gebhart/patrepeval huggingface dataset:
<b>HUMAN ERYTHROCYTIC CYCLOPHILINS: ISOLATION, CHARACTERIZATION AND STRUCTURE </b><b>ELUCIDATION </b> (1996)

Two cyclosporin A (CsA) binding proteins were purified to homogeneity from human erythrocytes by consecutive steps of repeated gel chromatography, hydrophobic HPLC, ion exchange HPLC and reverse phase HPLC. Purified proteins I and II showed almost identical molecular masses and peptidyl-prolyl cis-trans isomerase (PPIase) activities which were completely abolished in the presence of CsA. On the other hand, pl values of the two proteins were distinctly different, 9.1 and 8.1, respectively, and the CsA-binding affinity (Kd) of protein I was 15.3 nM and that of II 25.0 nM. Amino acid sequence analysis of protein I in intact form has shown to be Val as the amino terminal residue of the protein, while no phenylthiohydantoinylated amino acid was detected in the sequence analysis of intact protein II, suggesting the presence of a modified or blocked amino acid at the amino terminus of the protein. The complete amino acid sequence of protein I was identified with [Phe'"]-human cyclophilin A. Significantly high CsA-binding affinities of the present two proteins in human erythrocytes pose a problem of possible implication of CsA bound to such proteins in erythrocytes in pharmacology and/or toxicology of CsA through the blood cell fate.
ChemInform Abstract: Heck—Matsuda Reaction for Allylic Nitro Compounds: A Short Asymmetric Synthesis of an FTY720 Derivative. (2012)

Abstract By application of the optimal dibenzylideneacetone palladium catalyst Pd 2 (dba) 3 , (Ia), or (Ib), aryldiazonium salts bearing electron‐donating or electron‐deficient substituents are coupled with allylic nitro compound (II) at room temperature to give cinnamyl nitro compounds in good yields, with some exceptions.
Detonation waves in PBX 9501 (2006)

For a planar detonation wave propagating in the plastic-bonded explosive PBX 9501, measurements of the reaction zone display a classical ZND profile. Moreover, the reaction-zone width is substantially less than the average size of an explosive grain. We show that the reaction zone is compatible with realistic constitutive properties and an Arrhenius reaction rate based on the bulk temperature. Thus, contrary to conventional wisdom, hot spots are not needed to propagate a detonation wave. Conventional wisdom is based, in part, on shock desensitization experiments; the observation that precompressing a PBX with a weak shock – which eliminates voids as nucleation sites for hot spots – can quench a propagating detonation wave. By analysing the temperature behind two shocks compared to a single shock and the corresponding change of the induction time, we show that a detonation wave sustained by the bulk reaction rate from shock heating is compatible with shock desensitization. Shock desensitization depends on having a temperature sensitive rate, which usually is associated with detonation wave instability. However, for PBX 9501 the temperature variation in the reaction zone is small, and one-dimensional simulations show that this results in a stable detonation wave. Furthermore, we show that two additional phenomena are compatible with the perspective that bulk burn can sustain a planar detonation wave: failure diameter, which does depend on the heterogeneous structure of a PBX; and PBXs with a lower HE content which display an irregular detonation front.
Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion (2015)

Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.
Connectivity reflects coding: A model of voltage-based spike-timing-dependent-plasticity with homeostasis (2009)

Abstract Electrophysiological connectivity patterns in cortex often show a few strong connections in a sea of weak connections. In some brain areas a large fraction of strong connections are bidirectional, in others they are mainly unidirectional. In order to explain these connectivity patterns, we use a model of Spike-Timing-Dependent Plasticity where synaptic changes depend on presynaptic spike arrival and the postsynaptic membrane potential. The model describes several nonlinear effects in STDP experiments, as well as the voltage dependence of plasticity under voltage clamp and classical paradigms of LTP/LTD induction. We show that in a simulated recurrent network of spiking neurons our plasticity rule leads not only to receptive field development, but also to connectivity patterns that reflect the neural code: for temporal coding paradigms strong connections are predominantly unidirectional, whereas they are bidirectional under rate coding. Thus variable connectivity patterns in the brain could reflect different coding principles across brain areas.
Using virtualization for high availability and disaster recovery (2009)

Traditional high-availability and disaster recovery solutions require proprietary hardware, complex configurations, application-specific logic, highly skilled personnel, and a rigorous and lengthy testing process. The resulting high costs have limited their adoption to environments with the most critical applications. However, high availability and disaster recovery are becoming increasingly important in many environments that cannot bear the complexity and the expense involved. In this paper, we show that virtualization can be used to develop solutions that meet this market demand. We describe the recently released Virtual Availability Manager (VAM) product offering, which provides simplified availability solutions using Xen®-based virtualization, and which is available as part of the IBM Systems Director product. We present key design principles of VAM, explain its architecture and current capabilities, and describe the way it is being extended to enable recovery in case of disaster.
Image Completion Approaches Using the Statistics of Similar Patches (2014)

Image completion involves filling missing parts in images. In this paper we address this problem through novel statistics of similar patches. We observe that if we match similar patches in the image and obtain their offsets (relative positions), the statistics of these offsets are sparsely distributed. We further observe that a few dominant offsets provide reliable information for completing the image. Such statistics can be incorporated into both matching-based and graph-based methods for image completion. Experiments show that our method yields better results in various challenging cases, and is faster than existing state-of-the-art methods.
Angemessenheit der diagnostischen Koloskopie im Zeitalter der Vorsorge-Koloskopie. Sind bessere Auswahlkriterien erforderlich? – Ergebnisse einer prospektiven multizentrischen Privatpraxis-Studie (2005)

Hintergrund: Nachdem die Vorsorge-Koloskopie vor einem Jahr in Deutschland eingeführt wurde, entstand die Befürchtung, dass die Arbeitslast der Praxen durch diese Untersuchungen zu einer geringeren Inanspruchnahme der diagnostischen Koloskopie bei symptomatischen Patienten führt. Eine bessere Patientenauswahl ist daher unabdingbar. Kriterien für die Angemessenheit der Koloskopie sind verfügbar, sind aber nie in einer realistischen Situation in Endoskopiepraxen getestet worden.
EPR imaging of dose distributions aiming at applications in radiation therapy (2014)

A one-dimensional electron paramagnetic resonance (EPR) imaging method for visualisation of dose distributions in photon fields has been developed. Pressed pellets of potassium dithionate were homogeneously irradiated in a (60)Co radiation field to 600 Gy. The EPR analysis was performed with an X-Band (9.6 GHz) Bruker E540 EPR and EPR imaging spectrometer equipped with an E540 GC2X two-axis X-band gradient coil set with gradients along the y axis (along the sample tube) and z axis (along B0) and an ER 4108TMHS resonator. Image reconstruction, including deconvolution, baseline corrections and corrections for the resonator sensitivity, was performed using an in-house-developed Matlab code for the purpose to have a transparent and complete algorithm for image reconstruction. With this method, it is possible to visualise a dose distribution with an accuracy of ∼5 % within ±5 mm from the centre of the resonator.
SemEval-2015 Task 8: SpaceEval (2015)

Human languages exhibit a variety of strategies for communicating spatial information, including toponyms, spatial nominals, locations that are described in relation to other locations, and movements along paths. SpaceEval is a combined information extraction and classification task with the goal of identifying and categorizing such spatial information. In this paper, we describe the SpaceEval task, annotation schema, and corpora, and evaluate the performance of several supervised and semi-supervised machine learning systems developed with the goal of automating this task.
Scalability and Performance Evaluation of Edge Cloud Systems for Latency Constrained Applications (2018)

This paper presents an analysis of the scalability and performance of an edge cloud system designed to support latency-sensitive applications. A system model for geographically dispersed edge clouds is developed by considering an urban area such as Chicago and co-locating edge computing clusters with known Wi-Fi access point locations. The model also allows for provisioning of network bandwidth and processing resources with specified parameters in both edge and the cloud. The model can then be used to determine application response time (sum of network delay, compute queuing and compute processing time), as a function of offered load for different values of edge and core compute resources, and network bandwidth parameters. Numerical results are given for the city-scale scenario under consideration to show key system level trade-offs between edge cloud and conventional cloud computing. Alternative strategies for routing service requests to edge vs. core cloud clusters are discussed and evaluated. Key conclusions from the study are: (a) the core cloud-only system outperforms the edge-only system having low inter-edge bandwidth, (b) a distributed edge cloud selection scheme can approach the global optimal assignment when the edge has sufficient compute resources and high inter-edge bandwidth, and (c) adding capacity to an existing edge network without increasing the inter-edge bandwidth contributes to network wide congestion and can reduce system capacity.
Find What You Need, Understand What You Find (2007)

Abstract This article presents a framework for research and development in user interfaces that support information seeking. The information-seeking process is described, and each of the subprocesses are discussed with an eye toward making user interfaces that closely couple support mechanisms. Recent results from studies related to term suggestions for queries, coupling search and examination, and seamless interaction between overviews and previews are used to illustrate highly interactive information-seeking services.
A Novel Synthetic Steroid of 2β,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia (2019)

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that β,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs' reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.
Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients (pts) with advanced NSCLC. (2015)

3014 Background: The inhibitory PD-L1 and CTLA-4 pathways control T-cell activation. MEDI4736 (M) is a human IgG1 mAb that blocks PD-L1 binding to programmed cell death-1 and CD80 with high affinity and selectivity. Tremelimumab (T) is a selective human IgG2 mAb inhibitor of CTLA-4. M and T have demonstrated acceptable safety profiles and clinical activity as single agents. M and T block distinct interactions contributing to immunosuppression and the combination may provide greater antitumor activity versus either agent alone. Methods: A Phase 1, open-label dose escalation and expansion study (NCT02000947) is assessing the safety/tolerability and antitumor activity of M + T combinations in pts with advanced NSCLC. Results: As of 4 Dec 2014, 61 pts have been treated during the dose escalation phase (table). An MTD has not yet been defined; the Cohort 5a dose exceeded the MTD (n=2 with dose-limiting toxicities; Grade [G] 3 increased AST/ALT, G4 increased lipase). 64% of pts had ≥1 drug-related AE; the most frequent were fatigue (26%), diarrhea (21%), and increased amylase (13%). 31% of pts had ≥1 G3/4 related AE; the most frequent (>5%) were diarrhea (8%) and colitis (7%). Increasing doses of T with a constant dose of M were associated with greater severity and frequency of AEs. 18% of pts had drug-related AEs leading to discontinuation; the most frequent was colitis (7%). All AEs were manageable with standard therapy, including steroids, except G4 myasthenia gravis and G5 polymyositis in 1 pt in Cohort 2a. Of 31 pts with ≥18-week scan, 8 (26%) had partial response (PR) and 11 pts (35%) had stable disease. PRs occurred in 3 of 10 pts with PD-L1-negative tumors. Conclusions: The combination has a manageable safety profile with evidence of clinical activity, including in PD-L1-negative disease. These data support continued study of the combination; recruitment is ongoing. Clinical trial information: NCT02000947. M Q4W M Q2W Cohort 1a 2a 3a 3b 4 4a 5 5a 8 9 Dose M (mg/kg) + T (mg/kg) 3 + 1 10 + 1 15 + 1 10 + 3 20 + 1 15 + 3 15 + 10 20 + 3 10 + 1 10 + 3 n 3 3 11 3 6 11 9 6 3 6 Pts with ≥1 drug- related AE, n All grades 1 3 5 3 2 7 8 5 0 5 Grade 3/4 0 2 2 1 1 2 4 5 0 2 All grades leading to discontinuation 0 1 1 1 0 2 2 3 0 1
A Convergent Hetero‐Diels–Alder Strategy for Asymmetric Access to a Lactone Containing Two Lipidic Chains (2012)

Abstract Eu(fod) 3 ‐catalyzed heterocycloaddition of chiral β‐alkyl‐ N ‐vinyl‐1,3‐oxazolidin‐2‐ones with a heterodiene bearing a lipidic chain led to heterocycloadducts in high yield with excellent endo and facial selectivities. An original lipidic lactone, a potent precursor of a ceramide analog, was obtained in seven steps from the adduct in a convergent manner after appropriate functionalization.
Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans (2001)

The pathogenic fungus Candida albicans is capable of responding to a wide variety of environmental cues with a morphological transition from a budding yeast to a polarized filamentous form. We demonstrate that the Ras homologue of C. albicans, CaRas1p, is required for this morphological transition and thereby contributes to the development of pathogenicity. However, CaRas1p is not required for cellular viability. Deletion of both alleles of the CaRAS1 gene caused in vitro defects in morphological transition that were reversed by either supplementing the growth media with cAMP or overexpressing components of the filament-inducing mitogen-activated protein (MAP) kinase cascade. The induction of filament-specific secreted aspartyl proteinases encoded by the SAP4-6 genes was blocked in the mutant cells. The defects in filament formation were also observed in situ after phagocytosis of C. albicans cells in a macrophage cell culture assay and, in vivo, after infection of kidneys in a mouse model for systemic candidiasis. In the macrophage assay, the mutant cells were less resistant to phagocytosis. Moreover, the defects in filament formation were associated with reduced virulence in the mouse model. These results indicate that, in response to environmental cues, CaRas1p is required for the regulation of both a MAP kinase signalling pathway and a cAMP signalling pathway. CaRas1p-dependent activation of these pathways contributes to the pathogenicity of C. albicans cells through the induction of polarized morphogenesis. These findings elucidate a new medically relevant role for Ras in cellular morphogenesis and virulence in an important human infectious disease.
Missing Components of Training in the Chemical Sciences (2014)

As noted in a recent ACS Presidential Commission report and elsewhere training in the chemical sciences in the U.S. is, at best, inadequate and perhaps inappropriate. Industry is unable to find suitably-trained applicants for available positions and is petitioning Congress to relax immigration laws so that larger numbers of international candidates will be available. At the same time, unemployment among those trained in the chemical sciences is at an all-time high. Clearly, there is a disconnect between what universities are doing and what the country and the world needs. It is incumbent upon any program of training in the chemical sciences that it turn out not only degree holders but functional graduates. If the U.S. is to remain competitive in the area of science and technology, training in the chemical sciences must be redirected and improved. Most programs continue to be quite traditional in approach and slow to adapt to changing needs. The demarcation between fields of chemistry, and even among disciplines, is blurring. The base of the chemical sciences is broadening. This requires more integration in the training of students – more focus needs to be placed on the program rather than a set of courses. There are several areas in which inadequate training is provided. Perhaps most prominent is polymeric materials. These materials are essential for a high standard of living and most industrial chemists work in a polymer or polymer-related area, yet training in this area is often neglected. Every program should include a course in industrial chemistry which treats the actual chemistry of industry, the technology of industry (how the chemistry is utilized to produce items required by the consuming public) and the chemical environment (interrelationships, capital generation, a common business cycle, intellectual property/trade secrets, marketing, reporting, job performance, education, etc.). Students should complete a meaningful research project focused on a real societal problem and, if possible, an industrial internship.
Changes in the Extent of Microtubule Assembly Can Regulate Initiation of DNA Synthesisa (1986)

We have shown that MT depolymerization by colchicine and other drugs is sufficient to initiate DNA synthesis in serum-free cultures of embryonic fibroblasts and that stabilization of MTs with taxol inhibits this initiation. Growth factors and oncogenic DNA viruses also initiate DNA synthesis by a taxol-sensitive mechanism that appears to require MT depolymerization or rearrangements. Because we have shown that microtubule heterogeneity exists within single fibroblastic cells, we have carried out a series of experiments to determine the extent of microtubule disruption necessary to initiate DNA synthesis. We have compared the effects of various concentrations of colchicine and taxol on initiation of DNA synthesis with their effects on cytoplasmic MT complexes as visualized by indirect immunofluorescence microscopy and quantitated by direct binding of radiolabeled monoclonal antibody to cytoskeletons. The opposing effects of these drugs on MTs shows that there is a correlation between the extent of MT depolymerization and initiation of DNA synthesis. Initiation of DNA synthesis by colchicine in the presence of taxol is half-maximal when taxol and colchicine are added to cultures at a ratio of about 13 to 1. At this drug ratio, taxol stabilizes MTs near the nucleus, but MTs near the cell periphery are depolymerized. Maximal inhibition of DNA synthesis by taxol occurs only at taxol to colchicine ratios where MTs extend throughout the cytoplasm to the cell periphery. Thus, depolymerization of a small fraction of total MTs, particularly those near the periphery, may be sufficient to initiate proliferative events.
Robotic assembly of truss structures for space systems and future research plans (2003)

Many initiatives under study by both the space science and Earth science communities require large space systems, i.e. with apertures >15 m or dimensions >20 m. This paper reviews the effort in NASA Langley Research Center's Automated Structural Assembly Laboratory which laid the foundations for robotic construction of these systems. In the Automated Structural Assembly Laboratory reliable autonomous assembly and disassembly of an 8 m planar structure composed of 102 truss elements covered by 12 panels was demonstrated. The paper reviews the hardware and software design philosophy which led to reliable operation during weeks of near continuous testing. Special attention is given to highlight the features enhancing assembly reliability.