gebhart/patrepeval huggingface dataset:
The transmembrane glycoprotein CD38 is a catalytically active transporter responsible for generation and influx of the second messenger cyclic ADP‐ribose across membranes (1998)

CD38 is a type II transmembrane glycoprotein expressed in many vertebrate cells. It is a bifunctional ectoenzyme that catalyzes both the synthesis of Cyclic ADP-ribose (cADPR) from NAD+ and the degradation of cADPR to ADP-ribose by means of its ADP-ribosyl cyclase and cADPR-hydrolase activities, respectively. The cyclase also converts NGD+ to cyclic GDP-ribose (cGDPR), which is refractory to cADPR-hydrolase. cADPR, but not cGDPR, is a potent calcium mobilizer from intracellular stores. It has been demonstrated to be a new second messenger involved in the regulation of calcium homeostasis in many cell types, from plants to mammals. The number of physiological processes shown to be regulated by cADPR is steadily increasing. A topological paradox exists because ectocellularly generated cADPR acts intracellularly. Here we demonstrate that the catalytic functioning of CD38 is accompanied by a cADPR (cGDPR) -transporting activity across natural and artificial membranes. In resealed membranes from CD38(+) human erythrocytes, transport of catalytically generated cADPR or cGDPR was saturation dependent and occurred against a concentration gradient. Likewise, CD38-reconstituted proteoliposomes were active in concentrating NAD+ (NGD+) -derived cADPR (cGDPR) inside the vesicle compartment. Moreover, the cADPR-transporting activity in CD38 proteoliposomes prevented the hydrolase-catalyzed degradation to ADPR that occurs conversely with detergent-solubilized CD38, resulting in selective influx of cADPR. In the CD38 proteoliposomes, catalytically active CD38 exhibited monomeric, dimeric, and tetrameric structures. In CD38 sense- but not in antisense-transfected HeLa cells, externally added NAD+ resulted in significant, transient increases in cytosolic calcium. These data suggest that transmembrane juxtaposition of two or four CD38 monomers can generate a catalytically active channel for selective formation and influx of cADPR (cGDPR) to reach cADPR-responsive intracellular calcium stores.
Numerical modeling of DPSK pressure signals and their transmission characteristics in mud channels (2009)

一个数字模型和压力在泥隧道表明的 DPSK (调音的微分阶段移动) 的传播特征分析被介绍。与旋转阀门泥遥感勘测的控制逻辑分析，一个逻辑控制信号根据播送数据的二进制符号从一个门函数序列被造，一个阶段移动函数被集成逻辑控制信号获得。DPSK 压力信号的一个数学模型被 modulating 搬运人阶段与阶段移动功能基于通讯的原则造，压力波浪的数字模拟被 MATLAB 编程与数学模型一起实现。就沿着 drillpipes 的 drillpipe 压力和钻的液体温度侧面而言，一口垂直的井的 drillpipe 被划分成很多节。与以水为基的钻，液体，旅行距离的影响，搬运人频率， drillpipe 尺寸，和信号传播上的钻的液体被信号传播特征分析为所有节学习。数字计算结果比其它和信号将与信号的微分变细在波形弄歪的显示在在 DPSK 信号传播上钻液体钻液体和气体的体积部分的粘性的影响是更著名的经常的部件。
Hedgehog pathway activity in the LADY prostate tumor model (2007)

Our study shows no evidence for a generalized increase in Hh signaling during tumor development in the LADY mouse. It does reveal a selective increase in Ihh expression that is associated with increased expression of progenitor cell markers and decreased expression of terminal differentiation markers. These data suggest that Ihh expression may be a feature of a progenitor cell population that is involved in tumor development.
Slow Intravenous Administration of Low Dose Aspirin Inhibits Both Vascular and Platelet Cyclooxygenase Activity: An Experimental Study in the Rat (1986)

Aspirin irreversibly inhibits cyclooxygenase, thus preventing thromboxane (Tx)A2 production in platelets and prostacyclin in vascular cells. While it is generally accepted that the inhibitory effect of low dose aspirin is cumulative on platelet cyclooxygenase, it is still a matter of debate whether a similar phenomenon also occurs on vascular cyclooxygenase. We have measured in anesthetized rats the inhibitory effect of two doses of aspirin (2.5 and 5.0 mg/kg), given intravenously either as a bolus or as a continuous infusion (for 30 min), on platelet TxB2 and 6-ketoprostaglandin F1 alpha generation by different vascular segments. Aspirin significantly inhibited both platelet and vascular cyclooxygenase independently of the rate of drug administration. The aspirin peak plasma levels at the end of bolus injection was about 170 times higher than the average level measured during the slow infusion (1.21 +/- 0.15 micrograms/ml). At this concentration aspirin did not affect in vitro either platelet or vascular cyclooxygenase activity. Thus the inhibitory effect of aspirin on both platelet and vascular cyclooxygenase seems to be related to total exposure of the enzyme to the drug rather than to the maximal drug concentration attainable in the systemic circulation. These findings may be relevant to the current debate on optimal conditions for the biochemical selectivity of aspirin as an antithrombotic drug.
New England's training systems and regional economic competitiveness (1989)

Employees, Training of; Education; New England
<em>In vitro</em> Transcription and Capping of <em>Gaussia</em> Luciferase mRNA Followed by HeLa Cell Transfection (2012)

In vitro transcription is the synthesis of RNA transcripts by RNA polymerase from a linear DNA template containing the corresponding promoter sequence (T7, T3, SP6) and the gene to be transcribed (Figure 1A). A typical transcription reaction consists of the template DNA, RNA polymerase, ribonucleotide triphosphates, RNase inhibitor and buffer containing Mg(2+) ions. Large amounts of high quality RNA are often required for a variety of applications. Use of in vitro transcription has been reported for RNA structure and function studies such as splicing(1), RNAi experiments in mammalian cells(2), antisense RNA amplification by the "Eberwine method"(3), microarray analysis(4) and for RNA vaccine studies(5). The technique can also be used for producing radiolabeled and dye labeled probes(6). Warren, et al. recently reported reprogramming of human cells by transfection with in vitro transcribed capped RNA(7). The T7 High Yield RNA Synthesis Kit from New England Biolabs has been designed to synthesize up to 180 μg RNA per 20 μl reaction. RNA of length up to 10kb has been successfully transcribed using this kit. Linearized plasmid DNA, PCR products and synthetic DNA oligonucleotides can be used as templates for transcription as long as they have the T7 promoter sequence upstream of the gene to be transcribed. Addition of a 5' end cap structure to the RNA is an important process in eukaryotes. It is essential for RNA stability(8), efficient translation(9), nuclear transport(10) and splicing(11). The process involves addition of a 7-methylguanosine cap at the 5' triphosphate end of the RNA. RNA capping can be carried out post-transcriptionally using capping enzymes or co-transcriptionally using cap analogs. In the enzymatic method, the mRNA is capped using the Vaccinia virus capping enzyme(12,13). The enzyme adds on a 7-methylguanosine cap at the 5' end of the RNA using GTP and S-adenosyl methionine as donors (cap 0 structure). Both methods yield functionally active capped RNA suitable for transfection or other applications(14) such as generating viral genomic RNA for reverse-genetic systems(15) and crystallographic studies of cap binding proteins such as eIF4E(16). In the method described below, the T7 High Yield RNA Synthesis Kit from NEB is used to synthesize capped and uncapped RNA transcripts of Gaussia luciferase (GLuc) and Cypridina luciferase (CLuc). A portion of the uncapped GLuc RNA is capped using the Vaccinia Capping System (NEB). A linearized plasmid containing the GLuc or CLuc gene and T7 promoter is used as the template DNA. The transcribed RNA is transfected into HeLa cells and cell culture supernatants are assayed for luciferase activity. Capped CLuc RNA is used as the internal control to normalize GLuc expression.
Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence (1992)

The aim of this study was to determine the feasibility of utilizing a factor Xa-specific cleavage site within a recombinant protein containing the ricin A chain (RTA) sequence. Release of RTA is believed to be an essential step during the intracellular phase of ricin intoxication. Failure to incorporate such cleavage sites in fusions containing RTA results in a loss of toxin action (O'Hare, M., et al. (1990) FEBS Lett. 273,200. Kim, J., and Weaver, R.F. (1988) Gene 68,315). In this report we describe the introduction of a factor Xa-specific site in the linker of proricin, which we use here as a model substrate. Upon purification of the recombinant mutant proricin after expression in Xenopus oocytes, we demonstrate that the protease does have access to the engineered recognition sequence (albeit at low efficiency) and that the presence of the latter does not interfere with disulfide bond formation or the lectin activity of the ricin B chain moiety. Upon cleavage and reduction, the RTA polypeptide displays ribosome-inactivating ability, indicating that the presence of the modified linker at its C-terminus does not interfere with its catalytic activity. The general applicability of using such a cleavage site in recombinant fusions with RTA is discussed.
Cancer Stem Cells in Radiation Resistance (2007)

Highly tumorigenic subpopulations of several solid cancers share characteristics with somatic stem cells. We showed recently that cancer stem cells, or tumor-initiating cells, derived from human glioblastoma surgical specimens and xenografts display resistance to radiation due to increased activation of the DNA damage checkpoint. We additionally showed that these same tumor subpopulations promote tumor angiogenesis through increased expression of vascular endothelial growth factor. These studies and subsequent reports from other researchers support critical roles for cancer stem cells in determining tumor response to therapy. Hypoxia and stem cell maintenance pathways may provide therapeutic targets to sensitize cancer stem cells to cytotoxic therapies to improve cancer patient treatments.
Bias Reduction in Phase Refinement by Modified Interference Functions: Introducing the γ Correction (1997)

The chemical, physical and symmetry constraints of an electron-density map impose relationships between structure factors, and these relationships are exploited during refinement. However, constraints often allow an artificially high correlation between the model and the original structure factors, a flaw known as model or refinement bias. Elimination of the bias component of a constrained model, the component insensitive to constraints, enhances the power of phase-refinement techniques. The scale of the bias component, here denoted as gamma, is shown to be equal in magnitude to the origin vector of the interference function G that defines the relationships between the structure factors. The gamma correction leads to solvent flipping in the case of phase improvement by solvent flattening, and other types of constraint allow a similar treatment.
N-Myristoyltransferase from Leishmania donovani: Structural and Functional Characterisation of a Potential Drug Target for Visceral Leishmaniasis (2009)

N-Myristoyltransferase (NMT) catalyses the attachment of the 14-carbon saturated fatty acid, myristate, to the amino-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction. In these pathways, N-myristoylation facilitates association of substrate proteins with membranes or the hydrophobic domains of other partner peptides. NMT function is essential for viability in all cell types tested to date, demonstrating that this enzyme has potential as a target for drug development. Here, we provide genetic evidence that NMT is likely to be essential for viability in insect stages of the pathogenic protozoan parasite, Leishmania donovani, causative agent of the tropical infectious disease, visceral leishmaniasis. The open reading frame of L. donovani NMT has been amplified and used to overproduce active recombinant enzyme in Escherichia coli, as demonstrated by gel mobility shift assays of ligand binding and peptide-myristoylation activity in scintillation proximity assays. The purified protein has been crystallized in complex with the non-hydrolysable substrate analogue S-(2-oxo)pentadecyl-CoA, and its structure was solved by molecular replacement at 1.4 A resolution. The structure has as its defining feature a 14-stranded twisted beta-sheet on which helices are packed so as to form an extended and curved substrate-binding groove running across two protein lobes. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the carboxy-terminal lobe. These studies validate L. donovani NMT as a potential target for development of new therapeutic agents against visceral leishmaniasis.
Utility of Portable Chest Radiographs as a Predictor of Endotracheal Tube Cuff Pressure (1999)

Increased endotracheal tube cuff pressure causes mucosal ischemia that can lead to necrosis, infection, and, eventually, tracheomalacia or tracheal stenosis. Endotracheally intubated patients frequently undergo portable chest radiography. In this study we explored the relationship of endotracheal tube cuff pressure and the appearance on the tracheal air columns on the portable chest radiograph. We measured the endotracheal tube cuff pressure of intensive care unit patients 124 times immediately before portable chest radiography. On 64 of these radiographs we measured the width of the tracheal air column below the tip of the endotracheal tube and at the maximal diameter of the endotracheal tube balloon. We then analyzed the relationship of cuff pressure to tracheal dilation. The results of ANOVA of tracheal dilation for three groups (safe, borderline, and unsafe cuff pressures) were significant. Large overlapping ranges existed in each group. Regression analysis confirmed a linear relationship between cuff pressure and tracheal dilation (r = 0.435, p < 0.001). Predicted tracheal expansion at 20 mm Hg was a poor screen for endotracheal tube cuff inflation safety; the sensitivity was only 56% and specificity only 71%. The differences in the capacity for tracheal distension between patients make these findings not unexpected. The portable chest radiograph is a poor screening tool for unsafe endotracheal tube cuff pressure.
Sphenopalatine Ganglion Blockade: A Review and ProposedModification of the Transnasal Technique (2004)

The sphenopalatine ganglion block has been utilized over the last century for a wide variety of maladies. This paper provides a brief history of the use of the sphenopalatine ganglion block, a review of the sphenopalatine ganglion anatomy, and the diagnoses which currently warrant its use. The traditional transnasal sphenopalatine ganglion block is described and our modification of the traditional technique is proposed. A case study is described in which sphenopalatine block pain control in a patient with a 20-year history of poorly controlled pain from bilateral herpetic keratitis.
<title>Improvement of resist pattern fidelity with partial attenuated phase-shift mask</title> (1996)

To improve resist pattern fidelity, partial attenuated phase-shift mask (PA PSM) was developed. On this mask, some portions of opaque regions were changed to attenuated phase- shift regions. The performances of two PA PSMs (8 percent and 13 percent transmittance) were evaluated by using an NA equals 0.6, annular illumination i-line stepper. Resist pattern shortening of longer side was alleviated to the half of a conventional mask, and corner rounding was also improved without deteriorating process margin. Moreover, the width of attenuated region did not have much effect on the resist pattern size; almost the same pattern length was obtained with any phase shifted region width (0.2 approximately 0.4micrometers ). Therefore, we have a large process margin in this mask fabrication. Moreover, KrF PA PSM (7 percent transmittance) was fabricated and evaluated. The same effect was confirmed in KrF excimer laser lithography. In conclusion, PA PSM is a very promising technique for precise pattern formation.
Activation of Akt, mTOR, and the estrogen receptor as a signature to predict tamoxifen treatment benefit (2012)

The frequent alterations of the PI3K/Akt/mTOR-growth signaling pathway are proposed mechanisms for resistance to endocrine therapy in breast cancer, partly through regulation of estrogen receptor α (ER) activity. Reliable biomarkers for treatment prediction are required for improved individualized treatment. We performed a retrospective immunohistochemical analysis of primary tumors from 912 postmenopausal patients with node-negative breast cancer, randomized to either tamoxifen or no adjuvant treatment. Phosphorylated (p) Akt-serine (s) 473, p-mTOR-s2448, and ER phosphorylations-s167 and -s305 were evaluated as potential biomarkers of prognosis and tamoxifen treatment efficacy. High expression of p-mTOR indicated a reduced response to tamoxifen, most pronounced in the ER+/progesterone receptor (PgR) + subgroup (tamoxifen vs. no tamoxifen: hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.31-2.38; P = 0.78), whereas low p-mTOR expression predicted tamoxifen benefit (HR, 0.29; 95 % CI, 0.18-0.49; P = 0.000002). In addition, nuclear p-Akt-s473 as well as p-ER at -s167 and/or -s305 showed interaction with tamoxifen efficacy with borderline statistical significance. A combination score of positive pathway markers including p-Akt, p-mTOR, and p-ER showed significant association with tamoxifen benefit (test for interaction; P = 0.029). Cross-talk between growth signaling pathways and ER-signaling has been proposed to affect tamoxifen response in hormone receptor-positive breast cancer. The results support this hypothesis, as an overactive pathway was significantly associated with reduced response to tamoxifen. A clinical pre-treatment test for cross-talk markers would be a step toward individualized adjuvant endocrine treatment with or without the addition of PI3K/Akt/mTOR pathway inhibitors.
An Optical Clock Based on a Single Trapped 199 Hg + Ion (2001)

Microwave atomic clocks have been the de facto standards for precision time and frequency metrology over the past 50 years, finding widespread use in basic scientific studies, communications, and navigation. However, with its higher operating frequency, an atomic clock based on an optical transition can be much more stable. We demonstrate an all-optical atomic clock referenced to the 1.064-petahertz transition of a single trapped 199Hg+ ion. A clockwork based on a mode-locked femtosecond laser provides output pulses at a 1-gigahertz rate that are phase-coherently locked to the optical frequency. By comparison to a laser-cooled calcium optical standard, an upper limit for the fractional frequency instability of 7 x 10(-15) is measured in 1 second of averaging-a value substantially better than that of the world's best microwave atomic clocks.
Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo. (2000)

Missile therapy, which destroys cancer cells specifically, has been regarded as an effective treatment modality for carcinoma. The monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II was examined in a colony formation in vitro, and on athymic mice in vivo. The results of our study suggest that the <inhibitory concentration> or IC50, of the MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in vitro. The reductions in resected weights of target tumor cells, at the local site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein administration, and 38% with local administration, as compared with the untreated group, in vivo. There was no weight loss in treated mice. Our results suggest that this MSN-1-ADM immunoconjugate has potential clinical application in the treatment of endometrial adenocarcinomas.
Biological basis of radiation sensitivity. Part 2: Cellular and molecular determinants of radiosensitivity. (2000)

Recent studies have elucidated some of the molecular and cellular mechanisms that determine the sensitivity or resistance to ionizing radiation. These findings ultimately may be useful in devising new strategies to improve the therapeutic ratio in cancer treatment. Despite the rapid advances in knowledge of cellular functions that affect radiosensitivity, we still cannot account for most of the clinically observed heterogeneity of normal tissue and tumor responses to radiotherapy, nor can we accurately predict which individual tumors will be controlled locally and which patients will develop more severe normal tissue damage after radiotherapy. However, several candidate genes for which deletion or loss of function mutations may be associated with altered cellular radiosensitivity (e.g., ATM, p53, BRCA1, BRCA2, DNA-PK) have been identified. Some of the differences in normal tissue sensitivity to radiation may stem from mutations with milder effects, heterozygosity, or polymorphisms of these genes. Finally, molecular mechanisms linking genetic instability, radiosensitivity, and predisposition to cancer are being unraveled.
Review: Confirmation of Resistance to Herbicides and Evaluation of Resistance Levels (2013)

As cases of resistance to herbicides escalate worldwide, there is increasing demand from growers to test for weed resistance and learn how to manage it. Scientists have developed resistance-testing protocols for numerous herbicides and weed species. Growers need immediate answers and scientists are faced with the daunting task of testing an increasingly large number of samples across a variety of species and herbicides. Quick tests have been, and continue to be, developed to address this need, although classical tests are still the norm. Newer methods involve molecular techniques. Whereas the classical whole-plant assay tests for resistance regardless of the mechanism, many quick tests are limited by specificity to an herbicide, mode of action, or mechanism of resistance. Advancing knowledge in weed biology and genomics allows for refinements in sampling and testing protocols. Thus, approaches in resistance testing continue to diversify, which can confound the less experienced. We aim to help weed science practitioners resolve questions pertaining to the testing of herbicide resistance, starting with field surveys and sampling methods, herbicide screening methods, data analysis, and, finally, interpretation. More specifically, this article discusses approaches for sampling plants for resistance confirmation assays, provides brief overviews on the biological and statistical basis for designing and analyzing dose–response tests, and discusses alternative procedures for rapid resistance confirmation, including molecular-based assays. Resistance confirmation procedures often need to be slightly modified to suit a specific situation; thus, the general requirements as well as pros and cons of quick assays and DNA-based assays are contrasted. Ultimately, weed resistance testing research, as well as resistance management decisions arising from research, needs to be practical, feasible, and grounded in science-based methods.