gebhart/patrepeval huggingface dataset:
UNIX disk access patterns (1993)

Disk access patterns are becoming ever more important to understand as the gap between processor and disk performance increases. The study presented here is a detailed characterization of every lowlevel disk access generated by three quite different systems over a two month period. The contributions of this paper are the detailed information we provide about the disk accesses on these systems (many of our results are significantly different from those reported in the literature, which provide summary data only for file-level access on small-memory systems); and the analysis of a set of optimizations that could be applied at the disk level to improve performance. Our traces show that the majority of all operations are writes; disk accesses are rarely sequential; 25-- 50% of all accesses are asynchronous; only 13--41% of accesses are to user data (the rest result from swapping, metadata, and program execution); and I/O activity is very bursty: mean request queue lengths seen by an incoming request range from 1.7 to 8.9 (1.2--1.9 for reads, 2.0--14.8 for writes), while we saw 95th percentile queue lengths as large as 89 entries, and maxima of over 1000. Using a simulator to analyze the effect of write caching at the disk level, we found that using a small non-volatile cache at each disk allowed writes to be serviced considerably faster than with a regular disk. In particular, short bursts of writes go much faster -- and such bursts are common: writes rarely come singly. Adding even 8KB of non-volatile memory per disk could reduce disk traffic by 10-- 18%, and 90% of metadata write traffic can be absorbed with as little as 0.2MB per disk of nonvolatile RAM. Even 128KB of NVRAM cache in each disk can improve write performance by as much as a factor of three. FCFS scheduling...
The case for medical marijuana in epilepsy (2014)

Charlotte, a little girl with SCN1A-confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado-based medical marijuana group (Realm of Caring), Charlotte's mother started adjunctive therapy with a high concentration cannabidiol/Δ(9) -tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte's Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte's seizure frequency from nearly 50 convulsive seizures per day to now 2-3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her other antiepileptic drugs. We briefly review some of the history, preclinical and clinical data, and controversies surrounding the use of medical marijuana for the treatment of epilepsy, and make a case that the desire to isolate and treat with pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior to therapy with whole plant extracts. Much more needs to be learned about the mechanisms of antiepileptic activity of the phytocannabinoids and other constituents of Cannabis sativa.
Rosiglitazone Attenuates Age- and Diet-Associated Nonalcoholic Steatohepatitis in Male Low-Density Lipoprotein Receptor Knockout Mice (2010)

MS mice represent an ideal model to investigate NASH in the context of MS, as commonly occurs in human disease, and NASH development can be substantially attenuated by PPARγ activation, which enhances β-oxidation.
Real-Time LightCycler PCR for Detection and Discrimination of Bordetella pertussis and Bordetella parapertussis (2002)

Real-time PCR assays based on the LightCycler technology were developed for individual (simplex PCR) and simultaneous (duplex PCR) detection and discrimination of Bordetella pertussis and Bordetella parapertussis in clinical samples. The assays were evaluated with 113 specimens from patients with and without symptoms of pertussis. Results were compared to those from conventional culture and TaqMan real-time PCR. The analytical sensitivity ranged from 0.1 to 10 CFU for B. pertussis and B. parapertussis, and intra- and interassay variations were less than 7%. Results were available within 2 h. With the simplex format, 21 of 100 samples from patients with clinical symptoms of pertussis were positive for B. pertussis and/or B. parapertussis. With the duplex format, 18 of 100 samples were positive. LightCycler PCR increased the diagnostic sensitivity over that of culture by 2.0-fold (duplex PCR) (P = 0.08) to 2.3-fold (simplex PCR) (P = 0.02). Our data suggest that duplex PCR in this format showed good analytical sensitivity but lost some sensitivity on clinical samples compared with the simplex format.
A cryogenic scan mechanism for use in Fourier transform spectrometers (1995)

This paper describes the requirements, design, assembly and testing of the linear Scan Mechanism (SM) of the Composite Infrared Spectrometer (CIRS) Instrument. The mechanism consists of an over constrained flexible structure, an innovative moving magnet actuator, passive eddy current dampers, a Differential Eddy Current (DEC) sensor, Optical Limit Sensors (OLS), and a launch lock. Although all the components of the mechanism are discussed, the flexible structure and the magnetic components are the primary focus. Several problems encountered and solutions implemented during the development of the scan mechanism are also described.
MemorIES3 (2000)

Modern system design often requires multiple levels of simulation for design validation and performance debugging. However, while machines have gotten faster, and simulators have become more detailed, simulation speeds have not tracked machine speeds, As a result, it is difficult to simulate realistic problem sizes and hardware configurations for a target machine. Instead, researchers have focussed on developing sealing methodologies and running smaller problem sizes and configurations that attempt to represent the behavior of the real problem. Given the increasing size of problems today, it is unclear whether such an approach yields accurate results. Moreover, although commercial workloads are prevalent and important in today's marketplace, many simulation tools are unable to adequately profile such applications, let alone for realistic sizes.In this paper we present a hardware-based emulation tool that can be used to aid memory system designers. Our focus is on the memory system because the ever-widening gap between processor and memory speeds means that optimizing the memory subsystem is critical for performance. We present the design of the Memory I nstrumentation and E mulation S ystem (MemoriES). MemoriES is a programmable tool designed using FPGAs and SDRAMs. It plugs into an SMP bus to perform on-line emulation of several cache configurations, structures and protocols while the system is running real-life workloads in real-time, without any slowdown in application execution speed. We demonstrate its usefulness in several case studies, and find several important results. First, using traces to perform system evaluation can lead to incorrect results (off by 100% or more in some cases) if the trace size is not sufficiently large. Second. MemoriES is able to detect performance problems by profiling miss behavior over the entire course of a run, rather than relying on a small interval of time. Finally, we observe that previous studies of SPLASH2 applications using scaled application sizes can result in optimistic miss rates relative to real sizes on real machines, providing potentially misleading data when used for design evaluation.
Activation of a CrmA-insensitive, p35-sensitive Pathway in Ionizing Radiation-induced Apoptosis (1997)

The response of eukaryotic cells to ionizing radiation (IR) includes induction of apoptosis. However, the signals that regulate this response are unknown. The present studies demonstrate that IR treatment of U-937 cells is associated with: (i) internucleosomal DNA fragmentation; (ii) cleavage of poly(ADP-ribose) polymerase; (iii) cleavage of protein kinase C delta; and (iv) induction of an Ac-DEVD-p-nitroanilide cleaving activity. Overexpression of the cowpox protein CrmA blocked tumor necrosis factor (TNF)-induced apoptosis but had no effect on IR-induced DNA fragmentation or cleavage of poly(ADP-ribose) polymerase and protein kinase C delta. By contrast, overexpression of the baculovirus p35 protein blocked both IR- and TNF-induced apoptosis. The results further demonstrate that the IR-induced proteolytic activity is directly inhibited by the addition of purified recombinant p35, but not by CrmA. We show that the CPP32 protease is sensitive to p35 and not CrmA. We also show that IR induces activation of CPP32 and that this event, like induction of apoptosis, is sensitive to overexpression of p35 and not CrmA. These findings indicate that IR-induced apoptosis involves activation of CPP32 and that this CrmA-insensitive apoptotic pathway is distinct from those induced by TNF and certain other stimuli.
Cell-based Flow Cytometry Assay to Measure Cytotoxic Activity (2013)

Cytolytic activity of CD8+ T cells is rarely evaluated. We describe here a new cell-based assay to measure the capacity of antigen-specific CD8+ T cells to kill CD4+ T cells loaded with their cognate peptide. Target CD4+ T cells are divided into two populations, labeled with two different concentrations of CFSE. One population is pulsed with the peptide of interest (CFSE-low) while the other remains un-pulsed (CFSE-high). Pulsed and un-pulsed CD4+ T cells are mixed at an equal ratio and incubated with an increasing number of purified CD8+ T cells. The specific killing of autologous target CD4+ T cells is analyzed by flow cytometry after coculture with CD8+ T cells containing the antigen-specific effector CD8+ T cells detected by peptide/MHCI tetramer staining. The specific lysis of target CD4+ T cells measured at different effector versus target ratios, allows for the calculation of lytic units, LU₃₀/10(6) cells. This simple and straightforward assay allows for the accurate measurement of the intrinsic capacity of CD8+ T cells to kill target CD4+ T cells.
Antimicrobial strategies centered around reactive oxygen species – bactericidal antibiotics, photodynamic therapy, and beyond (2013)

Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics and nonpharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma, and medicinal honey. A brief final section covers reactive nitrogen species and related therapeutics, such as acidified nitrite and nitric oxide-releasing nanoparticles.
The Thymidine Kinase/Ganciclovir-Mediated “Suicide” Effect Is Variable in Different Tumor Cells (1995)

The herpes simplex virus thymidine kinase (HSV-TK) converts ganciclovir (GCV) into a toxic product and allows selective elimination of TK+ cells in vitro and in vivo. It is currently being used in clinical gene therapy trials as a therapeutic gene or as a safety marker. We have analyzed the susceptibility of different tumor cell lines to the TK/GCV-mediated "suicide" effect. Therefore, tumor cells TSA, J558L, EB, and ESB and, as a control, NIH-3T3 cells were infected with a retrovirus containing a hygromycin/TK fusion gene. All cell lines were sensitive to GCV in vitro; however, the concentration of GCV and the time needed to eliminate tumor cells completely considerably varied between different tumor cell lines. TSA-TK cells were completely eliminated within 10 days in 1 microg/ml GCV, whereas ESB-TK cells required 22 days in 10 microg/ml GCV. When two cell lines were examined, the differing sensitivity to GCV in vitro correlated with the ability to eradicate TK+ tumors in vivo. TSA-TK tumors could be eliminated in almost all animals by systemic GCV administration, whereas ESB-TK tumors were completely resistant. Different sensitivity to GCV was not due to different TK expression levels because the cells were similarly resistant to hygromycin, and Western blot analysis with an anti-TK antiserum revealed similar protein amounts in TSA/TK and ESB-TK cells. Together, the results demonstrate that tumor cells are highly different concerning the susceptibility to the TK/GCV effect, which, however, may be tested for in vitro.
Safety and efficacy of live and inactivated infectious bovine rhinotracheitis vaccines (1982)

Two commercial live virus infectious bovine rhinotracheitis (IBR) vaccines for intranasal administration and an inactivated polyvalent calf pneumonia vaccine were compared for safety and efficacy in calves against experimental IBR infections. All three products were clinically safe for use in young calves; a mild, transient, febrile response was induced by one of the live vaccines. Vaccinal virus was recovered for up to 16 days after vaccination from nasal secretions of all calves given live vaccine. Both live vaccines stimulated a serum neutralising antibody response, but the inactivated vaccine failed to elicit any serological response. Following intranasal challenge four months after the first dose of vaccine, all live virus vaccinates remained systemically healthy. A slight nasal discharge and a few rapidly healing ulcers of the nasal mucosa were the only abnormalities observed. Both the group given the inactivated vaccine and the unvaccinated controls developed clinical IBR with pyrexia, ocular and nasal discharges, severe ulceration of the nasal mucosa and tracheitis and tachypnoea to varying degrees of severity. Parenteral administration of dexamethasone six months after challenge induced reactivation of virus shedding followed by a rise in humoral antibody titre irrespective of the original vaccination history.
Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors (1992)

The pathogenic Neisseria species are capable of utilizing transferrin as their sole source of iron. A neisserial transferrin receptor has been identified and its characteristics defined; however, the biochemical identities of proteins which are required for transferrin receptor function have not yet been determined. We identified two iron-repressible transferrin-binding proteins in Neisseria gonorrhoeae, TBP1 and TBP2. Two approaches were taken to clone genes required for gonococcal transferrin receptor function. First, polyclonal antiserum raised against TBP1 was used to identify clones expressing TBP1 epitopes. Second, a wild-type gene copy was cloned that repaired the defect in a transferrin receptor function (trf) mutant. The clones obtained by these two approaches were shown to overlap by DNA sequencing. Transposon mutagenesis of both clones and recombination of mutagenized fragments into the gonococcal chromosome generated mutants that showed reduced binding of transferrin to whole cells and that were incapable of growth on transferrin. No TBP1 was produced in these mutants, but TBP2 expression was normal. The DNA sequence of the gene encoding gonococcal TBP1 (tbpA) predicted a protein sequence homologous to the Escherichia coli and Pseudomonas putida TonB-dependent outer membrane receptors. Thus, both the function and the predicted protein sequence of TBP1 were consistent with this protein serving as a transferrin receptor.
Direct growth of crystalline silicon on GaAs by low temperature PECVD: Towards hybrid tunnel junctions for III-V/Si tandem cells (2016)

Monolithical integration of III-V and Si is of strong interest to produce tandem solar cells reaching high conversion efficiencies. In the context of the French ANR research project IMPETUS, an innovative approach for III-V/Si multijunction solar cells is studied. The targeted device is a tandem cell composed of a III-V top cell (AlGaAs) and a IV bottom cell (Si <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1−x</inf> Ge <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> ). The choice of Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</inf> Ga <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1−y</inf> As as the top material is justified because it provides the optimum bandgap combination with Si <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1−x</inf> Ge <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> (1.63 eV/0.96 eV), with theoretical efficiencies in excess of 42% for such a tandem configuration. In our inverted metamorphic approach, we first use MOVPE to grow the AlGaAs top cell on a lattice matched GaAs substrate, and then perform low temperature PECVD heteroepitaxial SiGe on top. We show here the first structural and electrical characterizations of Si(PECVD)/III-V(MOVPE) interfaces. Furthermore, the epitaxial growth of highly doped crystalline Si by low-temperature PECVD on GaAs enables us to fabricate hybrid tunnel junctions with low resistivity and a high current, suitable to interconnect the two subcells in the tandem III-V/Si solar cell.
Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis (2003)

Type I polyketide synthases (PKSs) are multifunctional enzymes that are organized into modules, each of which minimally contains a beta-ketoacyl synthase, an acyltransferase (AT), and an acyl carrier protein. Here we report that the leinamycin (LNM) biosynthetic gene cluster from Streptomyces atroolivaceus S-140 consists of two PKS genes, lnmI and lnmJ, that encode six PKS modules, none of which contain the cognate AT domain. The only AT activity identified within the lnm gene cluster is a discrete AT protein encoded by lnmG. Inactivation of lnmG, lnmI, or lnmJ in vivo abolished LNM biosynthesis. Biochemical characterization of LnmG in vitro showed that it efficiently and specifically loaded malonyl CoA to all six PKS modules. These findings unveiled a previously unknown PKS architecture that is characterized by a discrete, iteratively acting AT protein that loads the extender units in trans to "AT-less" multifunctional type I PKS proteins for polyketide biosynthesis. This PKS structure provides opportunities for PKS engineering as exemplified by overexpressing lnmG to improve LNM production.
Recombinant Soluble Form of PSGL-1 Accelerates Thrombolysis and Prevents Reocclusion in a Porcine Model (1999)

Inhibition of leukocyte accumulation at the site of thrombosis with rPSGL-Ig may represent a safe therapeutic intervention that could be important in accelerating thrombolysis, achieving optimal reperfusion, and reducing incidence of acute reocclusion.
Ubiquitin in retrovirus assembly: Actor or bystander? (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Accuracy of AHnequilibrium geometries by single determinant molecular orbital theory (1974)

A simple level of ab initio molecular orbital theory with a split-valence shell basis with d-type polarization functions (6–31G*) is used to predict equilibrium geometries for the ground and some low-lying excited states of AHn molecules and cations where A is carbon, nitrogen, oxygen or fluorine. The results are shown to be close to the limit for single determinant wave functions in cases where corresponding computations with more extensive bases are available. Comparison with experimental results also shows good agreement although a systematic underestimation of bond lengths up to 3 per cent is evident. For systems where no experimental data are available, the results provide predictions of equilibrium geometry.
Asparagine synthetase is a predictive biomarker of l -asparaginase activity in ovarian cancer cell lines (2008)

We recently used RNA interference to show that a negative correlation of L-asparaginase (L-ASP) chemotherapeutic activity with asparagine synthetase (ASNS) expression in the ovarian subset of the NCI-60 cell line panel is causal. To determine whether that relationship would be sustained in a larger, more diverse set of ovarian cell lines, we have now measured ASNS mRNA expression using microarrays and a branched-DNA RNA assay, ASNS protein expression using an electrochemiluminescent immunoassay, and L-ASP activity using an MTS assay on 19 human ovarian cancer cell lines. Contrary to our previous findings, L-ASP activity was only weakly correlated with ASNS mRNA expression; Pearson's correlation coefficients were r = -0.21 for microarray data and r = -0.39 for the branched-DNA RNA assay, with just the latter being marginally statistically significant (P = 0.047, one-tailed). ASNS protein expression measured by liquid-phase immunoassay exhibited a much stronger correlation (r = -0.65; P = 0.0014, one-tailed). We conclude that ASNS protein expression measured by immunoassay is a strong univariate predictor of L-ASP activity in ovarian cancer cell lines. These findings provide rationale for evaluation of ASNS protein expression as a predictive biomarker of clinical L-ASP activity in ovarian cancer.
Contribution of nitric oxide to cutaneous microvascular dilation in individuals with type 2 diabetes mellitus (2006)

Microvascular pathophysiology associated with type 2 diabetes mellitus (T2DM) contributes to several aspects of the morbidity associated with the disease. We quantified the contribution of nitric oxide (NO) to the cutaneous vasodilator response to nonpainful local warming in subjects with T2DM (average duration of diabetes mellitus 7 +/- 1 yr) and in age-matched control subjects. We measured skin blood flow in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or vehicle during 35 min of local warming to 42 degrees C. Microdialysis of sodium nitroprusside (SNP) was used for assessment of maximum cutaneous vascular conductance (CVC). Resting CVC was higher in T2DM subjects at vehicle sites (T2DM: 19 +/- 2 vs. control: 11 +/- 3%maxCVC; P < 0.05); this difference was abolished by l-NAME (T2DM: 10 +/- 1 vs. control: 8 +/- 1%maxCVC; P > 0.05). The relative contribution of NO to the vasodilator response to local warming was not different between groups (T2DM: 46 +/- 4 vs. control: 44 +/- 6%maxCVC; P > 0.05). However, absolute CVC during local warming was approximately 25% lower in T2DM subjects (T2DM: 1.79 +/- 0.15 AU/mmHg; controls: 2.42 +/- 0.20 AU/mmHg; P < 0.01), and absolute CVC during SNP was approximately 20% lower (T2DM: 1.91 +/- 0.12 vs. control: 2.38 +/- 0.13 AU/mmHg; P < 0.01). We conclude that the relative contribution of NO to vasodilation during local warming is similar between subjects with T2DM and control subjects, although T2DM was associated with a lower absolute maximum vasodilation.