gebhart/patrepeval huggingface dataset:
80 nm 512M DRAM with enhanced data retention time using partially-insulated cell array transistor (PiCAT) (2004)

An 80 nm 512M DDR DRAM with partially-insulated cell array transistor (PiCAT) was fabricated. Si/SiGe epitaxial growth and selective SiGe etch process were used to form PiOX (Partially-Insulating OXide) under source and drain of the cell transistor. Using these technologies, partial-SOI (Silicon-On-Insulator) structure could be realized with excellent structural and electrical advantages on bulk Si wafer. Self-limited shallow junction under source/drain and halo doping effect at the channel region were formed by PiOX. With PiCAT, junction leakage current and SCE (Short Channel Effect) were reduced, and excellent data retention time was obtained.
Synthesis, characterization, and curing of hyperbranched allyl ether–maleate functional ester resins (1993)

Abstract A model two‐step synthesis of a saturated hyperbranched hydroxyl‐terminated ester has been developed to show a synthesis route. Three different series of hyperbranched esters with different terminations have been synthesized to relate some of their properties to their structures. This route has then been used to synthesize three different allyl ethermaleate functional hyperbranched ester resins in a two‐step procedure. The resins have been characterized with respect to rheology, structure, and properties, and the differences are discussed. The allyl ether‐maleate functional resins have also been studied with respect to curing performance and final film properties. © 1993 John Wiley &amp; Sons, Inc.
Lung protein leaks in ventilated lambs: effects of gestational age (1985)

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.
Susceptibility of Human Herpesvirus 6 to Antivirals In Vitro (1990)

Human herpesvirus 6 (HHV-6) is a recently recognized human herpesvirus isolated from lymphoid cells and thought to be the causative agent for exanthem subitum. Using dot blot hybridization, the HHV-6 sensitivity pattern to several antivirals was compared with those of herpes simplex virus type 1 and human cytomegalovirus. HHV-6 most closely resembled cytomegalovirus in that it was relatively resistant to the antiviral effects of acyclovir and bromovinyl-deoxyuridine but sensitive to ganciclovir and phosphonoacetic acid. From these results, it appears more likely that HHV-6 infections would respond to ganciclovir and foscarnet than to acyclovir should treatment be deemed advisable, although the low toxicity of acyclovir may allow for its use at doses that might affect replication of HHV-6.
Sensitivity of HIV-1 Reverse Transcriptase and Its Mutants to Inhibition by Azidothymidine Triphosphate (1994)

HIV-1 reverse transcriptase can catalyze the addition of either azidothymidine monophosphate (AZTMP) or thymidine monophosphate (dTMP) to a primer strand opposite template adenosine bases. The ratio of incorporation of AZTMP to dTMP as catalyzed by HIV-1 reverse transcriptase has been determined to be 0.4 using an RNA-DNA duplex substrate prepared from oligonucleotides with sequences taken from the HIV-1 genome sequence. Slight variations are found for the incorporation ratio of the two nucleotides on other substrates. Substrates containing more than one adenosine in the single-stranded part of the template allow for more chances to incorporate AZTMP and less full-length product. Variations in the intensity of bands on an autoradiograph of a DNA sequencing gel corresponding to different positions of incorporation of AZTMP suggest that not all template adenosine positions offer the same level of discrimination against incorporation of AZTMP. A reverse transcriptase containing a set of four mutations (D67N, K70R, T215Y, K219Q) known to cause resistance to AZT in cell culture assays has a ratio of incorporation that is 0.77 +/- 0.03 times the ratio for the wild-type reverse transcriptase opposite one specific template adenosine. In contrast, a hybrid mutant containing the same four mutations that cause resistance to AZT and an additional mutation, Y181C, which by itself causes resistance to the non-nucleoside inhibitor L-697,661 [Sardana et al. (1992), J. Biol. Chem. 267, 17526-17530], has a ratio of incorporation that is 1.34 +/- 0.01 times that of the wild-type, indicating that the hybrid mutant enzyme is more susceptible to inhibition by AZTTP than the wild-type reverse transcriptase.(ABSTRACT TRUNCATED AT 250 WORDS)
Emotional and Behavioural Response to Auditory Icons and Earcons in Driver-Vehicle Interfaces (2009)

Adequately designed, auditory displays in Driver- Vehicle Interfaces (DVIs) may give shorter reaction times, improved attention direction, and an increased quality impression. It is suggested that emotional reactions may guide the design of such auditory displays since emotion is central in our everyday life and has strong consequences for behavior and information processing. A simulator study with 30 participants (20 of which were professional drivers) was conducted to investigate the connection between emotional and behavioral responses to auditory DVIs as well as to evaluate various sound design parameters in realistic driving situations. Auditory icons were contrasted to abstract earcon sounds in more or less imminent collision scenarios and 3D sounds were tested against monophonic sounds in different lane change scenarios. Self-report measures (Self-Assessment Manikins, SAM) and physiological measures (Galvanic Skin Response, GSR and facial Electromyogram, EMG) of emotional response as well as behavioral measures (e.g. brake response time) were used. It was found that auditory icons were more efficient and gave up to 600ms faster brake response times than abstract sounds in imminent collision scenarios and that 3D sound gave a stronger emotional response in lane change scenarios. Moreover, the results show that emotion can predict behavior, e.g. sounds rated as being more activating and negative also gave quicker response times. Contrary to expectations however, the findings from the SAM ratings were not reflected in the physiological measurements. An explanation to this may be that the scenario itself caused a dominant stress reaction which overrode the physiological response to the warning sounds. Our findings nonetheless strengthen the importance of auditory displays as a means to enhance vehicle safety, and that emotions may be an efficient way of predicting behavioral response to auditory DVIs. Measurements of emotion may therefore facilitate the process of designing auditory DVIs. The full text of this paper may be found at: http://www-nrd.nhtsa.dot.gov/pdf/esv/esv21/09-0104.pdf For the covering abstract see ITRD E145407.
The critical roles of mitophagy in cerebral ischemia (2016)

Mitochondria play a key role in various cell processes including ATP production, Ca<sup>2</sup><sup>+</sup> homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.
Targeting adenoviral vectors using heterofunctional polyethylene glycol FGF2 conjugates (2003)

Bifunctional PEG (polyethylene glycol) molecules provide a novel approach to retargeting viral vectors without the need to genetically modify the vector. In a previous report we showed that modification of the viral capsid by the addition of a peptide with binding preference for differentiated ciliated airway epithelia allowed gene delivery to those cells by a novel entry pathway. Here we demonstrate further the versatility of this method by coupling a protein, FGF2, to the surface of an adenovirus (Ad). This modification results in the elimination of the endogenous tropism of the virus and confers upon the virus a novel route of entry. Adenoviral vectors modified by the addition of FGF2 show enhanced efficiency of transduction of the ovarian cancer cell line SKOV3.ip1. This enhancement in transduction is dependent on the binding of the coupled FGF2 to its high-affinity receptor and is independent of coxsackie and adenovirus viral receptors. In an intraperitoneal model of ovarian cancer, Ad/PEG/FGF2 generates increased transgene expression in tumor tissue compared to unmodified Ad. Furthermore, polymer modification of adenovirus vectors results in reduced localization of adenovirus to nontarget tissues and a marked decrease in Th1 and Th2 T cell responses. In conclusion, the approach described here may lead to the development of a gene therapy vector capable of targeting a therapeutic gene to diseased cells, while minimizing toxicity and expression in other tissues.
Peripheral analgesic blockade of hypernociception: Activation of arginine/NO/cGMP/protein kinase G/ATP-sensitive K + channel pathway (2004)

The final step in the direct restoration of the nociceptor threshold by peripheral administration of morphine and dipyrone was recently suggested to result from the opening of ATP-sensitive K(+) channels (K(ATP)(+)). This channel is known to be open either directly by cGMP or indirectly via protein kinase G (PKG) stimulation. In the present study, it was shown that the blockade was caused by a specific PKG inhibitor (KT5823) of the antinociceptive effect of morphine and dipyrone on acute hypernociception and of dipyrone on persistent hypernociception. It was also shown that, in both models, KT5823 prevented the peripheral antinociceptive effect of an analogue of cGMP, the nitric oxide (NO) donor (S-nitroso-n-acetyl-d,l-penicilamine). However, in acute hypernociception, KT5823 did not prevent the peripheral antinociceptive effect of diazoxide (a direct K(ATP)(+) opener). In persistent hypernociception, the sensitization plateau was induced by daily injections of prostaglandin E(2) (PGE(2), 100 ng) into the rat paw for 14 days. After cessation of PGE(2) injections, the pharmacological blockade of persistent hypernociception led to a quiescent phase in which a rather small stimulus restored the hypernociceptive plateau. In this phase, glibenclamide (which specifically closes K(ATP)(+)) fully restored persistent hypernociception, as did injection of PGE(2). Thus, the activation of the arginine/NO/cGMP pathway causes direct blockade of acute and persistent hypernociception by opening K(ATP)(+) via the stimulation of PKG. Analgesic stimulators of the neuronal arginine/NO/cGMP/PKG/K(ATP)(+) pathway constitute a previously undescribed well defined class of peripheral analgesics with a mechanism of action different from either glucocorticoids or inhibitors of cyclooxygenases.
The Regulation of Gluconeogenesis in Isolated Rat Liver Cells by Glucagon, Insulin, Dibutyryl Cyclic Adenosine Monophosphate, and Fatty Acids (1972)

Abstract Suspensions of rat liver cells from starved rats converted three carbon precursors to glucose and responded to hormones such as glucagon and insulin. Cells were isolated by perfusion of rat livers with calcium-free Hanks' solution containing 0.01 g% of collagenase and 0.08 g% of hyaluronidase in the presence of 4% defatted albumin. Cells from 18- to 24-hour starved rats synthesized glucose de novo from l-alanine at rates comparable to those observed in the perfused liver. Glucagon increased cyclic adenosine 3',5'-monophosphate accumulation in liver cells with the maximal effect being observed some 2 min after its addition. In cells from fed rats there was an immediate increase due to glucagon of glucose release which could be accounted for by glycogenolysis. In cells from starved rats there was almost no glycogen (0.5% for starved rats as compared to 7.5% for fed rats), and there was a 20-min lag period before glucose output was increased by glucagon. Glucagon stimulated gluconeogenesis in the presence of alanine, lactate, or pyruvate whereas added fatty acids inhibited gluconeogenesis from alanine and stimulated that from lactate or pyruvate. Insulin increased glycogen deposition in cells from starved rats, and this accounted for the decrease in glucose output seen with insulin. Dibutyryl cyclic AMP also stimulated gluconeogenesis in isolated liver cells. The effects of insulin and glucagon on liver cells were abolished by short term treatment of cell suspensions with trypsin. In contrast, the response to dibutyryl cyclic AMP was not altered in the trypsin-treated cells.
Safety of magnetic resonance imaging contrast agents (1999)

Many of the MR examinations performed in the world each year are accompanied by administration of one of these frequently used intravenous contrast agents: Magnevist, Omniscan, and ProHance. Accordingly, MR practitioners must understand the basic pharmacokinetics, side effects, and the potential for adverse events for these contrast agents. Additionally, MR practitioners must know how to manage side effects and adverse events that may occur in association with the administration of contrast agents. Notably, the use of MR imaging contrast agents in special patient populations must be understood. This article discusses each of these important issues.
Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization (1995)

Comparative genomic hybridization (CGH) is a recent molecular cytogenetic method that detects and localizes gains or losses in DNA copy number across the entire tumor genome. We used CGH to examine 9 glioma cell lines and 20 primary and 10 recurrent glioblastoma tumors. More than 25% of the primary tumors had gains on chromosome 7; they also had frequent losses on 9p, 10, 13 and Y. The losses on chromosome 13 included several interstitial deletions, with a common area of loss of 13q21. The recurrent tumors not only had gains on chromosome 7 and losses on 9p, 10, 13 and Y but also frequent losses on 6 and 14. One recurrent tumor had a deletion of 10q22-26. Cell lines showed gains of 5p, 7 and Xp; frequent amplifications at 8q22-24.2, 7q21-32 and 3q26.2-29 and frequent losses on 4, 10, 13, 14 and Y. Because primary and recurrent tumors and cell lines showed abnormalities of DNA copy number on chromosomes 7, 10, 13 and Y, these regions may play a fundamental role in tumor initiation and/or progression. The propensity for losses on chromosomes 6 and 14 to occur in recurrent tumors suggests that these aberrations play a role in tumor recurrence, the development of resistance to therapy or both. Analysis of common areas of loss and gain in these tumors and cell lines provides a basis for future attempts to more finely map these genetic changes.
Rapid isolation method for lipopolysaccharide and lipid A from Gram-negative bacteria (2000)

A fast, convenient extraction method for lipopolysaccharide (LPS), using a commercial RNA isolating reagent, allows the isolation of LPS or lipid A from low milligram (dry weight) quantities of bacterial cells. The method avoids the use of specialized equipment and has been used for processing relatively large numbers of samples. The major components of the commercial RNA isolating reagent, Tri-Reagent, are phenol and guanidinium thiocyanate in aqueous solution. The bacterial cell membranes are disrupted with guanidinium thiocyanate, which eliminates the need for mechanical cell disruption (e.g. French press) or heating. LPS and its degradation products, with particular attention paid to its bioactive lipid A portion, were measured and compared with those from the most common conventional extraction method, hot phenol-water. Negative ion quadrupole ion trap and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, fatty acid composition analysis by capillary gas chromatography, total and free phosphate by UV spectrophotometry and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that LPS and lipid A isolated using the Tri-Reagent approach were cleaner and suffered less degradation through loss of phosphate and (or) fatty acyl side chains from lipid A. The Tri-Reagent extraction method generated low free phosphate contamination, 11% of the total phosphate concentration, whereas the hot phenol-water extraction method gave approximately 58% as free, inorganic phosphate. Similar results were observed for the degradation of fatty acyl side chains. The time required by the new method is considerably shorter (two or three days) than that required by conventional hot phenol-water extraction (about two weeks).
High throughput DNA sequencing with a microfabricated 96-lane capillary array electrophoresis bioprocessor (2002)

High throughput DNA sequencing has been performed by using a microfabricated 96-channel radial capillary array electrophoresis (microCAE) microchannel plate detected by a 4-color rotary confocal fluorescence scanner. The microchannel plate features a novel injector for uniform sieving matrix loading as well as high resolution, tapered turns that provide an effective separation length of 15.9 cm on a compact 150-mm diameter wafer. Expanded common buffer chambers for the cathode, anode, and waste reservoirs are used to simplify electrode addressing and to counteract buffering capacity depletion arising from the high electrophoretic current. DNA sequencing data from 95 successful lanes out of 96 lanes run in parallel were batch-processed with basefinder, producing an average read length of 430 bp (phred q > or = 20). Phred quality values were found to exceed 40 (0.01% probability of incorrectly calling a base) for over 80% of the read length. The microCAE system demonstrated here produces sequencing data at a rate of 1.7 kbp/min, a 5-fold increase over current commercial capillary array electrophoresis technology. Additionally, this system permits lower reagent volumes and lower sample concentrations, and it presents numerous possibilities for integrated sample preparation and handling. The unique capabilities of microCAE technology should make it the next generation, high performance DNA sequencing platform.
Purinergic Receptors Are Required for HIV-1 Infection of Primary Human Macrophages (2012)

Macrophages play a significant role in HIV infection, viral rebound, and the development of AIDS. However, the function of host proteins in viral replication is incompletely characterized in macrophages. Purinergic receptors P2X and P2Y are major components of the macrophage immune response to pathogens, inflammation, and cellular damage. We demonstrate that these receptors are necessary for HIV infection of primary human macrophages. Inhibition of purinergic receptors results in a significant reduction in HIV replication in macrophages. This inhibition is independent of viral strain and is dose dependent. We also identify that P2X(1), P2X(7), and P2Y(1) receptors are involved in viral replication. We show that P2X(1), but not P2X(7) or P2Y(1), is necessary for HIV entry into macrophages. We demonstrate that interaction of the HIV surface protein gp120 with macrophages stimulates an increase in ATP release. Thus, we propose that HIV's binding to macrophages triggers a local release of ATP that stimulates purinergic receptors and facilitates HIV entry and subsequent stages of viral replication. Our data implicate a novel role for a family of host proteins in HIV replication in macrophages and suggest new therapeutic targets to reduce the devastating consequences of HIV infection and AIDS.
Combined Triplex/Duplex Invasion of Double-Stranded DNA by “Tail-Clamp” Peptide Nucleic Acid (2003)

"Tail-clamp" PNAs composed of a short (hexamer) homopyrimidine triplex forming domain and a (decamer) mixed sequence duplex forming extension have been designed. Tail-clamp PNAs display significantly increased binding to single-stranded DNA compared with PNAs lacking a duplex-forming extension as determined by T(m) measurements. Binding to double-stranded (ds) DNA occurred by combined triplex and duplex invasion as analyzed by permanganate probing. Furthermore, C(50) measurements revealed that tail-clamp PNAs consistently bound the dsDNA target more efficiently, and kinetics experiments revealed that this was due to a dramatically reduced dissociation rate of such complexes. Increasing the PNA net charge also increased binding efficiency, but unexpectedly, this increase was much more pronounced for tailless-clamp PNAs than for tail-clamp PNAs. Finally, shortening the tail-clamp PNA triplex invasion moiety to five residues was feasible, but four bases were not sufficient to yield detectable dsDNA binding. The results validate the tail-clamp PNA concept and expand the applications of the P-loop technology.
Lovastatin and Simvastatin - Inhibitors of HMG CoA Reductase and Cholesterol Biosynthesis (1990)

The microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is a key rate-controlling step early in the cholesterol biosynthetic pathway that catalyzes the conversion of HMG CoA to mevalonic acid. Since this enzyme plays a significant role in regulating cholesterol synthesis, it is a rational target for pharmacologic intervention. The first potent, specific inhibitor of HMG CoA was mevastatin (compactin, ML-236B), which was discovered in 1976 by Endo et al. [J Antibiot 1976:29:1346-1348]. Subsequently, lovastatin, a novel, more active fungal metabolite was isolated from a strain of Aspergillus terreus. Lovastatin, the first of this class of agents to be approved for clinical use, was chemically modified to form simvastatin. Simvastatin is superior to lovastatin in intrinsic inhibitory potency. Both are inactive lactone prodrugs that must be converted to their respective dihydroxy open-acid forms to elicit inhibitory activity. Pharmacologic characterization of lovastatin and simvastatin has demonstrated that these potent inhibitors of HMG CoA reductase specifically inhibit cholesterol synthesis in animal cells, as well as in vivo after oral administration of the agents. Oral administration of either lovastatin or simvastatin to dogs in the presence or absence of the bile acid sequestrant cholestyramine results in a marked, sustained lowering of plasma cholesterol. Associated with the cholesterol lowering is a decrease in urinary and plasma levels of mevalonic acid, the end product of the HMG CoA reductase reaction. The target organ for inhibitors of HMG CoA reductase is the liver, the primary site of cholesterol biosynthesis. Both lovastatin and simvastatin are preferentially extracted by this organ.(ABSTRACT TRUNCATED AT 250 WORDS)