gebhart/patrepeval huggingface dataset:
Increasing the instruction fetch rate via block-structured instruction set architectures (1996)

To exploit larger amounts of instruction level parallelism, processors are being built with wider issue widths and larger numbers of functional units. Instruction fetch rate must also be increased in order to effectively exploit the performance potential of such processors. Block-structured ISAs provide an effective means of increasing the instruction fetch rare. We define an optimization, called block enlargement, that can be applied to a block-structured ISA to increase the instruction fetch rate of a processor that implements that ISA. We have constructed a compiler that generates block-structured ISA code, and a simulator that models the execution of that code on a block-structured ISA processor. We show that for the SPECint95 benchmarks, the block-structured ISA processor executing enlarged atomic blocks outperforms a conventional ISA processor by 12% while using simpler microarchitectural mechanisms to support wide-issue and dynamic scheduling.
Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia (2010)

In this large cohort, heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest that the brain is not immune to long-term consequences of heavy smoking.
The struggle for the succession in late elizabethan England : politics, polemics and cultural representations (2004)

Textes issus pour la plupart d'un colloque organisé par l'Institut de recherche sur la Renaissance, l'âge classique et les Lumière, Université Paul-Valéry, Montpellier, 27-29 mars 2003
Analysis of genes involved in the biosynthesis of lantibiotic epidermin (1992)

The structural gene of the lanthionine-containing peptide antibiotic epidermin is located on a 54-kb plasmid of Staphylococcus epidermidis [Schnell et al. (1988) Nature 333, 276-278]. A 13.5-kb DNA region neighbouring the epidermin structural gene (epiA) was subcloned and its sequencing revealed five additional open reading frames. Three of these reading frames, epiB, epiC and epiD shared no homology with previously described proteins stored in data bases. They were located 3' adjacent to epiA. Using epiB as a probe, a 5-kb mRNA was identified indicating that three or all four reading frames are transcribed as an operon. Additionally, a 0.3-kb mRNA specific for epiA was identified. Two open reading frames (epiP and epiQ) were located 3' to epiA, epiB, epiC and epiD, but in the reverse orientation. The epiQ gene product shows similarity to the positive regulatory factor PhoB. This might indicate a regulatory function of epiQ in epidermin biosynthesis. The epiP gene product shows striking similarity to several serine proteases which makes epiP a likely candidate for processing the epidermin prepeptide. Heterologous epidermin synthesis in the non-producing organism Staphylococcus carnosus finally proved that these reading frames are necessary for epidermin biosynthesis.
High-Dose 5-Fluorouracil / Folinic Acid in Combination with Three-Weekly Mitomycin C in the Treatment of Advanced Gastric Cancer. A Phase II Study (2002)

High-dose 5-FU/FA/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur.
Microstructure Formation and Kinetics in the Random Sequential Adsorption of Polydisperse Tethered Nanoparticles Modeled as Hard Disks (2001)

Nanotechnological applications have been proposed which require components to self-assemble into mesoscale structures. For example, nanoscale sensors, quantum memory devices, or photonic materials might comprise regular arrays of particles assembled on a substrate. Previously, we studied the random sequential adsorption kinetics and the structural phase behavior of a two-dimensional model of particles (hard disks) tethered to a substrate. The tethers restrict particle surface mobility which affects the nonequilibrium phases of the developing monolayer adsorbed to the surface. Here, we explore the effect of Gaussian polydispersity on the tethered random sequential adsorption process. Liquid, hexatic, and crystal phases are observed in the simulations. For size-monodisperse systems, short tethers (one particle radius or less) allow only liquid structures, intermediate tethers (one to four particle radii) allow a hexatic structure at high coverages, and long-tethered systems develop through liquid and hexatic phases before becoming crystalline at high coverages. Polydispersity disrupts the order. Systems over approximately 8% polydispersity remain liquid, and systems between about 7 and 8% polydispersity form a hexatic phase even with very long tethers. For sufficiently long tethers, crystal formation requires 5−7% polydispersity or less. Histograms of particle size distributions on the surface reveal that short-tether systems yield bimodal distributions because of the persistence of small gaps in the layer. In contrast, systems with adequate surface mobility organize locally, which prevents small gaps and retains unimodal size distributions. Kinetics for polydisperse, tethered, random sequential adsorption processes follow a power law with constants that change rapidly for tether lengths less than one particle radius and polydispersities up to 10%. Jamming limit coverages generally increase with polydispersity but decrease as surface order is destroyed.
A mutant of barley lacking NADH-hydroxypyruvate reductase (1989)

A mutant of barley, LaPr 88/29, deficient in peroxisomal NADH-hydroxypyruvate reductase (HPR) activity has been identified. Compared to the wild type the activities of NADH-HPR and NADPH-HPR were severely reduced but the mutant was still capable of fixing CO{sub 2} at rates equivalent to 75% of that of the wild type in air. Although lacking an enzyme in the main photorespiratory pathway, there appeared to be little disruption to photorespiratory metabolism as ammonia release, CO{sub 2} efflux and {sup 14}CO{sub 2} release from L-(U-{sup 14}C) serine were similar in both mutant and wild type. LaPr 88/29 has been used to show that NADH-glyoxylate reductase (GR) and NADH-HPR are probably not catalyzed by the same enzyme in barley and that over 80% of the NADPH-HPR activity is due to the NADH-HPR enzyme. Immunological studies, using antibodies raised against spinach HPR, have shown that the NADH-dependent enzyme protein is absent in LaPr 88/29 but there appears to be enhanced synthesis of the NADPH-dependent enzyme protein.
Anti-HIV-1 Activity of Enfuvirtide (T-20) by Inhibition of Bystander Cell Death (2003)

Infection by human immunodeficiency virus type 1 (HIV-1) has been associated with increased cell death of both infected and bystander cells. The envelope glycoprotein complex appears to play an active role in HIV-induced death of bystander cells. We quantified cell-to-cell fusion, single cell death and membrane lipid mixing in cocultures of effector, HIV-1 envelope-expressing cells with peripheral blood mononuclear cells or purified CD4 T lymphocytes from HIV-negative donors, in the presence or the absence of the fusion inhibitor enfuvirtide (T-20, pentafuside, Fuzeon). T-20, which blocks gp41-dependent virus-cell fusion, showed a complete and dose-dependent inhibition of syncytium formation in cocultures of envelope-expressing cells with uninfected cells. Similarly, T-20 totally abrogated death of single bystander CD4 T cells with an IC50 of 0.04 microg/ml. Membrane lipid mixing, as a measure of interaction between envelope-expressing cells and CD4 cells, was also dose-dependently inhibited by T-20. Moreover, effector cells chronically infected with a T-20-resistant virus recovered the ability to induce bystander cell death in the presence of the drug, supporting the role of gp41 in single cell death. In conclusion, T-20 is able to protect CD4 T cells from envelope presentation with a dual effect: inhibition of virus replication and blockade of HIV-1 envelope-induced cell death of bystander CD4 T cells. Protection of cells prior to infection from HIV envelope-dependent bystander effect could lead to a better immune restoration of HIV-1-infected patients that are treated with T-20.
Asymmetric gate (AG) FET: a novel sub-micron MOS device structure with excellent performance (2002)

A novel field effect transistor (FET), asymmetric gate (AG) FET, is proposed and its excellent performance has been demonstrated numerically in this paper. Compared with the conventional MOSFET, the AGFET benefits from the special design of the gate oxide, which is divided into two regions, with one region at the source side thicker than that at the drain side. Two-dimensional (2-D) numerical simulations have proved that, in the novel structure, short-channel effects (SCE) can be greatly suppressed via channel being screened from the drain potential variations, while a significant velocity overshoot is achieved resulting in more drive current. It has shown that the AGFET will be one of the promising structures in design of sub-micron devices.
Gene Therapy for Myocardial Angiogenesis (1998)

This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that direct myocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardial perfusion in selected patients with chronic myocardial ischemia.
Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase (1999)

The copper chaperone for the superoxide dismutase (CCS) gene is necessary for expression of an active, copper-bound form of superoxide dismutase (SOD1) in vivo in spite of the high affinity of SOD1 for copper (dissociation constant = 6 fM) and the high intracellular concentrations of both SOD1 (10 microM in yeast) and copper (70 microM in yeast). In vitro studies demonstrated that purified Cu(I)-yCCS protein is sufficient for direct copper activation of apo-ySOD1 but is necessary only when the concentration of free copper ions ([Cu]free) is strictly limited. Moreover, the physiological requirement for yCCS in vivo was readily bypassed by elevated copper concentrations and abrogation of intracellular copper-scavenging systems such as the metallothioneins. This metallochaperone protein activates the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers. These results indicate that intracellular [Cu]free is limited to less than one free copper ion per cell and suggest that a pool of free copper ions is not used in physiological activation of metalloenzymes.
Determination of 8‐epi PGF 2 α concentrations as a biomarker of oxidative stress using triple‐stage liquid chromatography/tandem mass spectrometry (2009)

F2-isoprostanes are a family of prostaglandin F2-like compounds that are formed by free-radical-catalyzed peroxidation of arachidonic acid. Several F2-isoprostanes, but in particular 8-epi PGF(2alpha), are widely used as oxidative stress biomarkers. An analytical method based on liquid chromatography with negative electrospray ionization (ESI) coupled to tandem mass spectrometric detection (LC/MS/MS) was developed for the determination of 8-epi PGF(2alpha) concentrations in human plasma, whole blood, erythrocytes and urine. 8-epi PGF(2alpha)-d4, a stable isotope derivative of 8-epi PGF(2alpha), was used as an internal standard (IS). A 50 microL sample was focused on-column and separated on two 3 microm particle size SUPELCOSIL ABZ+Plus HPLC columns (15 cm x 4.6 mm and 7.5 cm x 4.6 mm) connected in series. An Applied Biosystems 4000 Q TRAP LC/MS/MS system with ESI was operated in multiple reaction monitoring (MRM) mode with the precursor-to-product ion transitions m/z 353.4 --> 193.1 (8-epi PGF(2alpha)), 357.4 --> 197.1 (8-epi PGF(2alpha)-d4), used for quantification. The assay was fully validated and found to have adequate accuracy, precision, linearity, sensitivity and selectivity. The mass limit of detection (mLOD) was 1 pg of analyte eluting from the column. The assay has been successfully applied to the analysis of human plasma, whole blood, erythrocytes and urine samples.
Abstract 3956: DLD microfluidic purification and characterization of intact and viable circulating tumor cells in peripheral blood (2016)

Abstract We have developed a microfluidic chip-to-chip approach to purify circulating tumor cells (CTC’s). The first, a DLD (deterministic lateral displacement) microchip contains an array of microposts arranged in sub-arrays of different gap sizes. The “product” outlet of the DLD chip is connected with a second magnetic-separation chip. In the DLD chip, cells and particles are deflected or “bumped” based on their size, whereas the second chip is designed to remove any cell or component tagged with a magnetic particle (MNP). Air pressure is applied to maintain a constant flow of sample and buffer throughout the system in a vertical fashion. First, whole blood is mixed with biotinylated antibodies to CD45 and strepavidin-MNP's for 20min, diluted in buffer and passed through the DLD chip where the blood interacts with the posts and cells are bumped based on a deterministic lateral displacement principle, thus separating blood components. The “product” fraction from the DLD chip containing white blood cells and other larger cells is directed to the magnetic chip and the “waste” fraction containing red blood cells, platelets, debris and soluble blood components is discarded. The second chip has an array of magnets, capturing the sav-MNP/CD45+-tagged cells thereby allowing the gentle free flow of rare cells towards the final product fraction. With the chip-to-chip configuration we are able to process up to 8ml of blood, removing &amp;gt;99.8% of red blood cells and &amp;gt;98% of white blood cells, with the remaining purified cell populations suitable for further analysis and characterization. Validation of the chip-to-chip approach using tumor-derived cancer cells, including MDA-MB-231, PC-3 and SKBR-3 cells, confirms a linear recovery of &amp;gt;80% of the spiked-cells with a viability of ∼90%. The minimum cell size captured by our approach is approximately 6μm ensuring the isolation of small-sized CTC’s. Multi-color flow cytometry and imaging analysis of the chip-to-chip isolated cells from blood of breast cancer patients confirms the purification and identification of unique populations of HER2+/CD45-/EpCAM+ and CD146+/CD44+ cells characteristic of breast carcinomas-among other rare cell populations. Our chip-to-chip approach allows a gentle purification of intact and viable rare cells from cancer patients’ blood, suitable for functional analysis, drug sensitivity tests and genetic characterization. Thus, we have developed a hands-free liquid biopsy capable of isolating and purifying rare circulating tumor cells. Citation Format: Myra Koesdjojo, Zendra Lee, Christopher Dosier, Tanisha Saini, Khushroo Gandhi, Alison Skelley, Lee Aurich, Gregory Yang, Tony Ward, Roberto Campos-González. DLD microfluidic purification and characterization of intact and viable circulating tumor cells in peripheral blood. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3956.
Alkaline Phosphatase, Soluble Extracellular Adenine Nucleotides, and Adenosine Production after Infant Cardiopulmonary Bypass (2016)

We identify alkaline phosphatase (AP) as the primary soluble ectonucleotidase in infants undergoing cardiopulmonary bypass and show decreased capacity to clear AMP when AP activity decreases post-bypass. Supplementation of AP ex vivo improves this capacity and may represent the beneficial therapeutic mechanism of AP infusion seen in phase 2 studies.
Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene. (1991)

The catalytic subunit (Mr approximately 124,000) of human DNA polymerase delta has been cloned by PCR using poly(A)+ RNA from HepG2 cells and primers designed from the amino acid sequence of regions highly conserved between bovine and yeast DNA polymerase delta. The human cDNA was 3443 nucleotides in length and coded for a polypeptide of 1107 amino acids. The enzyme was 94% identical to bovine DNA polymerase delta and contained the numerous highly conserved regions previously observed in the bovine and yeast enzymes. The human enzyme also contained two putative zinc-finger domains in the carboxyl end of the molecule, as well as a putative nuclear localization signal at the amino-terminal end. The gene coding for human DNA polymerase delta was localized to chromosome 19.
Identification of a novel therapeutic target for head and neck squamous cell carcinomas: A role for the neurotensin‐neurotensin receptor 1 oncogenic signaling pathway (2008)

Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Based on a genome-wide gene expression analysis using clinical specimens of HNSCC, we narrowed our focus to the analysis of the neurotensin (NTS) and neurotensin receptor 1 (NTSR1) oncogenic signal pathways. Kaplan-Meier curves and log rank tests revealed that high mRNA expression levels of NTS and NTSR1 had a significant adverse effect on metastasis-free survival rate, suggesting a contribution of this pathway in HNSCC cancer progression. In HNSCC cells, which expressed NTSR1, a NTS agonist promoted cellular invasion, migration and induction of several mRNAs, such as interleukin 8 and matrix metalloproteinase 1 transcripts. In addition, knock down of NTSR1 expression with small interfering RNAs resulted in reduction of cellular invasion and migration in HNSCC cell lines. Our findings suggest a critical role for the NTS and NTSR1 oncogenic pathways in invasion and migration of HNSCC cells during the metastatic process. Our study raises the possibility that NTS and NTSR1 could be a useful predictive marker of poor prognosis in patients with HNSCC and a molecular therapeutic target in antimetastatic strategies for HNSCCs.
Turbidite to storm transition in a migrating foreland basin: the Kendal Group (Upper Silurian), northwest England (1994)

Abstract The uppermost Windermere Supergroup (Kendal Group) of northwest England records the passage from Wenlock and lower Ludlow deep water ‘flysch’ deposits to upper Ludlow and Přídolí shallower water ‘molasse’ deposits within an evolving foreland basin. An upwards progression is preserved from oxygen-poor basin-slope turbidite deposits through more oxygenated, bioturbated dilute density flow deposits, to storm and wave-influenced sediments. The storm-influenced sediments display hummocky cross-stratification, a Skolithos ichnofacies, shelly lags, and symmetrical wave ripple cross-lamination. Convolute lamination increases in magnitude and frequency in the upper part of the sequence, apparently nucleated above ripple crests. Tropical hurricanes probably controlled storm deposition, as suggested by late Silurian palaeogeographic reconstructions. Structures in the heterolithic muddy siltstones suggest deposition in a lower energy, wave-influenced setting. Mud-drapes, short wavelength symmetrical ripples and multi-directional ripple cross-lamination are common. The Kendal Group shows a regional palaeocurrent distribution consistent with an arcuate basin geometry, bounded to the northwest and northeast by topographic slopes. As well as a temporal trend, facies and faunal diachroneity imply a southwards migration of the foreland basin depocentre through Ludlow and Přídolí time, probably ahead of a rising mountain front to the north. The increase in pre-lithification sediment disturbance may reflect greater earthquake activity as this mountain front advanced and the basin began to invert.
Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus (2008)

Chronic myocardial infarction (CMI) is associated with remodeling of the ventricle and evokes adaption in the cardiac neurohumoral control systems. To evaluate the remodeling of the intrinsic cardiac nervous system following myocardial infarction, the dorsal descending coronary artery was ligated in the guinea pig heart and the animals were allowed to recover for 7-9 wk. Thereafter, atrial neurons of the intrinsic cardiac plexus were isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no significant changes in passive membrane properties or action potential configuration compared with age-matched controls and sham-operated animals. The intrinsic cardiac neurons from chronic infarcted hearts did demonstrate an increase in evoked action potential (AP) frequency (as determined by the number of APs produced with depolarizing stimuli) and an increase in responses to exogenously applied histamine compared with sham and age-matched controls. Conversely, pituitary adenylate cyclase-activating polypeptide (PACAP)-induced increases in intrinsic cardiac neuron-evoked AP frequency were similar between control and CMI animals. Immunohistochemical analysis demonstrated a threefold increase in percentage of neurons immunoreactive for neuronal nitric oxide synthase (NOS) in CMI animals compared with control and the additional expression of inducible NOS by some neurons, which was not evident in control animals. Finally, the density of mast cells within the intrinsic cardiac plexus was increased threefold in preparations from CMI animals. These results indicate that CMI induces a differential remodeling of intrinsic cardiac neurons and functional upregulation of neuronal responsiveness to specific neuromodulators.
Development of an Early-Phase Bulk Enabling Route to Sodium-Dependent Glucose Cotransporter 2 Inhibitor Ertugliflozin (2014)

The development and optimization of a scalable synthesis of sodium-dependent glucose cotransporter 2 inhibitor, ertugliflozin, for the treatment of type-2 diabetes is described. Highlights of the chemistry are a concise, four-step synthesis of a structurally complex API from known intermediate 4 via persilylation–selective monodesilylation, primary alcohol oxidation, aldol-crossed-Cannizzaro reaction, and solid-phase acid-catalyzed bicyclic ketal formation. The final API was isolated as the l-pyroglutamic acid cocrystal.