gebhart/patrepeval huggingface dataset:
Cartilage injury by ramp compression near the gel diffusion rate (2003)

The mechanics of cartilage injuries have implications for repair strategies. We examined the role of strain rate in cartilage injury under compression near the "gel diffusion" rate (the inherent tissue mechanical relaxation rate). Bovine osteochondral explant disks were subjected to one radially unconfined axial compression at approximately 0.1, 1, 10, 100, or 1000 times the gel diffusion rate to a peak stress of 3.5, 7, or 14 MPa. Effects were monitored in terms of axial strain, changes in water content, superficial cracks, chondrocyte viability, and proteoglycan release. Injury worsened monotonically with peak stress, but varied substantially with strain rate. High strain rates resulted in significant matrix fluid pressurization and impact-like surface cracking with cell death near the superficial zone. Below the gel diffusion rate, cells died throughout the tissue depth during extensive matrix consolidation without cracks. At approximately the gel diffusion rate, no measurable injury occurred, even for peak stresses of 14 MPa and axial compressive strains near 0.8. The gel diffusion rate therefore represented a threshold separating different biomechanical regimes of injury, but at which cartilage was relatively "safe" from injury. Findings may help identify strategies for prevention and treatment of cartilage injury and suggest loading guidelines for tissue engineering.
AMF-26, a Novel Inhibitor of the Golgi System, Targeting ADP-ribosylation Factor 1 (Arf1) with Potential for Cancer Therapy (2011)

ADP-ribosylation factor 1 (Arf1) plays a major role in mediating vesicular transport. Brefeldin A (BFA), a known inhibitor of the Arf1-guanine nucleotide exchange factor (GEF) interaction, is highly cytotoxic. Therefore, interaction of Arf1 with ArfGEF is an attractive target for cancer treatment. However, BFA and its derivatives have not progressed beyond the pre-clinical stage of drug development because of their poor bioavailability. Here, we aimed to identify novel inhibitors of the Arf1-ArfGEF interaction that display potent antitumor activity in vivo but with a chemical structure distinct from that of BFA. We exploited a panel of 39 cell lines (termed JFCR39) coupled with a drug sensitivity data base and COMPARE algorithm, resulting in the identification of a possible novel Arf1-ArfGEF inhibitor AMF-26, which differed structurally from BFA. By using a pulldown assay with GGA3-conjugated beads, we demonstrated that AMF-26 inhibited Arf1 activation. Subsequently, AMF-26 induced Golgi disruption, apoptosis, and cell growth inhibition. Computer modeling/molecular dynamics (MD) simulation suggested that AMF-26 bound to the contact surface of the Arf1-Sec7 domain where BFA bound. AMF-26 affected membrane traffic, including the cis-Golgi and trans-Golgi networks, and the endosomal systems. Furthermore, using AMF-26 and its derivatives, we demonstrated that there was a significant correlation between cell growth inhibition and Golgi disruption. In addition, orally administrated AMF-26 (83 mg/kg of body weight; 5 days) induced complete regression of human breast cancer BSY-1 xenografts in vivo, suggesting that AMF-26 is a novel anticancer drug candidate that inhibits the Golgi system, targeting Arf1 activation.
An Oral Salmonella-Based Vaccine Inhibits Liver Metastases by Promoting Tumor-Specific T-Cell-Mediated Immunity in Celiac and Portal Lymph Nodes: A Preclinical Study (2016)

Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was orogastrically immunized with CVD 915, while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC) detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac and portal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4(+) and dendritic cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8(+)IFN-γ(+)) were found in the celiac and portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination.
Ultrafast optical nonlinearity by virtual charge polarization in DC-biased quantum well structures (1988)

An optical nonlinearity due to virtual charge polarization in a quantum-well structure biased by a DC electric field is proposed and discussed. The switching time of the nonlinearity is expected to be extremely short, on the order of 100 fs. An effective degenerative four-wave chi /sup 3/ parameter is estimated to be 1.0*10/sup -9/ (esu) for a graded gap AlGaAs quantum well and a detuning energy of pump light, 35 meV. The nonlinearity is observable and quite useful for designing an all-optical and ultrafast optical gate.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Heparin-induced thrombocytopenia: a clinical and economic review (2013)

Introduction Heparin-induced thrombocytopenia is a serious immune-mediated, drug adverse effect. Research over the last 20 years has vastly expanded knowledge, awareness and management of this condition. This review includes findings mostly from primary source clinical and economic literature from this time period to synthesise a concise summary. We have highlighted key points regarding the pathophysiology, epidemiology and presentation, diagnosis and management, as well as the economic impact of heparin-induced thrombocytopenia. It is established that heparininduced thrombocytopenia is relatively uncommon overall, despite the widespread use of heparin. However, delayed recognition leads to significantly increased morbidity, mortality and disability. Treatment requires prolonged courses of expensive alternative anticoagulants. All of these impose substantial costs to patients, hospitals and society. The aim of this review was to assess the clinical and economic factors influencing heparin-induced thrombocytopenia. Conclusion Heparin-induced thrombocytopenia remains a significant clinical problem and is associated with morbidity, mortality and disability. Using heparin products can reduce (but not eliminate) the incidence of heparininduced thrombocytopenia. Properly administered treatment with factor Xa inhibitors or direct thrombin inhibitors can significantly decrease the direst complications of this condition and mitigate its economic impact.
Biodistribution and Pharmacokinetics Study of siRNA-loaded Anti-NTSR1-mAb-functionalized Novel Hybrid Nanoparticles in a Metastatic Orthotopic Murine Lung Cancer Model (2016)

Small interfering RNA (siRNA) is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least 48 hours while the naked siRNA formulation showed lack of preferential accumulation in all of the organs monitored. The plasma terminal half-life of nanoparticle-delivered siRNA was 11 times higher (17-1.5 hours) than that of the naked siRNA formulation. The mean residence time and AUClast were 3.4 and 33 times higher than the corresponding naked siRNA formulation, respectively. High-performance liquid chromatography analysis showed that the hybrid nanoparticle carrier system protected the encapsulated siRNA against degradation in vivo. Our novel anti-NTSR1-mAb-functionalized hybrid nanoparticles provide a useful platform for in vivo targeting of siRNA for both experimental and clinical purposes.
Automatic Prediction of Rheumatoid Arthritis Disease Activity from the Electronic Medical Records (2013)

Automatic Rheumatoid Arthritis disease activity discovery from Electronic Medical Record data is a learnable task approximating human performance. As a result, this approach might have several research applications, such as the identification of patients for genome-wide pharmacogenetic studies that require large sample sizes with precise definitions of disease activity and response to therapies.
Delay-based adaptive load balancing in MPLS networks (2003)

In this paper, we propose a new adaptive load balancing mechanism for MPLS networks in that core LSRs are not required to perform traffic engineering. Based on measurements, we obtain the average one-way delay between a pair of label switched routers (LSR), and dynamically distribute traffic load among multiple label switched paths (LSP) according to this average. Simulation results indicate that our approach improves end-to-end throughput and decreases packet loss probability. Our work demonstrates that our algorithm is robust and simple to use.
Parallel-Plate Electrostatic Dual Mass Oscillator (1999)

A surface-micromachined two-degree-of-freedom system that was driven by parallel-plate actuation at antiresonance was demonstrated. The system consisted of an absorbing mass connected by folded springs to a drive mass. The system demonstrated substantial motion amplification at antiresonance. The absorber mass amplitudes were 0.8-0.85 pm at atmospheric pressure while the drive mass amplitudes were below 0.1 pm. Larger absorber mass amplitudes were not possible because of spring softening in the drive mass springs. Simple theory of the dual-mass oscillator has indicated that the absorber mass may be insensitive to limited variations in strain and damping. This needs experimental verification. Resonant and antiresonant frequencies were measured and compared to the designed values. Resonant frequency measurements were difficult to compare to the design calculations because of time-varying spring softening terms that were caused by the drive configuration. Antiresonant frequency measurements were close to the design value of 5.1 kHz. The antiresonant frequency was not dependent on spring softening. The measured absorber mass displacement at antiresonance was compared to computer simulated results. The measured value was significantly greater, possibly due to neglecting fringe fields in the force expression used in the simulation.
Preparation of 3-Methyl-5-aryl-2-cyclohexen-1-ones (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of 3-Methyl-5-aryl-2-cyclohexen-1-onesE. C. Horning and R. E. FieldCite this: J. Am. Chem. Soc. 1946, 68, 3, 384–387Publication Date (Print):March 1, 1946Publication History Published online1 May 2002Published inissue 1 March 1946https://pubs.acs.org/doi/10.1021/ja01207a012https://doi.org/10.1021/ja01207a012research-articleACS PublicationsRequest reuse permissionsArticle Views142Altmetric-Citations11LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
An extracellular mechanism that can explain the neurotoxic effects of α-synuclein aggregates in the brain (2012)

Neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), and Dementia with Lewy bodies (DLB), display an accumulation of proteins including α-synuclein aggregates in cortical and subcortical regions of the brain. PD is a complex, progressive disease which involves damage of motor and cognitive brain regions, as well as autonomic and sensory areas. Since α-synuclein is a neuronal cytosolic protein, it is assumed that pathogenic changes induced by α-synuclein aggregates occur only at the cytoplasmic level. However, recent studies have identified the presence of extracellular α-synuclein, suggesting that the pathogenic action of this protein may also occur in the extracellular milieu through an unknown mechanism. One of the hypotheses is that extracellular α-synuclein aggregates or oligomers may directly disrupt the neuronal membrane by the formation of a pore reminiscent to the ones formed by β-amyloid aggregates. Here, we will review some evidence that support this mechanism, analyzing the interactions of α-synuclein with components of the plasma membrane, the formation of pore/perforated structures, and the implications on ionic dyshomeostasis. Furthermore, we will also discuss how this mechanism can be integrated into a general phenomenon that may explain the synaptotoxicity and neurotoxicity observed in different neurodegenerative diseases.
Relationship between Scattered Intensity and Separation for Particles in an Evanescent Field (2005)

We describe measurements of the scattering of visible light from an evanescent field by both spherical particles (R = 1-10 mum) that are glued to atomic force microscopy (AFM) cantilevers, and by sharp tips (R < 60 nm) that were incorporated onto the cantilevers during manufacture. The evanescent wave was generated at the interface between a flat plate and an aqueous solution, and an atomic force microscope was used to accurately control the separation, h, between the particle and the flat plate. We find that, for sharp tips, the intensity of scattered light decays exponentially with separation between the tip and the plate all the way down to h approximately 0. The measured decay length of scattered intensity, delta, is the same as the theoretical decay length of the evanescent intensity in the absence of the sharp tip. For borosilicate particles, (R = 1-10 mum), the scattering also decays exponentially with separation at large separations. However, when the separation is less than roughly 3delta, the measured scattering intensity is smaller in magnitude than that which would be predicted by extrapolating the exponential decay observed at large separations. For these particles, the scattering approximately fits the sum of two exponentials. The magnitude of the deviation from exponential at contact was roughly 10-15% for R = 1 mum particles and about 30% for larger particles and is larger for s-polarized light. Preliminary experiments on polystyrene particles shows that the scattering is also smaller than exponential at small separations but that the deviation from exponential is larger for p-polarized light. In evanescent wave AFM (EW-AFM) the scattering-separation can be calibrated for situations where the scattering is not exponential. We discuss possible errors that could be introduced by assuming that exponential decay of scattering continues down to h = 0.
Foreign Exchange Volume: Sound and Fury Signifying Nothing? (1995)

Volume in the spot foreign exchange market dwarfs that in any other financial market. But is all this trading informative? This paper provides some empirical evidence. At the broadest level, my results help clarify why trading volume in this market is extraordinarily high. At a narrower level, I provide some sharp results regarding the relation between the intensity of trading and the informa-tiveness of trades. Specifically, I provide results that discriminate between polar views of trad-ing intensity, to which I refer as (1) the event-uncertainty view and (2) the hot potato view. The event-uncertainty view holds that trades are more informative when trading intensity is high; the hot potato view holds that trades are more informative when trading intensity is low. In general, theory admits both possi-bilities, depending primarily on the posited information structure. To understand the event-uncertainty view—that trades are more informative when trading intensity is high—consider the work of Easley and O&apos;Hara (1992). In contrast to earlier models where new information is known to exist,
The traY Gene Product and Integration Host Factor Stimulate Escherichia coli DNA Helicase I-catalyzed Nicking at the F Plasmid oriT (1995)

F plasmid conjugative transfer is initiated by the introduction of a site- and strand-specific nick within the plasmid origin of transfer (oriT). Genetic studies have shown nick formation to be dependent on both the traI and traY genes. However, highly purified TraIp, the traI gene product, nicks oriT in a site- and strand-specific manner in the absence of the traY gene product (TraYp) in vitro (Matson, S.W., and Morton, B.S. (1991) J. Biol. Chem. 266, 16232-16237). Analysis of the oriT region has revealed binding sites for TraYp and the host protein integration host factor (IHF). To explore possible interactions occurring at oriT, highly purified TraIp, TraYp, and IHF were incubated with a supercoiled oriT-containing DNA substrate. A marked enhancement of the nicking reaction catalyzed by TraIp was observed in a reaction that required both TraYp and IHF. In addition, TraIp was able to nick a linear oriT-containing double-stranded DNA substrate when IHF and TraYp were present in the reaction; such a substrate is not nicked by TraIp alone. Individual protein concentration requirements for the supercoiled and linear nicking reactions were similar, and the reactions occurred at equal velocity, suggesting that they are biochemically identical. Concentrations of TraYp and IHF that yield half-maximal activity in the nicking assays compare well with the reported KD values for the IHF and TraYp binding sites in oriT. These data, coupled with data presented in the accompanying report, suggest that TraYp and IHF bind independent of one another, forming a nucleo-protein complex with oriT that can be recognized and nicked by TraIp.
Evaluation of Plasma Resistant Hollow Fiber Membranes For Artificial Lungs (2004)

Hollow fiber membranes (HFMs) used in artificial lungs (oxygenators) undergo plasma leakage (or wetting) in which blood plasma slowly fills the pores of the fiber wall, plasma leaks into gas pathways, and overall gas exchange decreases. To overcome this problem plasma resistant fibers are being developed that are skinned asymmetric or composite symmetric versions of microporous oxygenator fibers. This report evaluates several candidate plasma resistant HFMs in terms of their gas permeance and plasma resistance as measured in a surfactant wet out test. Five candidate fibers were compared with each other and with a control fiber. CO2 and O2 gas permeance (in ml/s/cm2/cm Hg) in the plasma resistant fibers ranged from 3.15E-04 to 1.71E-03 and 3.40E-04 to 1.08E-03, respectively, compared with 1.62E-02 and 1.77E-02 for the control fiber. Maximum dye bleed through for the plasma resistant fibers in the forced wet out test were significantly less than for the control fiber. CO2 gas permeance of a plasma resistant fiber imposes the greatest constraint upon artificial lung design for sufficient gas exchange. However, our results suggest sufficient plasma resistance can be achieved using special skinned and composite HFMs while maintaining an acceptable CO2 gas permeance for a broad range of artificial lung applications.
Synthese optisch aktiver α‐Aminosäuren mit 8‐Azapurinyl‐Seitenkette (1975)

Abstract Durch Umsetzung von 4‐Amino‐6‐chlor‐5‐nitropyrimidin ( 1 ) bzw. 4‐Chlor‐5‐nitro‐6‐oxo‐1,6‐dihydropyrimidin ( 4 ) mit N α ‐Benzyloxycarbonyl‐ L ‐lysin ( 2a ) bzw. 6‐Aminohexansäure ( 2b ) lassen sich 6‐(5‐Nitro‐4‐pyrimidinylamino)hexansäuren ( 3a , b , 5a , b ) darstellen. Nach Reduktion der Nitrogruppe mit Natriumdithionit werden diese mit Natriumnitrit in essigsaurem Medium zu (Triazolo[4,5‐ d ]pyrimidin‐3‐yl)hexansäure‐Derivaten ( 7a , b , 9a , b ) cyclisiert. Die Aminosäure‐derivate 7a und 9a können zu optisch aktiven, 8‐azapurinyl‐substituierten α‐Aminosäuren ( 10 , 11 ) hydriert werden.
PMR polyimides with improved high temperature performance (1975)

Studies were performed to investigate the effect of substituting a hexafluoro isopropyl idene connecting group for a carbonyl group of a PMR polyimide monomeric reactant on the thermo-mechanical properties processability of graphite fiber reinforced PMR polyimide composites. Composites were fabricated utilizing PMR methodology. Monomeric reactant solutions of various stoichiometric ratios were used to impregnate Hercules HTS graphite fiber. The processing characteristics and elevated temperature (600 F) mechanical properties of the composites are described.
Critical evaluation of three analytical techniques for the determination of chromium(<scp>VI</scp>) in soil extracts (1992)

Three different analytical techniques [1,5-diphenylcarbazide spectrophotometry, chelating ion-exchange chromatography (Chelex-100), and ion-pairing reversed-phase high-performance liquid chromatography (RP-HPLC) combined with electrothermal atomic absorption spectrometry (ETAAS)] were critically evaluated for the determination of CrVI in soil extracts. Spectrophotometry was not applicable to the analysis of most soil extract samples owing to its high limit of detection (LOD = 30 ng cm–3), and the possibility of the instantaneous reduction of CrVI under the acidic conditions employed. A Chelex 100 column, although adequately sensitive (LOD = 1.5 ng cm–3), is inclined to give higher results as inhert and moderately labile CrIII complexes partially passed through the resin together with CrVI. In addition, very small particles (<0.45 µm) carrying chromium can produce severe positive systematic errors. In order to avoid this, filtration employing a 0.1 µm filter is recommended. Ion-pairing RP-HPLC was found to be the most sensitive technique (LOD = 0.3 ng cm–3). It might also give high chromate results if negatively charged CrIII complexes form ion pairs with tetrabutylammonium phosphate and their elution partially coincided with that of CrVI. Fulvate ligands showed this type of interference. Reversed-phase HPLC is not suitable for analysis of extracts obtained from soils with freshly added tannery waste owing to the effects of the undestroyed tannery waste matrix. This study showed that each method investigated was vulnerable to some type of interference.