gebhart/patrepeval huggingface dataset:
Practical problems in detecting abnormal mitochondrial function and genomes (2000)

Mitochondrial respiratory chain dysfunction causes a wide range of primary diseases in adults and children, with highly variable organ involvement. Diagnosis involves weighing evidence from a number of sources, including the clinical presentation, metabolic measurements in vivo, imaging studies, analysis of respiratory chain function or enzyme activities in vitro, studies of mitochondrial morphology after biopsy, and mitochondrial (mt) DNA mutation analysis. Irrespective of the category of the information, it can be difficult to determine whether abnormal results are due to primary defects of the respiratory chain or to practical problems that complicate the diagnostic methodology. This review describes six sources of such problems: genetic complexity, tissue and temporal variation, methodological limitations, secondary effects, logistical issues, and questions of interpretation. When these issues are all addressed, a reliable categorization of the diagnosis as definite, probable, or possible respiratory chain defect becomes possible.
Fluorescent Probes for Live-Cell RNA Detection (2009)

Commonly used techniques for analyzing gene expression, such as polymerase chain reaction (PCR), microarrays, and in situ hybridization, have proven invaluable in understanding RNA processing and regulation. However, these techniques rely on the use of lysed and/or fixed cells and are therefore limited in their ability to provide important spatial-temporal information. This has led to the development of numerous techniques for imaging RNA in living cells, some of which have already provided important insight into the dynamic role RNA plays in dictating cell behavior. Here we review the fluorescent probes that have allowed for RNA imaging in living cells and discuss their utility and limitations. Common challenges faced by fluorescent probes, such as probe design, delivery, and target accessibility, are also discussed. It is expected that continued advancements in live cell imaging of RNA will open new and exciting opportunities in a wide range of biological and medical applications.
Software Process Support in Software Development Environments (2005)

qnvironment consists of an infrastructure, often referred as framework, and a collection of tools. Various development tools support individual developers in different steps of the life cycle. These tools may :hange from project to project as the development methods change. Project management tools support the individual project manager in planning, scheduling, and monitoring a project. The plans, models of the software process, are translated into tasks to be enacted by humans. The environment infrastructure provides basic computing facilities such as user interface management, operating system functions, data
Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger (2009)

With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.
Prevalence and Extent of Atherosclerosis in Adolescents and Young Adults<SUBTITLE>Implications for Prevention From the Pathobiological Determinants of Atherosclerosis in Youth Study</SUBTITLE> (1999)

Atherosclerosis begins in youth. Fatty streaks and clinically significant raised lesions increase rapidly in prevalence and extent during the 15- to 34-year age span. Primary prevention of atherosclerosis, as contrasted with primary prevention of clinically manifest atherosclerotic disease, must begin in childhood or adolescence.
Chip Alignment Templates for Multichip Module Assembly (1987)

Future high-performance large-scale digital systems will increasingly require high-density multichip hybrid packaging techniques. Chip attachment by flip-chip mounting, as in the well-established eontrolled-collapse solder-bump contact approach, has several fundamental advantages over the more familiar wire-bonded hybrid assembly approach. However, testing of flip-chip mounted assemblies and replacement of defective parts, along with the alignment of chip bonding pads to substrate pads, involves substantial practical difficulties. A chip alignment template, aligned to and permanently mounted on the hybrid substrate, is proposed. Anisotropic etching of silicon wafers provides a high-precision technique compatible with batch fabrication of the templates. Fabrication of such templates and factors influencing chip alignment accuracy are discussed.
The Transport Layer Security (TLS) Protocol Version 1.3 (2018)

This document specifies version 1.3 of the Transport Layer Security
(TLS) protocol. TLS allows client/server applications to communicate
over the Internet in a way that is designed to prevent eavesdropping,
tampering, and message forgery. This document updates RFCs 4492, 5705,
and 6066 and it obsoletes RFCs 5077, 5246, and 6961. This document
also specifies new requirements for TLS 1.2 implementations.
Palladium-Catalyzed C(sp3)—H Oxygenation via Electrochemical Oxidation (2017)

Palladium-catalyzed C-H activation/C-O bond-forming reactions have emerged as attractive tools for organic synthesis. Typically, these reactions require strong chemical oxidants, which convert organopalladium(II) intermediates into the Pd<sup>III</sup> or Pd<sup>IV</sup> oxidation state to promote otherwise challenging C-O reductive elimination. However, previously reported oxidants possess significant disadvantages, including poor atom economy, high cost, and the formation of undesired byproducts. To overcome these issues, we report an electrochemical strategy that takes advantage of anodic oxidation of Pd<sup>II</sup> to induce selective C-O reductive elimination with a variety of oxyanion coupling partners.
The H2-phase of the lyotropic liquid crystal sodium 3,4,5-tris(omega-acryloyloxyundecyloxy)benzoate (2000)

The phase behaviour of the lyotropic liquid crystal sodium 3,4,5-tris(omega-acryloyloxyundecyloxy)-benzoate was investigated by small angle X-ray scattering. The water content of the lyotropic liquid crystal phase was varied between 8 and 20wt% and the investigations were performed in a temperature range up to 70oC. A reversed hexagonal structure (H2-phase) as well as the isotropic phase were observed. The lattice constant of the H2-phase was found to be independent of the water content. An extremely small dependence on temperature could be found. Based on the shape of the molecules and the observed structural properties, a model for the arrangement of the molecules within the H2-phase is given. The transition temperature from the H2-phase to the isotropic phase decreases significantly from 60oC for the sample with 8wt% water content to 30oC for the sample with 20wt% water content. © 2000 Taylor &amp;amp; Francis Group, LLC.
Detection of Antinuclear Antibodies by Solid-Phase Immunoassays and Immunofluorescence Analysis (2004)

In this study, the sensitivities of EIAs and IFA were largely comparable. However, EIAs without HEp-2 extracts included had a low sensitivity but a high specificity, particularly in nonselected populations. The choice of test is highly dependent on the clinical setting in which the ANA test is to be used and on laboratory policy.
Thematic Knight's Tour Quotes (1978)

Knight's Tour Quotes (KTQs), also called Knight's Tour Crypts, are a word puzzle enjoying a new vogue in the National Puzzlers' League since David Silverman reintroduced them in 1973. Dmitri Borgmann presented some examples in "Chesswords" in the May 1974 Word Ways. A KTQ is a quote written out along a knight's tour. It is a form, usually rectangular, with each square containing a single letter or punctuation mark. Stepping from letter to letter by knight's moves (two squares horizontally or vertically, then one square perpendicular to that), visiting all letters once, one can spell out a message. To reduce the task from drudgery to pleasure, the starting letter is underlined and the word lengths and punctuation of the message are given.
Transactivation by the Thyroid Hormone Receptor Is Dependent on the Spacer Sequence in Hormone Response Elements Containing Directly Repeated Half-Sites (1996)

The thyroid hormone receptor (TR) regulates the transcription of its target genes by interacting with specific hormone response elements consisting usually of directly repeated half-sites with the consensus sequence AGGTCA. To investigate the role of the spacer sequences separating the half-sites, heterodimers formed by TRalpha and the retinoid-X receptor (RXR) were used in a PCR based selection and amplification assay. The TRalpha/RXR heterodimer selected for elements with directly repeated half-sites having a spacer of 4 nucleotides (DR4). Preferences for nucleotides in the TR binding half-site motif as well as for the 4 nucleotides separating the two half-sites were found. DNA binding and transfection studies using DR4 elements with different spacer sequences showed the importance of these nucleotides for the activity of the response element: some spacer sequences allowed little or no transactivation from the element, whereas other sequences supported strong transactivation. A pyrimidine nucleotide in position three of the spacer enhanced TRalpha binding and transactivation. Additional experiments showed that heterodimers between RXR and other putative receptors exhibited a similar but distinct specificity for the spacer sequence. Our results thus suggest that the four nucleotides separating the two half-sites in hormone response elements have a major role in determining induction of hormone responsive genes.
ChemInform Abstract: Hetero‐Cope‐Rearrangements. Part 4. Regio‐Controlled Synthesis of Indoles. (1986)

Abstract The aniline derivatives (IV), which are easily transformed to the Z‐substituted indoles (V), are prepared by consecutive Michael addition and Cope rearrangement from hydroxylamines (I) and allenes (II) [the lithium salt is added in order to suppress the formation of by‐products due to isomerization of the intermediate allylic anion (III)].
Differentiation inducers of human promyelocytic leukemia cells HL-60. Azobenzenecarboxylic acids and stilbenecarboxylic acids. (1985)

Azobenzene-4-carboxylic acid derivatives are a new type of differentiation inducers of human myelogenous leukemia cell line HL-60. Induced cells are morphologically and functionally mature granulocytes. A study of substituent effects indicated that these compounds are related to the known synthetic retinoid, tetrahydrotetramethylnaphthyl-propenylbenzoic acid.
Peptides Displayed as High Density Brush Polymers Resist Proteolysis and Retain Bioactivity (2014)

We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease. Finally, we demonstrate that the proteolytic susceptibility of peptide brush polymers can be tuned by adjusting the density of the polymer brush and offer in silico models to rationalize this finding. We contend that this strategy offers a plausible method of preparing peptides for in vivo use, where rapid digestion by proteases has traditionally restricted their utility.
Comprehensive Investigation of Common Antibody-Dependent Cell-Mediated Cytotoxicity Antibody Epitopes of HIV-1 CRF01_AE gp120 (2012)

The antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism involves both innate and adaptive immune systems. While a number of epitope mapping studies of neutralizing (Nt) antibodies and cytotoxic T lymphocyte (CTL) against a variety of HIV-1 clades have been reported, there has been a paucity of similar studies aimed at identifying epitopes of ADCC-inducing antibodies. Herein we screened 35 sera from HIV-1 CRF01_AE-infected blood donors for ADCC antibody activity against gp120 utilizing an EGFP-CEM-NK(r) flow cytometric assay. Eighteen sera with high ADCC antibody activity were then comprehensively examined for ADCC antibody epitopes using the HIV-1 subtype CRF01_AE TH023 gp120 peptide set consisting of 126 peptides of 15 amino acids in length, overlapping by 11 amino acids. This peptide set was divided into five pools (E1-E5). Each positive peptide pool was further investigated for fine epitope mapping of ADCC antibody activity using a 5 by 5 peptide matrix format. Interestingly, six and three peptides from peptide pools E1 and E2, respectively, responded to at least 33.33% of the tested sera. These nine common ADCC epitopes were localized to the C1 and V2 region of gp120. Furthermore, 5/9 epitopes were also shown to serve as full or partial Nt antibody targets for HIV-1 subtypes B and CRF01_AE. We submit these data on epitope mapping of ADCC or dual ADCC-Nt antibodies against HIV-1 gp120 that should be considered in the formulation of vaccines against HIV-1.
TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis (2014)

TOPK (T-lymphokine-activated killer cell-originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. We report the development of a potent TOPK inhibitor, OTS964 {(R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one}, which inhibits TOPK kinase activity with high affinity and selectivity. Similar to the knockdown effect of TOPK small interfering RNAs (siRNAs), this inhibitor causes a cytokinesis defect and the subsequent apoptosis of cancer cells in vitro as well as in xenograft models of human lung cancer. Although administration of the free compound induced hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively caused complete regression of transplanted tumors without showing any adverse reactions in mice. Our results suggest that the inhibition of TOPK activity may be a viable therapeutic option for the treatment of various human cancers.
Tyrosine Kinase Inhibitors. 18. 6-Substituted 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Soluble, Irreversible Inhibitors of the Epidermal Growth Factor Receptor (2000)

4-Anilinoquinazoline- and 4-anilinopyrido[3,4-d]pyrimidine-6-acrylamides are potent pan-erbB tyrosine kinase inactivators, and one example (CI-1033) is in clinical trial. A series of analogues with a variety of Michael acceptor units at the 6-position were prepared to define the structural requirements for irreversible inhibition. A particular goal was to determine whether additional functions to increase solubility could be appended to the Michael acceptor. Substituted acrylamides were prepared by direct acylation of the corresponding 6-amines with the requisite acid or acid chloride. Vinylsulfonamide derivatives were obtained by acylation of the amines with chloroethylsulfonyl chloride followed by base-promoted elimination. Vinylsulfone and vinylsulfine derivatives were prepared by oxidation and base elimination of a hydroxyethylthio intermediate. The compounds were evaluated for their inhibition of phosphorylation of the isolated EGFR enzyme and for inhibition of EGF-stimulated autophosphorylation of EGFR in A431 cells and of heregulin-stimulated autophosphorylation of erbB2 in MDA-MB 453 cells. Substitution at the nitrogen of the acrylamide was tolerated only with a methyl group; larger substituents were dystherapeutic, and no substitution at all was tolerated at the acrylamide alpha-carbon. In contrast, while electron-donating groups at the acrylamide beta-carbon were not useful, even quite large electron-withdrawing groups (which increase its electrophilicity) were tolerated. A series of derivatives with solubility-enhancing substituents linked to the acrylamide beta-carbon via amides were potent irreversible inhibitors of isolated EGFR (IC50s = 0.4-1.1 nM), with weakly basic morpholine and imidazole derivatives being the best. Vinylsulfonamides were also potent and irreversible inhibitors, but vinylsulfones and vinylsulfines were reversible and only poorly active. Two compounds were evaluated against A431, H125, and MCF-7 xenografts in nude mice but were inferior in these assays to the clinical trial compound CI-1033.
Dipeptide processing activates recombinant human prochymase. (1993)

Human chymase (h-chymase) is a serine protease that efficiently converts angiotensin I to II. Its structure and homology to other serine proteases suggest that it is synthesized as a zymogen, and is processed to the active form by cleavage of a 19-residue signal peptide and of a dipeptide pro-segment. To evaluate maturational processing of this enzyme, the proteins encoded by three h-chymase cDNA constructs (wild-type, lacking the pro- or lacking the prepro-segment) were characterized after expression in COS-1 cells. These recombinant proteins were not catalytically active. Purification and NH2-terminal sequence analysis of the protein expressed from the wild-type construct revealed processing to the proenzyme. Prochymase activation was achieved by incubation with a B-cell lymphoma homogenate, which apparently contains a heterologous processing enzyme sensitive to thiol protease inhibitors. NH2-terminal sequence analysis of the activated h-chymase revealed cleavage of the pro-segment, and its biochemical characteristics were identical to those of native h-chymase purified from the myocardium. These findings indicate that processing of the dipeptide pro-segment is necessary and sufficient for activation of human chymase. Such processing is probably also required for the activation of related serine proteases, e.g., cathepsin G, which have homologous dipeptide pro-segments.
Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development (2009)

Proper thymocyte development is required to establish T-cell central tolerance and to generate naive T cells, both of which are essential for T-cell homeostasis and a functional immune system. Here we demonstrate that the loss of transcription factor Foxp1 results in the abnormal development of T cells. Instead of generating naive T cells, Foxp1-deficient single-positive thymocytes acquire an activated phenotype prematurely in the thymus and lead to the generation of peripheral CD4(+) T and CD8(+) T cells that exhibit an activated phenotype and increased apoptosis and readily produce cytokines upon T-cell receptor engagement. These results identify Foxp1 as an essential transcriptional regulator for thymocyte development and the generation of quiescent naive T cells.
The Nuclear Localization of ERK2 Occurs by Mechanisms Both Independent of and Dependent on Energy (2006)

The mitogen-activated protein (MAP) kinases ERK1 and ERK2 often accumulate in the nuclei of stimulated cells to mediate changes in transcription. The mechanisms underlying stimulus-dependent redistribution of these kinases remain unclear. We have used a permeabilized cell reconstitution assay in HeLa cells and human foreskin fibroblasts to explore the processes by which ERK2 enters and exits the nucleus. We previously reported that entry of unphosphorylated ERK2 into the nucleus occurs by facilitated diffusion not requiring cytosolic transport factors. We find that export, like import, can occur by an energy- and carrier-independent mechanism. An energy-dependent mechanism of ERK2 export can also be distinguished, mediated at least in part through the exportin CRM1. We have also examined import and export of thiophosphorylated, active ERK2. Import of active ERK2 is significantly enhanced by the addition of exogenous transport factors and an energy regeneration system. These studies support a model in which multiple constitutive and regulated processes control the subcellular distribution of ERK2.
Retrospective Analysis of Calls to Poison Control Centers Resulting from Exposure to the Insect RepellentN, N-diethyl-M-Toluamide (DEET) from 1985–1989 (1994)

This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide--containing insect repellents that were reported to Poison Control Centers from 1985-1989. Nearly two-thirds of those exposed had no adverse effects or only experienced minor symptoms that resolved rapidly. Symptoms were more likely to occur after ocular or inhalation exposures and least likely to occur if the product was ingested. The only reported death occurred in a patient who suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m-toluamide. Five patients may have experienced a serious or potentially life-threatening effect but the poison center record did not provide unequivocal substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the causative agent. From the analysis of those patients calling Poison Control Centers, it appears the risk of serious medical effects with the labeled use of N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with its reported annual use by about 30% of Americans. For patients contacting Poison Control Centers, the occurrence of adverse effects appears to be related to the route of exposure rather than age or gender of the patient or the concentration of N,N-diethyl-m-toluamide in the product.
A Man Named Don Larsen (1992)

In lieu of an abstract, below is the essay's first paragraph.\n"Baseball has always held that special magic for me. From the time I was a little girl, I loved hearing about the heroes of the game and listening IO Phil Rizzuto on the radio. My grand father first introduced me to the game before I could even talk. My mother often tells me of the times when he would change my diapers and talk about Babe Ruth and Joe DiMaggio."
Novel 3-D structure for ultra high density flash memory with VRAT (Vertical-Recess-Array-Transistor) and PIPE (Planarized Integration on the same PlanE) (2008)

A 3-D flash memory cell of VRAT (vertical-recess-array-transistor) has been fabricated using a unique and simple 3-D integration method of PIPE (planarized integration on the same plane), which allows for the successful implementation of ultra high density flash memory. In addition, procedures to increase the memory density further using another advanced structure, Zigzag-VRAT (Z-VRAT), are developed.