gebhart/patrepeval huggingface dataset:
The Nuclear Overhauser Effect in Structural and Conformational Analysis (1989)

This book is a comprehensive treatment of the nuclear Overhauser effect (NOE), an important branch of NMR spectroscopy concerned with structural and conformational problems. It is the only text in this area since 1971. Since that time there have been tremendous changes in the area, particularly with the growth of experiments such as NOE difference spectroscopy, NOESY, the heteronuclear NOE, with applications to an ever-increasing variety of structural and conformational problems in chemistry and biochemistry. The book gives a very clear and integrated account of all these developments. It covers theory, experimental practice, and applications in a unified manner including the influence of exchange and spin-spin-coupling as part of its underlying concepts, and applications to molecules as diverse as cyclobutanes and proteins. The book is of interest primarily to postgraduate organic and inorganic chemists and biochemists who use the NOE in their research, but it is also useful to those who wish to learn the background to the technique, for instance computational chemists , biophysicists, and physical chemists. Although it describes and explains the latest developments, the treatment is suitable for those with only a graduate-level background in chemistry and spectroscopy.
Application de l'allocation de contrôle sous contraintes non-linéaires pour optimiser les entrées de commande d'un véhicule industriel (2013)

Colloque avec actes et comité de lecture. Internationale.
Reduce, reuse, recycle: an approach to building large Internet caches (2002)

New demands brought by the continuing growth of the Internet will be met in part by more effective use of caching in the Web and other services. We have developed CRISP, a distributed Internet object cache targeted to the needs of the organizations that aggregate the end users of Internet services, particularly the commercial Internet Service Providers (ISPs) where much of the new growth occurs. A CRISP cache consists of a group of cooperating caching servers sharing a central directory of cached objects. This simple and obvious strategy is easily overlooked due to the well known drawbacks of a centralized structure. However, we show that these drawbacks are easily overcome for well configured CRISP caches. We outline the rationale behind the CRISP design, and report on early studies of CRISP caches in actual use and under synthetic load. While our experience with CRISP to date is at the scale of hundreds or thousands of clients, CRISP caches could be deployed to maximize capacity at any level of a regional or global cache hierarchy.
Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling (2017)

Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here, we apply cancer personalized profiling by deep sequencing (CAPP-seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I-III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first posttreatment blood sample, indicating reliable identification of MRD. Posttreatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months, and 53% of patients harbored ctDNA mutation profiles associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in patients with lung cancer can be accurately detected using CAPP-seq and may allow personalized adjuvant treatment while disease burden is lowest.<b>Significance:</b> This study shows that ctDNA analysis can robustly identify posttreatment MRD in patients with localized lung cancer, identifying residual/recurrent disease earlier than standard-of-care radiologic imaging, and thus could facilitate personalized adjuvant treatment at early time points when disease burden is lowest. <i>Cancer Discov; 7(12); 1394-403. ©2017 AACR.</i><i>See related commentary by Comino-Mendez and Turner, p. 1368</i><i>This article is highlighted in the In This Issue feature, p. 1355</i>.
Polarity of GaN Single Crystals Prepared with Na Flux (1998)

The polarity of GaN platelet and prismatic single crystals grown in sodium flux at 750°C was investigated by X-ray single-crystal diffraction. The smooth (0001) facet of platelet single crystals corresponded to the N-terminated side. The (0001) facet on which small hillocks were observed corresponded to the Ga-terminated plane. The c -axis direction from N to Ga atoms was defined as running from the pedion (flat base) to the pyramid (apex) of the prismatic crystals.
Data partitioning on chip multiprocessors (2008)

Partitioning is a key database task. In this paper we explore partitioning performance on a chip multiprocessor (CMP) that provides a relatively high degree of on-chip thread-level parallelism. It is therefore important to implement the partitioning algorithm to take advantage of the CMP's parallel execution resources. We identify the coordination of writing partition output as the main challenge in a parallel partitioning implementation and evaluate four techniques for enabling parallel partitioning. We confirm previous work in single threaded partitioning that finds L2 cache misses and translation lookaside buffer misses to be important performance issues, but we now add the management of concurrent threads to this analysis.
Effects of <i>L</i>-Glutamine on Various Gastric Lesions in Rats and Guinea Pigs (1976)

Effects of L-glutamine on gastric lesion models in rats and guinea pigs were studied. Shay ulceration in rats was not inhibited by oral L-glutamine. Although stress-induced gastric lesions in intact rats were not inhibited by L-glutamine, a strong antagonism of gastric lesions was induced in pylorus-ligated rats under the same stress by the amino acid. Histamine-induced gastric lesions in intact rats and guinea pigs were also markedly inhibited by L-glutamine. L-Glutamine inhibited the gastric lesions in rats induced by compound 48/80 but not significantly. Reserpine- or serotonin-induced gastric lesions in rats were not affected by L-glutamine. The mechanism of L-glutamine protection was discussed.
A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease (2019)

New treatments directly targeting polymerization of sickle hemoglobin (HbS), the proximate event in the pathophysiology of sickle cell disease (SCD), are needed to address the severe morbidity and early mortality associated with the disease. Voxelotor (GBT440) is a first-in-class oral therapy specifically developed to treat SCD by modulating the affinity of hemoglobin (Hb) for oxygen, thus inhibiting HbS polymerization and downstream adverse effects of hemolytic anemia and vaso-occlusion. GBT440-001 was a phase 1/2 randomized, double-blind, placebo-controlled, single and multiple ascending dose study of voxelotor in adult healthy volunteers and patients with SCD, followed by a single-arm, open-label extension study. This report describes results of voxelotor (500-1000 mg per day) in patients with sickle cell anemia. The study evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of voxelotor and established proof of concept by improving clinical measures of anemia, hemolysis, and sickling. Thirty-eight patients with SCD received 28 days of voxelotor 500, 700, or 1000 mg per day or placebo; 16 patients received 90 days of voxelotor 700 or 900 mg per day or placebo. Four patients from the 90-day cohort were subsequently enrolled in an extension study and treated with voxelotor 900 mg per day for 6 months. All patients who received multiple doses of voxelotor for ≥28 days experienced hematologic improvements including increased Hb and reduction in hemolysis and percentage of sickled red cells, supporting the potential of voxelotor to serve as a disease-modifying therapy for SCD. Voxelotor was well tolerated with no treatment-related serious adverse events and no evidence of tissue hypoxia. These trials were registered at www.clinicaltrials.gov as #NCT02285088 and #NCT03041909.
Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis (2001)

Serum amyloid P component (SAP) is a member of the pentraxin family of proteins. These proteins are characterized by cyclic pentameric structure, calcium-dependent ligand binding, and frequent regulation as acute-phase serum proteins. SAP is the serum precursor of the P component of amyloid. It binds to a broad group of molecules, including autoantigens, through a pattern recognition binding site. The related pentraxin, C-reactive protein (CRP), is a strong acute-phase reactant in man and an opsonin. We previously determined that the binding of CRP to leukocytes occurs through Fc receptors for IgG (FcgammaR). We now report that SAP also binds to FcgammaR and opsonizes particles for phagocytosis by human polymorphonuclear leukocytes (PMN). Specific, saturable binding of SAP to FcgammaRI, FcgammaRIIa, and FcgammaRIIIb expressed on transfected COS cells was detected using SAP-biotin and PE-streptavidin. Zymosan was used to test the functional consequences of SAP and CRP binding to FcgammaR. Both SAP and CRP bound to zymosan and enhanced its uptake by PMN. This enhanced phagocytosis was abrogated by treatment of PMN with wortmannin, a phosphatidylinositol-3 kinase inhibitor, or with piceatannol, a Syk inhibitor, consistent with uptake through FcgammaR. Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove FcgammaRIIIb also decreased phagocytosis of SAP-opsonized zymosan, but not CRP-opsonized zymosan. These results suggest that SAP may function in host defense. In addition, as SAP binds to chromatin, a major immunogen in systemic lupus erythematosus, it may provide a clearance mechanism for this Ag through FcgammaR bearing cells.
Editor's Note (1997)

Bruce Menning is currently instructor and foreign military analyst in the Strategic Studies Division of the Department of Joint and Multinational Operations at the U.S. Army Command and General Staff College, Fort Leavenworth, Kansas. One of the nation's foremost military historians, he is best known for his study of Russian military doctrine, Bayonets Before Bullets: The Imperial Russian Army, 1861-1914 (Bloomington: Indiana University Press, 1992). He is currently working on a book on strategy and war planning in Russia and the Soviet Union, 1871-1941.
Arthrobacter Endo‐β‐N‐Acetylglucosaminidase Shows Transglycosylation Activity on Complex‐Type N‐Glycan Oxazolines: One‐Pot Conversion of Ribonuclease B to Sialylated Ribonuclease C (2010)

Transforming protein glycosylation: The Arthrobacter endo-β-N-acetylglucosaminidase (Endo-A) was found to transglycosylate complex N-glycan oxazolines without product hydrolysis. Given its high activity in hydrolyzing high-mannose-type N-glycans, the newly discovered property enables a one-pot switch of glycans in a glycoprotein, as shown by the conversion of heterogeneous RNase B to homogeneous sialylated RNase C.
Something is Rotten in the State of Iceland: deCODE Genetics, Population Research and Informed Consent (2006)

This article considers the importance of protecting research subjects in genetic research. Specifically, it looks at one of the earliest, and most controversial, examples of population genetic research, that proposed to be undertaken by deCODE Genetics Inc on the Icelandic population. In undertaking its research deCODE proposed to establish three separate but interlinked databases each holding medical records, genetic information or genealogical records (named the Genealogy Genotype Phenotype Resource database (GGPR). This article considers the establishment and development of both deCODE and the GGPR, and the development of and legal challenge to the database of Icelandic medical records. This article also considered the mechanisms for consent used for participation in deCODE's research and whether such mechanisms adequately protect the participants in its research. This article argues that, rather than being an example to be followed, the story of deCODE should be a warning to others whose research equally depends on the enthusiastic participations of research subjects.
Several small GTP‐binding proteins are strongly down‐regulated in simian virus 40 (SV40) transformed human keratinocytes and may be required for the maintenance of the normal phenotype (1994)

High resolution two-dimensional (2-D) gel electrophoresis in combination with the blot overlay nucleotide binding assay was used to reveal low molecular weight GTP-binding proteins expressed by primary cultured, normal human keratinocytes. Forty one small GTP-binding proteins (30 isoelectric focusing, IEF; and 11 nonequilibrium pH gradient electrophoresis, NEPHGE) ranging in molecular weights from 18,000 to 30,000 and isoelectric points from 4.4 to 8.0 were detected and mapped in the master human keratinocyte database. Four GTP-binding proteins were identified by 2-D gel immunoblotting and these correspond to rap1 and 2 and two forms of rab6. ras-Proteins are most likely present in the [alpha 32P]GTP 2-D gel blots but their levels may be too low to be detected by immunoblotting. Quantitative changes in the relative expression levels of [alpha 32P]GTP-binding proteins in normal proliferating and simian virus 40 (SV40) transformed human keratinocytes (K 14) were determined by scintillation counting of the radioactive spots excised from the nitrocellulose blots. The results showed that thirteen of these proteins were not expressed in transformed K14 keratinocytes, implying that they may play a role in the maintenance of the normal cell phenotype.
Conserved Intermolecular Salt Bridge Required for Activation of Protein Kinases PKR, GCN2, and PERK (2007)

The protein kinases PKR, GCN2, and PERK phosphorylate translation initiation factor eIF2alpha to regulate general and genespecific protein synthesis under various cellular stress conditions. Recent x-ray crystallographic structures of PKR and GCN2 revealed distinct dimeric configurations of the kinase domains. Whereas PKR kinase domains dimerized in a back-to-back and parallel orientation, the GCN2 kinase domains displayed an antiparallel orientation. The dimerization interfaces on PKR and GCN2 were localized to overlapping surfaces on the N-terminal lobes of the kinase domains but utilized different intermolecular contacts. A key feature of the PKR dimerization interface is a salt bridge interaction between Arg(262) from one protomer and Asp(266) from the second protomer. Interestingly, these two residues are conserved in all eIF2alpha kinases, although in the GCN2 structure, the two residues are too remote to interact. To test the importance of this potential salt bridge interaction in PKR, GCN2, and PERK, the residues constituting the salt bridge were mutated either independently or together to residues with the opposite charge. Single mutations of the Asp (or Glu) and Arg residues blocked kinase function both in yeast cells and in vitro. However, for all three kinases, the double mutation designed to restore the salt bridge interaction with opposite polarity resulted in a functional kinase. Thus, the salt bridge interaction and dimer interface observed in the PKR structure is critical for the activity of all three eIF2alpha kinases. These results are consistent with the notion that the PKR structure represents the active state of the eIF2alpha kinase domain, whereas the GCN2 structure may represent an inactive state of the kinase.
Advantage of Recording Single-Unit Muscle Sympathetic Nerve Activity in Heart Failure (2012)

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF.
Meta-Analysis of Postactivation Potentiation and Power (2012)

There is no clear agreement regarding the ideal combination of factors needed to optimize postactivation potentiation (PAP) after a conditioning activity. Therefore, a meta-analysis was conducted to evaluate the effects of training status, volume, rest period length, conditioning activity, and gender on power augmentation due to PAP. A total of 141 effect sizes (ESs) for muscular power were obtained from a total of 32 primary studies, which met our criteria of investigating the effects of a heavy preconditioning activity on power in randomized human trials. The mean overall ES for muscle power was 0.38 after a conditioning activity (p < 0.05). Significant differences were found between moderate intensity (60-84%) 1.06 and heavy intensity (>85%) 0.31 (p < 0.05). There were overall significant differences found between single sets 0.24 and multiple sets 0.66 (p < 0.05). Rest periods of 7-10 minutes (0.7) after a conditioning activity resulted in greater ES than 3-7 minutes (0.54), which was greater than rest periods of >10 minutes (0.02) (p < 0.05). Significant differences were found between untrained 0.14 and athletes 0.81 and between trained 0.29 and athletes. The primary findings of this study were that a conditioning activity augmented power output, and these effects increased with training experience, but did not differ significantly between genders. Moreover, potentiation was optimal after multiple (vs. single) sets, performed at moderate intensities, and using moderate rest periods lengths (7-10 minutes).
Measurement of cell proliferation by labeling of DNA with stable isotope-labeled glucose: Studies in vitro , in animals, and in humans (1998)

A method for measuring DNA synthesis and, thus, cell proliferation, in vivo is presented. The technique consists of administering [6,6-2H2]Glc or [U-13C]Glc, isolating genomic DNA, hydrolyzing enzymatically to free deoxyribonucleosides, and derivatizing for GC-MS analysis of dA or dG isotopic enrichments, or both. Comparison of dA or dG to extracellular Glc enrichment (with a correction for intracellular dilution) reveals the fraction of newly synthesized DNA, by application of the precursor-product relationship. Thus, the technique differs from the widely used [3H]thymidine or BrdUrd techniques in that the de novo nucleotide synthesis pathway, rather than the nucleoside salvage pathway, is used to label DNA; the deoxyribose rather than the base moiety is labeled; purine rather than pyrimidine deoxyribonucleosides are analyzed; and stable isotopes rather than radioisotopes are used. The method is applied here in vitro to the growth of HepG2 and H9 cells in culture; in animals to proliferation of intestinal epithelium, thymus, and liver; and in humans to granulocyte turnover in blood. In all instances, measured cell proliferation kinetics were consistent with expected or independently measured kinetics. The method has several advantages over previously available techniques for measuring cell turnover, involves no radioactivity or potentially toxic metabolites, and is suitable for use in humans. The availability of a reliable and safe method for measuring cell proliferation in humans opens up a number of fundamental questions to direct experimental testing, including basic problems related to cancer, AIDS, and other pathologic states.
Two-dimensional numerical simulation of Schottky barrier MOSFET with channel length to 10 nm (1998)

We present simulation results of a silicon-based metal-oxide-semiconductor field-effect transistor (MOSFET), which has a structure similar to that of a conventional MOSFET, but the source and drain regions are now entirely replaced by metals. By using abrupt metal/silicon Schottky junctions, short-channel effects are avoided. Based on a few commonly used physical assumptions, we have calculated the transistor characteristics, and we find that this new three-terminal transistor can offer gain and impedance isolation, desirable for logic circuit applications.
AskStrider: What Has Changed on My Machine Lately? (2004)

As computer programs grow more complex, extensible, and connected, it becomes increasingly difficult for users to understand what has changed on their machines and what impact those changes have. In this paper, we describe a tool, called AskStrider, that answers those questions by correlating volatile process information with persistent-state context information and change history. AskStrider automatically scans a system for active components, matches them against a change log to identify recently updated and hence more interesting state, and searches for context information to help users understand the changes. We use several real-world cases to demonstrate the effectiveness of using AskStrider to quickly identify the presence of unwanted software, to determine if a software patch is potentially breaking an application, and to detect lingering components left over from an unclean uninstallation. 1.