gebhart/patrepeval huggingface dataset:
Suppression of Human T-Cell Responses to β-Cells by Activation of B7-H4 Pathway (2006)

B7-H4, a recently described member of the B7 family of cosignal molecules, is thought to be involved in the regulation of cellular and humoral immune responses through receptors on activated T and B cells. Human islet cells express positive B7-H4 mRNA in RT-PCR assays, but not B7-H4 protein on cell surface in flow cytometric analyses. To investigate the regulatory effects of activation of the B7-H4 pathway on the function of activated T cells of patients with type 1 diabetes (T1D), we have used our in vitro human experimental system, including human β-cell antigen-specific T-cell clones and human β-cell lines CM and HP62, as well as primary islet cells. B7-H4.Ig protein was purified from the culture supernatant of 293T cells transfected by a B7-H4.Ig plasmid (pMIgV, containing a human B7-H4 cDNA and a mouse IgG2a Fc cDNA). Our preliminary studies showed that immobilized fusion protein human B7-H4.Ig (coated with 5 μg/ml for 2 h at 37°C), but not control Ig, clearly inhibited the proliferation of activated CD4+ and CD8+ T cells of patients induced by anti-CD3 antibody in CFSE assays. B7-H4.Ig also arrested cell cycle progression of T cells in G<sub>0</sub>/G1 phase and induced T-cell apoptosis as measured by BrdU-7-AAD flow cytometric analysis. To determine the cytoprotective effects of B7-H4, we developed transfectants of human β-cell lines CM and HP62 and islet cells transfected with the B7-H4.Ig plasmid, using empty vector transfectants as controls. The results demonstrate that cell-associated B7-H4.Ig expressed on human β-cells clearly inhibits the cytotoxicity of the T-cell clones to targeted human β-cells in 51Cr release cytotoxicity assays. Activation of the B7-H4 pathway may represent a novel immunotherapeutic approach to inhibit T-cell responses for the prevention of β-cell destruction in T1D.
Insulin, blood glucose levels, and ischemic brain damage (1998)

Intensive efforts are presently directed toward developing pharmacologic therapy to protect the ischemic brain. Preclinical data from animal models indicate that insulin, already available for human use, may reduce damage in both global and focal ischemia. Two kinds of mechanisms may be involved: one in which insulin interacts directly with brain tissue and one in which insulin acts indirectly by reducing peripheral blood glucose levels. Animal data indicate that part of the former, direct mechanism is mediated by insulin-like growth factor-1 receptors. The direct effect appears to predominate in global ischemia. In focal ischemia, unlike global ischemia, the effect of insulin is predominantly via peripheral hypoglycemia, because neuroprotection is largely annulled by co-administration of glucose. The two clinical counterparts of global and focal ischemic models are, respectively, cardiac arrest encephalopathy and focal ischemic stroke. Insulin use in both of these clinical situations could be evaluated in clinical trials that attempt to reduce ischemic brain damage, because insulin has a long and safe history of human use in diabetes treatment.
A monolithic CMOS 10 MHz DPLL for burst-mode data retiming (1990)

A first-order digital phase locked loop (DPLL) that can acquire phase lock from the highly jittered preamble of a burst-mode, Manchester-coded, 10-Mb/s data packet using information acquired from only three transistors is described. A 16-stage delay line locked to a 10-MHz reference clock is embedded in the DPLL. This allows 3.125-ns phase steps to be generated without a high-speed clock. Implemented in a 1.75- mu m CMOS technology, the DPLL circuit occupies 4 mm/sup 2/ of silicon and consumes 125 mW from a 5-V supply.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cell Adhesion Mechanisms in Platelets (2008)

At sites of vascular injury, platelets come into contact with the subendothelial extracellular matrix which triggers their activation and the formation of a hemostatic plug. This process is crucial for normal hemostasis, but may also lead to pathological thrombus formation causing diseases such as myocardial infarction or stroke. The initial capture of flowing platelets is mediated by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor (vWF) immobilized on exposed collagens. This interaction allows the binding of the collagen receptor GPVI to its ligand and to initiate cellular activation, a process that is reinforced by locally produced thrombin and soluble mediators released from platelets. These events lead to the shift of β1 and β3 integrins on the platelet surface from a low to a high affinity state, thereby enabling them to bind their ligands and to mediate firm adhesion, spreading, coagulant activity, and aggregation. This review summarizes the most important structu...
AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling (2007)

The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. In certain cells (eg, neurones, endothelial cells, and lymphocytes), AMPK can also be activated by a Ca(2+)-dependent and AMP-independent process involving phosphorylation by an alternate upstream kinase, CaMKKbeta. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation. The AMPK complex contains 3 subunits, with the alpha subunit being catalytic, the beta subunit containing a glycogen-sensing domain, and the gamma subunits containing 2 regulatory sites that bind the activating and inhibitory nucleotides AMP and ATP. Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level. The AMPK system may be partly responsible for the health benefits of exercise and is the target for the antidiabetic drug metformin. It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome.
Flexible Full-Color AMOLED on Ultrathin Metal Foil (2007)

Full-color active-matrix organic light-emitting diode panels, driven by poly-Si thin-film transistors (poly-Si TFTs), were successfully fabricated on thin metal foil substrates. The p-channel poly-Si TFTs on metal foil showed a field-effect mobility of 82.9 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /Vmiddots, subthreshold slope of 0.34 V/dec, threshold voltage of -1.67 V, and off-current of 6.6times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-14</sup> A/mum. The 5.6-in panel had 160 times RGB times 350 pixels, each of which had a pixel circuit of two TFTs and one capacitor
Polymeric Nanocarriers: New Endeavors for the Optimization of the Technological Aspects of Drugs (2008)

Drug low solubility and stability in physiological environment constitutes a main hurdle in attaining the appropriate bioavailability. Several polymer-based nanotechnologies are being intended in order to optimize the technological (e.g., solubility, stability, bioavailability, etc.) aspects of drugs. Among them, polymeric nanoparticles, dendrimers, polymeric micelles and polymersomes appear as the most attractive and promising. Concomitant with efforts in the academic arena that aim at overcoming these drawbacks and, strongly motivated by a constant search for innovative therapeutic strategies, a very rich intellectual property has been produced in the last years. This phenomenon has been moved forward by the fact that aiming at registering off-patent or about to be off patent products, pharmaceutical companies develop new formulations of old products. Another ambit of research is the design of more sophisticated drug delivery devices (e.g., targeting, localized delivery) in order to minimize adverse effects that make the administration of certain drugs risky or to enhance the patient compliance. A recent report by Cientifica Ltd. foresees a critical expansion in the nano-based drug delivery market from its current $3.4B (about 10% of the total drug delivery market) to about $26B by 2012, being this only a promising beginning for the $220B forecasted by 2015. Given the present circumstances, we are probably witnessing a new revolution in therapeutics that will take treatment to a different dimension. The goal of the present review is to provide a comprehensive and updated patent compilation of the most recent inventions relying on polymer-based nanoparticulated carriers (polymeric nanoparticles, dendrimers, polymeric micellles and polymersomes) for the optimization of the technological aspects of therapeutic agents. This article also includes a thorough review of the patents made public in recent years (2003-2007). Keywords: Pharmaceutical nanotechnology, polymeric nanocarriers, polymeric nanoparticles, dendrimers, polymeric micelles, polymersomes, drug solubilization and stabilization, enhanced bioavailability
β-adrenergic Receptor Polymorphisms and Responses during Titration of Metoprolol Controlled Release/extended Release in Heart Failure* (2005)

Patients with the Gly389 variant and Ser49Ser genotype were significantly more likely to require increases in heart failure medications during beta-blocker titration and thus may require more frequent follow-up during titration.
Evidence That Apolipoprotein A-I Milano Has Reduced Capacity, Compared With Wild-Type Apolipoprotein A-I, to Recruit Membrane Cholesterol (1997)

Human carriers of apolipoprotein (apo) A-IMilano are heterozygous for an Arg173-->Cys substitution in the apoA-I primary sequence; despite severe reductions in HDL cholesterol concentrations, affected individuals do not develop coronary heart disease, suggesting that apoA-IMilano may possess antiatherogenic properties. As the beneficial effects of wild-type apoA-I are linked to its role in HDL cholesterol transport, we examined the capacity of apoA-IMilano to recruit cell cholesterol and activate lecithin:cholesterol acyltransferase (LCAT) (two key events in the antiatherogenic reverse cholesterol transport pathway). ApoA-IMilano and wild-type apoA-I were expressed in Chinese hamster ovary cells, and their ability to recruit membrane phospholipid and cholesterol for the assembly of nascent HDL was compared. Both clonal cell lines exhibited similar levels of apolipoprotein accumulation in serum-free medium (approximately 2 micrograms/mg cell protein per 24 hours), and 15% of each apolipoprotein was associated with membrane lipids to form nascent HDL (d = 1.063 to 1.21 g/mL). SDS-PAGE showed that a majority (66 +/- 12%) of the lipidated apoA-IMilano was in the homodimer form. Compositional analyses revealed that apoA-IMilano nascent HDL had a significantly lower (P < .001) unesterified cholesterol/phospholipid mole ratio (0.47 +/- 0.10) than wild-type apoA-I complexes (1.29 +/- 0.14), indicating that apoA-IMilano had a reduced capacity to recruit cell cholesterol. In addition to the reduced unesterified cholesterol/phospholipid ratio, apoA-IMilano nascent HDL consisted mostly of small 7.4-nm particles compared with wild-type apoA-I, in which 11- and 9-nm particles predominated. Despite these changes in nascent HDL particle size and composition, apoA-IMilano activated LCAT normally. We conclude that, even though apoA-IMilano is a normal activator of LCAT, it is less efficient that wild-type apoA-I in recruiting cell cholesterol, suggesting that the putative antiatherogenic properties attributed to apoA-IMilano may be unrelated to the initial stages of reverse cholesterol transport.
Synthesis of Electroluminescent Polymer Containing Charge Transport and Emissive Chromophores on Polymer Skeleton (1995)

Abstract Electroluminescent polymer with a distyrylbenzene unit as an emissive group and a triphenylamine unit as a charge transporting group on polymer backbone was designed and synthesized. A single-layer device was composed of ITO/electroluminescent polymer/MgAg, and the polymer layer was fabricated using a spin-coating method. Greenish blue electroluminescence was observed with an emission maximum at 488 nm. Maximum brightness of 22 cd/m2 was observed at a current density of 88 mA/cm2 under drive voltage of 28 V.
Synthesis and Characterization of Macrocyclic Polyaza(2,5)pyridinophanes Possessing Vitamin B6 Functionality (1986)

Abstract Series of macrocyclic polyaza[m](2,5)pyridinophanes (poly=tri, tetra, penta; m=9, 12, 15)(8–10) and polyaza[m]paracyclophanes (11–13) were synthesized in excellent yields by the reaction of dichloropyridoxine derivatives (4) and α,α′-dibromo-p-xylene (5), respectively, with a series of 1,2-ethanediamine derivatives (1–3). These phanes were characterized on the basis of 1H NMR spectra. The methyl group at C6 of the pyridoxine moiety (a-series) revealed restricted rotation for all bridge sizes (m=9–15). In 8–10 without the methyl group (b-series), m=12 was the boundary between restricted and free rotation. In series 11–13, only 11 (m=9) showed restricted rotation. Atomic group equivalence was discussed in terms of boundary restricted rotation and an empirical rule for the prediction of the relationship between the bridge size and restricted rotation was proposed.
Detailed characterization of a quad Pentium Pro server running TPC-D (2003)

While database workloads consume a major fraction of the cycles in today's machines, there are only a few public-domain performance studies that characterize in detail how these workloads exercise the machines. This fact is due to the complexity of setting up and tuning database workloads, the high cost of the equipment required to evaluate them, and the frequent use of proprietary systems. In this paper, we help redress this problem by presenting a detailed performance characterization of the TPC-D benchmark running on a 4-processor Pentium Pro SMP multiprocessor with Windows NT and Microsoft's SQL Server. We use the Pentium Pro built-in hardware event counters and software tools that monitor system activity. Our results show that TPC-D queries have a relatively low CPI. The CPIs, which are 1.27 on average for the 17 read-only queries, are comparable to values observed for technical workloads. The major sources of processor stall cycles are the instruction fetch bottleneck and data misses in the secondary cache. Kernel time is negligible, as queries spend less than 6% of their time on average in the kernel. Other results show that branch prediction is effective in TPC-D and that the exclusive state in the cache tags is largely unnecessary. Finally, we compare our results to the ones published for TPC-C.
Laron Syndrome (1993)

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A Statistical Approach Reveals Designs for the Most Robust Stochastic Gene Oscillators (2016)

The engineering of transcriptional networks presents many challenges due to the inherent uncertainty in the system structure, changing cellular context, and stochasticity in the governing dynamics. One approach to address these problems is to design and build systems that can function across a range of conditions; that is they are robust to uncertainty in their constituent components. Here we examine the parametric robustness landscape of transcriptional oscillators, which underlie many important processes such as circadian rhythms and the cell cycle, plus also serve as a model for the engineering of complex and emergent phenomena. The central questions that we address are: Can we build genetic oscillators that are more robust than those already constructed? Can we make genetic oscillators arbitrarily robust? These questions are technically challenging due to the large model and parameter spaces that must be efficiently explored. Here we use a measure of robustness that coincides with the Bayesian model evidence, combined with an efficient Monte Carlo method to traverse model space and concentrate on regions of high robustness, which enables the accurate evaluation of the relative robustness of gene network models governed by stochastic dynamics. We report the most robust two and three gene oscillator systems, plus examine how the number of interactions, the presence of autoregulation, and degradation of mRNA and protein affects the frequency, amplitude, and robustness of transcriptional oscillators. We also find that there is a limit to parametric robustness, beyond which there is nothing to be gained by adding additional feedback. Importantly, we provide predictions on new oscillator systems that can be constructed to verify the theory and advance design and modeling approaches to systems and synthetic biology.
Therapeutic approaches for tumor necrosis factor inhibition (2011)

Tumor necrosis factor (TNF) consists of an inflammatory cytokine essential for homeostasis and organism defense. Despite its physiological relevance, both increased biosynthesis and release of TNF lead to the exacerbation of inflammatory and oxidative responses, which are related to the pathogenesis of a host of diseases of an inflammatory, autoimmune and/or infectious nature. In this context, effective therapeutic approaches for the modulation of TNF have been the focus of research efforts. Approximately one million individuals worldwide have been treated with biotechnological inhibitors of this cytokine, the so-called anti-TNF biopharmaceuticals. However, given the high risk of infection and the limitations related to cost and administration routes, new therapeutic approaches aimed at biological targets that directly or indirectly modulate the production and/or activation of TNF appear promising alternatives for the discovery of new anti-inflammatory and immunomodulatory orally active drugs and are therefore discussed in this paper.
Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. (1999)

Telomerase-negative immortalized human cells maintain their telomeres by a mechanism known as alternative lengthening of telomeres (ALT). We report here that ALT cells contain a novel promyelocytic leukemia (PML) body (ALT-associated PML body, APB). APBs are large donut-shaped nuclear structures containing PML protein, telomeric DNA, and the telomere binding proteins human telomere repeat binding factors 1 and 2. Immunostaining showed that APBs also contain replication factor A, RAD51, and RAD52, proteins involved in DNA synthesis and recombination. During immortalization, APBs appeared at exactly the same time as activation of ALT. APBs were found in ALT tumors and cell lines but not in mortal cell strains or in telomerase-positive cell lines or tumors.
Ad hoc positioning system (APS) (2002)

Many ad hoc network protocols and applications assume the knowledge of geographic location of nodes. The absolute location of each networked node is an assumed fact by most sensor networks which can then present the sensed information on a geographical map. Finding location without the aid of GPS in each node of an ad hoc network is important in cases where GPS is either not accessible, or not practical to use due to power, form factor or line of sight conditions. Location would also enable routing in sufficiently isotropic large networks, without the use of large routing tables. We are proposing APS - a distributed, hop by hop positioning algorithm, that works as an extension of both distance vector routing and GPS positioning in order to provide approximate location for all nodes in a network where only a limited fraction of nodes have self location capability.
Enzymatic breakage and joining of deoxyribonucleic acid, I. Repair of single-strand breaks in DNA by an enzyme system from Escherichia coli infected with T4 bacteriophage. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Wearable computing and contextual awareness (1999)

Computer hardware continues to shrink in size and increase in capability. This trend has allowed the prevailing concept of a computer to evolve from the mainframe to the minicomputer to the desktop. Just as the physical hardware changes, so does the use of the technology, tending towards more interactive and personal systems. Currently, another physical change is underway, placing computational power on the user&amp;apos;s body. These wearable machines encourage new applications that were formerly infeasible and, correspondingly, will result in new usage patterns. This thesis suggests that the fundamental improvement offered by wearable computing is an increased sense of user context. I hypothesize that on-body systems can sense the user&amp;apos;s context with little or no assistance from environmental infrastructure. These body-centered systems that &amp;quot;see&amp;quot; as the user sees and &amp;quot;hear&amp;quot; as the user hears, provide a unique &amp;quot;first-person&amp;quot; viewpoint of the user&amp;apos;s environment. By exploiting models recovered ...
Carbon Nanotube Complementary Wrap-Gate Transistors (2013)

Among the challenges hindering the integration of carbon nanotube (CNT) transistors in digital technology are the lack of a scalable self-aligned gate and complementary n- and p-type devices. We report CNT transistors with self-aligned gates scaled down to 20 nm in the ideal gate-all-around geometry. Uniformity of the gate wrapping the nanotube channels is confirmed, and the process is shown not to damage the CNTs. Further, both n- and p-type transistors were realized by using the appropriate gate dielectric-HfO2 yielded n-type and Al2O3 yielded p-type-with quantum simulations used to explore the impact of important device parameters on performance. These discoveries not only provide a promising platform for further research into gate-all-around CNT devices but also demonstrate that scalable digital switches with realistic technological potential can be achieved with carbon nanotubes.