gebhart/patrepeval huggingface dataset:
A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research (2016)

Previous efforts to target the mouse genome for the addition, subtraction, or substitution of biologically informative sequences required complex vector design and a series of arduous steps only a handful of laboratories could master. The facile and inexpensive clustered regularly interspaced short palindromic repeats (CRISPR) method has now superseded traditional means of genome modification such that virtually any laboratory can quickly assemble reagents for developing new mouse models for cardiovascular research. Here, we briefly review the history of CRISPR in prokaryotes, highlighting major discoveries leading to its formulation for genome modification in the animal kingdom. Core components of CRISPR technology are reviewed and updated. Practical pointers for 2-component and 3-component CRISPR editing are summarized with many applications in mice including frameshift mutations, deletion of enhancers and noncoding genes, nucleotide substitution of protein-coding and gene regulatory sequences, incorporation of loxP sites for conditional gene inactivation, and epitope tag integration. Genotyping strategies are presented and topics of genetic mosaicism and inadvertent targeting discussed. Finally, clinical applications and ethical considerations are addressed as the biomedical community eagerly embraces this astonishing innovation in genome editing to tackle previously intractable questions.
The colorimetric estimation of formaldehyde by means of the Hantzsch reaction (1953)

Research Article| October 01 1953 The colorimetric estimation of formaldehyde by means of the Hantzsch reaction T. Nash T. Nash 1Air Hygiene Laboratory, Public Health Laboratory Service, Colindale Avenue, London, N.W. 9 Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1953) 55 (3): 416–421. https://doi.org/10.1042/bj0550416 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation T. Nash; The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 1 October 1953; 55 (3): 416–421. doi: https://doi.org/10.1042/bj0550416 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1953 CAMBRIDGE UNIVERSITY PRESS1953 Article PDF first page preview Close Modal You do not currently have access to this content.
Viscoelasticity of human alveolar epithelial cells subjected to stretch (2004)

Alveolar epithelial cells undergo stretching during breathing and mechanical ventilation. Stretch can modify cell viscoelastic properties, which may compromise the balance of forces in the alveolar epithelium. We studied the viscoelasticity of alveolar epithelial cells (A549) subjected to equibiaxial distention with a novel experimental approach. Cells were cultured on flexible substrates and subjected to stepwise deformations of up to 17% with a device built on an inverted microscope. Simultaneously, cell storage (G') and loss (G'') moduli were measured (0.1-100 Hz) with optical magnetic twisting cytometry. G' and G'' increased with strain up to 64 and 30%, respectively, resulting in a decrease in G''/G' (15%). This stretch-induced response was inhibited by disruption of the actin cytoskeleton with latrunculin A. G' increased with frequency following a power law with exponent alpha = 0.197. G'' increased proportionally to G' but exhibited a more marked frequency dependence at high frequencies. Stretching (14%) caused a fall in alpha (13%). At high stretching amplitudes, actual cell strain (14.4%) was lower than the applied substrate strain (17.3%), which could indicate a partial cell detachment. These data suggest that cytoskeletal prestress modulates the elastic and frictional properties of alveolar epithelial cells in a coupled manner, according to soft glassy rheology. Stretch-induced cell stiffening could compromise the balance of forces at the cell-cell and cell-matrix adhesions.
Marburgvirus Genomics and Association with a Large Hemorrhagic Fever Outbreak in Angola (2006)

In March 2005, the Centers for Disease Control and Prevention (CDC) investigated a large hemorrhagic fever (HF) outbreak in Uige Province in northern Angola, West Africa. In total, 15 initial specimens were sent to CDC, Atlanta, Ga., for testing for viruses associated with viral HFs known to be present in West Africa, including ebolavirus. Marburgvirus was also included despite the fact that the origins of all earlier outbreaks were linked directly to East Africa. Surprisingly, marburgvirus was confirmed (12 of 15 specimens) as the cause of the outbreak. The outbreak likely began in October 2004 and ended in July 2005, and it included 252 cases and 227 (90%) fatalities (report from the Ministry of Health, Republic of Angola, 2005), making it the largest Marburg HF outbreak on record. A real-time quantitative reverse transcription-PCR assay utilized and adapted during the outbreak proved to be highly sensitive and sufficiently robust for field use. Partial marburgvirus RNA sequence analysis revealed up to 21% nucleotide divergence among the previously characterized East African strains, with the most distinct being Ravn from Kenya (1987). The Angolan strain was less different ( approximately 7%) from the main group of East African marburgviruses than one might expect given the large geographic separation. To more precisely analyze the virus genetic differences between outbreaks and among viruses within the Angola outbreak itself, a total of 16 complete virus genomes were determined, including those of the virus isolates Ravn (Kenya, 1987) and 05DRC, 07DRC, and 09DRC (Democratic Republic of Congo, 1998) and the reference Angolan virus isolate (Ang1379v). In addition, complete genome sequences were obtained from RNAs extracted from 10 clinical specimens reflecting various stages of the disease and locations within the Angolan outbreak. While the marburgviruses exhibit high overall genetic diversity (up to 22%), only 6.8% nucleotide difference was found between the West African Angolan viruses and the majority of East African viruses, suggesting that the virus reservoir species in these regions are not substantially distinct. Remarkably few nucleotide differences were found among the Angolan clinical specimens (0 to 0.07%), consistent with an outbreak scenario in which a single (or rare) introduction of virus from the reservoir species into the human population was followed by person-to-person transmission with little accumulation of mutations. This is in contrast to the 1998 to 2000 marburgvirus outbreak, where evidence of several virus genetic lineages (with up to 21% divergence) and multiple virus introductions into the human population was found.
Nitric oxide-based therapies in sickle cell disease: The evidence continues to mount* (2007)

Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD
Neuropeptide Y: an overview of central distribution, functional aspects, and possible involvement in neuropsychiatric illnesses (1990)

Neuropeptide Y (NPY) was first discovered and characterized as a 36-amino-acid peptide neurotransmitter in 1982. It is widely distributed in the central nervous system, with particularly high concentrations within several limbic and cortical regions. A number of co-localizations with other neuromessengers such as noradrenaline, somatostatin, and gamma-aminobutyric acid have been demonstrated. A large number of physiological and pharmacological actions of NPY have been suggested. Recent clinical data also suggest the involvement of NPY in several neuropsychiatric illnesses, particularly in depressive and anxiety states. This article gives a comprehensive review of central distribution of NPY and its receptors, co-localizations and interactions with other neuromessengers, genetic aspects, pharmacological and physiological actions, influence on neuroendocrine functions, and possible involvement in various neuropsychiatric illnesses.
Highly Enantioselective Conjugate Addition of Nitroalkanes to Alkylidenemalonates Using Efficient Phase-Transfer Catalysis of N-Spiro Chiral Ammonium Bromides (2004)

Highly enantioselective conjugate addition of nitroalkanes to alkylidenemalonates has been accomplished for the first time by the utilization of efficient phase-transfer catalysis of N-spiro C2-symmetric chiral quaternary ammonium bromide 1. For instance, simple mixing of nitropropane (2, R1 = Et), diisopropyl benzylidienemalonate (3, R2 = Ph), Cs2CO3 (1 equiv), and (S,S)-1 (1 mol %) in toluene at 0 degrees C for 2.5 h gave rise to the desired conjugate addition product 4 (R1 = Et, R2 = Ph) quantitatively (anti/syn = 86:14) with 97% ee (anti isomer). The applicability of this procedure has been demonstrated with other representative alkylidenemalonates and nitroalkanes. Since 4 can be readily transformed into the corresponding gamma-amino acid hydrochloride 5 without loss of diastereo- and enantioselectivity, the present method provides a new and practical access to various optically active gamma-amino acid derivatives.
A relevance feedback architecture for content-based multimedia information retrieval systems (1997)

Content-based multimedia information retrieval (MIR) has become one of the most active research areas in the past few years. Many retrieval approaches based on extracting and representing visual properties of multimedia data have been developed. While these approaches establish the viability of MIR based on visual features, techniques for incorporating human expertise directly during the query process to improve retrieval performance have not drawn enough attention. To address this limitation, this paper introduces a human-computer interaction based approach to MIR in which the user guides the system during retrieval using relevance feedback. Our experiments show that the retrieval performance improves significantly by incorporating humans in the retrieval process
Towards detection of orthologues in sequence databases. (1998)

We therefore developed a method that attempts to construct a reconciled tree from a gene tree of selected sequences and its corresponding phylogenetic tree of the species involved (species tree). An interface on the Web is developed to enable users to analyse the BLAST result. BLAST outputs are parsed and, for the selected sequences, multiple alignments are constructed either globally or for local regions. Bootstrapped trees are returned and compared with the expected species tree. In cases of discrepancies, gene duplications are assumed and a reconciled tree is computed. The reconciled tree shows probable orthologues and paralogues as predicted.
Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials (2002)

High intake of fish oil may lower BP, especially in older and hypertensive subjects. The antihypertensive effect of lower doses of fish oil (< 0.5 g/day) however, remains to be established.
Synthesis of low-peak-factor signals and binary sequences with low autocorrelation (Corresp.) (1970)

This correspondence considers the problem of how to adjust the phase angles of a periodic signal with a given power spectrum to minimize its peak-to-peak amplitude. This "peak-factor problem" arises in radar, sonar, and numerous other applications. However, in spite of the wide-spread interest it has evoked, the peak-factor problem has so far defied solution except in cases where the number of spectral components is small enough to permit an effectively exhaustive search of all phase angle combinations. In this correspondence, a formula for the phase angles is derived that yields generally low peak factors, often comparable to that of a sinusoidal signal of equal power. A formula is also derived for the case in which the phase angles are restricted to 0 and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\pi</tex> . The latter formula is applicable to the problem of constructing binary sequences of arbitrary length with Iow autocorrelation coefficients for nonzero shifts.
<title>New approach to imaging spectroscopy using diffractive optics</title> (1997)

Over the past several years, Pacific Advanced Technology (PAT) has developed several hyperspectral imagers using diffractive optics as the dispersive media. This new approach has been patented and demonstrated in numerous field tests. PAT has developed hyperspectral cameras in the visible, mid-wave IR and is currently under contrast to the Air Force to develop a dual band hyperspectral lens for simultaneous spectral imaging in both the mid-wave and long- wave IR. The development of these cameras over the years have been sponsored by internal research and development, contracts from the Air Force Phillips Lab., Air Force Wright Labs Armament Division, BMDO and by the Office of Naval Research. Numerous papers have been presented in the past describing the performance of these various hyperspectral cameras. The purpose of this paper is to describe the theory behind the image multi-spectral sensing (IMSS) used in these hyperspectral cameras. IMSS utilizes a very simple optical design that enables a robust and low cost hyper-spectral imaging instrument. The IMSS is a dispersive spectrometer using a single diffractive optical element for both imaging and dispersion. The lens is tuned for a single wavelength giving maximum diffraction efficiency at that wavelength and high efficiency throughout the spectral band-pass of the camera. The diffractive optics disperse the light along the optical axis as opposed to perpendicular to the axis in conventional dispersive spectrometers. A detector array is used as the sensing medium and the spectral images are rad out electronically. POst processing is used to reduce spectral cross talk and to spatially sharpen the spectral images.
Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage (1980)

A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4(+), OKT5(+), OKT6(+) "common" thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4(+) and OKT5(+) subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of 25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3(+)) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.
Control of Core—Shell Latex Morphology (1992)

Composite latex particles with core-and-shell structures made via staged emulsion polymerization have gained interest in recent years. Control of particle structures has been a challenge, particularly when the desired core polymer is more hydrophillic than the shell polymer. The structure of a PMMA/PS system can be controlled by altering the thermodynamic and kinetic variables. These variables include particle surface polarity, stage ratio, core particle size, the mode of monomer addition, and the degree of crosslinking.
Controlled Release of Insulin From Polymer Matrices: Control of Diabetes in Rats (1986)

The controlled release of insulin from ethylene-vinyl acetate copolymer matrices was demonstrated for over 100 days in vivo. The matrices were designed to release sodium insulin at near-constant rates. These 0.06-cm3 implants were coated completely with an impermeable layer of polymer. An aperture was drilled in the center of one face of the matrix, restricting release through this opening. These devices were implanted into 13 streptozocin-induced diabetic rats. Plasma glucose concentrations fell from 386 +/- 18 to 119 +/- 35 mg/dl (mean +/- SEM), and urinary glucose was eliminated. Thee parameters were controlled for up to 105 days by a single implant. Glycosylated hemoglobin concentrations measured 90 days after implantation were 3.86 +/- 0.11% for the polymer-treated rats, 3.10 +/- 0.18% for the normal controls, and 5.42 +/- 0.33% for the diabetic controls. The average weight gain of the treated rats was similar to that of the controls, whereas the diabetic controls failed to thrive. In addition, all of the diabetic controls developed cataracts 1 mo after diabetes induction, whereas none of the treated rats developed cataracts.
Anti-mRNA: specific inhibition of translation of single mRNA molecules. (1984)

A plasmid was constructed to generate RNA complementary to the beta-galactosidase mRNA under control of the phage lambda PL promoter. When this anti-mRNA was produced, synthesis of beta-galactosidase was dramatically inhibited (98%). Syntheses of galactoside permease and transacetylase, whose coding sequences are downstream of the beta-galactosidase coding region, are inhibited to a lesser degree, 80% and 55%, respectively. The generation of anti-mRNA that can be targeted to inhibit a single species of mRNA molecule within cells provides a potent mechanism by which specific transcripts can be translationally inactivated. This can be used to determine the function of proteins as well as to select cloned genes in a single rapid and convenient step.
Photometric Monitoring of Triton at Sommers-Bausch Observatory in 2000 (2001)

We undertook pilot program to develop an observing and analysis strategy that can be used to measure Triton's B and V albedos with 0.05 magnitude accuracy at moderate-to-small telescopes, under moderate-to-poor seeing conditions. Additional information is contained in the original extended abstract.
Light scattering by red blood cells in ektacytometry: Fraunhofer versus anomalous diffraction (1993)

In the present literature on ektacytometry, small angle light scattering by ellipsoidal red blood cells is commonly approximated by Fraunhofer diffraction. Calculations on a sphere with the size and relative refractive index of a red cell, however, show that Fraunhofer diffraction deviates significantly from exact Mie theory. Anomalous diffraction is found to be a much better approximation. The anomalous diffraction theory is used to calculate the intensity distribution of the light scattered by an ellipsoidally deformed red blood cell. The derived expression shows that the ellipticity of isointensity curves in forward scattered light are equal to the ellipticity of the red blood cell. The theoretical expression is fitted to the intensity patterns measured with an ektacytometer. For the small observation angles used in ektacytometry, the experimental results confirm the validity of the anomalous diffraction approach.
Immune Protection of Infants against Rotavirus Gastroenteritis by a Serotype 1 Reassortant of Bovine Rotavirus WC3 (1990)

The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general.
Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. (1997)

The epidermal growth factor receptor (EGFR) and its ligand transforming growth factor (TGF) alpha are hypothesized to form an autocrine growth loop in non-small cell lung cancer (NSCLC) and to play an important role in tumor formation and progression. We studied the association between overexpression of EGFR, TGF-alpha, or both, and overall survival of patients with resectable NSCLC. Overexpression, defined as >20% of tumor cells staining on immunohistochemistry, was examined in 96 tumor samples from consecutive patients having resection of previously untreated, well-staged NSCLC who were then followed prospectively (median follow-up, 20.7 months). The expression of three other ligands for EGFR (epidermal growth factor, cripto, and amphiregulin) was examined by Northern analysis to determine whether they might also contribute to a potential growth stimulatory loop. Overall, survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using the log-rank test. Overexpression of EGFR only was found in 32% (31 of 96), of TGF-alpha only in 10% (10 of 96), of both EGFR and TGF-alpha in 38% (37 of 96), and of neither in 19% (19 of 96) of tumors. EGFR and TGF-alpha overexpression was observed in all tumor stages and histological types but was most frequent in squamous cell carcinoma. By univariate and multivariate analyses, only tumor stage, not histology or overexpression of EGFR, TGF-alpha, or both, had a significant impact on overall survival. No expression of epidermal growth factor or cripto was observed at the total cellular RNA level of Northern analysis in tumor or benign lung, suggesting that in NSCLC these ligands may not participate in an autocrine growth stimulatory loop with EGFR. Differential overexpression of amphiregulin in malignant versus normal lung was observed, but this expression pattern did not have a prognostic impact. Thus, EGFR and TGF-alpha overexpression is frequent in early-stage NSCLC but is not associated with a survival difference. These findings suggest that this growth factor/receptor loop is more important for lung tumor formation than for tumor progression.