gebhart/patrepeval huggingface dataset:
A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate? (2015)

It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722-0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
Evidence for Functional Binding and Stable Sliding of the TATA Binding Protein on Nonspecific DNA (1995)

The TATA binding protein (TBP) is required at RNA polymerase I, II, and III promoters that either contain or lack a TATA box. In an effort to understand how TBP might function at such a wide variety of promoters, we have investigated the specific and nonspecific DNA binding properties of human TBP. We show that TBP has less than a 10(3)-fold preference for binding a TATA box (TATAAAAG) than for an average nonspecific site. In contrast to TBP, which binds to the minor groove of DNA, major groove binding proteins typically display binding specificities in the range of 10(6). Once TBP is bound to DNA, whether it be a TATA box or nonspecific DNA, binding is quite stable with a t1/2 of dissociation in the range of 20-60 min for a 300-base pair DNA fragment. In this binding state, TBP appears to be capable of stable one-dimensional sliding along the DNA. Sequence-specific binding can be accounted for, in part, by different rates of sliding. Additional findings demonstrate that specific and nonspecific DNA impart upon TBP an enormous and equivalent degree of thermal stability, suggesting that the TBP-DNA interface on non-specific DNA is not radically different from that on TATA. Consistent with this notion, we find that nonspecifically bound TBP is competent in establishing pol II transcription complexes on DNA. Together, these finding provide a plausible mechanistic explanation for the ability of TBP to function at TATA-containing and TATA-less promoters.
Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38/JNK kinase inhibitor (2004)

Several steps in the HIV-1 virus life cycle appear to depend on cellular activation, including activation of the p38 pathway. Without activation virus replication is thought to be blocked due to incomplete reverse transcription and a lack of proviral DNA integration. The data collectively illustrate that inhibition of the p38 pathway can affect HIV-1 replication. Interruption of HIV infection by p38 inhibitors underscores the value of exploring antiviral drugs that target host cellular proteins.
A review of the role of oxidative stress in the pathogenesis of eye diseases (2011)

Free radicals, referred to as oxidants are molecules in the body with unpaired electrons, hence are unstable and ready to bond with other molecules with unpaired electrons. They include Reactive Oxygen Species (ROS) such as superoxide anion radicals (·O¯), hydrogen peroxide (H202), and hydroxyl free radicals (·OH). Endogenous sources of ROS include metabolic and other organic processes, while exogenous sources include ultraviolet radiation and environmental toxins such as smoke. Antioxidants (oxidant scavengers) such as ascorbate, alpha-tocopherol and glutathione as well as various enzymatic compounds such as superoxide dismutase (SOD), catalase and glutathione reductase are also present in the body and in manyfoods or food supplements. An imbalance between oxidants and antioxidants in favour of oxidantsis termed oxidative stress and can lead to cell or tissue damage and aging. Oxidative stress has been implicated in the pathogenesis of many serious systemic diseases such as diabetes, cancer and neurological disorders. Also, laboratory and epidemiological studies have implicated oxidative stress in the pathogenesis of the majority of common serious eye diseases such as cataract, primary open angle glaucoma and age-related macular degeneration. In this article, we reviewed the current information on the roles of oxidative stress in the pathogenesis of various eye diseases and the probable roles of antioxidants. Eye care practitioners will find this article useful as it provides information on the pathogenesis of common eye diseases. (S Afr Optom 2011 70(4) 182-190)
Hydrido and Allyl/Hydrido Complexes of Early Lanthanides Supported by an NNNN‐Type Macrocyclic Ligand (2013)

Abstract Hydrogenation of the neutral bis(allyl) complexes of the early lanthanides [Ln(Me 3 TACD)(η 3 ‐C 3 H 5 ) 2 ] [(Me 3 TACD)H = 1,4,7‐trimethyl‐1,4,7,10‐tetraazacyclododecane, Me 3 [12]aneN 4 ] with phenylsilane gave the tetranuclear octahydrido complexes [Ln(Me 3 TACD)(μ‐H) 2 ] 4 [Ln = Ce ( 1 ‐Ce), Pr ( 2 ‐Pr)] or the dinuclear allyl/hydrido complexes [Ln(Me 3 TACD)(η 3 ‐C 3 H 5 )(μ‐H)] 2 [Ln = Nd ( 3 ‐Nd), Sm ( 4 ‐Sm)], which were isolated and characterized. The structures of 1 ‐Ce and 2 ‐Pr are constructed of a tetrahedral Ln 4 H 8 core. Single‐crystal X‐ray diffraction analyses of 3 ‐Nd and 4 ‐Sm revealed a C 2 symmetric planar Ln 2 H 2 core. The experimental structures agreed with the results of DFT calculations, which predict that the nuclearity of the dihydrido complexes depend on the ionic radius of the metal. Compounds 1 ‐Ce, 2 ‐Pr, 3 ‐Nd and 4 ‐Sm were tested as catalysts in the copolymerization of cyclohexene oxide with CO 2 to give highly carbonate‐linked copolymers with moderate activities.
Precipitation of apo E-containing lipoproteins by precipitation reagents for apolipoprotein B. (1984)

We measured the solubility of apolipoprotein E (apo E) after precipitation, with heparin-Mn2+ or dextran sulfate-Mg2+, of lipoproteins containing apo B. Data from 46 randomly selected subjects suggest that apo E is readily precipitated by dextran sulfate-Mg2+, but that heparin-Mn2+ preferentially precipitates apo E associated with apo B-containing lipoproteins while leaving the apo E-containing fraction of high-density lipoproteins (HDL) in solution. In a more detailed analysis of three subjects, we measured the lipoprotein association of apo E by column chromatography on agarose beads, before and after its precipitation from plasma. This study confirmed the preferential solubility of apo E associated with HDL lipoproteins. Using plasma from two normolipidemic subjects, we maintained the heparin concentration at 1.30 g/L and varied the manganese concentration from 9.2 to 184 mmol/L. A 46 mmol/L concentration best separated apo E-containing HDL from apo B-containing lipoproteins. Thus, at these final concentrations, heparin-Mn2+ appears to precipitate the apo E associated with apo B-containing lipoproteins, leaving soluble most of the apo E associated with lipoproteins of HDL size.
Active Strobe Imager for Visualizing Dynamic Behavior of Tumors (2007)

This paper newly proposes the active strobe imager (ASI) that can visualize the dynamic behaviors of internal organ to medical doctors within Human dynamic eye sight, so that they can get a hint for detecting the location of tumors in real time during operation. The ASI is composed of a nozzle for supplying a pulsated air jet to an internal organ, a strobe system for visualizing the dynamic behaviors, a camera for capturing the image at the moment of strobe flashing, and a monitor for displaying the dynamic motion of internal organ, respectively. Without the assistance of strobe, medical doctors can not see what is really happening in real time, since the frequency of air jet is even more than the range of human dynamic eye sight. After explaining the basic principle, we show a couple of experiments for both artificial and real human lungs. Through these experiments, we newly found that the ASI is really helpful for discovering tumors or other diseases hidden in internal organs. Movies are available in Website.
Hyperfibrinolysis increases blood–brain barrier permeability by a plasmin- and bradykinin-dependent mechanism (2016)

Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis, and leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our aim was to develop an experimental model of hyperfibrinolysis and to study its effects on the homeostasis of the blood-brain barrier (BBB). We induced a sustained hyperfibrinolytic state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA). As revealed by near-infrared fluorescence imaging, hyperfibrinolytic mice presented a significant increase in BBB permeability. Using a set of deletion variants of tPA and pharmacological approaches, we demonstrated that this effect was independent of N-methyl-D-aspartate receptor, low-density lipoprotein-related protein, protease-activated receptor-1, or matrix metalloproteinases. In contrast, we provide evidence that hyperfibrinolysis-induced BBB leakage is dependent on plasmin-mediated generation of bradykinin and subsequent activation of bradykinin B2 receptors. Accordingly, this effect was prevented by icatibant, a clinically available B2 receptor antagonist. In agreement with these preclinical data, bradykinin generation was also observed in humans in a context of acute pharmacological hyperfibrinolysis. Altogether, these results suggest that B2 receptor blockade may be a promising strategy to prevent the deleterious effects of hyperfibrinolysis on the homeostasis of the BBB.
Nile: a query processing engine for data streams (2004)

We present the demonstration of the design of "STEAM", Purdue Boiler Makers' stream database system that allows for the processing of continuous and snap-shot queries over data streams. Specifically, the demonstration focuses on the query processing engine, "Nile". Nile extends the query processor engine of an object-relational database management system, PREDATOR, to process continuous queries over data streams. Nile supports extended SQL operators that handle sliding-window execution as an approach to restrict the size of the stored state in operators such as join.
A Highly Stackable Thin-Film Transistor (TFT) NAND-Type Flash Memory (2006)

For the first time, a successful TFT NAND-type flash memory is demonstrated using a low thermal budget process suitable for stacking the memories. A TFT-SONOS device using bandgap engineered SONOS (BE-SONOS) (Lue, et al. 2005) with fully-depleted (FD) poly silicon (50 nm) channel and tri-gate P <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -poly gate is integrated into a NAND array. Small devices (L/W=0.18/0.09 μm) with good DC performance are achieved, owing to the good control capability of the tri-gate FD structure. Successful NAND array functions are demonstrated, with more than 1 μA read current for a 16-string NAND array and good program disturb immunity. This new device also shows good endurance and data retention, and negligible read disturb. These results are very encouraging for future 3D flash memory
Quality Assessment of Established and Emerging Blood Components for Transfusion (2016)

Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor. Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma). Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation.
Gibberellin biosynthesis in bacteria: Separate ent‐copalyl diphosphate and ent‐kaurene synthases in Bradyrhizobium japonicum (2008)

Gibberellins are ent-kaurene-derived diterpenoid phytohormones produced by plants, fungi, and bacteria. The distinct gibberellin biosynthetic pathways in plants and fungi are known, but not that in bacteria. Plants typically use two diterpene synthases to form ent-kaurene, while fungi use only a single bifunctional diterpene synthase. We demonstrate here that Bradyrhizobium japonicum encodes separate ent-copalyl diphosphate and ent-kaurene synthases. These are found in an operon whose enzymatic composition indicates that gibberellin biosynthesis in bacteria represents a third independently assembled pathway relative to plants and fungi. Nevertheless, sequence comparisons also suggest potential homology between diterpene synthases from bacteria, plants, and fungi.
Selection for loss of tetracycline resistance by Escherichia coli (1981)

An improved medium for the direct, positive selection of tetracycline-sensitive clones from a population of tetracycline-resistant strains of Escherichia coli is described.
CCT244747 Is a Novel Potent and Selective CHK1 Inhibitor with Oral Efficacy Alone and in Combination with Genotoxic Anticancer Drugs (2012)

CCT244747 represents the first structural disclosure of a highly selective, orally active CHK1 inhibitor and warrants further evaluation alone or combined with genotoxic anticancer therapies.
Methodology for real‐time, multianalyte monitoring of fermentations using an in‐situ mid‐infrared sensor (2003)

An in-situ, mid-infrared sensor was used to monitor the major analyte concentrations involved in the cultivation of Gluconacetobacter xylinus and the production of gluconacetan, a food-grade exopolysaccharide. To predict the analyte concentrations, three different sets of standard spectra were used to develop calibration models, applying partial least-squares regression. It was possible to build a valid calibration model to predict the 700 spectra collected during the complete time course of the cultivation, using only 12 spectra collected every 10 h as standards. This model was used to reprocess the concentration profiles from 0 to 15 g/L of nine different analytes with a mean standard error of validation of 0.23 g/L. However, this calibration model was not suitable for real-time monitoring as it was probably based on non-specific spectral features, which were correlated only with the measured analyte concentrations. Valid calibration models capable of real-time monitoring could be established by supplementing the set of 12 fermentation spectra with 42 standards of measured analytes. A pulse of 5 g/L ethanol showed the robustness of the model to sudden disturbances. The prediction of the models drifted, however, toward the end of the fermentation. The most robust calibration model was finally obtained by the addition of 34 standard spectra of non-measured analytes. Although the spectra did not contain analyte-specific information, it was believed that this addition would increase the variability space of the calibration model. Therefore, an expanded calibration model containing 88 spectra was used to monitor, in real time, the concentration profiles of fructose, acetic acid, ethanol and gluconacetan and allowed standard errors of prediction of 1.11, 0.37, 0.22, and 0.79 g/L, respectively.
Modification of microfluidic paper-based devices with silica nanoparticles (2014)

This paper describes a silica nanoparticle-modified microfluidic paper-based analytical device (μPAD) with improved color intensity and uniformity for three different enzymatic reactions with clinical relevance (lactate, glucose, and glutamate). The μPADs were produced on a Whatman grade 1 filter paper and using a CO2 laser engraver. Silica nanoparticles modified with 3-aminopropyltriethoxysilane were then added to the paper devices to facilitate the adsorption of selected enzymes and prevent the washing away effect that creates color gradients in the colorimetric measurements. According to the results herein described, the addition of silica nanoparticles yielded significant improvements in color intensity and uniformity. The resulting μPADs allowed for the detection of the three analytes in clinically relevant concentration ranges with limits of detection (LODs) of 0.63 mM, 0.50 mM, and 0.25 mM for lactate, glucose, and glutamate, respectively. An example of an analytical application has been demonstrated for the semi-quantitative detection of all three analytes in artificial urine. The results demonstrate the potential of silica nanoparticles to avoid the washing away effect and improve the color uniformity and intensity in colorimetric bioassays performed on μPADs.
Sulfonate analogues of chenodeoxycholic acid: metabolism of sodium 3 alpha, 7 alpha-dihydroxy-25-homo-5 beta-cholane-25-sulfonate and sodium 3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholane-23-sulfonate in the hamster. (1992)

This report describes the chemical synthesis of a new bile acid analogue, namely, sodium 3 alpha, 7 alpha-dihydroxy-25-homo-5 beta-cholane-25-sulfonate from homochenodeoxycholic acid. The structure of the new compound was assigned by proton magnetic resonance and infrared spectrometry. Its metabolism was studied in the hamster in comparison with sodium 3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholane-23-sulfonate and sodium taurochenodeoxycholate. After intraduodenal administration of the 3H-labeled analogues into bile fistula hamsters, both sulfonates were absorbed from the intestine and nearly 80% of the radioactivity was secreted into bile within 8 h. Intra-ileal administration revealed that these compounds resembled taurochenodeoxycholate in that they were much more rapidly absorbed from the ileum than from the proximal small intestine: more than 85% of the radioactivity was recovered in bile within 1 h. After intravenous infusion the sulfonates were efficiently extracted by the liver at rates similar to that of sodium taurochenodeoxycholate. Chromatographic analysis of the bile showed that, regardless of the route of administration, most (> 95%) of the sulfonates were not biotransformed and they became major biliary bile acids. Sodium 3 alpha, 7 alpha-dihydroxy-25-homo-5 beta-cholane-25-sulfonate and, to a lesser extent, sodium 3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholane-23-sulfonate induced cholestasis at infusion rates at which sodium taurochenodeoxycholate produced choleresis.
Nanoscale Pipetting for Controlled Chemistry in Small Arrayed Water Droplets Using a Double-Barrel Pipet (2006)

We present a new methodology which provides for the miniaturization of one of the most common tools in use in chemistry and biology laboratories today-the micropipet. We have used glass-fabricated double-barrel nanopipets to controllably produce arrayed water droplets with volumes as small as a few attoliters under an organic layer. We have addressed individual droplets and added controlled amounts of either additional volume or reagents from one of the barrels of the pipet. We demonstrate that this method can be used for miniaturized cell-free protein expression.
Acquired Dendritic Channelopathy in Temporal Lobe Epilepsy (2004)

Inherited channelopathies are at the origin of many neurological disorders. Here we report a form of channelopathy that is acquired in experimental temporal lobe epilepsy (TLE), the most common form of epilepsy in adults. The excitability of CA1 pyramidal neuron dendrites was increased in TLE because of decreased availability of A-type potassium ion channels due to transcriptional (loss of channels) and posttranslational (increased channel phosphorylation by extracellular signal-regulated kinase) mechanisms. Kinase inhibition partly reversed dendritic excitability to control levels. Such acquired channelopathy is likely to amplify neuronal activity and may contribute to the initiation and/or propagation of seizures in TLE.
Platelets regulate lymphatic vascular development through CLEC-2–SLP-76 signaling (2010)

Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.
A Novel Label-Free Optical Biosensor Using Synthetic Oligonucleotides from E. coli O157:H7: Elementary Sensitivity Tests (2009)

SiO(2)-TiO(2) thin films for use as fiber optic guiding layers of optical DNA biosensors were fabricated by the sol-gel dip coating technique. The chemical structure and the surface morphology of the films were characterized before immobilization. Single probe DNA strands were immobilized on the surface and the porosity of the films before the hybridization process was measured. Refractive index values of the films were measured using a Metricon 2010 prism coupler. On the surface of each film, 12 different spots were taken for measurement and calculation of the mean refractive index values with their standard deviations. The increased refractive index values after the immobilization of single DNA strands indicated that immobilization was successfully achieved. A further refractive index increase after the hybridization with target single DNA strands showed the possibility of detection of the E. coli O157:H7 EDL933 species using strands of 20-mers (5'-TAATATCGGTTGCGGAGGTG -3') sequence.