gebhart/patrepeval huggingface dataset:
Integrated predicated and speculative execution in the IMPACT EPIC architecture (2002)

Explicitly Parallel Instruction Computing (EPIC) architectures require the compiler to express program instruction level parallelism directly to the hardware. EPIC techniques which enable the compiler to represent control speculation, data dependence speculation, and predication have individually been shown to be very effective. However these techniques have not been studied in combination with each other. This paper presents the IMPACT EPIC Architecture to address the issues involved in designing processors based on these EPIC concepts. In particular we focus on new execution and recovery models in which microarchitectural support for predicated execution is also used to enable efficient recovery from exceptions caused by speculatively executed instructions. This paper demonstrates that a coherent framework to integrate the three techniques can be elegantly designed to achieve much better performance than each individual technique could alone provide.
Alterations in cardiac DNA methylation in human dilated cardiomyopathy (2013)

Dilated cardiomyopathies (DCM) show remarkable variability in their age of onset, phenotypic presentation, and clinical course. Hence, disease mechanisms must exist that modify the occurrence and progression of DCM, either by genetic or epigenetic factors that may interact with environmental stimuli. In the present study, we examined genome-wide cardiac DNA methylation in patients with idiopathic DCM and controls. We detected methylation differences in pathways related to heart disease, but also in genes with yet unknown function in DCM or heart failure, namely Lymphocyte antigen 75 (LY75), Tyrosine kinase-type cell surface receptor HER3 (ERBB3), Homeobox B13 (HOXB13) and Adenosine receptor A2A (ADORA2A). Mass-spectrometric analysis and bisulphite-sequencing enabled confirmation of the observed DNA methylation changes in independent cohorts. Aberrant DNA methylation in DCM patients was associated with significant changes in LY75 and ADORA2A mRNA expression, but not in ERBB3 and HOXB13. In vivo studies of orthologous ly75 and adora2a in zebrafish demonstrate a functional role of these genes in adaptive or maladaptive pathways in heart failure.
Synthesis of novel C‐2 substituted pyrimidine nucleoside analogs (1993)

Abstract A series of 2‐(2‐oxoalkylidene)‐4(1 H )‐pyrimidinone nucleoside analogs were synthesized by the addition of the lithium enolates of methylketones to 2,5′‐ and 2,2′‐anhydrouridines and to 2,5′‐anhydrothymidines. Alternatively, 2‐thiouridine was alkylated with bromomethyl ketones to yield 2‐(2‐oxoalkyl)thio‐4(1 H )‐pyrimidinone ribofuranosides in good yields. These intermediates were subsequently transformed into the title compounds via an Eschenmoser sulfur extrusion reaction. The 2‐(2‐oxoalkylidene)‐4‐(1 H )‐pyrimidinone nucleoside analogs exhibit enol proton signals in their 1 H nmr spectra indicative of hydrogen bonding between N‐3 and keto oxygen. These structures offer functional groups with potential for Watson‐Crick hydrogen bonding.
Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus, cytoplasm, endothelium, and fibroblasts of human cancers. (2006)

Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) synthesized by the same gene decrease within 24 hours up to 97% the number of human breast, colon, pancreatic, and prostate adenocarcinoma cells as well as human small-cell and squamous carcinomas of the lung cells. These peptide hormones completely inhibit the growth of human pancreatic adenocarcinomas growing in athymic mice. Immunocytochemical investigations have revealed that LANP, vessel dilator, kaliuretic peptide and ANP localize to the nucleus and cytoplasm of human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer mediated by the intracellular messenger cyclic GMP. These peptide hormones also localize to the endothelium of capillaries and fibroblasts within these cancers. These are the first growth-inhibiting peptide hormones ever demonstrated to localize to the nucleus. Their ability to decrease the activation of growth promoting substances such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear Factor Kappa Beta (NFkappaB) suggests that in addition to inhibiting DNA synthesis their ability to decrease the activation of growth promoting substances helps to mediate their ability to inhibit the growth of human cancers.
Tumor treating fields (TTFields) in combination with sorafenib inhibit hepatocellular carcinoma <i>in vitro</i> and <i>in vivo.</i> (2022)

464 Background: Hepatocellular carcinoma (HCC) is a highly malignant liver cancer and a leading cause of cancer related mortality. Sorafenib was the first approved systemic treatment for HCC, and remains one of few front-line treatments for this malignancy. Tumor treating fields (TTFields) are low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields that exert antimitotic effects on cancerous cells. Results of the phase 2 HEPANOVA study of TTFields (150 kHz) plus sorafenib for advanced HCC support investigation of TTFields in a randomized controlled phase 3 study. The current research aimed to describe the in vitro and in vivo efficacy of this combination and to elucidate details regarding the underlying mechanism of action. Methods: In vitro examinations were performed in HepG2 and Huh-7D12 human HCC cell lines, to which TTFields at a frequency of 150 kHz were applied using the inovitro system. Autophagy was examined by western blot and fluorescence detection of microtubule-associated protein light chain 3 (LC3) levels, an accepted autophagy marker. The effect of TTFields in combination with sorafenib was evaluated using cytotoxic, clonogenic, and apoptotic assays. In vivo, SD rats were inoculated orthotopically into the left hepatic lobe with N1S1 HCC cells. 7 days later, TTFields or sham (heat) were applied to the abdominal region of the rats, continuously for 6 days. Daily intraperitoneal injections of sorafenib (10 mg/kg/day) or vehicle were performed during this time. To determine tumor volume growth, MRI images were acquired before and after treatment. Levels of autophagy and apoptosis were examined in tumor sections by immunohistochemistry for LC3 and cleaved PARP, respectively. Results: Application of TTFields induced autophagy in HCC cells. TTFields delivery was cytotoxic to the cells, reduced their colony forming ability, and induced apoptosis while combination with sorafenib elevated these effects. In vivo, tumor volume increased 6-fold in control animals vs 1.6-fold in animals treated with TTFields plus sorafenib. This effect was accompanied by significantly elevated levels of cleaved PARP and LC3 within the tumors of treated relative to control rats. Conclusions: The results demonstrate induction of autophagy and apoptosis in HCC following treatment with TTFields. Concomitant application of TTFields with sorafenib enhanced efficacy via a mechanism that may involve overwhelming autophagy, in vitro and in vivo.
Bulk Cryopreservation of Isolated Islets of Langerhans (1996)

Current methods to isolate human islets of Langerhans are limited and multiple donors are required for successful reversal of longstanding Type 1 diabetes mellitus. Cryopreservation of isolated islets is an effective method of storing and pooling islets. Current cryopreservation protocols are cumbersome due to current practices of placing small aliquots of islets per individual freezer tube. In the present study, we examined the application of a blood freezer bag for the cryopreservation of isolated islets by slow cooling and rapid thawing. Freezing and thawing profiles generated using thermocouples placed inside a 500 mL Cryocyte (Baxter) blood freezer bag showed that a longer equilibration period at −7.4°C was necessary to consistently achieve nucleation and cooling profiles similar to those observed in glass tubes. When known numbers of rat islets were placed in the freezer bag and the cryoprotectant dimethyl sulfoxide (DMSO) was added in a stepwise fashion and removed using a sucrose dilution, the islet recovery compared with glass tubes was 92 ± 4.8 vs. 90 ± 2.3% (n = 4, p = ns, Mann-Whitney U-test). When purified canine islets were cryopreserved in a single freezer bag or in multiple glass tubes, the recovery was similar (78.8 ± 12.5% recovery for freezer bag vs. 82.3 ± 5.3% for glass tubes; n = 6, p = ns). In vitro function was equivalent for both groups. The stimulation index of insulin release during glucose perifusion (stimulated over basal insulin secretion) for canine islets cryopreserved in a freezer bag vs. glass tubes was 3.2 ± 1.0 and 2.3 ± 1.3, respectively (n = 6, p = ns). These values were significantly lower than the nonfrozen control islets (6.9 ± 2.4, p < 0.05). When 2000 canine islets cryopreserved in either a freezer bag, or glass tubes were transplanted into diabetic nude mice, the animals became and remained normoglycemic posttransplant. We conclude that the survival of freshly isolated canine islets cryopreserved in a single freezer bag is equivalent to the glass tube method. Bulk cryopreservation of islets in a single freezer bag will facilitate effective low temperature tissue banking to support ongoing clinical trials of islet transplantation.
Super-amphiphobic, strong self-cleaning and high-efficiency water-based drilling fluids (2020)

Based on the amphiphobic theory on underground rock surface, a super-amphiphobic agent is developed and evaluated which can form nano-micro papilla structure on rock, filter cake and metal surface, reduce surface free energy, prevent collapse, protect reservoir, lubricate and increase drilling speed. With this super-amphiphobic agent as the core agent, a super-amphiphobic, strong self-cleaning and high-performance water-based drilling fluid system has been developed by combining with other agents based on drilled formation, and compared with high-performance water-based drilling fluid and typical oil based drilling fluid commonly used in oilfields. The results show that the super-amphiphobic, strong self-cleaning and high-performance water-based drilling fluid has better rheology, and high temperature and high pressure filtration similar with that of oil-based drilling fluid, inhibiting and lubricating properties close to oil based drilling fluid. Besides, the super-amphiphobic system is non-toxic, safe and environmentally friendly. Field tests show this newly developed drilling fluid system can prevent wellbore collapse, reservoir damage and pipe-sticking, increase drilling speed and lower drilling cost, meeting the requirement of safe, high efficient, economic and environmentally friendly drilling. Compared with other drilling fluids, this new drilling fluid system can reduce downhole complexities by 82.9%, enhance the drilling speed by about 18.5%, lower drilling fluid cost by 39.3%, and increase the daily oil output by more than 1.5 times in the same block.
<title>Cross-platform distributed heterogeneous simulation of a more-electric aircraft power system</title> (2005)

To support research and analysis requirements in the development of future power systems, a flexible and efficient means of predicting the dynamic performance of large-scale multi-disciplinary systems prior to hardware trials is crucial. With the development of Distributed Heterogeneous Simulation (DHS), the technology now exists to enable this type of investigation. Previously, DHS was shown to allow the interconnection of component simulations running on a single- or distributed-computer network and developed using any combination of a variety of commercial-off-the-shelf (COTS) software packages for the Microsoft Windows operating system. However, for large-scale systems, all subsystem models may not be developed in software packages operating under Windows thereby requiring a translation of such models in order to incorporate them within a system simulation. In this paper, the DHS technique is expanded to support the UNIX operating system, thus, allowing subsystem models developed and executed on either UNIX- or Windows-based computers to be interconnected to form a dynamic system simulation. For the purpose of demonstration, a more-electric fighter (MEF) power system, such as that found on the Joint Strike Fighter (JSF), has been selected as a study system. This system is comprised of ten component models each developed using MATLAB/Simulink, EASY5, or ACSL. Utilizing the system simulation, studies have been performed to illustrate the dynamic interactions between the subsystems when simulated on a heterogeneous computer network containing both Windows- and Unix-based machines.
Bi-magnitude processing framework for nonlinear acoustic echo cancellation on Android devices (2016)

This paper presents a new paradigm for acoustic echo control on mobile Android devices. The echo path on these devices has nonlinearities including not only the results of overdriven power amplifiers and miniaturized loudspeakers, but also those caused by hardware audio dynamic range compressor (ADRC). While the former form of nonlinearities was widely investigated in past research, the latter has not yet been taken into account. The ADRC adds extra gains to the echo path and makes it become a fast time-varying system. This presents a great challenge to traditional (both linear and nonlinear) echo cancellation systems. Here we propose a novel bi-magnitude processing framework, which is based on a two-state model for the echo path. The algorithm can deal with the ADRC problem and offers robust control for identification of input nonlinearities. The performance of the proposed approach is evaluated on recordings made in an anechoic chamber using real Android devices.
Development of Self-Contained Hydraulic Valve Lifter (1983)

<div class="htmlview paragraph">The conventional hydraulic valve lifters, which eliminate the valve clearance adjustment, normally use the pressurized engine lubricant for the working fluid. We have developed a quite new type lifter, named “self-contained hydraulic valve lifter”, which possesses the working fluid in itself. Because the new type lifter is independent of the pressurized engine lubricant, it has some advantages, especially that it can be applied to the existing engine using the mechanical valve gear without almost any engine modifications. And we have confirmed that the self-contained hydraulic valve lifter has good characteristics and reliability and have applied it to the mass production engine (i.e. Toyota 1.3L gasoline engine) for the first time in the world.</div> <div class="htmlview paragraph">This paper describes the construction, the characteristics and the reliability of this lifter.</div>
Anode‐Free Rechargeable Lithium Metal Batteries (2016)

Anode‐free rechargeable lithium (Li) batteries (AFLBs) are phenomenal energy storage systems due to their significantly increased energy density and reduced cost relative to Li‐ion batteries, as well as ease of assembly because of the absence of an active (reactive) anode material. However, significant challenges, including Li dendrite growth and low cycling Coulombic efficiency (CE), have prevented their practical implementation. Here, an anode‐free rechargeable lithium battery based on a Cu||LiFePO 4 cell structure with an extremely high CE (>99.8%) is reported for the first time. This results from the utilization of both an exceptionally stable electrolyte and optimized charge/discharge protocols, which minimize the corrosion of the in situly formed Li metal anode.
LogLog-Beta and More: A New Algorithm for Cardinality Estimation Based on LogLog Counting (2016)

The information presented in this paper defines LogLog-Beta. LogLog-Beta is a new algorithm for estimating cardinalities based on LogLog counting. The new algorithm uses only one formula and needs no additional bias corrections for the entire range of cardinalities, therefore, it is more efficient and simpler to implement. Our simulations show that the accuracy provided by the new algorithm is as good as or better than the accuracy provided by either of HyperLogLog or HyperLogLog++. In addition to LogLog-Beta we also provide another one-formula estimator for cardinalities based on order statistics, a modification of an algorithm developed by Lumbroso.
Association of a Four‐Basepair Insertion in the P34 Gene with the Low‐Allergen Trait in Soybean (2009)

The value of soybean [ Glycine max (L.) Merr.] is determined in part by functionality of major seed components, extractable oil and high protein meal. Soybean meal is an important protein source for animal feeds, and use of soybean meal by the food industry is increasing. Food allergens have negative impacts for both foods and feeds. The major soybean allergen, Gly m Bd 30K, was identified as the P34 protein, a low abundance but highly conserved seed protein. Recently, two soybean germplasm accessions (PI 567476 and PI 603570A) were identified as having reduced P34 content without other collateral changes in seed protein composition. In order to develop molecular markers to enhance breeding for low P34, our objective was to characterize the P34 gene region in wild‐type and low‐P34 soybean lines and exploit any sequence differences to allow direct selection for mutant P34 alleles. The results indicated the two low‐P34 germplasm accessions contain a four‐basepair insertion at the P34 start codon. The mutant allele may inhibit efficient translation initiation of the P34 protein. Inheritance of the mutant P34 alleles completely associated with the low‐P34 phenotype. Molecular markers were developed that were based on the mutant allele of the P34 gene.
Pyruvate Induces Transient Tumor Hypoxia by Enhancing Mitochondrial Oxygen Consumption and Potentiates the Anti-Tumor Effect of a Hypoxia-Activated Prodrug TH-302 (2014)

Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.
Inhibitors of sterol synthesis. Metabolism of [2,4-3H]5 alpha-cholest-8(14-)-en-3 beta-ol-15-one after intravenous administration to a nonhuman primate. (1988)

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of cholesterol synthesis with marked hypocholesterolemic activity, has been studied after the intravenous administration of a mixture of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one and [4-14C] cholesterol to a baboon. The levels of 3H in plasma which was associated with the free 15-ketosterol decreased very rapidly (T1/2 approximately 9 min) after injection of the labeled sterol. By 4 h, the level of the [3H]15-ketosterol in plasma was negligible. The rapid decrease in the levels of the free 15-ketosterol was associated with rapid formation of fatty acid esters of the 15-ketosterol. The maximum level of 3H-labeled 15-ketosteryl esters was observed at 20 min after the injection of the 15-ketosterol. Thereafter, the levels of the 15-ketosteryl esters decreased rapidly with an apparent T1/2 of approximately 3.5-4.0 h. The results also indicated rapid formation of 3H-labeled cholesterol and cholesteryl esters. Substantial formation of [3H]cholesterol was observed at 20 min after the injection of the 15-ketosterol and reached a maximum level in plasma at 2 h. The maximum levels of [3H]cholesteryl esters in plasma were observed much later. These and other findings indicated that the observed slow clearance of total 3H from plasma is a consequence of metabolism of the 15-ketosterol to cholesterol and cholesteryl esters, normal constituents of plasma whose turnover in the whole animal is known to be relatively slow.
Tropolones As Lead-Like Natural Products: The Development of Potent and Selective Histone Deacetylase Inhibitors (2013)

Natural products have long been recognized as a rich source of potent therapeutics but further development is often limited by high structural complexity and high molecular weight. In contrast, at the core of the thujaplicins is a lead-like tropolone scaffold characterized by relatively low molecular weight, ample sites for diversification, and metal-binding functionality poised for targeting a range of metalloenzyme drug targets. Here, we describe the development of this underutilized scaffold for the discovery of tropolone derivatives that function as isozyme-selective inhibitors of the validated anticancer drug target, histone deacetylase (HDAC). Several monosubstituted tropolones display remarkable levels of selectivity for HDAC2 and potently inhibit the growth of T-cell lymphocyte cell lines. The tropolones represent a new chemotype of isozyme-selective HDAC inhibitors.
Protective antigens of rodent and hum an bloodstage malaria (1984)

Bloodstage malaria parasites are antigenically complex, but individual antigens can be identified and analysed using monoclonal antibodies. Two monoclonal antibodies that recognize a 235 000 molecular mass Plasmodium yoelii rhoptry protein provide some protection when injected into mice against a challenge infection. The purified rhoptry protein also provides protective immunity against P. yoelii YM when used to vaccinate mice and fulminating infections are converted into self-limiting, reticulocyte-restricted infections. Another monoclonal antibody immunoprecipitates a 230 000 molecular mass protein and a series of proteolytic processing fragments. At least one of these processing fragments, probably a 90 000 molecular mass species, is located on the merozoite surface. Mice immunized with the purified protein were protected against challenge infection with P. yoelii YM. This antigen may provide protection by inducing a cell-mediated immune response. A monoclonal antibody raised against P. falciparum schizonts reacts with a 195 000 molecular mass protein which is synthesized in schizonts and subsequently cleaved. Fragments of the 195 000 molecular mass protein are expressed as major antigens on the merozoite surface. The 195 000 molecular mass P. falciparum protein and the 230 000 molecular mass P. yoelii protein belong to a class of malaria parasite antigens which probably is important in the induction of a protective immune response in the host.
In Vivo Therapeutic Gas Delivery for Neuroprotection With Echogenic Liposomes (2010)

This novel methodology may provide a noninvasive strategy for ultrasound-enhanced local therapeutic gas delivery for cerebral ischemia-related injury while minimizing systemic side effects.