gebhart/patrepeval huggingface dataset:
Mutational Analysis of Encephalitozoon cuniculi mRNA Cap (Guanine-N7) Methyltransferase, Structure of the Enzyme Bound to Sinefungin, and Evidence That Cap Methyltransferase Is the Target of Sinefungin's Antifungal Activity (2006)

Cap (guanine-N7) methylation is an essential step in eukaryal mRNA synthesis and a potential target for antiviral, antifungal, and antiprotozoal drug discovery. Previous mutational and structural analyses of Encephalitozoon cuniculi Ecm1, a prototypal cellular cap methyltransferase, identified amino acids required for cap methylation in vivo, but also underscored the nonessentiality of many side chains that contact the cap and AdoMet substrates. Here we tested new mutations in residues that comprise the guanine-binding pocket, alone and in combination. The outcomes indicate that the shape of the guanine binding pocket is more crucial than particular base edge interactions, and they highlight the contributions of the aliphatic carbons of Phe-141 and Tyr-145 that engage in multiple van der Waals contacts with guanosine and S-adenosylmethionine (AdoMet), respectively. We purified 45 Ecm1 mutant proteins and assayed them for methylation of GpppA in vitro. Of the 21 mutations that resulted in unconditional lethality in vivo,14 reduced activity in vitro to < or = 2% of the wild-type level and 5 reduced methyltransferase activity to between 4 and 9% of wild-type Ecm1. The natural product antibiotic sinefungin is an AdoMet analog that inhibits Ecm1 with modest potency. The crystal structure of an Ecm1-sinefungin binary complex reveals sinefungin-specific polar contacts with main-chain and side-chain atoms that can explain the 3-fold higher affinity of Ecm1 for sinefungin versus AdoMet or S-adenosylhomocysteine (AdoHcy). In contrast, sinefungin is an extremely potent inhibitor of the yeast cap methyltransferase Abd1, to which sinefungin binds 900-fold more avidly than AdoHcy or AdoMet. We find that the sensitivity of Saccharomyces cerevisiae to growth inhibition by sinefungin is diminished when Abd1 is overexpressed. These results highlight cap methylation as a principal target of the antifungal activity of sinefungin.
Barrett's esophagus. Prevalence and incidence of adenocarcinoma (1991)

Between January 1973 and January 1989, 241 patients with Barrett's esophagus were treated at the Lahey Clinic Medical Center, Burlington, Mass. Of these patients, 65 presented with adenocarcinoma in Barrett's esophagus for a prevalence rate of 27%. Of 176 patients followed up for a total of 497 patient-years, adenocarcinoma developed in five patients for an incidence of one per 99 patient-years. The development of adenocarcinoma during endoscopic surveillance 1, 2, 2, 4, and 10 years after the initial diagnosis of Barrett's esophagus emphasizes the importance of long-term endoscopic and histologic surveillance. All five patients had severe dysplasia before adenocarcinoma developed. Yearly endoscopic follow-up examination is recommended for all patients with Barrett's esophagus unless mild dysplastic changes are found, in which case surveillance should be increased. Patients with severe dysplasia who are otherwise acceptable candidates for operation should be advised to have esophageal resection. (<i>Arch Intern Med</i>. 1991;151:2212-2216)
Intragastric balloons In adolescents with morbid obesity (1999)

We observed a failure to lose weight with the help of an intragastric balloon in five selected adolescents. Since the beneficial effect of intragastric balloons in the five adolescents studied was only temporary, these balloons seem not to be indicated in adolescents with morbid obesity.
Interchain disulfide bond formation in types I and II procollagen. Evidence for a protein disulfide isomerase catalyzing bond formation. (1987)

The assembly of reduced pro-alpha chains of type I and type II procollagen into the native triple-helical molecule was examined in vitro in the presence and absence of pure protein disulfide isomerase. The data clearly indicates that protein disulfide isomerase is able to accelerate the formation of native interchain disulfide bonds in these procollagens. It takes about 6 min after disulfide bonding before triple-helical molecules exist, while the time required to produce triple-helical type I procollagen in the presence of protein disulfide isomerase is 9.4 min and that for type II procollagen 17.2 min. These values agree with those obtained for type I and II procollagen in vivo suggesting that protein disulfide isomerase is also an enzyme catalyzing interchain disulfide bond formation in procollagen in vivo. The formation of native disulfide bonds can proceed without any enzyme catalysis but then requires the presence of reduced and oxidized glutathione. Bonding is rather slow in such a case, however, resulting in a delay in the formation of the triple helix.
Optical alignment of a multipass Fabry-Perot Brillouin scattering spectrometer (1979)

A straightforward and accurate method is described for alignment of a multipass Fabry-Perot interferometer with its associated optical components for Brillouin scattering measurements.
Differential Regulation of Rat and Human<i>CYP7A1</i>by the Nuclear Oxysterol Receptor Liver X Receptor-α (2003)

In rodent liver, transcription of the gene encoding cholesterol 7alpha-hydroxylase (CYP7A1), which catalyzes the rate-limiting step in the classic bile acid synthetic pathway, is stimulated by the liver X receptor alpha (LXRalpha), a nuclear receptor for oxysterol metabolites of cholesterol. This feed-forward regulatory loop provides a mechanism for the elimination of excess cholesterol from the body. In this report, we demonstrate that in primary cultures of human hepatocytes, activation of LXRalpha has the opposite effect, repressing CYP7A1 expression. This repression is mediated, at least in part, through induction of the orphan nuclear receptor, short heterodimer partner (SHP), which is also induced by bile acids. We demonstrate that SHP is regulated directly by LXRalpha through a DNA response element that overlaps with the previously characterized bile acid response element. Our data reveal a fundamental difference in the regulation of CYP7A1 in rodent and human hepatocytes and provide evidence that different species employ distinct molecular strategies to regulate cholesterol homeostasis.
Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants (2003)

The purpose of this study was to determine the effects of inhibitors of Rho kinase (ROK) and matrix metalloproteinases (MMPs) on angiogenesis and tumor growth and to evaluate ROK activity in human prostate cancer PC3 cells and endothelial cells (HUVECs). Vacuolation by endothelial cells and lumen formation, the earliest detectable stages of angiogenesis, were inhibited by the ROK inhibitor Wf-536. Combining Wf-536 with the MMP inhibitor Marimastat greatly enhanced in vitro inhibition of endothelial vacuolation, lumen and cord formation, and VEGF- and HGF-stimulated endothelial sprout formation from aorta. Inhibition of sprout formation by the two inhibitors was synergistic. Both agents inhibited migration of HUVECs. The regulatory subunit (MYPT1) of the myosin phosphatase was phosphorylated in PC3 cells and HUVECs, and phosphorylation of MYPT1 and the myosin regulatory light chain was reduced by Wf-536, providing direct evidence of ROK activity. Early treatment of immuno-incompetent mice bearing xenotransplants of PC3 cells with a combination of Wf-536 plus Marimastat with or without Paclitaxel, significantly inhibited tumor growth, prevented tumor growth escape after discontinuation of Paclitaxel, and increased survival.
Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta (1997)

Chymase shows a catalytic efficiency in the formation of angiotensin (Ang) II. In the present study, the characterization and primary structure of monkey chymase were determined, and the pathophysiological role of chymase was investigated on the atherosclerotic monkey aorta. Monkey chymase was purified from cheek pouch vascular tissue using heparin affinity and gel filtration columns. The enzyme rapidly converted Ang I to Ang II (Km = 98 microM, k(cat) = 6203/min) but did not degrade several peptide hormones such as Ang II, substance P, vasoactive intestinal peptide and bradykinin. The primary structure, which was deduced from monkey chymase cDNA, showed a high homology to that of human chymase (98%). The mRNA levels of the aorta chymase were significantly increased in the atherosclerotic aorta of monkeys fed a high-cholesterol diet. These results indicate that monkey chymase has a highly specific Ang II-forming activity and may be related to the pathogenesis of atherosclerosis.
The Tangram framework: asynchronous circuits for low power (2002)

Asynchronous CMOS circuits have the potential for very low power consumption, because they only dissipate when and where active. In addition they have favorable EMC properties, since they emit less energy, which in addition is evenly distributed over the spectrum. The Tangram framework supports the design of asynchronous circuits in a high-level programming language. Using this framework we have designed several chips, for instance for pagers and smart cards, which are clearly superior to synchronous designs.
Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids (1997)

Abstract When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein‐containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.
Automated DNA Fragments Recognition and Sizing Through AFM Image Processing (2005)

This paper presents an automated algorithm to determine DNA fragment size from atomic force microscope images and to extract the molecular profiles. The sizing of DNA fragments is a widely used procedure for investigating the physical properties of individual or protein-bound DNA molecules. Several atomic force microscope (AFM) real and computer-generated images were tested for different pixel and fragment sizes and for different background noises. The automated approach minimizes processing time with respect to manual and semi-automated DNA sizing. Moreover, the DNA molecule profile recognition can be used to perform further structural analysis. For computer-generated images, the root mean square error incurred by the automated algorithm in the length estimation is 0.6% for a 7.8 nm image pixel size and 0.34% for a 3.9 nm image pixel size. For AFM real images we obtain a distribution of lengths with a standard deviation of 2.3% of mean and a measured average length very close to the real one, with an error around 0.33%.
Monolithic Teflon® membrane valves and pumps for harsh chemical and low-temperature use (2007)

Microfluidic diaphragm valves and pumps capable of surviving conditions required for unmanned spaceflight applications have been developed. The Pasteur payload of the European ExoMars Rover is expected to experience temperatures ranging between -100 degrees C and +50 degrees C during its transit to Mars and on the Martian surface. As such, the Urey instrument package, which contains at its core a lab-on-a-chip capillary electrophoresis analysis system first demonstrated by Mathies et al., requires valving and pumping systems that are robust under these conditions before and after exposure to liquid samples, which are to be analyzed for chemical signatures of past or present living processes. The microfluidic system developed to meet this requirement uses membranes consisting of Teflon and Teflon AF as a deformable material in the valve seat region between etched Borofloat glass wafers. Pneumatic pressure and vacuum, delivered via off-chip solenoid valves, are used to actuate individual on-chip valves. Valve sealing properties of Teflon diaphragm valves, as well as pumping properties from collections of valves, are characterized. Secondary processing for embossing the membrane against the valve seats after fabrication is performed to optimize single valve sealing characteristics. A variety of different material solutions are found to produce robust devices. The optimal valve system utilizes a membrane of mechanically cut Teflon sandwiched between two thin spun films of Teflon AF-1600 as a composite "laminated" diaphragm. Pump rates up to 1600 nL s(-1) are achieved with pumps of this kind. These high pumping rates are possible because of the very fast response of the membranes to applied pressure, enabling extremely fast pump cycling with relatively small liquid volumes, compared to analogous diaphragm pumps. The developed technologies are robust over extremes of temperature cycling and are applicable in a wide range of chemical environments.
Syntheses of Quinazoline-2,4-dione Alkaloids and Analogues from Mexican Zanthoxylum Species † (2004)

Quinazolinone and quinazolinedione derivatives are of considerable interest due to their wide array of pharmacological properties. In this paper we report the synthesis of ten quinazolinediones. The previous isolation of two of these compounds, namely 1-methyl-3-(2'-phenylethyl)-1H,3H-quinazoline-2,4-dione and 1-methyl-3-[2'-(4'- methoxyphenyl)ethyl]-lH,3H-quinazoline-2,4-dione, from the seed husks of Mexican Zanthoxylum species has been reported.
Optimizing the Photocurrent Efficiency of Dye-Sensitized Solar Cells through the Controlled Aggregation of Chalcogenoxanthylium Dyes on Nanocrystalline Titania Films (2008)

Chalcogenoxanthylium dyes were characterized as sensitizers of nanocrystalline titania in dye-sensitized solar cells (DSSCs). Four series of dyes were characterized: 2,7-bis(dimethylamino)-9-(2-thienyl-5-carboxy)chalcogenoxanthylium dyes (1-E, where E = O, S, Se); 2,7-bis(dimethylamino)-9-(3-thienyl-2-carboxy)chalcogenoxanthylium dyes (2-E, where E = S, Se); a 2,7-bis(dimethylamino)-9-(2-thienyl)selenoxanthylium dye (3-Se); 4-Se, a constrained analog of 1-Se. The orientation and aggregation state of the dyes were controlled by varying the position of the surface-attachment group relative to the xanthylium core. Series 1 dyes and 4-Se underwent H-aggregation on titania surfaces, whereas series 2 dyes adsorbed in amorphous monolayers. (3-Se did not adsorb appreciably to titania films, due to the lack of a tethering group.) The H-aggregated dyes exhibited broader absorption bands, increased light-harvesting efficiencies, and improved photoelectrochemical performance compared to the dyes which adsorbed in amorphous monolayers. The maximum incident photon-to-current efficiencies (IPCEs) of series 1 dyes ranged from 70% to 84%, whereas those of 2-S and 2-Se were 11% and 20%. Our findings reveal that the light-harvesting efficiency, IPCE, and absorbed photon-to-current efficiency (APCE) of DSSCs with organic dyes can be optimized by systematically varying the structure of the dyes and their orientation and aggregation state on the surface.
Basal cell carcinoma (1997)

Basal cell carcinoma is the commonest malignancy in Caucasians with incidence rates of 300 per 100,000 reported in the USA. Rates are increasing at over 10% per year leading to a lifetime risk of 30%. Although mortality is low, the disease is responsible for considerable morbidity and places a substantial burden on health service provision in the UK. Furthermore, lesions may recur and patients often develop multiple tumours giving major implications for treatment and follow-up. Four main types of basal cell carcinoma are seen: nodulo-ulcerative; pigmented; morpheaform and superficial. Diagnosis is by histological evaluation although many tumours have a characteristic clinical appearance. The differential diagnosis is large. Identified risk factors include male gender, skin type 1, red/blonde hair and increasing age. Patients with basal cell carcinoma are more likely to develop malignant melanoma and squamous cell carcinoma but it is still unclear whether there is a link with internal malignancy. The main treatment modalities are surgery and radiotherapy. Each has advantages and disadvantages. The choice of treatment depends on many factors. Principles of treatment include identification of high-risk patients to enable early detection, complete removal of the lesion, and careful follow-up to detect recurrence or new lesions. Approximately 10% of tumours recur, depending on site, size and treatment modality. Metastatic basal cell carcinoma and the association of ultraviolet radiation to basal cell carcinoma risk are reviewed.
Research on task allocation in multiple logistics robots based on an improved ant colony algorithm (2016)

In order to solve the multi-robot task allocation problem in logistics warehouse environment, first a robot task allocation model is established in which a corresponding benefit function is established with a consideration of two mainly factors including time window and distance. Then the ant colony algorithm pheromone updating rule is improved combining with working environment and task allocation of logistics robots to seek optimized task allocation scheme. At last, the comprehensive benefit value of the improved ant colony algorithm is compared with that o f the original algorithm and the simulation results show that it can be more effective to solve the multi-robot task allocation problem by using the improved ant colony algorithm.
Copper-specific Transcriptional Repression of Yeast Genes Encoding Critical Components in the Copper Transport Pathway (1997)

Copper is an essential micronutrient that is toxic in excess. To maintain an adequate yet non-toxic concentration of copper, cells possess several modes of control. One involves copper uptake mediated by genes encoding proteins that play key roles in high affinity copper transport. These include the FRE1-encoded Cu2+/Fe3+ reductase and the CTR1 and CTR3-encoded membrane-associated copper transport proteins. Each of these genes is transcriptionally regulated as a function of copper availability: repressed when cells are grown in the presence of copper and highly activated during copper starvation. Our data demonstrate that repression of CTR3 transcription is exquisitely copper-sensitive and specific. Although copper represses CTR3 gene expression at picomolar metal concentrations, cadmium and mercury down-regulate CTR3 expression only at concentrations 3 orders magnitude greater. Furthermore, copper-starvation rapidly and potently induces CTR3 gene expression. We demonstrate that the CTR1, CTR3, and FRE1 genes involved in high affinity copper uptake share a common promoter element, TTTGCTC, which is necessary for both copper repression and copper-starvation activation of gene expression. Furthermore, the Mac1p is essential for down- or up-regulation of the copper-transport genes. In vivo footprinting studies reveal that the cis-acting element, termed CuRE (copper-response element), is occupied under copper-starvation and accessible to DNA modifying agents in response to copper repression, and that this regulated occupancy requires a functional MAC1 gene. Therefore, yeast cells coordinately express genes involved in high affinity copper transport through the action of a common signaling pathway.
First-class synchronization barriers (1996)

Our purpose is to promote a second-class mechanism --- the synchronization barrier --- to a first-class value. We introduce the synchron, a novel synchronization mechanism that enables the coordination of a dynamically varying set of concurrent threads that share access to a first-class synchronization token. We demonstrate how synchrons can be used to modularly manage resources in cases where existing techniques are either inapplicable or non-modular. In particular, synchronized lazy aggregates enable the first space-efficient aggregate data decomposition of a wide range of algorithms. We also introduce explicit-demand graph reduction, a new semantic framework that we have developed to describe concurrency and explain the meaning of a synchron rendezvous.
The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies (2011)

The unfolded protein response (UPR) is a stress response activated upon disturbed homeostasis in the endoplasmic reticulum (ER). Previously, we reported that the activation of the UPR closely correlates with the presence of phosphorylated tau (p-tau) in Alzheimer's disease (AD). As well as increased presence of intracellular p-tau, AD brains are characterized by extracellular deposits of β amyloid (Aβ). Recent in vitro studies have shown that Aβ can induce ER stress and activation of the UPR. The aim of the present study is to investigate UPR activation in sporadic tauopathies like progressive supranuclear palsy (PSP) and Pick's disease (PiD), and familial cases with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) which carry mutations in the gene encoding for tau (MAPT). The presence of phosphorylated pancreatic ER kinase (pPERK) and phosphorylated inositol requiring enzyme 1α (pIRE1), which are indicative of an activated UPR, was assessed by immunohistochemistry in cases neuropathologically defined as frontotemporal lobar degeneration with tau pathology (FTLD-tau). Increased presence of UPR activation markers pPERK and pIRE1 was observed in neurons and glia in FTLD-tau cases, in contrast to FTLD subtypes negative for tau pathology or in non-neurological controls. pPERK and pIRE1 were also prominently present in relatively young carriers of MAPT mutation. A strong association between the presence of UPR activation markers and p-tau was observed in the hippocampus of FTLD-tau cases. Double immunohistochemical staining on FTLD-tau cases revealed that UPR activation is predominantly observed in neurons that show diffuse staining of p-tau. These data demonstrate that UPR activation is intimately connected with the accumulation and aggregation of p-tau, and occurs independently from Aβ deposits. Our findings provide new pathological insight into the close association between p-tau and UPR activation in tauopathies.
Temperature stabilized effusion cell evaporation source for thin film deposition and molecular-beam epitaxy (2000)

A simple effusion cell evaporation source for thin film deposition and molecular-beam epitaxy is described. The source consists of a crucible with a thermocouple temperature sensor heated by a resistive crucible heater. Radiation heat transfer from the crucible to the thermocouple produces a consistent and reproducible thermocouple temperature for a given crucible temperature, without direct contact between the thermocouple and the crucible. The thermocouple temperature is somewhat less than the actual crucible temperature because of heat flow from the thermocouple junction along the thermocouple lead wires. In a typical case, the thermocouple temperature is 1007 °C while the crucible is at 1083 °C. The crucible temperature stability is estimated from the measured sensitivity of the evaporation rate of indium to temperature, and the observed variations in the evaporation rate for a fixed thermocouple temperature. The crucible temperature peak-to-peak variation over a one hour period is 1.2 °C. Machined molybdenum crucibles were used in the indium and copper sources for depositing CuInSe2 thin films for solar cells.