gebhart/patrepeval huggingface dataset:
Transmembrane-Bound IL-15–Promoted Epithelial-Mesenchymal Transition in Renal Cancer Cells Requires the Src-Dependent Akt/GSK-3β/β-Catenin Pathway (2015)

Intrarenal interleukin-15 (IL-15) plays a major role controlling epithelial survival and polarization both in physiological and pathologic conditions. Herein, we confirmed that human renal cell carcinomas (RCCs) express a membrane-bound IL-15 isoform displaying an unusual molecular weight of 27 kDa. Its stimulation with soluble IL-15 receptor α chain (s-IL-15Rα) triggers epithelial-mesenchymal transition (EMT) process as shown by the down-regulation of E-cadherin and zona occludens 1 and the up-regulation of vimentin and N-cadherin and promotes the migratory and invasive properties of RCC. S-IL-15Rα treatment triggered the Src/PI3K/Akt/GSK-3β pathway and promoted β-catenin nuclei translocation. Deactivation of this pathway by using Src-specific inhibitor PP2, PI3K inhibitor LY294002, and AKT inhibitor MK2206 hampered β-catenin nuclei translocation and suppressed EMT, migration, and invasion of RCC. S-IL-15Rα treatment also enhanced Src-dependent phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (Erk1/2). FAK knockdown significantly decreased the migration and invasion of RCC, which suggest that Src-FAK signaling was involved in s-IL-15Rα-favored migration and invasion of RCC. At the same time, inhibitors of Erk1/2 also significantly decreased the migration and invasion of RCC but could not reverse s-IL-15Rα-induced EMT. Taken together, our results reveal that Src-dependent PI3K/Akt/GSK3b/β-catenin pathway is required for s-IL-15Ra-dependent induction of EMT in RCC, while Src-FAK and Src-Erk1/2 signaling were involved in s-IL-15Rα-promoted migration and invasion properties of RCC. Our study provides a better understanding of IL-15 signaling in RCC tumor progression, which may lead to novel targeted therapies and provide some suggestions when using IL-15 in clinic.
Spherulitic growth rates and morphology of absorbable poly(<i>p</i>‐dioxanone) homopolymer and its copolymer by hot‐stage optical microscopy (2001)

Abstract Hot‐stage optical microscopy was used to study the crystal morphology, nucleation, and spherulitic growth rates of poly( p ‐dioxanone) (PDS) homopolymer and an 89/11 PDS/glycolide segmented block copolymer. A wide range of crystallization conditions were experimentally accessible, allowing the inspection of various morphological features and accurate estimations of characteristic growth parameters, including radial growth and nucleation rates. Although the regime analysis of the crystallization kinetics indicated no breaks in the growth rate curve, the isothermal data were in excellent agreement with the Hoffman–Lauritzen theory. Spherulitic growth rates obtained from optical measurements are compared with values of the half‐time of crystallization determined earlier by differential scanning calorimetry. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 3073–3089, 2001
The Synthesis of a 5′-Deoxyadenosylcobalamin-agarose Adsorbent and Its Utility in the Purification of Ribonucleotide Reductase (1972)

Abstract A 5'-deoxyadenosylcobalamin-agarose adsorbent has been prepared for the purification by affinity chromatography of enzymes which require 5'-deoxyadenosylcobalamin as a coenzyme. The synthesis involved the covalent attachment of cyanocobalamin to agarose through a 12 carbon chain. This hydrocarbon chain was attached to the corrin nucleus by reacting diaminododecane with cyanocobalamin e-carboxylic acid in the presence of water-soluble carbodiimide. The substituted cobalamin was then coupled to agarose activated by cyanogen bromide. The complex was reduced with chromous chloride and reacted with 5'-O-p-tolylsulfonyl-adenosine to yield the desired adsorbent. This adsorbent has been successfully used in the purification of ribonucleotide reductase from Lactobacillus leichmannii, which requires 5'-deoxyadenosylcobalamin as a coenzyme. Ribonucleotide reductase is retained by the adsorbent if it is applied in the presence of a dithiol and an allosteric effector. The enzyme is readily eluted with a solution containing only buffer and dithiol.
ApproxANN: an approximate computing framework for artificial neural network (2015)

Artificial Neural networks (ANNs) are one of the most well-established machine learning techniques and have a wide range of applications, such as Recognition, Mining and Synthesis (RMS). As many of these applications are inherently error-tolerant, in this work, we propose a novel approximate computing framework for ANN, namely ApproxANN. When compared to existing solutions, ApproxANN considers approximation for both computation and memory accesses, thereby achieving more energy savings. To be specific, ApproxANN characterizes the impact of neurons on the output quality in an effective and efficient manner, and judiciously determine how to approximate the computation and memory accesses of certain less critical neurons to achieve the maximum energy efficiency gain under a given quality constraint. Experimental results on various ANN applications with different datasets demonstrate the efficacy of the proposed solution.
Prosthetic Valves for the Small Aortic Root (1994)

Mechanical aortic valves (AVs) are frequently implanted in small (19 and 21 mm) aortic roots because bioprosthetic valves have unacceptably high gradients and many surgeons do not implant allograft valves. Three mechanical valves in common use today in the United States are the Starr-Edwards (SE), St. Jude Medical (SJ), and the Medtronic-Hall (MH). Clinical hemodynamic studies reveal that the 21-mm SE valve (size 8A) has peak systolic gradients of 13 to 58 mmHg (N = 6) with a calculated effective orifice of 0.7 to 1.4 cm2. The 19-mm SJ valve has a gradient at peak pressure of 17 mmHg and a mean gradient of 22 mmHg (N = 6) with respective exercise gradients of 32 and 38 mmHg (N = 5). For the 21-mm SJ valve the mean gradient was 5.2 +/- 5.3 (N +/- 12) and the gradient at peak pressure was 6.0 mmHg (N = 15). The 21-mm MH valve had resting gradients at peak pressure of 10.5 (N = 3) and 12.4 mmHg (N = 9) and exercise gradients of 15.8 mmHg (N = 9). Six months after AV replacement with small SJ or MH (N = 14) or large (23 mm or greater) (N = 83) valves, cardiac output was 4.7 versus 6.4 L/min (p < 0.03), percent reduction in left ventricular mass index (LVMI) was -8% versus -21% (p < 0.01), exercise duration was 370 versus 555 seconds, and congestive heart failure (CHF) class was 1.9 versus 1.1 (p < 0.0001). Change in LVMI and valve size were the only independent predictors of CHF class.(ABSTRACT TRUNCATED AT 250 WORDS)
Asymmetric Diels−Alder Reactions of 2-Pyrones with a Bifunctional Organic Catalyst (2007)

The reactions of 2-pyrones with electron-deficient dienophiles constitute a synthetically useful class of Diels−Alder reaction. By exploring cinchona alkaloid-derived organic molecules as acid−base bifunctional catalysts, we successfully developed the first highly enantioselective and diastereoselective catalytic Diels−Alder reaction with 2-pyrones. Furthermore, we demonstrated the possibility of using such catalysts to control the endo/exo selectivity in a Diels−Alder reaction.
Lipolytic Effects of Human Growth Hormone in Resistant Obesity 1 (1965)

Plasma levels of free fatty acids (FFA) increased comparably in subjects of normal weight and in the extremely obese 4 hr after human growth hormone (HGH) was given intramuscularly in a body weight-related dose. Pretreatment of the very obese with HGH did not modify the subnormal response of plasma FFA to infused epinephrine.
Reaction Mechanism of Glyoxalase I Explored by an X-ray Crystallographic Analysis of the Human Enzyme in Complex with a Transition State Analogue (1999)

The structures of human glyoxalase I in complexes with S-(N-hydroxy-N-p-iodophenylcarbamoyl)glutathione (HIPC-GSH) and S-p-nitrobenzyloxycarbonylglutathione (NBC-GSH) have been determined at 2.0 and 1.72 A resolution, respectively. HIPC-GSH is a transition state analogue mimicking the enediolate intermediate that forms along the reaction pathway of glyoxalase I. In the structure, the hydroxycarbamoyl function is directly coordinated to the active site zinc ion. In contrast, the equivalent group in the NBC-GSH complex is approximately 6 A from the metal in a conformation that may resemble the product complex with S-D-lactoylglutathione. In this complex, two water molecules occupy the liganding positions at the zinc ion occupied by the hydroxycarbamoyl function in the enediolate analogue complex. Coordination of the transition state analogue to the metal enables a loop to close down over the active site, relative to its position in the product-like structure, allowing the glycine residue of the glutathione moiety to hydrogen bond with the protein. The structure of the complex with the enediolate analogue supports an "inner sphere mechanism" in which the GSH-methylglyoxal thiohemiacetal substrate is converted to product via a cis-enediolate intermediate. The zinc ion is envisioned to play an electrophilic role in catalysis by directly coordinating this intermediate. In addition, the carboxyl of Glu 172 is proposed to be displaced from the inner coordination sphere of the metal ion during substrate binding, thus allowing this group to facilitate proton transfer between the adjacent carbon atoms of the substrate. This proposal is supported by the observation that in the complex with the enediolate analogue the carboxyl group of Glu 172 is 3.3 A from the metal and is in an ideal position for reprotonation of the transition state intermediate. In contrast, Glu 172 is directly coordinated to the zinc ion in the complexes with S-benzylglutathione and with NBC-GSH.
High yield photoreagents for protein crosslinking and affinity labeling (1978)

4-Nitrophenyl ethers are proposed as new high-yield photoreagents for protein crosslinking and affinity labeling. These are totally unreactive in the dark under biological conditions, but react quantitatively with amines at pH 8 upon irradiation with 366-nm light. The reaction of monoalkoxy-p-nitrobenzenes with an amine yields the corresponding free alcohol and substituted nitrophenylamine. In essence, the nitrophenyl group is transferred from the alcohol to the amine. Bifunctional affinity reagents of this type could be especially useful for placing the p-nitrophenyl chromophore adjacent to a binding site without blocking it. The corresponding 2-methoxy-4-nitrophenyl ethers react with amines by displacement of the methoxyl group. Thus, bifunctional reagents of this class could be photocrosslinkers. A maleimide-containing 2-methoxy-4-nitrophenyl ether was attached to human fetal hemoglobin at gamma-cysteine F9 stoichiometrically. Subsequent ultraviolet irradiation yielded a gamma-gamma crosslinked hemoglobin in 80% yield. The oxygenation properties of the derivative indicate that it is locked in a high affinity conformation and that all cooperativity is lost.
Low‐risk identification in multiple myeloma using a new 14‐gene model (2012)

Identifying the best gene expression pattern associated with low-risk disease in patients with newly diagnosed multiple myeloma (MM) is important to direct clinical treatments. The MM Survival Index14 (MMSI14) was developed from GEP data sets of 22 normal plasma cells (NPC), 5 MM cell lines (MMCL), 44 monoclonal gammopathy of undetermined significance (MGUS), and 351 newly diagnosed MM patients. R/bioconductor and siggenes package were used to obtain heatmap, boxplot and histogram whose results were then analyzed by Kaplan-Meier analysis. Fourteen genes associated with low-risk disease in MM were identified. We validated the disease prognostic power of MMSI14 with an independent data set of other 214 newly diagnosed MM patients and also compared our model with the 70-gene, the 8-subgroup, IFM15, and HMCLs7 models. Survival analysis showed that a low MMSI14 signature was associated with longer survival. Applying MMSI14 to independent data sets, we were able to classify 39% of patients as low-risk, with a survival probability of more than 90% at 60 months. Multiple clinical parameters confirmed significant correlation between low- and high-risk subgroups defined by MMSI14. Comparing previously published models to the same data sets the MMSI14 model retained the best prognostic value. We have developed a new gene model (MMSI14) for defining low-risk, newly diagnosed MM. The multivariate comparative analysis confirmed that MMSI14 is the best available model to predict clinical outcome in MM patients.
Characterization of granularity and redundancy for SRAMs for optimal yield-per-area (2008)

Memories are significant proportions of most digital systems and memory-intensive chips continue to lead the migration to new nano-fabrication processes. As these processes have increasingly higher defect rates, especially when they are first adopted, such early migration necessitates the use of increasing levels of redundancy to obtain high yield (per area). We show that as we move into nanometer processes with high defect rates, the level of redundancy needed to optimize yield-per-area is sufficiently high so as to significantly influence design tradeoffs. We then report a first step towards considering the overheads of redundancy during design optimization by characterizing the tradeoffs between the granularity of a design and the level of redundancy that optimizes the yield-per-area of static RAMs (SRAMs). Starting with physical layouts of cells and the desired memory size, we derive probabilities of failure at a range of abstractions - transistor level, cell level, and system level. We then estimate optimal memory granularity, i.e., the size of memory blocks, as well as the optimal number of spare rows and columns that maximize yield-per-area. In particular, we demonstrate the non-monotonic nature of these tradeoffs and present efficient designs for large SRAMs. Our ongoing research is characterizing several other specific tradeoffs, for SRAMs as well as logic blocks.
Aluminum: a requirement for activation of the regulatory component of adenylate cyclase by fluoride. (1982)

Activation of the purified guanine nucleotide-binding regulatory component (G/F) of adenylate cyclase by F- requires the presence of Mg2+ and another factor. This factor, which contaminates commercial preparations of various nucleotides and disposable glass test tubes, has been identified as Al3+. In the presence of 10 mM Mg2+ and 5 mM F-, AlCl3 causes activation of G/F with an apparent activation constant of approximately 1-5 muM. The requirement for Al3+ is highly specific; of 28 other metals tested, only Be2+ promoted activation of G/F by F-.
Decline in bone marrow proliferative capacity as a function of age (1982)

Bone marrow from old (greater than 2 yr of age) and young (8-10 wk of age) male C3H/HeJ mice was grown in long-term bone marrow cultures and assayed for weekly hematopoietic stem cell (CFUs) production and interval self-renewal capacity (R5). Greater numbers of CFUs were noted in old marrow as compared to young marrow cultures over the first 4 wk duration, but subsequently, greater numbers of CFUs were seen weekly in the young marrow cultures. Over 1 3 wk in culture, the total CFUs determination was greater in young marrow cultures. Similarly. self-renewal capacity (R1) was greater in old as compared to young marrow-adherent CFUs over the first
Origins of the Iowa Granger Law (1954)

Journal Article Origins of the Iowa Granger Law Get access George H. Miller George H. Miller Search for other works by this author on: Oxford Academic Google Scholar Journal of American History, Volume 40, Issue 4, March 1954, Pages 657–680, https://doi.org/10.2307/1895862 Published: 01 March 1954
Inductive learning for risk classification (1990)

The authors discuss the application of inductive learning to credit risk analysis. Three risk classification problems are addressed: business loan evaluation, bond rating, and bankruptcy prediction. The use of a system called Marble, a knowledge-based decision-support system that uses approximately 80 decision rules to evaluate commercial loans, is discussed. In particular, an aspect of Marble that uses inductive learning to classify financial risks is described, and the effectiveness of the technique is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Drug development costs when financial risk is measured using the Fama–French three‐factor model (2009)

In a widely cited article, DiMasi, Hansen, and Grabowski (2003) estimate the average pre-tax cost of bringing a new molecular entity to market. Their base case estimate, excluding post-marketing studies, was $802 million (in $US 2000). Strikingly, almost half of this cost (or $399 million) is the cost of capital (COC) used to fund clinical development expenses to the point of FDA marketing approval. The authors used an 11% real COC computed using the capital asset pricing model (CAPM). But the CAPM is a single factor risk model, and multi-factor risk models are the current state of the art in finance. Using the Fama-French three factor model we find that the cost of drug development to be higher than the earlier estimate.
[Long-term consequences of the damaging effect of cytostatic drugs on hematopoiesis and lymphoid tissue]. (1990)

The evidence on the changes detectable in remote periods (at 1, 3, and 6 months) is presented. It shows that the quantitative and functional defects are retained in the hemopoietic and lymphoid tissues within 3-6 months after exposure to the effects of various cytostatic agents. These defects may be corrected by means of immunomodulators.
Amino acid neurotransmitter levels in gliomas and their relationship to the incidence of epilepsy (1988)

The cause of epilepsy due to gliomas is not known. Explanations that is due to mass effect, infiltration and site of the tumour appear insufficient. We have investigated the possibility that epilepsy due to gliomas is caused by interference with normal GABA and glutamate uptake and metabolism in the surrounding cortex. Analysis of human glioma biopsy specimens for the amino acid neurotransmitters and glutamine has shown that gliomas associated with epilepsy have a higher concentration of glutamine. This may be of importance since an elevated concentration of glutamine has been shown to be associated with the onset and severity of cobalt-induced epilepsy.
Quantitative determination of the dielectric constant of the interfacial layer in PZT ferroelectric capacitors (2002)

The crystallization of PbZr/sub 0.2/Ti/sub 0.8/O/sub 3/ thin films was investigated by varying the crystallization temperature and time. Some of the films were not fully crystallized presenting amorphous top layers. The films have been structurally characterized by XTEM and XRD, and electrically characterized by hysteresis and CV measurements. The evolution of orientation and crystallization is observed for the different conditions and is correlated with hysteresis loops. The dielectric constant is determined for both the amorphous layers and the crystalline phase, and the CV behavior is explained.
Treecube: visualization tool for browsing 3D multimedia data (2004)

We propose a new 3D visualization tool for hierarchical information. A 2D visualization tool for hierarchical information called treemap has already been proposed by Ben Shneiderman, et al. in 1992. In general, hierarchical information is represented as a tree structure. Treemap hierarchically lays out each node as a bounding box whose size is the same as the specific weight or attribute value of the node. After the original treemap algorithm called slice-and-dice, some extensions to it have been proposed: squarified treemap (M. Buls et al., 2000), ordered treemap (B. Shneiderman et al., 2001) and strip treemap (B.B. Bederson et al., 2002). Furthermore, quantum treemap (B.B. Bederson et al., 2002) is a quantization version of these extensions. We propose a new 3D visualization tool for hierarchical information called treecube that can be taken as a 3D extension of treemap. Especially, we show its usefulness for browsing 3D multimedia data, i.e., 2D images, 3D shape models, motion data, etc., originally stored in a file system.
<i>Mycobacterium bovis</i>BCG Urease Attenuates Major Histocompatibility Complex Class II Trafficking to the Macrophage Cell Surface (2004)

We have previously shown that Mycobacterium tuberculosis attenuates cell surface expression of major histocompatibility complex class II molecules in response to gamma interferon (IFN-gamma) by a mechanism dependent on intracellular sequestration of alpha,beta dimers. In this study we examined whether intracellular alkalinization due to mycobacterial urease could account for the defect in intracellular trafficking of class II molecules. Phagocytosis of wild-type Mycobacterium bovis BCG was associated with secretion of ammonia intracellularly, which increased substantially upon addition of exogenous urea to the culture medium. Increased intracellular ammonia, due to urea degradation by the bacterium, correlated with inhibition of class II surface expression. Conversely, no ammonia was detected in cells infected with a urease-negative mutant strain of M. bovis BCG, which also displayed a reduced effect on surface expression of class II molecules. A direct cause-effect relationship between urease and class II molecule trafficking was established with experiments where cells ingesting beads coated with purified urease showed an increased ammonia level and decreased surface expression of class II in response to IFN-gamma. In contrast to BCG, infection of macrophages with Mycobacterium smegmatis, which expresses relatively greater urease activity in cell-free culture, had a marginal effect on both the intracellular level of ammonia and class II expression. The limited effect of M. smegmatis was consistent with a failure to resist intracellular killing, suggesting that urease alone is not sufficient to resist macrophage microbicidal mechanisms and that this is required for a more distal effect on cell regulation. Our results demonstrate that alkalinization of critical intracellular organelles by pathogenic mycobacteria expressing urease contributes significantly to the intracellular retention of class II dimers.
Pandora's box and the history of the respiratory viruses: a case study of serendipity in research. (1992)

As fastidious human parasites, the respiratory viruses other than influenza viruses have been among the last of the human viruses to be isolated. Their recognition has been dependent upon the evolving technology of cell culture and equally upon a series of fortuitous observations by astute investigators. Adenoviruses were discovered independently by two different groups of scientists, one utilizing explantation of ostensibly normal human tissues and the other recovering virus directly from epidemics of acute disease. In other studies, a technique developed for detection of influenza virus in cell culture led to the discovery of other hemagglutinating viruses, now known as parainfluenza viruses. From such shreds of laboratory evidence, the structural and molecular characteristics of these diverse viruses have been defined, and each in turn has been retrospectively linked to a legacy of previously described clinical syndromes and epidemic patterns. Thus, neither technology or human imagination alone is sufficient for scientific advance, but, when combined, are the essence of scientific discovery.
An Experimental Study of Cavitation in a Mixed Flow Pump Impeller (1960)

A mixed flow impeller design was tested with six, five, and four vanes in a closed water loop to study the effects of cavitation on hydraulic performance and the results were compared with the work of other investigators. Two idealized flow models for incipient cavitation were derived to illustrate limits of cavitation design. It was found that both vane blockage and solidity effects are important when designing for optimum cavitation performance. Data showing incidence and speed effects plus the tip static pressure profiles in cavitating and noncavitating flow are also presented.