinct HLA class I-restricted epitopes were identified, including two epitopes in the amino-terminal portion of the core protein. These studies provide evidence that the highly conserved core protein is a target for HCV-specific CTL and identify CTL epitopes within the more highly variable E2 envelope protein. Our studies also suggest that HCV-specific CTL are localized at the site of tissue injury in infected persons with chronic hepatitis. Identification of the epitopes recognized by HCV-specific CTL will facilitate exploration of their role in disease pathogenesis and may provide information useful in development of therapeutic interventions or vaccines.
High performance UV‐cured coatings containing fluorinated monomers (1999)

UV‐curable systems based on the copolymerisation of a typical acrylic resin with low amount of fluorinated monomers (less than 1 per cent w/w) were prepared. The bulk properties of the films were unchanged, while a strong modification of the surface was obtained, depending on the monomer structure, on its concentration and on the type of substrate.
The role of IFN-gamma in the pathology of experimental endotoxemia. (1990)

Proinflammatory cytokines provoked by circulating bacterial LPS mediate many of the destructive host responses characteristic of septic shock. To determine if the lymphokine IFN-gamma has a similar pathogenic role during endotoxic shock, mice were pretreated with murine rIFN-gamma (rMuIFN-gamma) at various times relative to challenge with Salmonella enteritidis LPS. Subsequent mortality was increased when rMuIFN-gamma was administered before or up to 4 h after endotoxin challenge. Pretreatment with rMuIFN-gamma resulted in nearly fivefold increases in serum TNF during endotoxemia, but TNF levels were unaffected by IFN administered after endotoxin. The increased levels of serum TNF probably reflected enhanced translation of this factor, as tissue expression of TNF mRNA did not increase correspondingly in IFN-pretreated mice. To examine the role of IFN-gamma produced endogenously during endotoxemia, mice were pretreated with 0.5 mg of anti-IFN-gamma mAb before endotoxin injection. This treatment significantly reduced mortality from endotoxic shock but caused only minor decreases in serum TNF. Anti-IFN-gamma administered 2 h after endotoxin was similarly protective. These results demonstrate a significant role for IFN-gamma in the pathology of septic shock, both indirectly as an activator of monokines known to promote lethality and possibly by other, late-acting mechanisms.
Evaluation of Passively Transferred, Nonneutralizing Antibody-Dependent Cellular Cytotoxicity-Mediating IgG in Protection of Neonatal Rhesus Macaques against Oral SIVmac251 Challenge (2006)

Previously, Ab-dependent cellular cytotoxicity (ADCC) was significantly correlated with reduced acute viremia upon intrarectal SIVmac251 challenge of immunized rhesus macaques. To directly assess ADCC protective efficacy, six neonatal macaques were infused s.c. with immune IgG (220 mg/kg) purified from the immunized animals and positive for ADCC and Ab-dependent cell-mediated viral inhibition (ADCVI) activities. Six neonates received control IgG. The neonates were challenged twice orally with 10(5) 50% inhibiting tissue culture-infective dose of SIVmac251 2 days post-IgG infusion. At challenge, plasma of neonates that received immune IgG did not neutralize SIVmac251 but had geometric mean ADCC titers of 48,130 and 232,850 against SIVmac251 -infected and gp120-coated targets, respectively. Peak ADCVI activity varied from 62 to 81%. ADCC activity declined with the 2-wk IgG half-life but was boosted at wk 4, together with de novo ADCC-mediating Abs in controls, by postchallenge viremia. ADCVI activity was similarly induced. No protection, assessed by viral burdens, CD4 counts, and time to euthanasia was observed. Possible factors contributing to the discrepancy between the previous correlation and lack of protection here include: the high oral challenge dose compared with the 400-fold lower intrarectal dose; the challenge route with regard to viral dissemination and distribution of infused IgG; insufficient NK effector activity and/or poor functionality in newborns; insufficient immune IgG; and the possibility that the previous correlation of ADCC with protection was augmented by cellular immune responses also present at challenge. Future studies should explore additional challenge routes in juvenile macaques using higher amounts of potent IgG preparations.
Subband image coding using entropy-coded quantization over noisy channels (1992)

Under the assumption of noiseless transmission the authors develop two entropy-coded subband image coding schemes. The difference between these schemes is the procedure used for encoding the lowest frequency subband: predictive coding is used in one system and transform coding in the other. After demonstrating the unacceptable sensitivity of these schemes to transmission noise, the authors also develop a combined source/channel coding scheme in which rate-compatible convolutional codes are used to provide protection against channel noise. A packetization scheme to prevent infinite error propagation is used and an algorithm for optimal assignment of bits between the source and channel encoders of different subbands is developed. It is shown that, in the presence of channel noise, these channel-optimized schemes offer dramatic performance improvements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Predicted Polishing Behavior Of Plasma Assisted Chemical Etching (PACE) From A Unified Model Of The Temporal Evolution Of Etched Surfaces (1989)

We study the smoothing behavior of PACE using a differential equation which describes the temporal evolution of a solid surface subject to any etch (or deposition) process. The differential equation explicitly exhibits the evolution of any surface to be a product of a geometric factor, common to all such processes, and a rate factor that depends on the process physics. We take the rate factor to be a combination of isotropic and anisotropic processes. In general, it must be derived from first principles or deduced by comparing the topography predicted by the surface evolution equation with the observed etch topography for a particular physical hypothesis. An example of this is shown for the etched shape of microelectronic &quot;deep isolation trenches&quot; fabricated by a purely anisotropic process. Good agreement with observation is achieved when the rate coefficient is taken to have a local surface curvature or local electric field dependence. Finally, the surface evolution equation is used to explore the ability of PACE to smooth and polish an initially rough surface by obtaining the time dependence of the spatial Fourier coefficients of the surface shape from the differential equation. This analysis provides a vivid exposition of the PACE smoothing process. Both the anisotropic and isotropic etching regimes of PACE are considered.
An Emergency Handling Scheme for Superframe-Structured MAC Protocols in WBANs (2011)

Wireless body area networks (WBANs) provide medical and/or consumer electronics (CE) services within the vicinity of a human body. In a WBAN environment, immediate and reliable data transmissions during an emergency situation should be supported for medical services. In this letter, we propose a flexible emergency handling scheme for WBAN MAC protocols. The proposed scheme can be applied to superframe-structured MAC protocols such as IEEE 802.15.4 and its extended versions. In addition, our scheme can be incorporated into the current working draft for IEEE 802.15.6 standards. Extensive simulations were performed and the low latency of emergent traffics was validated.
Anti-Inflammatory Activity of Two Flavonoids from Tanacetum microphyllum (1993)

The CH2Cl2 extract of Tanacetum microphyllum aerial parts exhibited anti-inflammatory activity and yielded two anti-inflammatory flavonoids: 5,7,3'-trihydroxy-3,6,4'-trimethoxyflavone (centaureidin) [1], and 5,3'-dihydroxy-4'-methoxy-7-carbomethoxyflavonol [2]. This is the first report of the chemical composition of Ta. microphyllum and of the isolation of centaureidin from the genus Tanacetum.
Macroporous Silicon as a Model for Silicon Wire Array Solar Cells (2008)

Macroporous silicon samples have been investigated in photoelectrochemical cells, and their behavior has been compared to that of conventional, planar, Si/liquid junctions. The liquid electrolyte junction provided a conformal contact to the macroporous Si and allowed assessment of the trade-offs between increased surface area and decreased carrier collection distances in such systems relative to the behavior of planar semiconductor/liquid photoelectrochemical junctions. The electrolyte contained the dimethylferrocene/dimethylferrocenium redox system in methanol because this system has been shown previously to produce bulk recombination-diffusion-limited contacts at planar Si(100) electrodes under 100 mW cm^(-2) of simulated air mass 1.5 illumination. Introduction of a network of ∼2−3 μm diameter, ∼80 μm long pores into the Si was found to slightly reduce the short-circuit photocurrent density and the open-circuit voltage of the system, but energy-conversion efficiencies in excess of 10% were nevertheless obtained from such samples. This system therefore validates the concept of using interpenetrating networks to produce efficient solar energy conversion devices in systems that do not have long carrier collection distances.
Similarities in the Induction of Post-Golgi Vesicles by the Vaccinia Virus F13L Protein and Phospholipase D (2002)

Intracellular mature vaccinia virions are wrapped by cisternae, derived from virus-modified trans-Golgi or endosomal membranes, and then transported via microtubules to the cell periphery. Two viral proteins, encoded by the F13L and B5R open reading frames, are essential for the membrane-wrapping step. Previous transfection studies indicated that F13L induces the formation of post-Golgi vesicles that incorporate the B5R protein and that this activity depends on an intact F13L phospholipase motif. Here we show that the F13L protein has a general effect on the trafficking of integral membrane proteins from the Golgi apparatus, as both the vaccinia virus A36R protein and the vesicular stomatitis virus G protein also colocalized with the F13L protein in vesicles. In addition, increased expression of cellular phospholipase D, which has a similar phospholipase motif as, but little amino acid sequence identity with, F13L, induced post-Golgi vesicles that contained B5R and A36R proteins. Butanol-1, which prevents the formation of phosphatidic acid by phospholipase D and specifically inhibits phospholipase D-mediated vesicle formation, also inhibited F13L-induced vesicle formation, whereas secondary and tertiary alcohols had no effect. Moreover, inhibition of phospholipase activity by butanol-1 also reduced plaque size and decreased the formation of extracellular vaccinia virus without affecting the yield of intracellular mature virus. Phospholipase D, however, could not complement a vaccinia virus F13L deletion mutant, indicating that F13L has additional virus-specific properties. Taken together, these data support an important role for F13L in inducing the formation of vesicle precursors of the vaccinia virus membrane via phospholipase activity or activation.