gebhart/patrepeval huggingface dataset:
&amp;#947;-Secretase Inhibitors and Modulators for the Treatment of Alzheimer's Disease: Disappointments and Hopes (2011)

According to the β-amyloid (Aβ) hypothesis, compounds that inhibit or modulate γ secretase, the pivotal enzyme that generates Aβ, are potential therapeutics for Alzheimer's disease (AD). Studies in both transgenic and non-transgenic animal models of AD have indicated that γ-secretase inhibitors, administered by the oral route, are able to lower brain Aβ concentrations. However, scanty data are available on the effects of these compounds on brain Aβ deposition after chronic administration. Behavioral studies are also scarce with only one study indicating positive cognitive effects of a peptidomimetic compound acutely administered (DAPT). γ-Secretase inhibitors may cause abnormalities in the gastrointestinal tract, thymus, spleen and skin in experimental animals and in man. These toxic effects are likely due to inhibition of Notch cleavage, a transmembrane receptor involved in regulating cell-fate decisions. Some non-steroidal anti-inflammatory drugs (NSAIDs) and other small organic molecules have been found to modulate γ secretase shifting its cleavage activity from longer to shorter β-amyloid species without affecting Notch cleavage. Long-term histopathological and behavioral animal studies are available with these NSAIDs (mainly ibuprofen) but it is unclear if the observed in vivo effects on Aβ brain pathology and learning depend on their activity on γ-secretase or on other biological targets. The most studied γ-secretase inhibitor, semagacestat (LY-450139), was shown to dose-dependently decrease the generation of Aβ in the cerebrospinal fluid of healthy humans. Unfortunately, two large Phase 3 clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of detrimental effects on cognition and functionality in patients receiving the drug compared to those receiving placebo. These detrimental effects were mainly ascribed to the inhibition of Notch processing and to the accumulation of the neurotoxic precursor of Aβ (the carboxy-terminal fragment of APP, or CTFβ) resulting from the block of the γ-secretase cleavage activity on APP. Two large Phase 3 studies in mild AD patients with tarenflurbil (R flurbiprofen), a putative γ-secretase modulator, were also completely negative. The failure of tarenflurbil was ascribed to low potency and brain penetration. New Notch-sparing γ-secretase inhibitors and more potent, more brain penetrant γ-secretase modulators are being developed with the hope of overcoming the previous setbacks.
Combined flow cytometry and confocal laser scanning microscopy for evaluation of BR96 antibody cancer cell targeting and internalization (2007)

The spatial-temporal pattern by BR96 cell targeting and internalization processes of BR96/LeY into the cancer cells expressing LeY was demonstrated by FCM and CLSM. Used together, the FCM and CLSM techniques provide a valuable tool for preclinical analyses of antibody targeting and their capacities as carriers of cytotoxic conjugates for the use in cancer therapy.
Quasi-static and Dynamic Torsion Testing of Ceramic Micro and Nano-structured Coatings Using Speckle Photography (2006)

An experimental methodology for the quasi-static and dynamic testing of Al2O3/TiO2 and WC/Co coatings on aluminum substrates is presented. A stored energy Kolsky bar apparatus was used for both quasi-static and dynamic loading. Acquisition of speckle images at different loading stages allowed the determination of the shear strains in the gage region of the specimen and the identification of deformation mechanisms as a function of coating grain size. The interaction between coating and substrate is investigated by correlating damage to measured stress-strain curves. It was identified that as cracks develop in the coating, they are bridged by the underlying ductile substrate. Optical and SEM interrogation of the coating fracture surface also show a low percentage of porosity and severe damage created by residual stresses. These residual stresses arise during the coating manufacturing process. The pre-existing damage is believed to be the cause of the low shear moduli and strengths exhibited by the coatings. A comparison between quasi-static and dynamic response is carried out, to assess strain-rate effects, as well as micro versus nano grain size coatings of the same composition.
Biological Monitoring of Hexavalent Chromium and Serum Levels of the Senescence Biomarker Apolipoprotein J/Clusterin in Welders (2008)

Welding fumes contain metals and other toxic substances known or strongly suspected to be related with oxidative stress and premature cellular senescence. Apolipoprotein J/Clusterin (ApoJ/CLU) is a glycoprotein that is differentially regulated in various physiological and disease states including ageing and age-related diseases. In vitro data showed that exposure of human diploid fibroblasts to hexavalent chromium (Cr(VI)) resulted in premature senescence and significant upregulation of the ApoJ/CLU protein. In this study we analyzed blood and urine samples from shipyard industry welders being exposed to different levels of Cr(VI) over a period of five months in order to assay in vivo the relation of ApoJ/CLU serum levels with Cr(VI). Our findings confirmed the previously reported in vitro data since reduction of Cr levels, after a worksite intervention, associated with lower levels of ApoJ/CLU serum levels. We concluded that the human ApoJ/CLU gene is responsive to the acute in vivo oxidative stress induced by heavy metals such as hexavalent chromium.
Data-Driven Network Path Simulation with iBox (2022)

While network simulation is widely used for evaluating network protocols and applications, ensuring realism remains a key challenge. There has been much work on simulating network mechanisms faithfully (e.g., links, buffers, etc.), but less attention on the critical task of configuring the simulator to reflect reality. We present iBox ("Internet in a Box"), which enables data-driven network path simulation, using input/output packet traces gathered at the sender/receiver in the target network to create a model of the end-to-end behaviour of a network path. Our work builds on recent work in this direction and makes three contributions: (1) estimation of a lightweight non reactive cross-traffic model, (2) estimation of a more powerful reactive cross-traffic model based on Bayesian optimization, and (3) evaluation of iBox in the context of congestion control variants in an Internet research testbed and also controlled experiments with known ground truth.
Syntheses of 3-[(Alkylamino)methylene]-6-methylpyridine-2,4(1H,3H)-diones, 3-Substituted 7-Methyl-2H-pyrano[3,2-c]pyridine-2,5(6H)-dione Fluorescence Probes, and Tetrahydro-1H,9H-2,10-dioxa-9-azaanthracen-1-ones (2014)

Various condensation and ring-closing reactions were used for the syntheses of 3-[(alkylamino)methylene]-6-methylpyri-dine-2,4(1<i>H</i>,3<i>H</i>)-diones, bicyclic pyridinones, and tricyclic morpholinopyrones. For instance, 3-[(dialkylamino)methylene]-6-methylpyridine-2,4(1<i>H</i>,3<i>H</i>)-diones were synthesized from the condensation of dialkylamines and 3-formyl-4-hydroxy-6-methylpyridin-2(1<i>H</i>)-one. 3-Formyl-4-hydroxy-6-methylpyridin-2(1<i>H</i>)-one, derived from 3-formyl-4-hydroxy-6-methylpyridin-2(1<i>H</i>)-one, was used to construct a number of bicyclic pyridinones via a one-pot Knoevenagal and intramolecular lactonization reaction. Tricyclic morpholinopyrones were assembled from a dialkylation reaction involving a dinucleophile, 3-amino-4-hydroxy-6-methyl-2<i>H</i>-pyran-2-one, and a dielectrophile, <i>trans</i>-3,6-dibromocyclohexene. Depending on the reaction conditions, isomers of the tricyclic molecules can be selectively produced, and their chemical structures were unequivocally determined using single-crystal X-ray analyses and 2D COSY spectroscopy. The fluorescently active bicyclic pyridinone compounds show longer absorption (368-430 nm; maximum) and emission wavelengths (450-467 nm) than those of 7-amino-4-methylcoumarin (AMC; λ<sub>abs,max</sub> = 350 nm; λ<sub>em</sub> = 430 nm) suggesting these molecules, such as 3-(2-aminoacetyl)-7-methyl-2<i>H</i>-pyrano[3,2-<i>c</i>]pyridine-2,5(6<i>H</i>)-dione, can be employed as fluorescence activity based probes for tracing biological pathways.
Gain reciprocity in fibre optical parametric amplifiers (2006)

A fibre optical parametric ampifier operating in the small-signal gain regime can exhibit the same gain when amplifying in either direction. This is true even in the presence of random dispersion and birefringence variations along the fibre.
Water-cooled stacked-actuator deformable mirror for atmospheric applications (2019)

High-power laser systems are widely used for technological purposes or laser fusion experiments, but also to deliver the energy to some remote places here on the Earth as well as in space. Probably the only instrument to improve the phase structure of the laser beam is to use methods and elements of adaptive optics. The heart of any adaptive optical system is of course the deformable mirror. That is why the research and development of such optical elements continues for many years already. Here we propose a new stacked actuator mirror to be used to correct for not just the turbulent phase fluctuations, but also it should work with high CW power laser beams. Therefore, our mirror is a water-cooled one. Another important feature of this device is that each actuator could be easily substituted in case of failure. The mirror is 120 mm in diameter and has 121 control elements. Main characteristics of a mirror are presented in this work.
High-Spin ( <i>S</i> = 1) Blatter-Based Diradical with Robust Stability and Electrical Conductivity (2022)

Triplet ground-state organic molecules are of interest with respect to several emerging technologies but usually show limited stability, especially as thin films. We report an organic diradical, consisting of two Blatter radicals, that possesses a triplet ground state with a singlet-triplet energy gap, Δ<i>E</i><sub>ST</sub> ≈ 0.4-0.5 kcal mol<sup>-1</sup> (2<i>J</i>/<i>k</i> ≈ 220-275 K). The diradical possesses robust thermal stability, with an onset of decomposition above 264 °C (TGA). In toluene/chloroform, glassy matrix, and fluid solution, an equilibrium between two conformations with Δ<i>E</i><sub>ST</sub> ≈ 0.4 kcal mol<sup>-1</sup> and Δ<i>E</i><sub>ST</sub> ≈ -0.7 kcal mol<sup>-1</sup> is observed, favoring the triplet ground state over the singlet ground-state conformation in the 110-330 K temperature range. The diradical with the triplet ground-state conformation is found exclusively in crystals and in a polystyrene matrix. The crystalline neutral diradical is a good electrical conductor with conductivity comparable to the thoroughly optimized bis(thiazolyl)-related monoradicals. This is surprising because the triplet ground state implies that the underlying π-system is cross-conjugated and thus is not compatible with either good conductance or electron delocalization. The diradical is evaporated under ultra-high vacuum to form thin films, which are stable in air for at least 18 h, as demonstrated by X-ray photoelectron and electron paramagnetic resonance (EPR) spectroscopies.
Liquidus Temperature Data for DWPF Glass (1999)

This report provides new liquidus temperature (TL) versus composition data that can be used to reduce uncertainty in TL calculation for DWPF glass. According to the test plan and test matrix design PNNL has measured TL for 53 glasses within and just outside of the current DWPF processing composition window. The TL database generated under this task will directly support developing and enhancing the current TL process-control model. Preliminary calculations have shown a high probability of increasing HLW loading in glass produced at the SRS and Hanford. This increase in waste loading will decrease the lifecycle tank cleanup costs by decreasing process time and the volume of waste glass produced.
Confidential Inference via Ternary Model Partitioning (2018)

Today's cloud vendors are competing to provide various offerings to simplify and accelerate AI service deployment. However, cloud users always have concerns about the confidentiality of their runtime data, which are supposed to be processed on third-party's compute infrastructures. Information disclosure of user-supplied data may jeopardize users' privacy and breach increasingly stringent data protection regulations. In this paper, we systematically investigate the life cycles of inference inputs in deep learning image classification pipelines and understand how the information could be leaked. Based on the discovered insights, we develop a Ternary Model Partitioning mechanism and bring trusted execution environments to mitigate the identified information leakages. Our research prototype consists of two co-operative components: (1) Model Assessment Framework, a local model evaluation and partitioning tool that assists cloud users in deployment preparation; (2) Infenclave, an enclave-based model serving system for online confidential inference in the cloud. We have conducted comprehensive security and performance evaluation on three representative ImageNet-level deep learning models with different network depths and architectural complexity. Our results demonstrate the feasibility of launching confidential inference services in the cloud with maximized confidentiality guarantees and low performance costs.
Growth Conditions Influence Expression of Cell Surface Hydrophobicity of Staphylococci and Other Wound Infection Pathogens (1995)

The initial adhesion of microbes to tissue and solid surfaces can be mediated by hydrophobic interaction. Expression of microbial cell surface hydrophobicity (CSH) is influenced by growth conditions, and often best expressed after growth under nutrient-poor conditions, or "starvation". In the present study, the CSH of 133 strains of Enterobacteriaceae, Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, group A streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Bacteroides fragilis, Peptococcus magnus, and of 8 Candida albicans strains was measured by the salt aggregation test after growth on hematin agar in a 5% CO2 atmosphere, or under anaerobiosis. Cells of all but 8 strains expressed pronounced or moderate CSH, i.e., they aggregated in 0.01-2 M ammonium sulfate. When the agar surface was covered by human serum (diluted 1:5) to mimic growth conditions in a wound, 94 strains expressed higher CSH, and 44 strains the same CSH as after growth without serum. The CSH of 12 strains of different species was measured after growth on blood, hematin and PDM agar, with or without serum, and in an aerobic or a 5% CO2 atmosphere. The highest CSH was expressed after growth in 5% CO2 with serum, and the lowest growth after on blood agar in aerobic atmosphere. Identical results were obtained with native and heat-inactivated (56 C, 20 min) serum. The reduced surface tension obtained in 5% CO2, as well as yet unidentified serum factors, promotes expression of CSH.
Extreme Elevation of Serum Growth Hormone-Binding Protein Concentrations Resulting from a Novel Heterozygous Splice Site Mutation of the Growth Hormone Receptor Gene (2009)

In silico analysis of the altered sequence suggested that 785-3(C>A) is a splicing mutation, with either retention of intron 7 or the skipping of exon 8. The consequence is a truncated GHR lacking the transmembrane domain (encoded by exon 8) and the cytoplasmic domain. We hypothesize that this GHR variant cannot anchor to the cell membrane, and the continual secretion into the circulation explains the elevated levels of serum GHBP detected in the patient and his mother. Despite this mutation, the presence of the wild-type GHR allele, presumably, permits some normality in GH-induced action.
Controlling nucleation of the cyclic heteropolyanion {P<sub>8</sub>W<sub>48</sub>}: a cobalt-substituted phosphotungstate chain and network (2008)

Two cyclic cobalt-substituted heteropolyoxometalates K15Li5[Co10(H2O)34(P8W48O184)]·54H2O (1) and K8Li12[Co10(H2O)44(P8W48O184)]·60H2O (2) have been synthesised from the reaction of Co(II) ions and the superlacunary {P8W48} polyanion in mildly acidic aqueous media. The cluster's anion cavities are filled with Co(II) and K cations and careful manipulation of reaction conditions determines the formation of distinct Co-linked frameworks.
&lt;title&gt;Acousto-optic precision direction-finding system&lt;/title&gt; (1993)

The Acousto-Optic Precision Direction Finding (AOPDF) system is a demonstration EW receiver in development at the Naval Research Laboratory as a DARPA sponsored activity. A two-dimensional Acousto-Optic processing element extracts frequency, angle of arrival (AOA), and time of arrival (TOA) on a pulse-by-pulse basis. Performance advantages achieved through use of Acousto-Optic technology include a wide instantaneous RF bandwidth, multiple simultaneous signal capture, and accurate AOA measurement over a quadrant field of view. This paper describes the conceptual design, system development, and evaluation of a demonstration unit based on the AOPDF concept.
A Novel Momentum-Preserving Energy-Decaying Algorithm for Finite Element Multibody Procedures (2000)

We present a new methodology for the integration of general non-linear multibody systems within a finite-element framework, with special attention to numerical robustness. The outcome is a non-linearly unconditionally stable algorithm with dissipation properties. This algorithm exactly preserves the total linear and angular momenta of holonomically constrained multibody systems, which implies the satisfaction of Newton's Third law of Action and Reaction. Furthermore, the scheme strictly dissipates the total mechanical energy of the system. This is accomplished by selective damping of the unresolved high-frequency components of the response. We derive the governing equations relying on the 6-D compact representation of motion and we employ a parameterization based on the Cayley transform which ensures geometric invariance of the resulting numerical schemes. We present some numerical tests in order to illustrate the main features of the methodology, and to demonstrate the properties predicted in the analysis.
Output-Only Subspace-Based Damage Detection - Application to a Reticular Structure (2003)

The output-only vibration-based structural health monitoring problem is addressed as the task of detecting damages modeled as changes in the eigenstructure of a linear dynamic system. The proposed damage detection algorithm is based on a residual generated from a subspace-based covariance-driven identification method and on the statistical local approach to the design of detection algorithms. This algorithm computes a global test, which performs a sensitivity analysis of the residuals to the damages, relative to uncertainties and noises. Numerical results are reported, which show the efficiency of the proposed method. They have been obtained on a geometrically simple test article designed, assembled and tested dynamically under impact and random shaker excitation. The method allows detecting damage in an early stage, and it does not require the extraction of the modal parameters from each newly collected data set. This characteristic is very well suited for monitoring purposes: it does not need continuous user interaction and it can easily be made automatic.
Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon (2000)

The mercury rejected in the water system, from mining operations and lixiviation of soils after deforestation, is considered to be the main contributors to the contamination of the ecosystem in the Amazon Basin. The objectives of the present study were to examine cytogenetic functions in peripheral lymphocytes within a population living on the banks of the Tapajós River with respect to methylmercury (MeHg) contamination, using hair mercury as a biological indicator of exposure. Our investigation shows a clear relation between methylmercury contamination and cytogenetic damage in lymphocytes at levels well below 50 micrograms/gram, the level at which initial clinical signs and symptoms of mercury poisoning occur. The first apparent biological effect with increasing MeHg hair level was the impairment of lymphocyte proliferation measured as mitotic index (MI). The relation between mercury concentration in hair and MI suggests that this parameter, an indicator of changes in lymphocytes and their ability to respond to culture conditions, may be an early marker of cytotoxicity and genotoxicity in humans and should be taken into account in the preliminary evaluation of the risks to populations exposed in vivo. This is the first report showing clear cytotoxic effects of long-term exposure to MeHg. Although the results strongly suggest that, under the conditions examined here, MeHg is both a spindle poison and a clastogen, the biological significance of these observations are as yet unknown. A long-term follow-up of these subjects should be undertaken.
Continuous feedback fluid queues (2003)

We investigate a fluid buffer which is modulated by a stochastic background process, while the momentary behavior of the background process depends on the current buffer level in a continuous way. Loosely speaking the feedback is such that the background process behaves `as a Markov process' with generator $Q(y)$ at times when the buffer level is $y$, where the entries of $Q(y)$ are continuous functions of $y$. Moreover, the flow rates for the buffer may also depend continuously on the current buffer level. Such models are interesting in the context of closed-loop telecommunication networks, in which sources interact with network buffers, but may also be deployed in the study of certain production systems.
Nopal (Opuntia ficus indica) protects from metabolic endotoxemia by modifying gut microbiota in obese rats fed high fat/sucrose diet (2017)

Current efforts are directed to reducing the gut dysbiosis and inflammation produced by obesity. The purpose of this study was to investigate whether consuming nopal, a vegetable rich in dietary fibre, vitamin C, and polyphenols can reduce the metabolic consequences of obesity by modifying the gut microbiota and preventing metabolic endotoxemia in rats fed a high fat and sucrose diet. With this aim, rats were fed a high fat diet with 5% sucrose in the drinking water (HFS) for 7 months and then were fed for 1 month with HFS + 5% nopal (HFS + N). The composition of gut microbiota was assessed by sequencing the 16S rRNA gene. Nopal modified gut microbiota and increased intestinal occludin-1 in the HFS + N group. This was associated with a decrease in metabolic endotoxemia, glucose insulinotropic peptide, glucose intolerance, lipogenesis, and metabolic inflexibility. These changes were accompanied by reduced hepatic steatosis and oxidative stress in adipose tissue and brain, and improved cognitive function, associated with an increase in B. fragilis. This study supports the use of nopal as a functional food and prebiotic for its ability to modify gut microbiota and to reduce metabolic endotoxemia and other obesity-related biochemical abnormalities.
Progress Towards the Development of Anti-Inflammatory Inhibitors of IKK&amp;#946; (2009)

The IkappaB kinases (IKKs) are essential components of the signaling pathway by which the NF-kappaB p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNFalpha). NF-kappaB signaling results in the expression of numerous genes involved in innate and adaptive immune responses. The pathway is also implicated in chronic inflammatory disorders including rheumatoid arthritis (RA), chronic obstructive pulmonary disorder (COPD), and asthma. Inhibition of the kinase activity of the IKKs is therefore a promising mechanism for intervention in these diseases. Here, we will review the literature describing small molecule inhibitors of IKKbeta (IKK2), the most widely studied of the IKKs.