gebhart/patrepeval huggingface dataset:
The Emerging Pharmacogenomics of the β‐Adrenergic Receptors (2004)

Beta-adrenergic signaling mechanisms are of central importance to cardiovascular health and disease. Modulation of these pathways represents an important pharmacologic approach to the treatment of heart failure and hypertension. Advances in molecular genetics have identified genetic polymorphisms in the human beta-adrenergic receptor genes; some of this variation predicts changes in protein sequence/structure, and potentially changes in function, of the b-adrenergic receptors. This article reviews the current state of knowledge and understanding of the genetic variation present in the three human beta-adrenergic receptor genes. Already, variation in these genes has been associated with observed differences in several cardiovascular phenotypes. This work has led to the demonstration of functional differences in activity between receptors with certain known polymorphisms and "wild-type" receptors. An understanding of these polymorphisms is key to the development of studies of how differences in drug response/effects may be mediated by these polymorphisms. Such studies are anticipated to provide a foundation for the development of novel pharmacologic approaches where selection of and dosing of cardiovascular therapy is tailored to individuals on the basis of each patient's specific genetic makeup.
Using surface-bound rubidium ions for protein phasing (2001)

Rubidium is a monovalent metal that can be used as a counterion in protein solutions. X-ray anomalous scattering from rubidium ions bound to the protein surface was used for phasing of the crystal structure of the hsp60 apical domain from Thermus thermophilus. Multiple-wavelength anomalous dispersion (MAD) data were collected from a crystal obtained from a solution containing 0.2 M rubidium salt. One molecule of protein (147 amino acids) binds one well ordered and one poorly ordered Rb atom. Phases calculated with the program SHARP were sufficient for automatic tracing and side-chain assignment using the program ARP/wARP. The data show that bound rubidium ions can be used to determine protein structures and to study the interaction of monovalent metal ions with proteins and other macromolecules.
The efficacy of a lysine-based dendritic hydrogel does not differ from those of commercially available tissue sealants and adhesives: an ex vivo study (2015)

The efficacy of the PEG-LysNH2 was significantly superior to conventional injury repair methods (sutures) and did not differ from those of commercially available products when sealing small incisions.
Abstract 13869: Statin Therapy Improves Fractional Catabolic Rate of LDL without Affecting Impaired VLDL and VLDL Remnant Catabolism in Homozygous FH Patient Due to PCSK9 Gene Mutation: Evidence from Kinetic Study with Stable Isotope (2012)

Background: Statin decreases plasma low-density lipoprotein (LDL) cholesterol through activation of sterol regulatory element binding protein 2 (SREBP2) and ensuing induction of LDL receptor. SREBP...
Characterization and In Vivo Testing of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells (2011)

Mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of tissues through homing to injured areas, especially to hypoxic, apoptotic, or inflamed areas and releasing factors that hasten endogenous repair. In some cases genetic engineering of the MSC is desired, since they are excellent delivery vehicles. We have derived MSCs from the human embryonic stem cell (hESC) line H9 (H9-MSCs). They expressed CD105, CD90, CD73, and CD146, and lacked expression of CD45, CD34, CD14, CD31, and HLA-DR, the hESC pluripotency markers SSEA-4 and Tra-1-81, and the hESC early differentiation marker SSEA-1. Marrow-derived MSCs showed a similar phenotype. H9-MSCs did not form teratoma in our initial studies, whereas the parent H9 line did so robustly. H9-MSCs differentiated into bone, cartilage, and adipocytes in vitro, and displayed increased migration under hypoxic conditions. Finally, using a hindlimb ischemia model, H9-MSCs were shown to home to the hypoxic muscle, but not the contralateral limb, by 48 h after IV injection. In summary, we have defined methods for differentiation of hESCs into MSCs and have defined their characteristics and in vivo migratory properties.
Cloning and characterization of a novel human gene related to vascular endothelial growth factor. (1996)

This paper describes the cloning and characterization of a new member of the vascular endothelial growth factor (VEGF) gene family, which we have designated VRF for VEGF-related-factor. Sequencing of cDNAs from a human fetal brain library and RT-PCR products from normal and tumor tissue cDNA pools indicate two alternatively spliced messages with open reading frames of 621 and 564 bp, respectively. The predicted proteins differ at their carboxyl ends resulting from a shift in the open reading frame. Both isoforms show strong homology to VEGF at their amino termini, but only the shorter isoform maintains homology to VEGF at its carboxyl terminus and conserves all 16 cysteine residues of VEGF165. Similarity comparisons of this isoform revealed overall protein identity of 48% and conservative substitution of 69% with VEGF189. VRF is predicted to contain a signal peptide, suggesting that it may be a secreted factor. The VRF gene maps to the D11S750 locus at chromosome band 11q13, and the protein coding region, spanning approximately 5 kb, is comprised of 8 exons that range in size from 36 to 431 bp. Exons 6 and 7 are contiguous and the two isoforms of VRF arise through alternate splicing of exon 6. VRF appears to be ubiquitously expressed as two transcripts of 2.0 and 5.5 kb; the level of expression is similar among normal and malignant tissues.
Pancreatic Cyst Disease (2016)

The management of pancreatic cysts requires risk stratification for malignant potential based on the presence or absence of symptoms and high-risk features on cross-sectional imaging. Because pancreatic cysts are becoming more frequently diagnosed, clinicians should have a systematic approach for establishing a diagnosis and determining which patients require treatment.
Fundamental relations between the LMS algorithm and the DFT (1987)

The digital Fourier transform (DFT) and the adaptive least mean square (LMS) algorithm have existed for some time. This paper establishes a connection between them. The result is the "LMS spectrum analyzer," a new means for the calculation of the DFT. The method uses a set of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> periodic complex phasors whose frequencies are equally spaced from dc to the sampling frequency. The phasors are weighted and then are summed to generate a reconstructed signal. Weights are adapted to realize a best least squares fit between this reconstructed signal and the input signal whose spectrum is to be estimated. The magnitude squares of the weights correspond to the power spectrum. For a proper choice of adaptation speed, the LMS spectrum analyzer will provide an exact <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> -sample DFT. New DFT outputs will be available in steady flow after the introduction of each new data sample.
Microlithography by Using Neutral Metastable Atoms and Self-Assembled Monolayers (1995)

Lithography can be performed with beams of neutral atoms in metastable excited states to pattern self-assembled monolayers (SAMs) of alkanethiolates on gold. An estimated exposure of a SAM of dodecanethiolate (DDT) to 15 to 20 metastable argon atoms per DDT molecule damaged the SAM sufficiently to allow penetration of an aqueous solution of ferricyanide to the surface of the gold. This solution etched the gold and transformed the patterns in the SAMs into structures of gold; these structures had edge resolution of less than 100 nanometers. Regions of SAMs as large as 2 square centimeters were patterned by exposure to a beam of metastable argon atoms. These observations suggest that this system may be useful in new forms of micro- and nanolithography.
Systematic review of the psychometric properties, interpretability and feasibility of self-report pain intensity measures for use in clinical trials in children and adolescents (2006)

The aim of this study was to systematically review the psychometric properties, interpretability and feasibility of self-report pain intensity measures for children and adolescents for use in clinical trials evaluating pain treatments. Databases were searched for self-report measures of single-item ratings of pain intensity for children aged 3-18 years. A total of 34 single-item self-report measures were found. The measures' psychometric properties, interpretability and feasibility, were evaluated independently by two investigators according to a set of psychometric criteria. Six single-item measures met the a priori criteria and were included in the final analysis. While these six scales were determined as psychometrically sound and show evidence of responsivity, they had varying degrees of interpretability and feasibility. No single scale was found to be optimal for use with all types of pain or across the developmental age span. Specific recommendations regarding the most psychometrically sound and feasible measures based on age/developmental level and type of pain are discussed. Future research is needed to strengthen the measurement of pain in clinical trials with children.
Developing Virtual CD-ROM Collections: The Voyager Company Publications (2012)

Over the past 20 years, many thousands of CD-ROM titles were published; many of these have lasting cultural significance, yet present a difficult challenge for libraries due to obsolescence of the supporting software and hardware, and the consequent decline in the technical knowledge required to support them. The current trend appears to be one of abandonment – for example, the Indiana University Libraries no longer maintain machines capable of accessing early CD-ROM titles.In previous work, we proposed an access model based upon networked ‘virtual collections’ of CD-ROMs which can enable consortia of libraries to pool the technical expertise necessary to provide continued access to such materials for a geographically sparse base of patrons, who may have limited technical knowledge.In this paper, we extend this idea to CD-ROMs designed to operate on ‘classic’ Macintosh systems with an extensive case study – the catalog of the Voyager Company publications, which was the first major innovator in interactive CD-ROMs. The work described includes emulator extensions to support obsolete CD formats and to enable networked access to the virtual collection.
Overview of radiation tolerant unlimited write cycle non-volatile memory (2002)

We describe X2000, a new concept in JPL's avionics development. Further, a need for non-volatile radiation hardened memory is brought forth. A 1 Megabit/in/sup 2/ memory density specification: 10 year lifetime, 1-MegaRad total ionizing radiation dose survivability, and >10/sup 13/ write cycles is drawn for such NASA's missions as Europa Orbiter as the first delivery for X2000. We present an overview related with the Government development effort for three such new memory technologies.
[Role of initial immunologic status of patients with congenital heart defects in the development of postoperative infectious complications]. (1990)

Before surgical correction of the defect, the immune status was examined in 65 patients with congenital heart disease who developed postoperative infectious complications. The patients showed significant changes in peripheral blood levels of various lymphocyte populations (E-, EAC-ROC) and immunoglobulins M, G, A. It was concluded that the occurrence of infections complications was related to the initial immunological status of patients with congenital heart disease.
RANSAC-based DARCES: a new approach to fast automatic registration of partially overlapping range images (1999)

In this paper, we propose a new method, the RANSAC-based DARCES method (data-aligned rigidity-constrained exhaustive search based on random sample consensus), which can solve the partially overlapping 3D registration problem without any initial estimation. For the noiseless case, the basic algorithm of our method can guarantee that the solution it finds is the true one, and its time complexity can be shown to be relatively low. An extra characteristic is that our method can be used even for the case that there are no local features in the 3D data sets.
A cell line that supports the growth of a defective early region 4 deletion mutant of human adenovirus type 2. (1983)

Cell lines that produce viral gene products and that can support the growth of viral mutants lacking those products have been valuable in the genetic analysis of the transforming regions of several animal viruses. To extend the advantages of such complementing cell systems to regions of the adenoviral genome not directly involved in transformation, we have constructed a cell line that will support the growth of a defective adenoviral deletion mutant, H2dl808, that lacks most of early region 4 (E4). The right-hand terminal adenovirus 5 EcoRI restriction fragment, which contains all of E4, was first inserted into the vector pSV2gpt, and the recombinant plasmid was introduced into Vero cells by calcium phosphate precipitation. Clones containing the hybrid plasmid were selected by their resistance to mycophenolic acid. Five mycophenolic acid-resistant clones were then tested for the ability to support the growth of H2dl808. One of the five lines, W162, permits plaque formation by H2dl808 at an efficiency that is greater than 10(6)-fold higher than that of the parental Vero cells and allows the production of high-titer, helper-free H2dl808 stocks. Thus, W162 cells are permissive for at least one defective E4 mutant. The line carries, as expected, an intact E4, detected by hybridization. Using an H2dl808 lysate produced on W162 cells, we have accurately mapped the 808 deletion. It extends from between BclI and SmaI sites at positions 91.4 and 92.0, respectively, to just beyond a HindIII site at position 97.2 and, therefore, falls entirely within E4. H2dl808 and W162 should be of value in determining the physiological role of E4 in adenoviral infection.
Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. (1994)

Human apolipoprotein (apo) E4 (arginine at residue 112) preferentially associates with very low density lipoproteins (VLDL), and apoE3 (cysteine at 112) associates with high density lipoproteins. It has been postulated that the amino-terminal domain, which contains residue 112, influences the lipoprotein preference by interacting with the carboxyl-terminal domain, which contains the lipid-binding region. To delineate the region in the carboxyl-terminal domain mediating lipoprotein binding and involved in isoform preference, we produced truncated apoE3 and apoE4 variants (terminating at residues 251, 260, 266, or 272) in Escherichia coli and assessed them for lipoprotein association. This analysis suggested that residues 260-272 contain important determinants for complete lipoprotein association and isoform preferences. To determine whether positive charge at residue 112 was an absolute requirement for the apoE4 VLDL preference, we compared the distributions of rabbit apoE (equivalent to apoE3, with cysteine at a position corresponding to 112), canine apoE (arginine at the corresponding site), and cysteamine-treated rabbit apoE (cysteine converted to a positively charged residue). Surprisingly, all distributed like human apoE3, suggesting that positive charge at a position corresponding to 112 was not directly responsible for the isoform preference and that other residues in the amino-terminal domain were involved. To determine which residues were involved, the structure of the apoE4 22-kDa fragment (the amino-terminal two-thirds of the molecule) was determined to 2.5 A by x-ray crystallography. Compared with the known four-helix bundle structure of apoE3, the only significant differences in the apoE4 structure were that glutamic acid 109 formed a salt bridge with arginine 112 and that the arginine 61 side chain was displaced to a new position. Site-directed mutagenesis of glutamic acid 109 in apoE3 and arginine 61 in apoE4 demonstrated that the position of the arginine 61 side chain in apoE4 was critical in determining apoE4 lipoprotein distribution, suggesting that arginine 61 interacted with the carboxyl-terminal domain to direct binding to VLDL.
Contribution of Cutinase Serine 42 Side Chain to the Stabilization of the Oxyanion Transition State, (1996)

Cutinase from the fungus Fusarium solani pisi is a lipolytic enzyme able to hydrolyze both aggregated and soluble substrates. It therefore provides a powerful tool for probing the mechanisms underlying lipid hydrolysis. Lipolytic enzymes have a catalytic machinery similar to those present in serine proteinases. It is characterized by the triad Ser, His, and Asp (Glu) residues, by an oxyanion binding site that stabilizes the transition state via hydrogen bonds with two main chain amide groups, and possibly by other determinants. It has been suggested on the basis of a covalently bond inhibitor that the cutinase oxyanion hole may consist not only of two main chain amide groups but also of the Ser42 O gamma side chain. Among the esterases and the serine and the cysteine proteases, only Streptomyces scabies esterase, subtilisin, and papain, respectively, have a side chain residue which is involved in the oxyanion hole formation. The position of the cutinase Ser42 side chain is structurally conserved in Rhizomucor miehei lipase with Ser82 O gamma, in Rhizopus delemar lipase with Thr83 O gamma 1, and in Candida antartica B lipase with Thr40 O gamma 1. To evaluate the increase in the tetrahedral intermediate stability provided by Ser42 O gamma, we mutated Ser42 into Ala. Furthermore, since the proper orientation of Ser42 O gamma is directed by Asn84, we mutated Asn84 into Ala, Leu, Asp, and Trp, respectively, to investigate the contribution of this indirect interaction to the stabilization of the oxyanion hole. The S42A mutation resulted in a drastic decrease in the activity (450-fold) without significantly perturbing the three-dimensional structure. The N84A and N84L mutations had milder kinetic effects and did not disrupt the structure of the active site, whereas the N84W and N84D mutations abolished the enzymatic activity due to drastic steric and electrostatic effects, respectively.
ICI 180080, a novel selective thromboxane receptor antagonist: synthesis and relative activity (1986)

The preparation of a novel potent thromboxane receptor antagonist ICI 180080, 5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid, is described together with its methyl ether and methyl ester. Thromboxane antagonist pA2 data against U 46619 is presented for rabbit thoracic aorta in-vitro (ICI 180080, pA2 = 7.5). The relative antagonist pA2 values obtained are discussed in terms of the chemical structure of the molecules. The potent activity of ICI 180080 is attributed to a specific orientation of the phenolic oxygen, due to an intramolecular hydrogen bond.
Participation and indigenous peoples (1995)

The characteristics of indigenous groups make participatory approaches especially critical to safeguarding their interests in the development process. Such approaches, recognizing the right of indigenous peoples to participate actively in planning their own futures, are supported by major donors and international organizations, including the World Bank, but are difficult to implement. They call for changes in attitudes, policies and legislation to address the key issues: recognizing rights to land and natural resources; ensuring culturally appropriate procedures for consultation and communication; and building on the strengths of traditional lifestyles and institutions. The authors address the great need to focus on participation and the key elements in a participatory approach which are defined in the following: 1) the legal and policy framework; 2) rights to land and natural resources; 3) culturally appropriate communication; 4) building on traditional strengths; 4) direct funding; and 5) the role of the Bank.
Biosynthesis of pimeloyl-CoA, a biotin precursor in Escherichia coli, follows a modified fatty acid synthesis pathway: 13C-labeling studies (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of pimeloyl-CoA, a biotin precursor in Escherichia coli, follows a modified fatty acid synthesis pathway: 13C-labeling studiesIndrajit Sanyal, Sheng-Lian Lee, and Dennis H. FlintCite this: J. Am. Chem. Soc. 1994, 116, 6, 2637–2638Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ja00085a061https://doi.org/10.1021/ja00085a061research-articleACS PublicationsRequest reuse permissionsArticle Views481Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
The induction of ovulation using pulsatile luteinizing hormone releasing hormone in clinical practice (1985)

Until recently induction of ovulation in patients resistant to clomiphene has required gonadotrophin therapy. This has entailed intensive biochemical monitoring to ascertain the correct dosage and to avoid ovarian hyperstimulation. Described here is a simple, safe effective method of ovulation induction, using pulsed luteinizing hormone releasing hormone and requiring only minimal, readily available monitoring methods.
Physical Activity‐Associated Gene Expression Signature in Nonhuman Primate Motor Cortex (2011)

It has been established that weight gain and weight loss are heavily influenced by activity level. In this study, we hypothesized that the motor cortex exhibits a distinct physical activity-associated gene expression profile, which may underlie changes in weight associated with movement. Using DNA microarrays we profiled gene expression in the motor cortex of a group of 14 female rhesus monkeys (Macaca mulatta) with a wide range of stable physical activity levels. We found that neuronal growth factor signaling and nutrient sensing transcripts in the brain were highly correlated with physical activity. A follow-up of AKT3 expression changes (a gene at the apex of neuronal survival and nutrient sensing) revealed increased protein levels of total AKT, phosphorylated AKT, and forkhead box O3 (FOXO3), one of AKT's main downstream effectors. In addition, we successfully validated three other genes via quantitative polymerase chain reaction (qPCR) (cereblon (CRBN), origin recognition complex subunit 4-like, and pyruvate dehydrogenase 4 (PDK4)). We conclude that these genes are important in the physical activity-associated pathway in the motor cortex, and may be critical for physical activity-associated changes in body weight and neuroprotection.