gebhart/patrepeval huggingface dataset:
Identification of a Selective RORγ Ligand That Suppresses T<sub>H</sub>17 Cells and Stimulates T Regulatory Cells (2012)

Nuclear receptors (NRs) are ligand-regulated transcription factors, many of which are validated targets for clinical purposes. The retinoic acid receptor-related orphan nuclear receptors alpha and gamma t (RORα and RORγt) are considered to be the master regulators of development of T(H)17 cells, a subset of T cells that have been implicated in the pathology of several autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). We report here the identification of a novel RORγ-specific synthetic ligand, SR1555, that not only inhibits T(H)17 cell development and function but also increases the frequency of T regulatory cells. Our data suggests synthetic RORγ ligands can be developed that target both suppression of T(H)17 and stimulation of T regulatory cells, offering key advantages in development of therapeutics targeting autoimmune diseases.
Response Surface Bandits (1995)

SUMMARY In this paper we define a response surface bandit as the sequential design problem that maximizes an expected bandit utility but where the outcomes yn are continuous and can be related through a response surface to a set of controllable variables xn = (x 1n, x 2n,···, xkn). We link this problem to other traditional optimization problems from industrial engineering and to the traditional bandit problem. We consider two approaches to the problem. The first is based on a myopic sequential design. The second approach uses the best design out of a family of designs related to upper bounds for the predicted surface; the family includes myopic and sequential versions of D-optimal designs. These approaches can be generalized to more broadly defined sequential problems.
Design of Organic Dyes and Cobalt Polypyridine Redox Mediators for High-Efficiency Dye-Sensitized Solar Cells (2010)

Dye-sensitized solar cells (DSCs) with cobalt-based mediators with efficiencies surpassing the record for DSCs with iodide-free electrolytes were developed by selecting a suitable combination of a cobalt polypyridine complex and an organic sensitizer. The effect of the steric properties of two triphenylamine-based organic sensitizers and a series of cobalt polypyridine redox mediators on the overall device performance in DSCs as well as on transport and recombination processes in these devices was compared. The recombination and mass-transport limitations that, previously, have been found to limit the performance of these mediators were avoided by matching the properties of the dye and the cobalt redox mediator. Organic dyes with higher extinction coefficients than the standard ruthenium sensitizers were employed in DSCs in combination with outer-sphere redox mediators, enabling thinner TiO(2) films to be used. Recombination was reduced further by introducing insulating butoxyl chains on the dye rather than on the cobalt redox mediator, enabling redox couples with higher diffusion coefficients and more suitable redox potential to be used, simultaneously improving the photocurrent and photovoltage of the device. Optimization of DSCs sensitized with a triphenylamine-based organic dye in combination with tris(2,2'-bipyridyl)cobalt(II/III) yielded solar cells with overall conversion efficiencies of 6.7% and open-circuit potentials of more than 0.9 V under 1000 W m(-2) AM1.5 G illumination. Excellent performance was also found under low light intensity indoor conditions.
An efficient PE-ALD process for TiO<sub>2</sub> thin films employing a new Ti-precursor (2016)

A new Ti-precursor for low-temperature PE-ALD of titanium dioxide thin films as gas barrier layers on polymer substrates.
Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis. (1999)

Rheumatoid arthritis (RA) is a chronic disease affecting up to 3% of the population in most countries. The causes of RA have not been completely elucidated. This paper aims to review the role of reactive oxygen and nitrogen species in the etiopathogenesis of RA. Reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl radical and hypochlorous acid, as well as reactive nitrogen species (RNS), such as nitric oxide and peroxynitrite, contribute significantly to tissue injury in RA. Several mechanisms are involved in the generation and action of ROS and RNS. Superoxide radical, hydrogen peroxide and nitric oxide do not directly damage the majority of biological molecules. They are however converted into the highly reactive hydroxyl radical, which reacts with almost all molecules in living cells. The resulting chronic inflammation process can be reduced with antioxidant therapy. To date, scavenging, preventive, and enzyme antioxidants are available. The most important mode is scavenging of the hydroxyl radical and of hypochlorous acid. Another important way is to inhibit production of RNS and ROS by neutrophils, monocytes, and macrophages. The control of inflammation in arthritic patients by natural as well as synthetic antioxidants could become a relevant component of antirheumatic prevention and therapy.
Dependence of Effective Molarity on Linker Length for an Intramolecular Protein−Ligand System (2007)

This paper reports dissociation constants and "effective molarities" (M(eff)) for the intramolecular binding of a ligand covalently attached to the surface of a protein by oligo(ethylene glycol) (EG(n)) linkers of different lengths (n = 0, 2, 5, 10, and 20) and compares these experimental values with theoretical estimates from polymer theory. As expected, the value of M(eff) is lowest when the linker is too short (n = 0) to allow the ligand to bind noncovalently at the active site of the protein without strain, is highest when the linker is the optimal length (n = 2) to allow such binding to occur, and decreases monotonically as the length increases past this optimal value (but only by a factor of approximately 8 from n = 2 to n = 20). These experimental results are not compatible with a model in which the single bonds of the linker are completely restricted when the ligand has bound noncovalently to the active site of the protein, but they are quantitatively compatible with a model that treats the linker as a random-coil polymer. Calorimetry revealed that enthalpic interactions between the linker and the protein are not important in determining the thermodynamics of the system. Taken together, these results suggest that the manifestation of the linker in the thermodynamics of binding is exclusively entropic. The values of M(eff) are, theoretically, intrinsic properties of the EG(n) linkers and can be used to predict the avidities of multivalent ligands with these linkers for multivalent proteins. The weak dependence of M(eff) on linker length suggests that multivalent ligands containing flexible linkers that are longer than the spacing between the binding sites of a multivalent protein will be effective in binding, and that the use of flexible linkers with lengths somewhat greater than the optimal distance between binding sites is a justifiable strategy for the design of multivalent ligands.
Engagement of MHC class II molecules by staphylococcal superantigens activates src‐type protein tyrosine kinases (1994)

Staphylococcal exotoxins (SE) are superantigens that bind to monomorphic determinants on major histocompatibility complex (MHC) class II molecules and stimulate human peripheral blood T lymphocytes in a V beta-specific manner. SE also deliver activation signals via MHC class II molecules that initiate cell adhesion and cytokine gene transcription. These events are preceded by tyrosine phosphorylation and are antagonized by inhibitors of tyrosine kinases, indicating an essential role for these kinases in signaling via class II molecules. We report that stimulation of human peripheral blood monocytes with SE induced rapid and selective activation of the src-related protein tyrosine kinases (PTK) fgr and hck. SE also induced the activation of fgr and lyn in B cells. PTK activation by SE required MHC class II expression, and was greatly potentiated in the presence of T cells bearing toxin-specific V beta chains. These results indicate that in addition to their antigen and superantigen-presenting function, MHC class II molecules act as signal-transducing receptors that are coupled to src-type PTK.
Grasp quality measures: review and performance (2014)

The correct grasp of objects is a key aspect for the right fulfillment of a given task. Obtaining a good grasp requires algorithms to automatically determine proper contact points on the object as well as proper hand configurations, especially when dexterous manipulation is desired, and the quantification of a good grasp requires the definition of suitable grasp quality measures. This article reviews the quality measures proposed in the literature to evaluate grasp quality. The quality measures are classified into two groups according to the main aspect they evaluate: location of contact points on the object and hand configuration. The approaches that combine different measures from the two previous groups to obtain a global quality measure are also reviewed, as well as some measures related to human hand studies and grasp performance. Several examples are presented to illustrate and compare the performance of the reviewed measures.
Learning Saliency Maps for Object Categorization (2006)

Abstract. We present a novel approach for object category recognition that can find objects in challenging conditions using visual attention technique. It combines saliency maps very closely with the extraction of random subwindows for classification purposes. The maps are built online by the classifier while being used by it to classify the image. Saliency is therefore automatically suited to the abilities of the classifier and not an additional concept that is tried to fit into another method. Our results show that we can obtain state of the art results on commonly used datasets with using only little information and thus achieve high efficiency and short processing times. 1
Systemic Administration of Combinatorial dsiRNAs via Nanoparticles Efficiently Suppresses HIV-1 Infection in Humanized Mice (2011)

We evaluated the in vivo efficacy of structurally flexible, cationic PAMAM dendrimers as a small interfering RNA (siRNA) delivery system in a Rag2(-)/-γc-/- (RAG-hu) humanized mouse model for HIV-1 infection. HIV-infected humanized Rag2-/-γc-/- mice (RAG-hu) were injected intravenously (i.v.) with dendrimer-siRNA nanoparticles consisting of a cocktail of dicer substrate siRNAs (dsiRNAs) targeting both viral and cellular transcripts. We report in this study that the dendrimer-dsiRNA treatment suppressed HIV-1 infection by several orders of magnitude and protected against viral induced CD4(+) T-cell depletion. We also demonstrated that follow-up injections of the dendrimer-cocktailed dsiRNAs following viral rebound resulted in complete inhibition of HIV-1 titers. Biodistribution studies demonstrate that the dendrimer-dsiRNAs preferentially accumulate in peripheral blood mononuclear cells (PBMCs) and liver and do not exhibit any discernable toxicity. These data demonstrate for the first time efficacious combinatorial delivery of anti-host and -viral siRNAs for HIV-1 treatment in vivo. The dendrimer delivery approach therefore represents a promising method for systemic delivery of combinations of siRNAs for treatment of HIV-1 infection.
A Flexible Dynamic Partitioning Algorithm for Optimistic Distributed Simulation (2007)

The performance of distributed simulation depends very much on the partitioning of the simulation model among the participating hosts. Usually, when starting a simulation run, an initial partitioning is determined by taking into account the available computing resources as well as the expected workload and the communication structure of the simulation model. However, as hosts can be subject to background load or the model behavior can change in the course of the simulation, a dynamic partitioning mechanism is required to avoid inefficiencies. In this paper, we introduce a new dynamic partitioning algorithm for optimistic distributed simulation. The algorithm is generally applicable but can also be configured to meet the requirements of specific scenarios. It is based on performance estimates for both computation and communication workload, the calculation of which is completely platform-independent. Our experiments show that the algorithm has low overhead and reacts reliably to changes of both model behavior and external resources.
An <i>E. coli</i> Ribonucleoprotein Containing 4.5 <i>S</i> RNA Resembles Mammalian Signal Recognition Particle (1990)

The signal recognition particle (SRP) plays a central role in directing the export of nascent proteins from the cytoplasm of mammalian cells. An SRP-dependent translocation machinery in bacteria has not been demonstrated in previous genetic and biochemical studies. Sequence comparisons, however, have identified (i) a gene in Escherichia coli (ffh) whose product is homologous to the 54-kilodalton subunit (SRP54) of SRP, and (ii) an RNA encoded by the ffs gene (4.5S RNA) that shares a conserved domain with the 7SL RNA of SRP. An antiserum to Ffh precipitated 4.5S RNA from E. coli extracts, implying that the two molecules reside in a complex. The 4.5S RNA can also bind to SRP54 and can replace 7SL RNA in an enzymatic assay. The product of a dominant mutation in the ffs gene (4.5S RNAdl1) is also coprecipitated by the antiserum to Ffh protein and is lethal when expressed from an inducible promoter. After induction of 4.5S RNAdl1, the earliest observed phenotype was a permanent induction of the heat shock response, suggesting that there was an accumulation of aberrant proteins in the cytoplasm. Late after induction, translocation of beta-lactamase was impaired; this may be an indirect effect of heat shock, however, because translocation of ribose binding protein or of the porin, OmpA, was unaffected. An unusual separation of the inner and outer membranes, suggestive of a defect in cell envelope, was also observed. Protein synthesis did not cease until very late, an indication that 4.5S RNA probably does not have a direct role in this process.
Symptomatic responses to stimulation of sensory pathways in the jejunum (1992)

We hypothesized that intestinal afferent pathways inducing perception may be selectively activated by transmucosal electrical nerve stimulation, without disruption of the intrinsic myoelectrical rhythm. Hence, in 12 healthy subjects we measured perception (by a questionnaire) and jejunal slow wave activity (by electromyography), and we randomly applied for 1 min at 5-min intervals graded electrical (15 Hz, 100 microseconds) and mechanical stimuli (balloon distension) in the jejunum up to the respective discomfort threshold. Electrical and mechanical stimuli induced dose-related perception; the perception and discomfort thresholds were 39 +/- 7 and 63 +/- 6 mA and 31 +/- 3 and 49 +/- 5 ml for electrical and mechanical stimuli, respectively. More than one-half of electrical stimuli elicited clinical-type symptoms (abdominal pressure, fullness, colicky or sharp sensation) similar to those induced by mechanical stimuli; the remaining electrical stimuli (38 +/- 10%) induced paresthesia or flutterlike sensation. Similar types of symptoms were perceived with weak and strong stimuli. Jejunal slow wave activity (11.3 +/- 0.4 cycles/min) was not modified by either stimuli. We conclude that activation of intestinal sensory pathways, either by transmucosal nerve stimulation or via mechanoreceptors, induces a similar dose-related symptomatic response, without interfering with the intrinsic myoelectrical activity.
Multi-band radio-frequency filters fabricated using polyimide-based membrane transfer bonding technology (2010)

In this paper, we present a polyimide-based Si membrane transfer bonding technology and its application to CMOS-compatible integration of different modes of AlN/Si composite piezoelectric MEMS resonators. The thermosetting polyimide, which has excellent chemical resistance and thermal stability, is used as a bonding adhesion, and is successfully removed as a sacrificial layer by O2 plasma to release free-standing MEMS devices. The whole process temperature is below 350 °C and compatible with CMOS LSI. Using this technology, different modes of AlN/Si resonators, which are film bulk acoustic wave resonators and wine-glass mode disk-type resonators, have been co-fabricated on the same wafer. We also fabricated a ladder-type FBAR filter with a center frequency of 7.71 GHz and a mechanically coupled disk-array filter with a center frequency of 292.8 GHz.
IS IPO THE DEATH OF INNOVATION (2009)

This study examines whether changes made in the composition of the board of directors at the time of a firm’s initial public offering are related to changes in the firm’s innovation activity. The dependent variable is the change in R&D intensity from the pre-IPO period to the post-IPO period. Using a sample of 93 biotechnology or semiconductor firms with an IPO during the years 1996 – 2005, we find that changes in R&D intensity are negatively related to changes in (a) board size, (b) the percentage of members who are venture capitalists, and (c) the percentage of members with a science education and positively related to the change in age diversity.
Tissue‐engineered composites for the repair of large osteochondral defects (2002)

Composites of tissue-engineered cartilage and a subchondral support promote the orderly remodeling of large osteochondral defects in adult rabbits.
Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model (2015)

Human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells could replace lost tissue in geographic atrophy (GA) but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model.
High performance control of a three-level IGBT inverter fed AC drive (2002)

Three-level PWM inverters have been increasingly employed in industry and traction applications where high power and efficiency energy conversions are required. This paper presents a high performance control of a cage induction motor drive fed by a 100 hp three-level IGBT inverter operating at a low switching frequency. A practical mathematical model of the drive control system is established to aid in the control design to improve the system stability, dynamic performance and robustness over a wide speed range. The modeling and the simulation in Matlab/Simulink facilitate the self-tuning of the regulators in the multi-loop systems. The field oriented control and three-level space-vector modulation together with the drive protection and diagnostics are implemented in software based on a DSP TMS320C31. Experimental results based on the IGBT inverter prototype are given to verify the design and performance. Test results in motor common-mode voltage reduction and inverter neutral-point potential control are also briefly presented.
Towards a specific architecture for international information systems: An exploratory study (1996)

Despite their acknowledged importance, international information technology applications - defined as supporting a business activity across a number of diverse environments - are still largely unstudied and under-explored. Scholarly research has been relatively sparse, but there is anecdotal evidence of the serious difficulties facing the developer of international systems. In this exploratory paper it is investigated whether there is a specific architecture, generically common to international information systems which could provide a framework for the development of international systems. The linkage between the global business strategy of international firms and the organization and structure of their information systems is discussed. Building on the body of research into the structure of global information systems and distilling from it some fundamental commonalities, an architecture consisting of a two-dimensional topology and five systems elements is proposed as a basic construct for the design of systems which operate across diverse environments. The potential benefits of the architecture and the resulting implications for the design of international information systems are set out and the need for future research to validate and develop the architecture model further is emphasized.
Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine. (1995)

Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Using a rat model of focal cerebral ischemia, we show that systemically administered AGE-modified bovine serum albumin (AGE-BSA) significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA administration were dose- and time-related and associated with a paradoxical increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross-linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.
Analysis of the Diaphragm Forming of Continuous Fiber Reinforced Thermoplastics (1988)

This paper presents a computational procedure for the analysis of the diaphragm forming of thermoplastic composite materials. The objective of the analysis is to simulate the diaphragm forming process and predict the resulting fiber orientation and transverse thickness distribution. A computational algonthm of the procedure is presented along with a description of each submodel in the analysis. Predictions are presented for the resulting thickness distributions and fiber orientations for a series of circular disk geometries.