gebhart/patrepeval huggingface dataset:
Early Metabolic Defects in Persons at Increased Risk for Non-Insulin-Dependent Diabetes Mellitus (1989)

To identify early metabolic abnormalities in non-insulin-dependent diabetes mellitus (NIDDM), we measured sensitivity to insulin and insulin secretion in 26 first-degree relatives of patients with NIDDM and compared these subjects both with 14 healthy control subjects with no family history of NIDDM and with 19 patients with NIDDM. The euglycemic insulin-clamp technique, indirect calorimetry, and infusion of [3-3H]glucose were used to assess insulin sensitivity. Total-body glucose metabolism was impaired in the first-degree relatives as compared with the controls (P less than 0.01). The defect in glucose metabolism was almost completely accounted for by a defect in nonoxidative glucose metabolism (primarily the storage of glucose as glycogen). The relatives with normal rates of metabolism (mean +/- SEM, 1.81 +/- 0.27 mg per kilogram of body weight per minute) and impaired rates (1.40 +/- 0.22 mg per kilogram per minute) in oral glucose-tolerance tests had the same degree of impairment in glucose storage as compared with healthy control subjects (3.76 +/- 0.55 mg per kilogram per minute; P less than 0.01 for both comparisons). During hyperglycemic clamping, first-phase insulin secretion was lacking in patients with NIDDM (P less than 0.01) and severely impaired in their relatives with impaired glucose tolerance (P less than 0.05) as compared with control subjects; insulin secretion was normal in the relatives with normal glucose tolerance. We conclude that impaired glucose metabolism is common in the first-degree relatives of patients with NIDDM, despite their normal results on oral glucose-tolerance tests. Both insulin resistance and impaired insulin secretion are necessary for the development of impaired glucose tolerance in these subjects.
Sleep stage and skin temperature regulation during night‐sleep in winter (1999)

To clarify the thermally comfortable environment for satisfied sleep, we investigated the relationship between skin temperatures and sleep stages during night-sleep in winter, summer and autumn. Four healthy young females served as the subjects. The experiments were performed in a climate chamber under three conditions: at 13 degrees C-RH70% with futon and blanket in winter, at 20-18 degrees C-RH60% with futon and towelket in autumn and at 29 degrees C-RH70% with towelket in summer. The subjects' skin temperature on the sole was lower until about 4 hours after lights off in winter than in autumn and summer, and the percentage of st.2 was lower and st.4 was higher in winter than in autumn and summer, although the bed climate both in winter and autumn was much the same.
Overexpression of c-K-<i>ras</i>, c-N-<i>ras</i> and transforming growth factor β co-segregate with tumorigenicity in morphologically transformed C3H 10T1/2 cell lines (1994)

Morphologic transformation and tumorigenicity are separate cellular phenotypes in transformed 10T1/2 cells. We have investigated the levels of expression of genes for c-myc, c-H-ras, c-K-ras, c-N-ras, TGF beta and Rb in 42 morphologically transformed 10T1/2 cell lines, in an attempt to define the molecular mechanisms governing morphologic transformation and tumorigenicity in the 10T1/2 cell system. The 10T1/2 cell lines investigated generally overexpressed mRNAs for c-myc, c-H-ras, and TGF beta relative to the levels expressed by wild-type 10T1/2 cells (levels of expression > 1.5-fold that of wild-type 10T1/2 cells). In contrast, only half of these cell lines overexpressed mRNAs for c-N-ras and/or Rb relative to wild-type 10T1/2 cells, and only 25% overexpressed c-K-ras mRNA. The mean levels of mRNA expression for each of c-K-ras, c-N-ras and TGF beta genes in tumorigenic cell lines were significantly greater than the mean levels of expression in non-tumorigenic cell lines, suggesting an association between tumorigenicity and the levels of expression of these specific genes. In contrast, levels of expression for c-myc, c-H-ras and Rb genes were not correlated with tumorigenicity. Cell lines that coexpressed high levels of c-K-ras, c-N-ras and TGF beta genes were likely to be tumorigenic (11/12 cell lines were tumorigenic), whereas cell lines that coexpressed low levels of these genes were unlikely to be tumorigenic (1/10 cell lines were tumorigenic). High expression of TGF beta was sufficient for tumorigenicity in the absence of high levels of expression of c-K-ras and c-N-ras (5/5 cell lines were tumorigenic). Elevated expression of either c-K-ras or c-N-ras alone was insufficient for tumorigenicity, however, coordinate overexpression of both c-K-ras and c-N-ras was associated with tumorigenicity irrespective of the expression status for TGF beta (13/15 cell lines were tumorigenic). These results suggest that overexpression of c-myc, c-H-ras and TGF beta are commonly associated with, and possibly mechanistically related to, the process of morphologic transformation in 10T1/2 cells. In addition, these results suggest that progression from morphologic transformation to tumorigenicity in 10T1/2 cell lines is frequently accompanied by overexpression of c-K-ras and c-N-ras, and by enhancement of the level of overexpression of TGF beta.
Manipulation of the sodium‐potassium ratio as a lever for controlling cell growth and improving cell specific productivity in perfusion CHO cell cultures (2017)

Perfusion processes typically require removal of a continuous or semi-continuous volume of cell culture in order to maintain a desired target cell density. For fast growing cell lines, the product loss from this stream can be upwards of 35%, significantly reducing the overall process yield. As volume removed is directly proportional to cell growth, the ability to modulate growth during perfusion cell culture production thus becomes crucial. Leveraging existing media components to achieve such control without introducing additional supplements is most desirable because it decreases process complexity and eliminates safety and clearance concerns. Here, the impact of extracellular concentrations of sodium (Na) and potassium (K) on cell growth and productivity is explored. High throughput small-scale models of perfusion revealed Na:K ratios below 1 can significantly suppress cell growth by inducing cell cycle arrest in the G0/1 phase. A concomitant increase in cell specific productivity was also observed, reaching as high as 115 pg/cell/day for one cell line studied. Multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrated similar responses to lower Na:K media, indicating the universal applicability of such an approach. Product quality attributes were also assessed and revealed that effects were cell line specific, and can be acceptable or manageable depending on the phase of the drug development. Drastically altering Na and K levels in perfusion media as a lever to impact cell growth and productivity is proposed.
Preparation and study of model magnetorheological fluids (2008)

Purpose: The aim of this work was preparation of the model magnetorheological (MR) fluids. Basic properties of prepared MR fluids, as their response to an external magnetic field and their stability, were investigated. Moreover (furthermore) few results concerning stabilizing effect of various additives are presented. Design/methodology/approach: Model MR fluid was prepared using three type of carriers: silicone oil OKS 1050, synthetic oil OKS 352, mineral oil OKS 600 mixed with carbonyl iron powder CI HQ. Furthermore, to reduce sedimentation Aerosil 200 and 972, Arsil 1100 and Arabic gum were added as stabilizers. MR effect was measured using device working as Couette’s viscosimeter equipped with coil generating magnetic field. Sedimentation was measured by simply observation of changes in boundary position between clear and turbid part of MR fluid placed into glass tube. Findings: Influence of the additives presence on the MR effect was determined. The presence of additives did not diminish the magnetic effect but even increased the dynamic viscosity in existence of an external magnetic field. The stability of MR fluid was improved by adding additives to the formulation. Moreover, increasing stabilizer concentration further enhanced the MR fluid stability. The best result was achieved in case of Aerosil 9782 at 2 % content. Research limitations/implications: MR fluids with excellent properties can be applied in various fields of civil and safety engineering, transportation and life science. However, due to sedimentation, MR fluid response to magnetic field is restricted and in an extreme situation could lead to the fail that is why further efforts must be still made in order to obtain even better results. Originality/value: This article provides set of new data about improvement of MR fluid stability in the presence of selected stabilizers and contains few remarks how the formulation of MR fluid affect its properties.
Messinian salinity crisis impact on the groundwater quality in Kert aquifer NE Morocco: Hydrochemical and statistical approaches (2012)

Groundwater’s studies at middle Kert aquifer in northeast of Morocco are very important due to the semi-arid character and its geological history. The region is recognized by messinian salinity crisis already 5.6 Ma. Water chemistry is mainly dominated by dissolution of evaporate rocks (Halite and Gypsum) related to outcropping and basement limits developed in Messinian age. Freshwater with total dissolved solids 740 mg/l (average value) in Tafersite district is chemically distinct from saline water with total dissolved solids of 9803 mg/l in the south zone. In wadis, water is S04-Cl-Ca type; they are influenced by the surrounding highlands located at the south of the plain. The investigation reveals that weathering of evaporated rocks is the processes responsible for high Na+, Ca2+, Mg2+, Cl- and SO42- concentrations. Also, hydro chemical data displays that freshwater observed in the northwest part reflect the influence of freshwaters coming from metamorphic massive of Temsamane. The factorial analysis reveal three sources of salinization, the principal one is described above, whilst the dissolution of carbonates and human influence represented by NO3-, played only a secondary role.

	 

	Key words: Salinization, groundwater, Messinian crisis, hydrochemistry, statistical, Kert aquifer, NE Morocco.
Purine nucleoside phosphorylases from hyperthermophilic <i>Archaea</i> require a CXC motif for stability and folding (2009)

5'-Deoxy-5'-methylthioadenosine phosphorylase II from Sulfolobus solfataricus (SsMTAPII) and purine nucleoside phosphorylase from Pyrococcus furiosus (PfPNP) are hyperthermophilic purine nucleoside phosphorylases stabilized by intrasubunit disulfide bonds. In their C-terminus, both enzymes harbour a CXC motif analogous to the CXXC motif present at the active site of eukaryotic protein disulfide isomerase. By monitoring the refolding of SsMTAPII, PfPNP and their mutants lacking the C-terminal cysteine pair after guanidine-induced unfolding, we demonstrated that the CXC motif is required for the folding of these enzymes. Moreover, two synthesized CXC-containing peptides with the same amino acid sequences present in the C-terminal regions of SsMTAPII and PfPNP were found to act as in vitro catalysts of oxidative folding. These small peptides are involved in the folding of partially refolded SsMTAPII, PfPNP and their CXC-lacking mutants, with a concomitant recovery of their catalytic activity, thus indicating that the CXC motif is necessary to obtain complete reversibility from the unfolded state of the two proteins. The two CXC-containing peptides are also able to reactivate scrambled RNaseA. The data obtained in the present study represent the first example of how the CXC motif improves both stability and folding in hyperthermophilic proteins with disulfide bonds.
ADVANCES IN NONLINEAR NON-SCALING FFAGs (2011)

Accelerators are playing increasingly important roles in basic science, technology, and medicine. Ultra high-intensity and high-energy (GeV) proton drivers are a critical technology for accelerator-driven sub-critical reactors (ADS) and many HEP programs (Muon Collider) but remain particularly challenging, encountering duty cycle and space-charge limits in the synchrotron and machine size concerns in the weaker-focusing cyclotrons; a 10–20 MW proton driver is not presently considered technically achievable with conventional re-circulating accelerators. One, as-yet, unexplored re-circulating accelerator, the Fixed-field Alternating Gradient or FFAG, is an attractive alternative to the other approaches to a high-power beam source. Its strong focusing optics can mitigate space charge effects and achieve higher bunch charges than are possible in a cyclotron, and a recent innovation in design has coupled stable tunes with isochronous orbits, making the FFAG capable of fixed-frequency, CW acceleration, as in the classical cyclotron but beyond their energy reach, well into the relativistic regime. This new concept has been advanced in non-scaling nonlinear FFAGs using powerful new methodologies developed for FFAG accelerator design and simulation. The machine described here has the high average current advantage and duty cycle of the cyclotron (without using broadband RF frequencies) in combination with the strong focusing, smaller losses, and energy variability that are more typical of the synchrotron. The current industrial and medical standard is a cyclotron, but a competing CW FFAG could promote a shift in this baseline. This paper reports on these new advances in FFAG accelerator technology and presents advanced modeling tools for fixed-field accelerators unique to the code COSY INFINITY. 1
Thermal infrared detection using dipole antenna-coupled metal-oxide-metal diodes (2009)

This work focuses on dipole antenna-coupled metal-oxide-metal diodes, which can be used for the detection of long wave infrared radiation. These detectors are defined using electron beam lithography and fabricated with shadow evaporation metal deposition. Along with offering complementary metal oxide semiconductor compatible fabrication, these detectors promise high speed and frequency selective detection without biasing, a small pixel footprint, and full functionality at room temperature without cooling. Direct current current-voltage characteristics are presented along with detector response to 10.6μm radiation. The detection characteristics can be tailored to provide for multispectral imaging in specific applications by modifying device geometries.
Design and calculation of induction-heating coils (1957)

THROUGH the years the author has had considerable experience with induction-heating calculating methods and has studied the reaction of others confronted with the problem of designing coils and predicting performance. It is a difficult job at best when one considers the great variety of materials heated and the almost limitless variety of shapes encountered. It is little wonder that the average engineer resists using calculating methods as much as he does. In an effort to develop a more or less standard calculating procedure for internal use in his company, the author arrived at the plan described in this paper.
Study on ultra-thin gate dielectrics: surface preparation and reliability (2002)

Wafer preparation and breakdown characteristics are some of the major issues of gate dielectrics in the deep sub-micron regime. In this paper, conventional and a modified HF-last cleaning methods were performed and compared. Dry oxide, N/sub 2/O oxynitride and oxide grown on N implanted substrate were used to prepare several kinds of gate dielectrics. The results indicate that after trace amount of IPA was added to HF solution in HF-last cleaning, gate dielectrics showed superior electrical properties. The N/sub 2/O oxynitride sample had higher Q/sub bd/ than the O/sub 2/ oxide sample. In addition, the reversed relation between gate oxide thickness and N implantation dose was observed. Poor breakdown characteristics of gate oxide grown on N implanted substrate was obtained.
Organic Rankine cycle as efficient alternative to steam cycle for small scale power generation (2011)

Paper presented at the 8th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Mauritius, 11-13 July, 2011.
Novel synthesis of substituted 4′-hydroxy-2,2′:6′,2″-terpyridines (1997)

4-Substituted-2,6-diacetylpyridines 2–4 have been synthesised; by using the Kröhnke-methodology, chalcone and methylacylpyridinium salts have been reacted to yield 4′-ethoxy-2,2′:6′,2″-terpyridines 5–7. These novel 2,2′:6′,2″-terpyridines are functionalised at C(4′) and possess substituents at C(4), C(5) and C(6) of both terminal pyridines, respectively. The ethyl ether protecting group has been cleaved to obtain 4′-hydroxy-2,2′:6′,2″-terpyridine 8.
Caldesmon Inhibits Nonmuscle Cell Contractility and Interferes with the Formation of Focal Adhesions (1999)

Caldesmon is known to inhibit the ATPase activity of actomyosin in a Ca(2+)-calmodulin-regulated manner. Although a nonmuscle isoform of caldesmon is widely expressed, its functional role has not yet been elucidated. We studied the effects of nonmuscle caldesmon on cellular contractility, actin cytoskeletal organization, and the formation of focal adhesions in fibroblasts. Transient transfection of nonmuscle caldesmon prevents myosin II-dependent cell contractility and induces a decrease in the number and size of tyrosine-phosphorylated focal adhesions. Expression of caldesmon interferes with Rho A-V14-mediated formation of focal adhesions and stress fibers as well as with formation of focal adhesions induced by microtubule disruption. This inhibitory effect depends on the actin- and myosin-binding regions of caldesmon, because a truncated variant lacking both of these regions is inactive. The effects of caldesmon are blocked by the ionophore A23187, thapsigargin, and membrane depolarization, presumably because of the ability of Ca(2+)-calmodulin or Ca(2+)-S100 proteins to antagonize the inhibitory function of caldesmon on actomyosin contraction. These results indicate a role for nonmuscle caldesmon in the physiological regulation of actomyosin contractility and adhesion-dependent signaling and further demonstrate the involvement of contractility in focal adhesion formation.
Glycosidation, 13; anticancer agents, 10. Novel stable bioactivated cyclophosphamide derivatives for selective cancer chemotherapy, synthesis of aldophosphamide acetal‐glycosides and their glycoconjugates (1990)

Abstract Stimulation of tumor cell glycolysis in vivo leads to an increase of lactic acid formation and thus a decrease of pH in malignant tissue compared with a normal cell population. The difference in pH may be used to cleave a nontoxic prodrug selectively in a tumor to give a highly cytotoxic compound. In this respect, acetal‐glycosides of aldophosphamide ( 3 ), a biological active metabolite of the anticancer agent cyclophosphamide ( 1 ) with α‐ D ‐ and β‐ D ‐glucose as well as α‐ D ‐mannose have been synthesized. Reaction of the trimethylsilyl glycosides 8a , 8b , and 8c with the acetals 9a , 9b , and 9c in the presence of TMS–OTf at −78°C gave selectively according to the anomeric center the acetal‐glycosides 10a – e in 68–88% yield. Debenzylation, reaction with the phosphorous acid amide dichloride 12 and ammonia, led to the aldophosphamide derivatives 15a – e . For coupling with biopolymers, the ester moiety in 15d and 15e was hydrolyzed to give 16a and 16b . As a model study, coupling of 16a and 16b with the lysine derivative 17 using 1‐hydroxybenzotriazol ( 18 ) and an excess of diisopropyl carbodiimide ( 19 ) was accomplished to afford 16c and 16d which were acetylated to give 16e and 16f .
Analysis of ribonucleotide reductase M2 mRNA levels in patient samples after GTI-2040 antisense drug treatment (2006)

This study describes the development of a rapid and practical real-time RT-PCR method to quantify ribonucleotide reductase M2 (RRM2) mRNA in tumor and peripheral white blood cells (WBCs) from patients treated with GTI-2040, an antisense drug currently in clinical trials. In order to assess target down-regulation by GTI-2040, RRM2 mRNA expression levels were analyzed in pre- and post-treatment samples from a phase II clinical trial of GTI-2040 combined with capecitabine in patients with metastatic breast cancer. Target gene RRM2 mRNA levels were evaluated using quantitative RT-PCR method: real-time PCR (TaqMan) with fluorescein labeled probes on an ABI 7900HT instrument, with additional post-processing of the data to adjust for differences in total RNA in-put across the samples. Data are presented from a patient for whom both biopsy and PBMC samples were available, demonstrating applicability of this reproducible, highly sensitive real-time RT-PCR method for the detection and quantification of mRNAs for RRM2 in human WBC and tissue samples. By providing quantitative measurement of changes in target gene expression, this method may provide an opportunity to determine the correlation between target response to GTI-2040 antisense and clinical response in patients. Furthermore this assay may assess whether WBC samples are an appropriate surrogate tissue for approximating target down-regulation in the tumor.
A distributed simulation methodological framework for OR/MS applications (2016)

Distributed Simulation (DS) allows existing models to be composed together to form sim- ulations of large-scale systems, or large models to be divided into models that execute on separate computers. Among its claimed benefits are model reuse, speedup, data pri- vacy and data consistency. DS is arguably widely used in the defence sector. However, it is rarely used in Operations Research and Management Science (OR/MS) applications in areas such as manufacturing and healthcare, despite its potential advantages. The main barriers to use DS in OR/MS are the technical complexity in implementation and a gap between the world views of DS and OR/MS communities. In this paper, we propose a new method that attempts to link together the methodological practices of OR/MS and DS. Using a rep- resentative case study, we show that our methodological framework simplifies significantly DS implementation.
The prophenoloxidase‐activating system in invertebrates (2004)

A major innate defense system in invertebrates is the melanization of pathogens and damaged tissues. This important process is controlled by the enzyme phenoloxidase (PO) that in turn is regulated in a highly elaborate manner for avoiding unnecessary production of highly toxic and reactive compounds. Recent progress, especially in arthropods, in the elucidation of mechanisms controlling the activation of zymogenic proPO into active PO by a cascade of serine proteinases and other factors is reviewed. The proPO-activating system (proPO system) is triggered by the presence of minute amounts of compounds of microbial origins, such as beta-1,3-glucans, lipopolysaccharides, and peptidoglycans, which ensures that the system will become active in the presence of potential pathogens. The presence of specific proteinase inhibitors prevents superfluous activation. Concomitant with proPO activation, many other immune reactions will be produced, such as the generation of factors with anti-microbial, cytotoxic, opsonic, or encapsulation-promoting activities.