gebhart/patrepeval huggingface dataset:
Sphingosine-induced apoptosis is dependent on lysosomal proteases (2001)

We propose a new mechanism for sphingosine-induced apoptosis, involving relocation of lysosomal hydrolases to the cytosol. Owing to its lysosomotropic properties, sphingosine, which is also a detergent, especially when protonated, accumulates by proton trapping within the acidic vacuolar apparatus, where most of its action as a detergent would be exerted. When sphingosine was added in low-to-moderate concentrations to Jurkat and J774 cells, partial lysosomal rupture occurred dose-dependently, starting within a few minutes. This phenomenon preceded caspase activation, as well as changes of mitochondrial membrane potential. High sphingosine doses rapidly caused extensive lysosomal rupture and ensuing necrosis, without antecedent apoptosis or caspase activation. The sphingosine effect was prevented by pre-treatment with another, non-toxic, lysosomotropic base, ammonium chloride, at 10mM. The lysosomal protease inhibitors, pepstatin A and epoxysuccinyl-l-leucylamido-3-methyl-butane ethyl ester (‘E-64d’), inhibited markedly sphingosine-induced caspase activity to almost the same degree as the general caspase inhibitor benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone (‘Z-VAD-FMK’), although they did not by themselves inhibit caspases. We conclude that cathepsin D and one or more cysteine proteases, such as cathepsins B or L, are important mediators of sphingosine-induced apoptosis, working upstream of the caspase cascade and mitochondrial membrane-potential changes.
The Where, When, How, and Why of Hyaluronan Binding by Immune Cells (2015)

Hyaluronan is made and extruded from cells to form a pericellular or extracellular matrix (ECM) and is present in virtually all tissues in the body. The size and form of hyaluronan present in tissues are indicative of a healthy or inflamed tissue, and the interactions of hyaluronan with immune cells can influence their response. Thus, in order to understand how inflammation is regulated, it is necessary to understand these interactions and their consequences. Although there is a large turnover of hyaluronan in our bodies, the large molecular mass form of hyaluronan predominates in healthy tissues. Upon tissue damage and/or infection, the ECM and hyaluronan are broken down and an inflammatory response ensues. As inflammation is resolved, the ECM is restored, and high molecular mass hyaluronan predominates again. Immune cells encounter hyaluronan in the tissues and lymphoid organs and respond differently to high and low molecular mass forms. Immune cells differ in their ability to bind hyaluronan and this can vary with the cell type and their activation state. For example, peritoneal macrophages do not bind soluble hyaluronan but can be induced to bind after exposure to inflammatory stimuli. Likewise, naïve T cells, which typically express low levels of the hyaluronan receptor, CD44, do not bind hyaluronan until they undergo antigen-stimulated T cell proliferation and upregulate CD44. Despite substantial knowledge of where and when immune cells bind hyaluronan, why immune cells bind hyaluronan remains a major outstanding question. Here, we review what is currently known about the interactions of hyaluronan with immune cells in both healthy and inflamed tissues and discuss how hyaluronan binding by immune cells influences the inflammatory response.
Real-Time In-Memory Checkpointing for Future Hybrid Memory Systems (2015)

In this paper, we study real-time in-memory checkpointing as an effective means to improve the reliability of future large-scale parallel processing systems. Under this context, the checkpoint overhead can become a significant performance bottleneck. Novel memory system designs with upcoming non-volatile random access memory (NVRAM) technologies are emerging to address this performance issue. However, we find that those designs can still have prohibitively high checkpoint overhead and system downtime, especially when checkpoints are taken frequently to implement a reliable system. In this paper, we propose a novel in-memory checkpointing system, named Mona, for reducing the checkpoint overhead of hybrid memory systems with NVRAM and DRAM. To minimize the in-memory checkpoint overhead, Mona dynamically writes partial checkpoints from DRAM to NVRAM during application execution. To reduce the interference of partial checkpointing, Mona utilizes runtime idle periods and leverages a cost model to guide partial checkpointing decisions for individual DRAM ranks. We further develop load-balancing mechanisms to balance checkpoint overheads across different DRAM ranks. Simulation results demonstrate the efficiency and effectiveness of Mona in reducing the checkpoint overhead, downtime and restarting time.
High-potency benzodiazepines: recent clinical results. (2004)

As high-potency benzodiazepines, essentially alprazolam, clonazepam, and lorazepam, have been used to treat anxiety disorders for almost 2 decades, most efficacy and safety data appeared several years ago. The release of new formulations of 2 of them, clonazepam and alprazolam, invites review of these broadly effective anxiolytics. Clonazepam has recently become available in a lyophilized wafer that disintegrates when exposed to saliva and enhances ease of administration without altering its pharmacology, as shown by bioequivalence studies. Two U.S. multicenter trials carried out in the 1990s, among others, have provided strong confirmatory evidence for the use of clonazepam in panic disorder. Other recently published data on clonazepam pertain to its use as augmentation therapy with selective serotonin reuptake inhibitors and in the prevention of recurrences of major depressive disorder. A new, extended-release formulation of alprazolam now allows for once-daily rather than t.i.d. or q.i.d. dosing. With extended release, the blood drug concentrations of alprazolam remain within the therapeutic window for several hours, which should reduce fluctuation in therapeutic effect and curb the clock-watching phenomenon between doses. The literature concerning the use of this new formulation of alprazolam in panic disorder is reviewed.
Situation Analysis for Fighter Aircraft Combat Survivability (2011)

Fighter pilots operate in environments where an erroneous decision may have fatal consequences. A tactical decision support system (TDSS) could aid the pilots to analyze the situation and make correct decisions. The TDSS can, for instance, highlight important information and suggest suitable actions. The aim of this thesis is to provide a situation analysis model of combat survival that can be utilized in a TDSS. The first part of this thesis describes an analysis of what the model needs to describe and how it can be used. It is concluded that the model should evaluate the outcome of different actions with respect to combat survival. This evaluation can guide the pilot’s decision making, so that actions leading to dangerous situations are avoided. The analysis also highlights the need of handling uncertainties, both measurement precision uncertainty regarding the locations and capabilities of the threats (enemies) and inference uncertainties regarding the prediction of how the threats will act. Finally, arguments for focusing the rest of the work on a single fighter aircraft and threats located on the ground are presented. The second part of the thesis suggests a model, which describes the survivability, i.e., the probability that the aircraft can fly a route without being hit by fire from ground-based threats. Thus, the model represents the inference uncertainty, since it describes the probability of survival. The model’s characteristics are discussed, e.g., that the model is implementable and can be adapted to describe different kinds of ground-based threats. Uncertainty in terms of measurement precision influences the estimate of the survivability. Two different ways of representing this is discussed: calculating the worst case scenario or describing the input as random variables and the resulting survivability as a random variable with a probability distribution. Monte Carlo simulations are used for estimating the distribution for survivability in a few illustrative scenarios, where the input is represented as random variables. The simulations show that when the uncertainty in input is large, the survivability distribution may be both multimodal and mixed. Two uncertainty measures are investigated that condense the information in the distributions into a single value: standard deviation and entropy. The simulations show that both of these measures reflect the uncertainty. Furthermore, the simulations indicate that the uncertainty measures can be used for sensor management, since they point out which information that is the most valuable to gather in order to decrease the uncertainty in the survivability. Finally, directions for future work are suggested. A number of TDSS functions that can be developed based on the model are discussed e.g., warnings, countermeasure management, route-planning and sensor management. The design of these functions could require extending the threat model to incorporate airborne threats and the effects of countermeasures. Further investigations regarding the uncertainty in the model are also suggested.
A new non-linear GARCH model (1997)

This dissertation contains four papers in the field of financial econometrics. In the first paper, A Smooth Transition ARCH Model for Asset Returns, a new class of ARCH models is introduced. The model class allows for non-linearity in the equation for the conditional variance. Two forms of non-linearity are considered: (i) asymmetry regarding the sign of residuals, and (ii) non-linearity regarding the size of residuals. Furthermore, specification tests for the models are presented. The second paper, Specification Tests for Asymmetric GARCH, presents two new Lagrange multiplier test statistics designed for testing the null of GARCH(1,1), against the alternative of asymmetric GARCH. Small sample properties for the statistics are presented and the power of both tests is shown to be superior to that of previously proposed tests. This is true for a large group of asymmetric GARCH models, providing that the proposed tests can detect general GARCH asymmetry. The third paper, Modeling Nordic Stock Returns with Asymmetric GARCH models, investigates the presence of asymmetric GARCH effects in a number of equity return series, and compares the modeling performance of seven different asymmetric GARCH models. The data consists of daily returns for 45 Nordic stocks, for the period July 1991 to July 1996. The paper also introduces three new procedures for asymmetry testing. The proposed LM tests allow for heterokurtosis under the null. The final paper, Discrete Time Hedging of OTC Options in a GARCH Environment: A Simulation Experiment, examines the effect of using the Black and Scholes formula for pricing and hedging options in a discrete time heteroskedastic environment using a simulation procedure. It is shown that the variance of the returns on the hedged position is considerably higher in a GARCH(1,1) environment than in a homoskedastic environment. The variance of returns is heavily dependent on the level of kurtosis in the returns process and on the first-order autocorrelation in centered and squared returns.Each paper is self-contained and can be read in an order chosen by the reader.In an introductory chapter, the reader is given a general summary of the ARCH literature and will gain a clear understanding of how the four essays relate to previous work in the econometrics and finance literature, and to practical considerations of econometric modeling.
Resolution enhancement in passive SAR imaging using distributed multiband fusion (2013)

Taking advantage of the spectrum diversity of multiple emitters, we present a `fusion-before-imaging' method for passive synthetic aperture radar (SAR) imaging to effectively fuse target signature data from multiple receivers in order to achieve a synthesized target reflectivity with a broader bandwidth coverage. The proposed method jointly compensates the phase offsets among sub-band signals due to geographically varied bistatic radar configurations and estimates the missing spectral data to mitigate the image artifacts in conventional direct Fourier based imaging technique.
Toll‐Like Receptor (TLR)4 and MyD88 are Essential for Atheroprotection by Peritoneal B1a B Cells (2016)

TLR4-MyD88 expression on B1a cells is critical for their IgM-dependent atheroprotection that not only reduced lesion apoptotic cells and necrotic cores, but also decreased CD4 and CD8 T-cell infiltrates and augmented TGF-β1 expression accompanied by reduced lesion inflammatory cytokines TNF-α, IL-1β, and IL-18.
BOREHOLE-TYPE TILTMETER AND THREE-COMPONENT STRAINMETER FOR EARTHQUAKE PREDICTION (1986)

Borehole-type instruments have many advantages over the conventional instruments usually installed in vaults. The primary merit is that the location is not restricted by geomorphic conditions. This decisively helps us to establish an observation network in a plain field area for earthquake prediction. The borehole-type tiltmeter developed is, as a principle, a pendulum tiltmeter with an electric feedback circuit. Tiltmeters are usually installed in boreholes at depths of about 100 m. Now, we have 23 stations in operation in the Kanto-Tokai area, central Japan. The measuring range is 400 microradian, the resolution is 0.006 microradian, and the long-term stability is better than a few microradian per year. This observation system is expected to be very effective for detecting anomalous tilt changes of the order of 0.05 microradian per day with a time constant of from several hours to tens of days. Recently, an anomalous tilt change of up to 0.4 microradian was detected in the vicinity of the focal area preceding an earthquake of magnitude 6.0. The borehole-type three-component strainmeter invented has a dual cylinder of which the narrow clearance is equally divided into three chambers. Two sets of strainmeters of this type were installed in two boreholes at depths of 160 m at Yasato, Ibaraki-ken. They have often detected strain steps caused by big earthquakes. Detectable strain steps can be as small as 10-10. Strain steps observed by the two instruments agree with each other very well, and are in good harmony with the theoretical strain steps calculated on dislocation models. These facts have proven that instruments of this type have high credibility. Such high performances can be attributed to the fact that the whole system is free from solid friction and less affected by shock and vibration at the time of earthquakes. The future plan is to unify the tiltmeter and the three-component strainmeter to one unit which would be called the Integrated Borehole Observation System (IBOS).
Evaluation of RT-PCR as a Tool for Diagnosis of Secondary Dengue Virus Infection (2003)

Dengue fever and dengue hemorrhagic fever are serious illnesses in many tropical and subtropical countries. Laboratory tests are essential for the confirmation of dengue virus infection. In the present study, we examined the reliability of reverse transcriptase polymerase chain reaction (RT-PCR) in the laboratory diagnosis of dengue, especially in secondary dengue virus infections. We defined the day when fever subsided as fever day 0. In primary dengue virus infection, the dengue viral genome was detected in all of the 7 samples which were collected on fever day -1 or earlier, in 3 of 4 samples on fever day 0, and in 1 of 2 samples on fever day 1. None of the samples collected on fever day 2 or later were positive by RT-PCR. In secondary dengue virus infection, the dengue viral genome was detected in all of the 28 samples which were collected on fever day -2 or earlier, in 25 of 26 on fever day -1, in 29 of 34 on fever day 0, and in 5 of 10 on fever days 1-2. None of the samples collected on fever day 3 or later were positive. Virus isolation and direct titration were attempted using the plasma samples. When the data of secondary infection cases were analyzed based on fever day, dengue viruses were isolated from all of the 5 samples which were collected on fever day -2 or earlier, in 5 of 13 samples on fever day -1, and in 4 of 22 on fever day 0, but were not isolated from any of the 4 samples collected on fever days 1-2. Viruses were directly detected in 7 of 11 samples on fever day -2 or earlier, in 4 of 13 on fever day -1, and in 1 of 16 on fever day 0. These results indicate that RT-PCR is more sensitive than virus isolation and direct virus titration for determining secondary dengue virus infection. The results also suggest that RT-PCR is a useful diagnostic test for confirmation of dengue virus infection in secondary infection as well as in primary infection, especially when plasma samples are collected before the fever subsides.
Compression of 1.8 μm laser pulses to sub two optical cycles with bulk material (2010)

We demonstrate a simple scheme to generate 0.4 mJ 11.5 fs laser pulses at 1.8 μm. Optical parametrically amplified pulses are spectrally broadened by nonlinear propagation in an argon-filled hollow-core fiber and subsequently compressed to 1.9 optical cycles by linear propagation through bulk material in the anomalous dispersion regime. This pulse compression scheme is confirmed through numerical simulations.
Effects of Massed versus Distributed Practice on Gross and Fine Motor Proficiency of Educable Mentally Handicapped Adolescents (1991)

Gross and fine motor proficiency were studied in a sample of 52 educable mentally handicapped students (M = 15.8 yr.), half of whom were assigned to 15 30-sec. trials, a relatively massed practice schedule with 5 sec. between trials, and half to a distributed practice schedule with 30-sec. rests. 5 trials were given 24 hr. later. All subjects performed the stabilometer balance task to measure gross motor proficiency and a 45-rpm pursuit rotor task to measure fine motor proficiency. No significant differences with regard to the practice schedule used early in learning were found, however, boys scored significantly higher on the pursuit rotor than girls.
Mapping of the Rat's Motor Area after Hemispherectomy: The Hemispheres as Potentially Independent Motor Brains (2003)

The results suggest that each motor area has the latent capacity to control motricity bilaterally, and that such capacity is brought into function after removal of the opposite hemisphere. The same neuronal population that gives afference to one segment contralaterally seems to give afference to the same segment ipsilaterally.
Improving Digital-to-Analog Converter Linearity by Large High-Frequency Dithering (2016)

A new method for reducing harmonic distortion due to element mismatch in digital-to-analog converters is described. This is achieved by using a large high-frequency periodic dither. The reduction in nonlinearity is due to the smoothing effect this dither has on the nonlinearity, which is only dependent on the amplitude distribution function of the dither. Since the high-frequency dither is unwanted in the output of the digital-to-analog converter, the dither is removed by an output filter. The fundamental frequency component of the dither is attenuated by a passive notch filter and the remaining fundamental component and harmonic components are attenuated by the low-pass reconstruction filter. Two methods that further improve performance are also presented. By reproducing the dither on a second channel and subtracting it using a differential amplifier, additional dither attenuation is achieved; and by averaging several channels, the noise-floor of the output is improved. Experimental results demonstrate more than 10 dB improvement in the signal-to-noise-and-distortion ratio.
Symmetry and Asymmetry in Bouncing Gaits (2010)

In running, hopping and trotting gaits, the center of mass of the body oscillates each step below and above an equilibrium position where the vertical force on the ground equals body weight. In trotting and low speed human running, the average vertical acceleration of the center of mass during the lower part of the oscillation equals that of the upper part, the duration of the lower part equals that of the upper part and the step frequency equals the resonant frequency of the bouncing system: we define this as on-offground symmetric rebound. In hopping and high speed human running, the average vertical acceleration of the center of mass during the lower part of the oscillation exceeds that of the upper part, the duration of the upper part exceeds that of the lower part and the step frequency is lower than the resonant frequency of the bouncing system: we define this as on-off-ground asymmetric rebound. Here we examine the physical and physiological constraints resulting in this on-off-ground symmetry and asymmetry of the rebound. Furthermore, the average force exerted during the brake when the body decelerates downwards and forwards is greater than that exerted during the push when the body is reaccelerated upwards and forwards. This landing-takeoff asymmetry, which would be nil in the elastic rebound of the symmetric spring-mass model for running and hopping, suggests a less efficient elastic energy storage and recovery during the bouncing step. During hopping, running and trotting the landing-takeoff asymmetry and the mass-specific vertical stiffness are smaller in larger animals than in the smaller animals suggesting a more efficient rebound in larger animals.
Ion beam hydrogenation of amorphous silicon (1987)

A Kaufman ion beam source was used to implant hydrogen atoms into glow-discharge-deposited amorphous silicon materials in which the hydrogen content had been driven out by heating. We found that the hydrogen atoms introduced by this low-energy (less than 700 eV) ion implantation method bonded predominantly as SiH. An air mass one, photo-to-dark-conductivity ratio as high as 5.6×105 has been obtained with hydrogen-implanted materials. No light-induced reduction of the photo- and dark conductivities has been observed in these materials after 20 h of AMl illumnination.
Telomere Length Reprogramming in Embryos and Stem Cells (2014)

Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism's lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg's capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening mechanisms in the reprogramming of early embryos and stem cells, which we review here.
Purification and Characterization of Neutral and Alkaline Invertase from Carrot (1996)

Neutral and alkaline invertase were identified in cells of a suspension culture of carrot (Daucus carota L.) and purified to electrophoretic homogeneity. Neutral invertase is an octamer with a molecular mass of 456 kD and subunits of 57 kD, whereas alkaline invertase is a tetramer with a molecular mass of 504 kD and subunits of 126 kD. Both enzymes had sharp pH profiles, with maximal activities at pH 6.8 for neutral invertase and pH 8.0 for alkaline invertase, and both hydrolyzed sucrose with typical hyperbolic kinetics and similar Km values of about 20 mM at pH 7.5. Neutral invertase also hydrolyzed raffinose and stachyose and, therefore, is a beta-fructofuranosidase. In contrast, alkaline invertase was highly specific for sucrose. Fructose acted as a competitive inhibitor of both enzymes, with Ki values of about 15 mM. Glucose was a noncompetitive inhibitor of both neutral and alkaline invertase, with a Ki of about 30 mM. Neither enzyme was inhibited by HgCl2. Alkaline invertase was markedly inhibited by CaCl2, MgCl2, and MnCl2, and neutral invertase was not. In contrast to alkaline invertase, neutral invertase was inhibited by the nucleotides ATP, CTP, GTP, and UTP.