gebhart/patrepeval huggingface dataset:
Predictability of load/store instruction latencies (1993)

Due to increasing cache-miss latencies, cache control instructions are being implemented for future systems. The authors study the memory referencing behavior of individual machine-level instructions using simulations of fully-associative caches under MIN replacement. Their objective is to obtain a deeper understanding of useful program behavior that can be eventually employed at optimizing programs and to motivate architectural features aimed at improving the efficacy of memory hierarchies. The simulation results show that a very small number of load/store instructions account for a majority of data cache misses. Specifically, fewer than 10 instructions account for half the misses for six out of nine SPEC89 benchmarks. Selectively prefetching data referenced by a small number of instructions identified through profiling can reduce overall miss ratio significantly while only incurring a small number of unnecessary prefetches. >
Chemical Genetic Analysis of Apg1 Reveals A Non-kinase Role in the Induction of Autophagy (2003)

Macroautophagy is a catabolic membrane trafficking phenomenon that is observed in all eukaryotic cells in response to various stimuli, such as nitrogen starvation and challenge with specific hormones. In the yeast Saccharomyces cerevisiae, the induction of autophagy involves a direct signal transduction mechanism that affects membrane dynamics. In this system, the induction process modifies a constitutive trafficking pathway called the cytoplasm-to-vacuole targeting (Cvt) pathway, which transports the vacuolar hydrolase aminopeptidase I, from the formation of small Cvt vesicles to the formation of autophagosomes. Apg1 is one of the proteins required for the direct signal transduction cascade that modifies membrane dynamics. Although Apg1 is required for both the Cvt pathway and autophagy, we find that Apg1 kinase activity is required only for Cvt trafficking of aminopeptidase I but not for import via autophagy. In addition, the data support a novel role for Apg1 in nucleation of autophagosomes that is distinct from its catalytic kinase activity and imply a qualitative difference in the mechanism of autophagosome and Cvt vesicle formation.
<title>Active pixel sensors: are CCDs dinosaurs?</title> (1993)

Charge-coupled devices (CCDs) are presently the technology of choice for most imaging applications. In the 23 years since their invention in 1970, they have evolved to a sophisticated level of performance. However, as with all technologies, we can be certain that they will be supplanted someday. In this paper, the Active Pixel Sensor (APS) technology is explored as a possible successor to the CCD. An active pixel is defined as a detector array technology that has at least one active transistor within the pixel unit cell. The APS eliminates the need for nearly perfect charge transfer--the Achilles' heel of CCDs. This perfect charge transfer makes CCD's radiation 'soft,' difficult to use under low light conditions, difficult to manufacture in large array sizes, difficult to integrate with on-chip electronics, difficult to use at low temperatures, difficult to use at high frame rates, and difficult to manufacture in non-silicon materials that extend wavelength response. With the active pixel, the signal is driven from the pixel over metallic wires rather than being physically transported in the semiconductor. This paper makes a case for the development of APS technology. The state of the art is reviewed and the application of APS technology to future space-based scientific sensor systems is addressed.
Schottky MOSFET for VLSI (1981)

Recently MOSFET with Schottky source and drain has been considered an important candidate for VLSI because of its ultra-shallow junctions to minimize short-channel effects, low source and drain series resistances, simplified processes, and the elimination of minority carrier injection into the substrate [1]. We present results of MOSFETs with 300Å PtSi as the source and drain contacts. The devices are fabricated on 2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> , oriented n-Si substrates; and the gate oxide thickness is 250-300Å. Long-channel behavior is observed for devices with channel lengths down to 1 µm, in very good agreement with the generalized guide for MOSFET miniaturization[2]. We observe that the output currents are smaller than those for the conventional MOSFETs. This is explained by the potential barrier arising in the gap between the Schottky source contact and the inversion channel. Extensive Arrhenius plots indicate that the gap has a profound effect in enhancing the corner field which in turn can greatly increase the current availability from the source. By reducing the gap to about 100Å, the current approaches that as expected from the Pao-Sah theory[3].
A MATHEMATICAL ALGORITHM FOR ECG SIGNAL DENOISING USING WINDOW ANALYSIS (2007)

Although, the simplicity of the method, fast implementation, and preservation of characteristics of ECG waves represent it as a suitable algorithm, there may be some difficulties due to pre-stage detection of QRS complexes and specification of algorithm's parameters for varying morphology cases.
Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier (2011)

The blood-brain barrier (BBB) is comprised of specialized endothelial cells that form the capillary microvasculature of the CNS and is essential for brain function. It also poses the greatest impediment in the treatment of many CNS diseases because it commonly blocks entry of therapeutic compounds. Here we report that adenosine receptor (AR) signaling modulates BBB permeability in vivo. A(1) and A(2A) AR activation facilitated the entry of intravenously administered macromolecules, including large dextrans and antibodies to β-amyloid, into murine brains. Additionally, treatment with an FDA-approved selective A(2A) agonist, Lexiscan, also increased BBB permeability in murine models. These changes in BBB permeability are dose-dependent and temporally discrete. Transgenic mice lacking A(1) or A(2A) ARs showed diminished dextran entry into the brain after AR agonism. Following treatment with a broad-spectrum AR agonist, intravenously administered anti-β-amyloid antibody was observed to enter the CNS and bind β-amyloid plaques in a transgenic mouse model of Alzheimer's disease (AD). Selective AR activation resulted in cellular changes in vitro including decreased transendothelial electrical resistance, increased actinomyosin stress fiber formation, and alterations in tight junction molecules. These results suggest that AR signaling can be used to modulate BBB permeability in vivo to facilitate the entry of potentially therapeutic compounds into the CNS. AR signaling at brain endothelial cells represents a novel endogenous mechanism of modulating BBB permeability. We anticipate these results will aid in drug design, drug delivery and treatment options for neurological diseases such as AD, Parkinson's disease, multiple sclerosis and cancers of the CNS.
Substrate Specificity of the Sialic Acid Biosynthetic Pathway (2001)

Unnatural analogues of sialic acid can be delivered to mammalian cell surfaces through the metabolic transformation of unnatural N-acetylmannosamine (ManNAc) derivatives. In previous studies, mannosamine analogues bearing simple N-acyl groups up to five carbon atoms in length were recognized as substrates by the biosynthetic machinery and transformed into cell surface sialoglycoconjugates [Keppler, O. T., et al. (2001) Glycobiology 11, 11R-18R]. Such structural alterations to cell surface glycans can be used to probe carbohydrate-dependent phenomena. This report describes our investigation into the extent of tolerance of the pathway toward additional structural alterations of the N-acyl substituent of ManNAc. A panel of analogues with ketone-containing N-acyl groups that varied in the length or steric bulk was chemically synthesized and tested for metabolic conversion to cell surface glycans. We found that extension of the N-acyl chain to six, seven, or eight carbon atoms dramatically reduced utilization by the biosynthetic machinery. Likewise, branching from the linear chain reduced metabolic conversion. Quantitation of metabolic intermediates suggested that cellular metabolism is limited by the phosphorylation of the N-acylmannosamines by ManNAc 6-kinase in the first step of the pathway. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic acid biosynthesis provides a target for expanding the metabolic promiscuity of mammalian cells.
Myelodysplastic syndromes (2007)

The current results indicated that >10,000 incident cases of MDS are diagnosed annually in the United States, and the survival of patients with MDS is poor. The availability of descriptive epidemiologic data on MDS can be used now to facilitate much needed research on the etiology and outcomes of MDS.
Fabrication of a Micro Coil for Magnetooptical Data Storage (2006)

A magnetic field modulation (MFM) micro coil was developed and fabricated as part of a magnetooptical recording system. The center of the coil is transparent, allowing a beam of blue laser light to pass through and heat up locally the magnetooptical storage layer, which is then magnetized by the micro coil for data recording. The micro coil therefore not only needs to be located at a very small working distance ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$≪50 mu$</tex> m) from the disc, it also requires the magnetic coil to be mounted between a high numerical aperture (NA) lens <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$( NA≫0.8)$</tex> and the disc. As a result, the micro coil has to be fabricated on a glass wafer being only 100 <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$mu$</tex> m thick, which posed considerable technology challenges. To match these requirenments, a microcoil was developed which fulfills the system integration and operating requirements of the magnetooptical system.
Fundamental Frequency Estimation Based on Pitch-Scaled Harmonic Filtering (2007)

In this paper, we present an algorithm for robustly estimating the fundamental frequency in speech signals. Our approach is based on pitch-scaled harmonic filtering (PSHF). Following PSHF, we perform a filtering in the frequency domain using the short-time Fourier transform in order to separate the harmonic and non-harmonic parts of the processed signal. We enhance the standard PSHF approach by using a range of window lengths and a cost function that is applied to each window size. This cost function takes into account the energy at the harmonic and non-harmonic frequency coefficients to estimate harmonic energy for a frame. By using energy peaks and applying a cost function that considers the change in pitch in subsequent frames, we then determine the final pitch contour. We evaluated our approach on the Keele database. As the experimental results demonstrate, our methods performs robustly for noisy speech and has a good performance for clean speech in comparison with state-of-the-art algorithms.
Thermodynamics of Melittin Binding to Lipid Bilayers. Aggregation and Pore Formation (2009)

Lipid membranes act as catalysts for protein folding. Both alpha-helical and beta-sheet structures can be induced by the interaction of peptides or proteins with lipid surfaces. Melittin, the main component of bee venom, is a particularly well-studied example for the membrane-induced random coil-to-alpha-helix transition. Melittin in water adopts essentially a random coil conformation. The cationic amphipathic molecule has a high affinity for neutral and anionic lipid membranes and exhibits approximately 50-65% alpha-helix conformation in the membrane-bound state. At higher melittin concentrations, the peptide forms aggregates or pores in the membrane. In spite of the long-standing interest in melittin-lipid interactions, no systematic thermodynamic study is available. This is probably caused by the complexity of the binding process. Melittin binding to lipid vesicles is fast and occurs within milliseconds, but the binding process involves at least four steps, namely, (i) the electrostatic attraction of the cationic peptide to an anionic membrane surface, (ii) the hydrophobic insertion into the lipid membrane, (iii) the conformational change from random coil to alpha-helix, and (iv) peptide aggregation in the lipid phase. We have combined microelectrophoresis (measurement of the zeta potential), isothermal titration calorimetry, and circular dichroism spectroscopy to provide a thermodynamic analysis of the individual binding steps. We have compared melittin with a synthetic analogue, [D]-V(5,8),I(17),K(21)-melittin, for which alpha-helix formation is suppressed and replaced by beta-structure formation. The comparison reveals that the thermodynamic parameters for the membrane-induced alpha-helix formation of melittin are identical to those observed earlier for other peptides with an enthalpy h(helix) of -0.7 kcal/mol and a free energy g(helix) of -0.2 kcal/mol per peptide residue. These thermodynamic parameters hence appear to be of general validity for lipid-induced membrane folding. As g(helix) is negative, it further follows that helix formation leads to an enhanced membrane binding for the peptides or proteins involved. In this study, melittin binds by approximately 2 orders of magnitude better to the lipid membrane than [D]-V(5,8),I(17),K(21)-melittin which cannot form an alpha-helix. We also found conditions under which the isothermal titration experiment reports only the aggregation process. Melittin aggregation is an entropy-driven process with an endothermic heat of reaction (DeltaH(agg)) of approximately 2 kcal/mol and an aggregation constant of 20-40 M(-1).
Myocytes Die by Multiple Mechanisms in Failing Human Hearts (2003)

We tested the hypothesis that myocyte loss in failing human hearts occurs by different mechanisms: apoptosis, oncosis, and autophagic cell death. Explanted hearts from 19 patients with idiopathic dilated cardiomyopathy (EF< or =20%) and 7 control hearts were analyzed. Myocyte apoptosis revealed by caspase-3 activation and TUNEL staining occurred at a rate of 0.002+/-0.0005% (P<0.05 versus control) and oncosis assessed by complement 9 labeling at 0.06+/-0.001% (P<0.05). Cellular degeneration including appearance of ubiquitin containing autophagic vacuoles and nuclear disintegration was present at the ultrastructural level. Nuclear and cytosolic ubiquitin/protein accumulations occurred at 0.08+/-0.004% (P<0.05). The ubiquitin-activating enzyme E1 and the ligase E3 were not different from control. In contrast, ubiquitin mRNA levels were 1.8-fold (P<0.02) elevated, and the conjugating enzyme E2 was 2.3-fold upregulated (P<0.005). The most important finding, however, is the 2.3-fold downregulation of the deubiquitination enzyme isopeptidase-T and the 1.5-fold reduction of the ubiquitin-fusion degradation system-1, which in conjunction with unchanged proteasomal subunit levels and proteasomal activity results in massive storage of ubiquitin/protein complexes and in autophagic cell death. A 2-fold decrease of cathepsin D might be an additional factor responsible for the accumulation of ubiquitin/protein conjugates. It is concluded that in human failing hearts apoptosis, oncosis, and autophagy act in parallel to varying degrees. A disturbed balance between a high rate of ubiquitination and inadequate degradation of ubiquitin/protein conjugates may contribute to autophagic cell death. Together, these different types of cell death play a significant role for myocyte disappearance and the development of contractile dysfunction in failing hearts.
Polymerase chain reaction evidence of Ehrlichia chaffeensis, an etiologic agent of human ehrlichiosis, in dogs from southeast Virginia (1996)

Canine E chaffeensis infection may be more prevalent than E canis or E ewingii infection in this region of the United States.
Multi-Channel Goes Mobile: MPEG Surround Binaural Rendering (2006)

Surround sound is on the verge of broad adoption in consumers ’ homes, for digital broadcasting and even for Internet services. The currently developed MPEG Surround technology offers bitrate efficient and mono/stereo compatible transmission of high-quality multi-channel audio. This enables multi-channel services for applications where mono or stereo backwards compatibility is required as well as applications with severely bandwidth limited distribution channels. This paper outlines a significant addition to the MPEG Surround specification which enables computationally efficient decoding of MPEG Surround data into binaural stereo as is appropriate for appealing surround sound reproduction on mobile devices, such as cellular phones. The publication describes the basics of the underlying MPEG Surround architecture, the binaural decoding process, and subjective testing results.
A Seamless Modular Approach for Real-Time Video Analysis for Surveillance (2004)

In this paper we present a generic, flexible and robust approach for an intelligent real-time visual surveillance system. The proposed architecture integrates advanced video analysis tools, such as segmentation, tracking and events detection. The goal of these advanced tools is to provide help to operators by detecting events of interest in visual scenes. The approach is new because it is a seamless collaboration of many processing techniques from image space to dynamic scene space. We describe thoroughly an important section the vision system and prove its intrinsic modularity. The system is then demonstrated in an antiterrorist scenario of automatic detection of events in public facilities. A performance evaluation of the system is performed.
The Role of Invariant Natural Killer T Cells in Dendritic Cell Licensing, Cross-Priming, and Memory CD8+ T Cell Generation (2015)

New vaccination strategies focus on achieving CD8(+) T cell (CTL) immunity rather than on induction of protective antibody responses. While the requirement of CD4(+) T (Th) cell help in dendritic cell (DC) activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help-independent manner. Invariant natural killer T cells (iNKT cells) can substitute for Th cell help and license DC as well. iNKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines, while Th cell-licensed DCs produce CCR5 ligands, iNKT cell-licensed DCs produce CCL17, which attracts CCR4(+) CD8(+) T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites but also play a role in viral infections. The inclusion of iNKT cell ligands in influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8(+) T cell formation.
Improving IS Service Quality (2000)

The growth of end-user computing has led to an awareness of the need to evaluate the quality of services provided by the information systems function. This paper discusses the two primary schools of thought or approaches concerning service quality. While the disconfirmation-based approach conceptualizes service quality as âsimilar to an attitude, the performance-based approach conceptualizes service quality as âattitude-based.â The literature concerning the application of both service quality approaches in an IS context are discussed and analyzed. Special attention is paid to the service orientation of IS employees as they relate to IS users. Prescriptions for improvements to the quality of IS service are suggested in four management areas: 1) service orientation of IS providers, 2) training/education of IS providers and IS users, 3) reward system for IS employees, and 4) linking IT strategy to business strategy. Lastly, SERVQUAL and SERVPERF are discussed as two quantitative measures of IS service quality.
The Natural Product Dihydrotanshinone I Provides a Prototype for Uncharged Inhibitors That Bind Specifically to the Acetylcholinesterase Peripheral Site with Nanomolar Affinity (2013)

Cholinergic synaptic transmission often requires extremely rapid hydrolysis of acetylcholine by acetylcholinesterase (AChE). AChE is inactivated by organophosphates (OPs) in chemical warfare nerve agents. The resulting accumulation of acetylcholine disrupts cholinergic synaptic transmission and can lead to death. A potential long-term strategy for preventing AChE inactivation by OPs is based on evidence that OPs must pass through a peripheral site or P-site near the mouth of the AChE active site gorge before reacting with a catalytic serine in an acylation site or A-site at the base of the gorge. An ultimate goal of this strategy is to design compounds that bind tightly at or near the P-site and exclude OPs from the active site while interfering minimally with the passage of acetylcholine. However, to target the AChE P-site with ligands and potential drugs that selectively restrict access, much more information must be gathered about the structure-activity relationships of ligands that bind specifically to the P-site. We apply here an inhibitor competition assay that can correctly determine whether an AChE inhibitor binds to the P-site, the A-site, or both sites. We have used this assay to examine three uncharged, natural product inhibitors of AChE, including aflatoxin B1, dihydrotanshinone I, and territrem B. The first two of these inhibitors are predicted by the competition assay to bind selectively to the P-site, while territrem B is predicted to span both the P- and A-sites. These predictions have recently been confirmed by X-ray crystallography. Dihydrotanshinone I, with an observed binding constant (KI) of 750 nM, provides a good lead compound for the development of high-affinity, uncharged inhibitors with specificity for the P-site.
Further study on S-nitrosation by nitrite (2003)

At neutral pH, S-nitrosoglutathione was formed by the reaction of reduced glutathione and sodium nitrite. The degradation of S-nitrosoglutathione, presumably by transnitrosation/denitrosation, was catalyzed by L-cysteine, or CoA-SH. Additionally, from the crude extract of rat brain, one protein with a large molecular mass was nitrosolated with nitrite, and was split into duplet peptides noted in Western blot. Furthermore, the incubation of nitrite with IgG may generate the intermediates of active nitrogen/oxygen species and lead to significant production of gas bubbles.