gebhart/patrepeval huggingface dataset:
A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes. (2000)

Type 2 diabetes is a polygenic disease characterized by defects in both insulin secretion and insulin action. We have previously reported that isolated insulin resistance in muscle by a tissue-specific insulin receptor knockout (MIRKO mouse) is not sufficient to alter glucose homeostasis, whereas beta-cell-specific insulin receptor knockout (betaIRKO) mice manifest severe progressive glucose intolerance due to loss of glucose-stimulated acute-phase insulin release. To explore the interaction between insulin resistance in muscle and altered insulin secretion, we created a double tissue-specific insulin receptor knockout in these tissues. Surprisingly, betaIRKO-MIRKO mice show an improvement rather than a deterioration of glucose tolerance when compared to betaIRKO mice. This is due to improved glucose-stimulated acute insulin release and redistribution of substrates with increased glucose uptake in adipose tissue and liver in vivo, without a significant decrease in muscle glucose uptake. Thus, insulin resistance in muscle leads to improved glucose-stimulated first-phase insulin secretion from beta-cells and shunting of substrates to nonmuscle tissues, collectively leading to improved glucose tolerance. These data suggest that muscle, either via changes in substrate availability or by acting as an endocrine tissue, communicates with and regulates insulin sensitivity in other tissues.
Selection of Potential Markers for Epithelial Ovarian Cancer with Gene Expression Arrays and Recursive Descent Partition Analysis (2004)

Our data are consistent with the possibility that a limited number of markers in combination might identify >99% of epithelial ovarian cancers despite the heterogeneity of the disease.
Creation of Laguerre-Gaussian laser modes using diffractive optics (2002)

Diffractive optics are used to create low- and high-order Laguerre-Gaussian (LG) beams from the output of a diode laser. We examine the mode purities, conversion efficiencies, extinction ratios, and propagation characteristics. We present detailed analyses of the beam profiles for one low-order $({\mathrm{LG}}_{0}^{1})$ and one high-order $({\mathrm{LG}}_{1}^{2})$ Laguerre-Gaussian mode. Modeling the ${\mathrm{LG}}_{1}^{2}$ beam as a superposition of LG modes, we find $(99.3\ifmmode\pm\else\textpm\fi{}0.9%)$ of the laser intensity in the ${\mathrm{LG}}_{1}^{2}$ mode, a mode purity greater than for LG beams created by other methods external to the laser cavity. The high mode purity may be useful in making atom traps for precision measurements and for Bose-Einstein condensation.
New Ancillary Services Using a Television Channel (1977)

A data-broadcasting system implemented in France by the CCETT is discussed. Employing an ordinary television channel, the system provides at least three new ancillary services, and more are under development. The first service accomplishes the automatic recording of preselected programs for any user with a keypad, memory unit and VTR; the second provides scrambling and unscrambling of a television signal as for pay TV and theater projection; and the third uses the ANTIOPE teletext system to transmit “magazines” in page form to the home viewer. If the teletext system uses time-division multiplexing with an ordinary program, subtitling in any of several languages is possible along with transmission on request of special news-flash pages. Otherwise, when magazine pages only are transmitted on the channel, a page rate of about 20,000 per minute (24 lines of 40 characters each) is possible.
Convergent scheduling (2002)

Convergent scheduling is a general framework for cluster assignment and instruction scheduling on spatial architectures. A convergent scheduler is composed of independent passes, each implementing a heuristic that addresses a particular problem or constraint. The passes share a simple, common interface that provides spatial and temporal preference for each instruction. Preferences are not absolute; instead, the interface allows a pass to express the confidence of its preferences, as well as preferences for multiple space and time slots. A pass operates by modifying these preferences. By applying a series of passes that address all the relevant constraints, the convergent scheduler can produce a schedule that satisfies all the important constraints. Because all passes are independent and need to understand only one interface to interact with each other, convergent scheduling simplifies the problem of handling multiple constraints and co-developing different heuristics. We have applied convergent scheduling to two spatial architectures: the Raw processor and a clustered VLIW machine. It is able to successfully handle traditional constraints such as parallelism, load balancing, and communication minimization, as well as constraints due to preplaced instructions, which are instructions with predetermined cluster assignment. Convergent scheduling is able to obtain an average performance improvement of 21% over the existing space-time scheduler of the Raw processor, and an improvement of 14% over state-of-the-art assignment and scheduling techniques on a clustered VLIW architecture.
Secondary Prevention by Raising HDL Cholesterol and Reducing Triglycerides in Patients With Coronary Artery Disease (2000)

Bezafibrate was safe and effective in elevating HDL-C levels and lowering triglycerides. An overall trend in a reduction of the incidence of primary end points was observed. The reduction in the primary end point in patients with high baseline triglycerides (> or =200 mg/dL) requires further confirmation.
Particle filters for positioning, navigation, and tracking (2002)

A framework for positioning, navigation, and tracking problems using particle filters (sequential Monte Carlo methods) is developed. It consists of a class of motion models and a general nonlinear measurement equation in position. A general algorithm is presented, which is parsimonious with the particle dimension. It is based on marginalization, enabling a Kalman filter to estimate all position derivatives, and the particle filter becomes low dimensional. This is of utmost importance for high-performance real-time applications. Automotive and airborne applications illustrate numerically the advantage over classical Kalman filter-based algorithms. Here, the use of nonlinear models and non-Gaussian noise is the main explanation for the improvement in accuracy. More specifically, we describe how the technique of map matching is used to match an aircraft's elevation profile to a digital elevation map and a car's horizontal driven path to a street map. In both cases, real-time implementations are available, and tests have shown that the accuracy in both cases is comparable with satellite navigation (as GPS) but with higher integrity. Based on simulations, we also argue how the particle filter can be used for positioning based on cellular phone measurements, for integrated navigation in aircraft, and for target tracking in aircraft and cars. Finally, the particle filter enables a promising solution to the combined task of navigation and tracking, with possible application to airborne hunting and collision avoidance systems in cars.
Generating optical orbital angular momentum at visible wavelengths using a plasmonic metasurface (2014)

Abstract Light beams with a helical phase-front possess orbital angular momentum along their direction of propagation in addition to the spin angular momentum that describes their polarisation. Until recently, it was thought that these two ‘rotational’ motions of light were largely independent and could not be coupled during light–matter interactions. However, it is now known that interactions with carefully designed complex media can result in spin-to-orbit coupling, where a change of the spin angular momentum will modify the orbital angular momentum and vice versa . In this work, we propose and demonstrate that the birefringence of plasmonic nanostructures can be wielded to transform circularly polarised light into light carrying orbital angular momentum. A device operating at visible wavelengths is designed from a space-variant array of subwavelength plasmonic nano-antennas. Experiment confirms that circularly polarised light transmitted through the device is imbued with orbital angular momentum of ±2 ħ (with conversion efficiency of at least 1%). This technology paves the way towards ultrathin orbital angular momentum generators that could be integrated into applications for spectroscopy, nanoscale sensing and classical or quantum communications using integrated photonic devices.
Employing End-Functional Polythiophene To Control the Morphology of Nanocrystal−Polymer Composites in Hybrid Solar Cells (2004)

A poly(3-hexylthiophene) containing an interacting amino chain end enhances the performance of P3HT/CdSe solar cells by increasing the dispersion of CdSe nanocrystals and improving the morphology of the nanocomposite without introducing insulating surfactants.
Virus‐Directed Enzyme/Prodrug Therapy (VDEPT) Selectively Engineering Drug Sensitivity into Tumors (1994)

A gene therapy approach has been described that generates a tumor-selective qualitative difference in the metabolic capability in tumor cells. This is the result of the selective expression of a nonmammalian enzyme in tumor cells. Selective expression is achieved by utilization of a chimeric gene composed of the TRS from a tumor-associated marker gene linked to the coding domain of a gene encoding a nonmammalian enzyme. We have described the application of this approach for the treatment of metastatic CRC. This approach involves creation of a chimeric gene composed of the CEA TRS linked to the coding domain of the CD gene. Selective expression of CD in the tumor cells will allow the selective conversion of the prodrug 5-FCyt to 5-FCyt in the tumor while sparing normal cells. Most importantly, delivery and expression of CD into a small fraction of tumor cells may be sufficient to achieve a significant antitumor effect.
On the Mechanism of Nonaqueous Li–O2 Electrochemistry on C and Its Kinetic Overpotentials: Some Implications for Li–Air Batteries (2012)

Quantitative differential electrochemical mass spectrometry and cyclic voltammetry have been combined to probe possible mechanisms and the kinetic overpotentials, responsible for discharge and charge in a Li–O2 battery, using C as the cathode and an electrolyte based on dimethoxyethane as the solvent. Previous spectroscopy experiments (X-ray diffraction, μRaman, IR, XPS) have shown that Li2O2 is the principle product formed during Li–O2 discharge using this electrolyte/cathode combination. At all discharge potentials and charge potentials <4.0 V, the observed electrochemistry is ∼2e–/O2 consumed or produced, also implying that Li2O2 is the dominant thermodynamically stable species formed and consumed in the electrochemistry. No evidence exists at any potential for formation of stable LiO2 (1e–/O2) or Li2O (4e–/O2) during discharge. At charging potentials >4.0 V, the electrochemistry requires significantly more than 2e–/O2, and we take this as evidence for electrolyte decomposition. We find that sequential concerted (Li+ + e–) ion transfers to/from adsorbed O2* and LiO2* to produce/consume Li2O2 is the mechanism that is most compatible with these experiments. The kinetic overpotentials are extremely low relative to aqueous O2 reduction and evolution, and this implies that in principle a discharge–charge Li–O2 cycle is possible with high voltaic efficiency (∼85%) if electrolyte and cathode stability issues are resolved.
Evidence of a key role for photosynthetic oxygen release in oil storage in developing soybean seeds (2005)

• Based on the topographical analysis of photosynthesis and oil storage, we propose in a companion paper that photosynthetic oxygen release plays a key role in the local energy state, storage metabolism and flux toward lipid biosynthesis in developing soybean seeds. To test this hypothesis, we combined topographical analysis of ATP gradients across tissues, microsensor quantifications of internal O2 levels, assays of energy balance, metabolite profiles and isotope-labelling studies. • Seeds show a marked degree of oxygen starvation in vivo (minimum O2 levels 0.1 kPa, ≈ 1.3 µm), affecting ATP gradients, overall energy state, metabolite pools and storage activity. • Despite the low light availability, photosynthesis supplies significant amounts of oxygen to the hypoxic seed tissue. This is followed by an increase in local ATP levels, most prominently within the lipid-synthesizing (inner) regions of the embryo. Concomitantly, partitioning of 14C-sucrose to lipids is increased, suggesting higher rates of lipid biosynthesis. • It is concluded that both respiratory and biosynthetic fluxes are dynamically adjusted to photosynthetic oxygen supply.
Tetramethylenedisulfotetramine Alters Ca2+ Dynamics in Cultured Hippocampal Neurons: Mitigation by NMDA Receptor Blockade and GABAA Receptor-Positive Modulation (2012)

Tetramethylenedisulfotetramine (TETS) is a potent convulsant that is considered a chemical threat agent. We characterized TETS as an activator of spontaneous Ca²⁺ oscillations and electrical burst discharges in mouse hippocampal neuronal cultures at 13-17 days in vitro using FLIPR Fluo-4 fluorescence measurements and extracellular microelectrode array recording. Acute exposure to TETS (≥ 2 µM) reversibly altered the pattern of spontaneous neuronal discharges, producing clustered burst firing and an overall increase in discharge frequency. TETS also dramatically affected Ca²⁺ dynamics causing an immediate but transient elevation of neuronal intracellular Ca²⁺ followed by decreased frequency of Ca²⁺ oscillations but greater peak amplitude. The effect on Ca²⁺ dynamics was similar to that elicited by picrotoxin and bicuculline, supporting the view that TETS acts by inhibiting type A gamma-aminobutyric acid (GABA(A)) receptor function. The effect of TETS on Ca²⁺ dynamics requires activation of N-methyl-D-aspartic acid (NMDA) receptors, because the changes induced by TETS were prevented by MK-801 block of NMDA receptors, but not nifedipine block of L-type Ca²⁺ channels. Pretreatment with the GABA(A) receptor-positive modulators diazepam and allopregnanolone partially mitigated TETS-induced changes in Ca²⁺ dynamics. Moreover, low, minimally effective concentrations of diazepam (0.1 µM) and allopregnanolone (0.1 µM), when administered together, were highly effective in suppressing TETS-induced alterations in Ca²⁺ dynamics, suggesting that the combination of positive modulators of synaptic and extrasynaptic GABA(A) receptors may have therapeutic potential. These rapid throughput in vitro assays may assist in the identification of single agents or combinations that have utility in the treatment of TETS intoxication.
Physiology and pathology of notch signalling system (2005)

Notch proteins encode a family of transmembrane receptors that are part of a signalling transduction system known as Notch signalling, an extremely conserved and widely used mechanism regulating programs governing growth, apoptosis and differentiation in metazoans. Notch signalling begins when the Notch receptor binds ligands and ends when the Notch intracellular domain enters the nucleus and activates transcription of target genes. This core pathway is subjected to a wide array of regulatory influences and protein-protein interactions and is correlated with other signalling pathway. This review will summarize recent findings concerning the physiology and pathology of Notch signalling in vascular development and homeostasis. Moreover, the clinical phenotypes of Notch3 signalling system pathology will be described, with particular regard to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) for which the most recent pathogenetic hypotheses are reported.
Molecular Genetics of Brain Tumors (1999)

As many as 40000 patients are newly diagnosed each year as having brain tumors. About half of these are metastatic foci of tumors originating outside the central nervous system, while the other half are primary tumors of central nervous system tissues. These are a diverse group of neoplasms. Currently, primary brain tumors are classified in a manner that reflects their histological appearance and location. The identification of cancer as a disorder of genes, however, has opened the possibility of classifying tumors according to the genetic alterations that underlie their pathogenesis and that regulate their malignant behavior. Two major classes of genes critical for the development of all types of cancer, including brain tumors, are now recognized: tumor suppressor genes, which encode genes that function to inhibit cell proliferation and tumor development, and oncogenes, which encode proteins that stimulate proliferation and mediate biological activities important for invasion, neoangiogenesis, immune escape, and other characteristics of malignancy. While in most cases the specific pathways regulating tumor characteristics such as tumor neoangiogenesis and tissue invasion remain to be defined, recognition of the genetic changes characteristic of individual tumor types should provide opportunities to develop more effective, less toxic therapies.
Effective Intravenous Therapy of Murine Pulmonary Metastases with an Oncolytic Herpes Virus Expressing Interleukin 12 (2004)

The i.v. delivery of an oncolytic herpes virus may achieve effective infection, oncolysis, and transgene expression at distant tumor sites. This approach to systemic therapy combining oncolysis with IL-12 immune stimulation led to significantly improved survival in animals with disseminated SCC.
Comparative evaluation of a natural language dialog based system and a menu driven system for information access: a case study (2000)

This paper describes the evaluation of a natural language dialog based navigation system (HappyAssistant) that helps users access e-commerce sites to find relevant information about products and services. The prototype system leverages technologies in natural language processing and human computer interaction to create a faster and more intuitive way of interacting with websites, especially for the less experienced users. The result of a comparative study shows that users prefer the natural language enabled navigation two to one over the menu driven navigation. In addition, the study confirmed the efficiency of using natural language dialog in terms of the number of clicks and the amount of time required to obtain the relevant information. In the case study, comparing to the menu driven system, the average number of clicks used in the natural language system was reduced by 63.2 % and the average time was reduced by 33.3%.
Towards Autonomic Fault Recovery in System-S (2007)

System-S is a stream processing infrastructure which enables program fragments to be distributed and connected to form complex applications. There may be potentially tens of thousands of interdependent and heterogeneous program fragments running across thousands of nodes. While the scale and interconnection imply the need for automation to manage the program fragments, the need is intensified because the applications operate on live streaming data and thus need to be highly available. System-S has been designed with components that autonomically manage the program fragments, but the system components themselves are also susceptible to failures which can jeopardize the system and its applications. The work we present addresses the self healing nature of these management components in System-S. In particular, we show how one key component of System-S, the job management orchestrator, can be abruptly terminated and then recover without interrupting any of the running program fragments by reconciling with other autonomous system components. We also describe techniques that we have developed to validate that the system is able to autonomically respond to a wide variety of error conditions including the abrupt termination and recovery of key system components. Finally, we show the performance of the job management orchestrator recovery for a variety of workloads.
A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control (2016)

The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform. We demonstrate two parallel circuits of connected airway and liver modules on a platform containing 62 electromagnetic microactuators, with precise and controlled flow rates as well as functional biological metrics over a two week time course. Technical advancements enabled by this platform include the use of non-sorptive construction materials, enhanced scalability, portability, flow control, and usability relative to conventional flow control modes (such as capillary action, pressure heads, or pneumatic air lines), and a reconfigurable and modular organ model format with common fluidic port architecture. We demonstrate stable biological function for multiple pairs of airway-liver models for periods of 2 weeks in the platform, with precise control over fluid levels, temperature, flow rate and oxygenation in order to support relevant use cases involving drug toxicity, efficacy testing, and organ-organ interaction.
Enzyme-immunoassay: a review. (1984)

The main principles of heterogeneous and homogeneous enzyme-immunoassays are reviewed. Furthermore, an overview is given of enzymes currently used as labels and methods applied for conjugate preparation. The reliability and practicability of enzyme-immunoassays are discussed. Special consideration is given to possible interferences, the detection limits and the mechanization of these assays. A range of curve-fitting methods for evaluation of the results is listed. Future prospects for the further development of enzyme-immunoassay and application of this technique are discussed.