gebhart/patrepeval huggingface dataset:
Metformin and its Liver Targets in the Treatment of Type 2 Diabetes (2003)

Although a number of assessments disagree, the preponderance of the evidence indicates that the major therapeutic action of metformin in type 2 diabetes (DM2) is on the liver, and glucose production (EGP) in particular. At the level of this organ, the actions of metformin can be characterized as pleiotropic. The major questions addressed here are therefore: (i) the methodological aspects of the determination of glucose fluxes: when glucose production is not found to be elevated in type 2 diabetes, it is not surprising that little action of metformin on this flux is found. The issues of populations examined, experimental protocols, and quantitative methods of flux determination are important in answering this question. Early morning EGP is increased and constitutes a valid target for metformin. (ii) the multiple targets of metformin: metformin acts at a number of sites and interacts with metabolites and hormones. Some of these actions may be expressed at different doses. Although their net effect is therapeutic, not all are oriented towards lowering hyperglycemia, perhaps explaining the more modest effect of this drug than could be anticipated from individual actions. Sites of metformin action can therefore be considered as a compilation of valid therapeutic targets in DM2. Gluconeogenesis, glycogenolysis and glycogen synthesis can be altered by metformin, although in vivo, this also depends on the methodology. Component processes from substrate supply and liver uptake, through a number of glucogenic enzymes, as well as glycogen synthase and phosphorylase have all been shown to be affected. (iii) unifying concepts: reported actions of metformin on the mitochondrial respiratory chain, free fatty acid metabolism, AMP-activated protein kinase, and on membrane proteins directly may all explain subsets of actions that are seen, providing more integrated targets for consideration in the therapy of DM2.
A Single-Phase Photovoltaic Inverter Topology With a Series-Connected Energy Buffer (2013)

Module integrated converters (MICs) have been under rapid development for single-phase grid-tied photovoltaic applications. The capacitive energy storage implementation for the double-line-frequency power variation represents a differentiating factor among existing designs. This paper introduces a new topology that places the energy storage block in a series-connected path with the line interface block. This design provides independent control over the capacitor voltage, soft-switching for all semiconductor devices, and the full four-quadrant operation with the grid. The proposed approach is analyzed and experimentally demonstrated.
Biochemical Characterization of the Catalytic Domain of Human Matrix Metalloproteinase 19 (2000)

We have recently cloned MMP-19, a novel matrix metalloproteinase, which, due to unique structural features, was proposed to represent the first member of a new MMP subfamily (Pendás, A. M., Knäuper, V. , Puente, X. S., Llano, E., Mattei, M. G., Apte, S., Murphy, G., and López-Otin, C. (1997) J. Biol. Chem. 272, 4281-4286). A recombinant COOH-terminal deletion mutant of MMP-19 (proDelta(260-508)MMP-19), comprising the propeptide and the catalytic domain, was expressed in Escherichia coli, refolded, and purified. Interestingly, we found that proDelta(260-508)MMP-19 has the tendency to autoactivate, whereby the Lys(97)-Tyr(98) peptide bond is hydrolyzed, resulting in free catalytic domain. Mutation of two residues (Glu(88) --> Pro and Pro(90) --> Val) within the propeptide latency motif did not prevent autoactivation but the autolysis rate was somewhat reduced. Analysis of the substrate specificity revealed that the catalytic domain of MMP-19 was able to hydrolyze the general MMP substrate Mca-Pro-Leu-Gly-Dpa-Ala-Arg-NH(2) and, with higher efficiency, the stromelysin substrate Mca-Pro-Leu-Ala-Nva-Dpa-Ala-Arg-NH(2). Kinetic analysis of the interactions of the catalytic domain of MMP-19 with the natural MMP inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), showed strong inhibition using TIMP-2, TIMP-3, and TIMP-4, while TIMP-1 was less efficient. We also demonstrated that synthetic hydroxamic acid-based compounds efficiently inhibited the enzyme. The catalytic domain of MMP-19 was able to hydrolyze the basement membrane components type IV collagen, laminin, and nidogen, as well as the large tenascin-C isoform, fibronectin, and type I gelatin in vitro, suggesting that MMP-19 is a potent proteinase capable of hydrolyzing a broad range of extracellular matrix components. Neither the catalytic domain nor the full-length MMP-19 was able to degrade triple-helical collagen. Finally, and in contrast to studies with other MMPs, MMP-19 catalytic domain was not able to activate any of the latent MMPs tested in vitro.
CSF1 Receptor Targeting in Prostate Cancer Reverses Macrophage-Mediated Resistance to Androgen Blockade Therapy (2015)

Growing evidence suggests that tumor-associated macrophages (TAM) promote cancer progression and therapeutic resistance by enhancing angiogenesis, matrix-remodeling, and immunosuppression. In this study, prostate cancer under androgen blockade therapy (ABT) was investigated, demonstrating that TAMs contribute to prostate cancer disease recurrence through paracrine signaling processes. ABT induced the tumor cells to express macrophage colony-stimulating factor 1 (M-CSF1 or CSF1) and other cytokines that recruit and modulate macrophages, causing a significant increase in TAM infiltration. Inhibitors of CSF1 signaling through its receptor, CSF1R, were tested in combination with ABT, demonstrating that blockade of TAM influx in this setting disrupts tumor promotion and sustains a more durable therapeutic response compared with ABT alone.
Replication of plasmids in gram-negative bacteria (1989)

Replication of plasmid deoxyribonucleic acid (DNA) is dependent on three stages: initiation, elongation, and termination. The first stage, initiation, depends on plasmid-encoded properties such as the replication origin and, in most cases, the replication initiation protein (Rep protein). In recent years the understanding of initiation and regulation of plasmid replication in Escherichia coli has increased considerably, but it is only for the ColE1-type plasmids that significant biochemical data about the initial priming reaction of DNA synthesis exist. Detailed models have been developed for the initiation and regulation of ColE1 replication. For other plasmids, such as pSC101, some hypotheses for priming mechanisms and replication initiation are presented. These hypotheses are based on experimental evidence and speculative comparisons with other systems, e.g., the chromosomal origin of E. coli. In most cases, knowledge concerning plasmid replication is limited to regulation mechanisms. These mechanisms coordinate plasmid replication to the host cell cycle, and they also seem to determine the host range of a plasmid. Most plasmids studied exhibit a narrow host range, limited to E. coli and related bacteria. In contrast, some others, such as the IncP plasmid RK2 and the IncQ plasmid RSF1010, are able to replicate in nearly all gram-negative bacteria. This broad host range may depend on the correct expression of the essential rep genes, which may be mediated by a complex regulatory mechanism (RK2) or by the use of different promoters (RSF1010). Alternatively or additionally, owing to the structure of their origin and/or to different forms of their replication initiation proteins, broad-host-range plasmids may adapt better to the host enzymes that participate in initiation. Furthermore, a broad host range can result when replication initiation is independent of host proteins, as is found in the priming reaction of RSF1010.
Tamoxifen in the Treatment of Breast Cancer (1998)

Breast cancer is the most common cancer in women in the Western world. Because breast cancer is estrogen-dependent, reducing estrogen secretion by oophorectomy, hypophysectomy, or adrenalectomy can cause the cancer to regress. The need for these surgical procedures was reduced by the introduction of tamoxifen, which acts as an antiestrogen by inhibiting the binding of estrogen to estrogen receptors. Tamoxifen was approved by the Food and Drug Administration in 1977 for the treatment of women with advanced breast cancer and several years later for adjuvant treatment of primary breast cancer.1 Pharmacology and EndocrinologyPharmacologic and Pharmacokinetic PropertiesThe compound administered . . .
Model-Based Shape Estimation for Soft Robotic Manipulators: The Planar Case (2013)

Soft robotic manipulators are continuum robots made of soft materials that undergo continuous elastic deformation and produce motion with a smooth backbone curve. In many applications, these manipulators offer significant advantages over traditional manipulators due to their ability to conform to their surroundings, and manipulate objects of widely varying size using whole arm manipulation. Theoretically, soft robots have infinite degrees of freedom (DOF), but the number of sensors and actuators are limited. Many DOFs of soft robots are not directly observable and/or controllable, complicating shape estimation and control. In this paper, we present three methods of shape sensing for soft robotic manipulators based on a geometrically exact mechanical model. The first method uses load cells mounted at the base of the manipulator, the second method makes use of cable encoders running through the length of the manipulator, and the third method uses inclinometers mounted at the end of each section of the manipulator. Simulation results show an endpoint localization error of less than 3% of manipulator length with typical sensors. The methods are validated experimentally on the OctArm VI manipulator.
A heartbeat mechanism and its application in gigascope (2005)

Data stream management systems often rely on ordering properties of tuple attributes in order to implement non-blocking operators. However, query operators that work with multiple streams, such as stream merge or join, can often still block if one of the input stream is very slow or bursty. In principle, punctuation and heartbeat mechanisms have been proposed to unblock streaming operators. In practice, it is a challenge to incorporate such mechanisms into a highperformance stream management system that is operational in an industrial application. In this paper, we introduce a system for punctuation-carrying heartbeat generation that we developed for Gigascope, a high-performance streaming database for network monitoring, that is operationally used within AT&amp;amp;T&amp;apos;s IP backbone. We show how heartbeats can be regularly generated by low-level nodes in query execution plans and propagated upward unblocking all streaming operators on its way. Additionally, our heartbeat mechanism can be used for other applications in distributed settings such as detecting node failures, performance monitoring, and query optimization. A performance evaluation using live data feeds shows that our system is capable of working at multiple Gigabit line speeds in a live, industrial deployment and can significantly decrease the query memory utilization.
Function minimization on special computers (1980)

For the purposes of discussion, a special computer will be taken to be one in which it is not possible to employ standard mathematical software libraries. Thus we are concerned with the ubiquitous personal computers, various array or pipeline machines, and some mini and micro computers primarily destined to tasks other than general purpose computing (e.g. control applications).
Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer (2007)

This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.
Author Index for Volumes 1-5 (1993)

No abstract available for this article.
Palladium-Catalyzed Reaction of 2-Hydroxyaryl and Hydroxyheteroaryl Halides with 1-Alkynes: An Improved Route to the Benzo[b]furan Ring System (1986)

The reaction of 2-hydroxyaryl and hydroxyheteroaryl halides with a variety of 1-alkynes in the presence of a base, bis[triphenyl-phosphine]-palladium(II) diacetate, and copper(I) iodide at room temperature or 60°C produces 2-substituted benzo[b]furans, usually in good yield.
CaM kinase augments cardiac L-type Ca2+current: a cellular mechanism for long Q-T arrhythmias (1999)

Early afterdepolarizations (EAD) caused by L-type Ca2+ current (ICa, L) are thought to initiate long Q-T arrhythmias, but the role of intracellular Ca2+ in these arrhythmias is controversial. Rabbit ventricular myocytes were stimulated with a prolonged EAD-containing action potential-clamp waveform to investigate the role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase) in ICa,L during repolarization. ICa,L was initially augmented, and augmentation was dependent on Ca2+ from the sarcoplasmic reticulum because the augmentation was prevented by ryanodine or thapsigargin. ICa,L augmentation was also dependent on CaM kinase, because it was prevented by dialysis with the inhibitor peptide AC3-I and reconstituted by exogenous constitutively active CaM kinase when Ba2+ was substituted for bath Ca2+. Ultrastructural studies confirmed that endogenous CaM kinase, L-type Ca2+ channels, and ryanodine receptors colocalized near T tubules. EAD induction was significantly reduced in current-clamped cells dialyzed with AC3-I (4/15) compared with cells dialyzed with an inactive control peptide (11/15, P = 0.013). These findings support the hypothesis that EADs are facilitated by CaM kinase.
Identification and purification of a cpn60 heat shock protein homolog from Helicobacter pylori (1992)

Helicobacter pylori is associated with gastritis and peptic ulcer disease in humans. We have identified a homolog of the chaperonin cpn60 family of heat shock proteins in H. pylori, referred to as Hp54K. Hp54K, purified from water-extractable H. pylori proteins, migrated as a single band at 54 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its native molecular mass was 740 kDa; thus, Hp54K apparently comprises a 14-mer. The N-terminal 33 residues of Hp54K exhibited 60.6, 57.6, 54.5, 54.5, 51.5, and 51.5% identity with corresponding sequences in the following cpn60 homologs: HtpB (Legionella pneumophila), P1 (human mitochondria), GroEL (Escherichia coli), BA60K (Brucella abortus), HypB (Chlamydia trachomatis), and the 65-kDa immunodominant protein of Mycobacterium bovis BCG, respectively. Hp54K was the only protein recognized in whole-cell preparations of H. pylori by immunoblotting using monospecific antisera against cpn60 homologs from L. pneumophila, E. coli, C. trachomatis, and M. bovis BCG. Antiserum against Hp54K recognized proteins with molecular masses of 50 to 60 kDa in a large number of gram-negative bacteria, consistent with the known highly conserved nature of cpn60 proteins. Hp54K is a major protein and is immunogenic in humans infected with H. pylori. Thus, Hp54K shares many similarities with known cpn60 homologs. On the basis of the proposed role of other cpn60 proteins in induction of chronic inflammation, immune cross-reactivity between Hp54K and gastric tissue may provide an important link between H. pylori infection and gastritis.
Synthesis and Function of 3-Phosphorylated Inositol Lipids (2001)

The 3-phosphorylated inositol lipids fulfill roles as second messengers by interacting with the lipid binding domains of a variety of cellular proteins. Such interactions can affect the subcellular localization and aggregation of target proteins, and through allosteric effects, their activity. Generation of 3-phosphoinositides has been documented to influence diverse cellular pathways and hence alter a spectrum of fundamental cellular activities. This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles. Much knowledge has recently been gained through structural insights into the lipid kinases, their interaction with inhibitors, and the way their 3-phosphoinositide products interact with protein targets. This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease.
Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas (1996)

A few cases had overlapping alterations, and the incidence of one or more RB, p53, or p16(CDKN2) changes appeared to be relatively high in human astrocytomas. These results suggest that cell cycle regulatory gene alterations may play an important role in the development of gliomas.
Sound onset detection by applying psychoacoustic knowledge (1999)

A system was designed, which is able to detect the perceptual onsets of sounds in acoustic signals. The system is general in regard to the sounds involved and was found to be robust for different kinds of signals. This was achieved without assuming regularities in the positions of the onsets. In this paper, a method is first proposed that can determine the beginnings of sounds that exhibit onset imperfections, i.e., the amplitude envelope of which does not rise monothinically. Then the mentioned system is described, which utilizes band-wise processing and a psychoacoustic model of intensity coding to combine the results from the separate frequency bands. The performance of the system was validated by applying it to the detection of onsets in musical signals ranging from rock to classical and big band recordings.
IL-2-PE40 is cytotoxic for activated T lymphocytes expressing IL-2 receptors. (1988)

IL-2-PE40 is a chimeric molecule in which IL-2 is attached to the amino end of modified Pseudomonas exotoxin molecule lacking cell recognition domain. This molecule was extremely toxic for Con A-stimulated spleen cells from mice. Moreover, IL-2-PE40 has suppressive effect against Ag-activated cells; it inhibits the generation of cytotoxic T lymphocyte activity in a MLC. IL-2-PE40 could be a useful agent in IL-2R targeting therapy including immunosuppressive therapy for allograft rejection or some autoimmune diseases.
EYES ON THE ROAD : PRIVACY AND ITS (1995)

This article discusses the issue of privacy in Intelligent Transportation Systems (ITS). In particular, it discusses privacy loss that is involved in automated toll collection systems and automatic vehicle identification.
A Role for Triggering Receptor Expressed on Myeloid Cells-1 in Host Defense During the Early-Induced and Adaptive Phases of the Immune Response (2003)

Triggering receptor expressed on myeloid cells (TREM)-1 is a cell surface molecule expressed on neutrophils and monocytes implicated in the propagation of the inflammatory response. To further characterize the function of this molecule in different phases of the immune response, we examined TREM-1 in the context of host defense against microbial pathogens. In primary human monocytes TREM-1 activation did not trigger innate antimicrobial pathways directed against intracellular Mycobacterium tuberculosis, and only minimally improved phagocytosis. However, activation of TREM-1 on monocytes did drive robust production of proinflammatory chemokines such as macrophage inflammatory protein-1alpha and IL-8. Engagement of TREM-1 in combination with microbial ligands that activate Toll-like receptors also synergistically increased production of the proinflammatory cytokines TNF-alpha and GM-CSF, while inhibiting production of IL-10, an anti-inflammatory cytokine. Expression of TREM-1 was up-regulated in response to TLR activation, an effect further enhanced by GM-CSF and TNF-alpha but inhibited by IL-10. Functionally, primary monocytes differentiated into immature dendritic cells following activation through TREM-1, evidenced by higher expression of CD1a, CD86, and MHC class II molecules. These cells had an improved ability to elicit T cell proliferation and production of IFN-gamma. Our data suggest that activation of TREM-1 on monocytes participates during the early-induced and adaptive immune responses involved in host defense against microbial challenges.
B meson decays to final states containing charmonia at LHCb (2013)

LHCb measurements of B mesons containing charmonia in the final state are presented, using data collected during 2010 and 2011. Branching ratios of various B (2S)X and B J/X decays are measured. The values of the polarization amplitudes of the decay B 0 s J/K * 0 are determined the for first time. A Dalitz analysis of B 0 s J/ + -decays allows the determination of the + -resonance structure and the CP content of the decay.
Concept as a Generalization of Class and Principles of the Concept-Oriented Programming (2005)

In the paper we describe a new construct which is referred to as concept and a new concept-oriented approach to program-ming. Concept generalizes conventional classes and consists of two parts: an objects class and a reference class. Each concept has a parent concept specified via inclusion relation. Instances of reference class are passed by value and are intended to rep-resent instances of child object classes. The main role of con-cepts consists in indirecting object representation and access. In concept-oriented programming it is assumed that a system con-sists of (i) conventional target business methods (BMs), and (ii) hidden representation and access (RA) methods. If conventional classes are used to describe only BMs then concepts allow the programmer to describe both types of functionality including its hidden intermediate functions which are automatically executed when objects are being accessed.
Cell-Specific Delivery of Diverse Cargos by Bacteriophage MS2 Virus-like Particles (2011)

Virus-like particles (VLPs) of bacteriophage MS2 possess numerous features that make them well-suited for use in targeted delivery of therapeutic and imaging agents. MS2 VLPs can be rapidly produced in large quantities using in vivo or in vitro synthesis techniques. Their capsids can be modified in precise locations via genetic insertion or chemical conjugation, facilitating the multivalent display of targeting ligands. MS2 VLPs also self-assemble in the presence of nucleic acids to specifically encapsidate siRNA and RNA-modified cargos. Here we report the use of MS2 VLPs to selectively deliver nanoparticles, chemotherapeutic drugs, siRNA cocktails, and protein toxins to human hepatocellular carcinoma (HCC). MS2 VLPs modified with a peptide (SP94) that binds HCC exhibit a 10(4)-fold higher avidity for HCC than for hepatocytes, endothelial cells, monocytes, or lymphocytes and can deliver high concentrations of encapsidated cargo to the cytosol of HCC cells. SP94-targeted VLPs loaded with doxorubicin, cisplatin, and 5-fluorouracil selectively kill the HCC cell line, Hep3B, at drug concentrations <1 nM, while SP94-targeted VLPs that encapsidate a siRNA cocktail, which silences expression of cyclin family members, induce growth arrest and apoptosis of Hep3B at siRNA concentrations <150 pM. Impressively, MS2 VLPs, when loaded with ricin toxin A-chain (RTA) and modified to codisplay the SP94 targeting peptide and a histidine-rich fusogenic peptide (H5WYG) that promotes endosomal escape, kill virtually the entire population of Hep3B cells at an RTA concentration of 100 fM without affecting the viability of control cells. Our results demonstrate that MS2 VLPs, because of their tolerance of multivalent peptide display and their ability to specifically encapsidate a variety of chemically disparate cargos, induce selective cytotoxicity of cancer in vitro and represent a significant improvement in the characteristics of VLP-based delivery systems.