gebhart/patrepeval huggingface dataset:
Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy (2009)

Microarrays are frequently used to profile genome-wide copy number (CN) aberrations. While generally robust for detecting CN variants in germline DNA, the methods used to derive CN from signal intensity values have been suboptimal when applied to cancer genomes. The complexity of genomic aberrations in cancer makes it more difficult to discriminate between signal and noise, and measuring CN as a discrete variable does not account for tumor heterogeneity. Furthermore, standard normalization approaches detect CN changes relative to the overall DNA content, which is often not diploid in cancer. We propose an algorithm that uses the degree of allelic imbalance as well as probe intensity, with a correction for aneuploidy, for a quantitative CN assessment and scoring of allelic ratios. This algorithm results in a more precise definition of CN and allelic aberration in the cancer genome, which is essential for translational efforts focused on using these tools for molecular diagnostics and for the discovery of therapeutic targets.
A Stereoselective Formal Synthesis of Leucascandrolide A (2011)

A stereoselective formal synthesis of leucascandrolide A was accomplished through the tandem and organocatalytic oxa-Michael reactions, which were promoted by the gem-disubstituent effect, in conjunction with the dithiane coupling reaction.
A Novel Site on the Gα-protein That Recognizes Heptahelical Receptors (2001)

Specific domains of the G-protein alpha subunit have been shown to control coupling to heptahelical receptors. The extreme N and C termini and a region between alpha4 and alpha5 helices of the G-protein alpha subunit are known to determine selective interaction with the receptors. The metabotropic glutamate receptor 2 activated both mouse Galpha(15) and its human homologue Galpha(16), whereas metabotropic glutamate receptor 8 activated Galpha(15) only. The extreme C-terminal 20 amino acid residues are identical between the Galpha(15) and Galpha(16) and are therefore unlikely to be involved in coupling selectivity. Our data reveal two regions on Galpha(16) that inhibit its coupling to metabotropic glutamate receptor 8. On a three-dimensional model, both regions are found in a close proximity to the extreme C terminus of Galpha(16). One module comprises alpha4 helix, alpha4-beta6 loop (L9 Loop), beta6 sheet, and alpha5 helix. The other, not described previously, is located within the loop that links the N-terminal alpha helix to the beta1 strand of the Ras-like domain of the alpha subunit. Coupling of Galpha(16) protein to the metabotropic glutamate receptor 8 is partially modulated by each module alone, whereas both modules are needed to eliminate the coupling fully.
LaeA Control of Velvet Family Regulatory Proteins for Light-Dependent Development and Fungal Cell-Type Specificity (2010)

VeA is the founding member of the velvet superfamily of fungal regulatory proteins. This protein is involved in light response and coordinates sexual reproduction and secondary metabolism in Aspergillus nidulans. In the dark, VeA bridges VelB and LaeA to form the VelB-VeA-LaeA (velvet) complex. The VeA-like protein VelB is another developmental regulator, and LaeA has been known as global regulator of secondary metabolism. In this study, we show that VelB forms a second light-regulated developmental complex together with VosA, another member of the velvet family, which represses asexual development. LaeA plays a key role, not only in secondary metabolism, but also in directing formation of the VelB-VosA and VelB-VeA-LaeA complexes. LaeA controls VeA modification and protein levels and possesses additional developmental functions. The laeA null mutant results in constitutive sexual differentiation, indicating that LaeA plays a pivotal role in inhibiting sexual development in response to light. Moreover, the absence of LaeA results in the formation of significantly smaller fruiting bodies. This is due to the lack of a specific globose cell type (Hülle cells), which nurse the young fruiting body during development. This suggests that LaeA controls Hülle cells. In summary, LaeA plays a dynamic role in fungal morphological and chemical development, and it controls expression, interactions, and modification of the velvet regulators.
Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis (1995)

To evaluate the value of C-reactive protein and leukocyte indices in the workup of patients suspected of having infection in a neonatal intensive care setting, a literature search was conducted in all languages using MEDLINE (1966 to May, 1994), EMBASE (1988 to May, 1994), bibliographic lists of primary and review articles and personal files. Citations identified as potentially relevant were reviewed by two independent investigators; only studies meeting preset criteria for population, diagnostic test and data presentation were included. Two observers independently assessed studies using explicit methodologic criteria. All data from the articles were extracted by one observer, whereas the second reviewer checked these data for accuracy. Four of the selected studies dealt with leukocyte count and ratios. The chi square test for homogeneity of proportions revealed significant heterogeneity across studies (P = 0.014 for the ratios; P < 0.001 for white blood cell count), suggesting that test properties varied widely across studies. Fifteen of the selected studies evaluated C-reactive protein; of these six were qualitative using a latex agglutination method. Among these studies the chi square test for homogeneity of proportions was highly significant (P < 0.01), reflecting the great heterogeneity across studies. Among the nine studies that evaluated five different quantitative methods heterogeneity was again present (P < 0.001). Because of the striking heterogeneity among the studies evaluated, pooling to give a summary point estimate of the sensitivity and specificity of the various studies was not possible and the results are reported as ranges.(ABSTRACT TRUNCATED AT 250 WORDS)
The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability (2012)

The functional consequences of altering the conformational flexibility in the C-terminal tail of H4 are severe. Interestingly, despite the detrimental effects of the histone H4 G94P mutant on viability, nucleosome formation was not markedly affected in vivo. However, histone octamer stability and nucleosome stability as well as nucleosome sliding ability were altered in vitro. These studies highlight an important role for correct interactions of the histone H4 C-terminal tail within the histone octamer and suggest that maintenance of a stable histone octamer in vivo is an essential feature of chromatin dynamics.
Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11+0 to 13+6 weeks of gestation (2008)

Birth weight is predetermined by placental development during the first trimester of pregnancy.
Simplified approach for quantitative digital holographic phase contrast imaging of living cells (2011)

Many interferometry-based quantitative phase contrast imaging techniques require a separately generated coherent reference wave. This results in a low phase stability and the demand for a precise adjustment of the intensity ratio between object and reference wave. To overcome these problems, the performance of a Michelson interferometer approach for digital holographic microscopy was analyzed that avoids a separately generated reference wave by superposition of different image areas. It is shown that this simplified arrangement yields improved phase stability. Furthermore, results from time-lapse investigations on living pancreas tumor cells demonstrate the capability of the method for reliable quantitative phase contrast imaging.
Peptide Mimetic HIV Protease Inhibitors Are Ligands for the Orphan Receptor SXR (2001)

The orphan nuclear receptor SXR coordinately regulates drug clearance in response to a wide variety of xenobiotic compounds. This signaling system protects the body from exposure to toxic compounds; however, it can also pose a severe barrier to drug therapy. We now demonstrate that the human immunodeficiency virus (HIV) protease inhibitor ritonavir binds SXR and activates its target genes. This represents an example of a commonly used therapeutic agent that effectively activates SXR. We also show that other protease inhibitors are weaker (saquinavir) or unable to activate SXR (nelfinavir, indinavir) thus defining analogs that fail to induce SXR-regulated clearance pathways. Interestingly, HIV protease inhibitors are distinct from previously known SXR ligands in that they are peptide mimetic compounds. This expands the ligand specificity of SXR to include this unique chemical class whose pharmaceutical significance is expanding. Finally, we show that SXR ligands activate expression of multiple resistance protein 2, a critical regulator of bile flow and biliary drug excretion. These findings have important implications for the role of SXR in regulating drug clearance and hepatic disorders associated with impaired bile flow.
High quality GaN grown on Si(111) by gas source molecular beam epitaxy with ammonia (1999)

We describe the growth of hexagonal GaN on Si(111) by gas source molecular beam epitaxy with ammonia. The initial deposition of Al, at 1130–1190 K, resulted in a very rapid transition to a two-dimensional growth mode of AlN. The rapid transition is essential for the subsequent growth of high quality GaN and AlGaN. This procedure also resulted in complete elimination of cracking in thick (&amp;gt;2 μm) GaN layers. For layers thicker than 1.5 μm, the full width at half maximum of the (0002) GaN diffraction peak was less than 14 arc sec. We show that a short period superlattice of AlGaN/GaN grown on the AlN buffer can be used to block defects propagating through GaN, resulting in good crystal and luminescence quality. At room temperature, the linewidth of the GaN exciton recombination peak was less than 40 meV, typical of the best samples grown on sapphire.
Reduction of Blood Cholesterol in Man (1953)

Dietary cholesterol contributes to the development and maintenance of hypercholesteremia in man. Intake of sitosterol prevents cholesterol resorption. This results in lowering of blood cholesterols to a basal endogenous level. Upon cessation of sitosterol intake hemocholesterols return to the original level. Excess supply of plant sterol was required in clinical experiments because the material used contained but 75 to 80 per cent of sitosterol and because of the large amount of endogenous cholesterol which has to be inactivated by the sitosterol, besides exogenous cholesterol.
Mouse hematopoietic stem cells and the interaction ofc‐kirreceptor and steel factor (1991)

Hematopoietic stem cells (HSCs) are distinguished from other hematopoietic progenitors in bone marrow by their unique ability to undergo multilineage differentiation and self-renewal. Two mouse mutations, dominant spotting (W) and steel (Sl), have pleiotropic effects on hematopoiesis, gametogenesis, and melanoblast development. These two mutations have been shown to be intrinsic (W) and microenvironmental (Sl) defects. Recently, molecular studies revealed that the W and Sl loci encode the c-kit receptor and steel factor (SLF), respectively. The c-kit receptor is expressed on HSCs and hematopoietic progenitors, while SLF is produced by stromal cells. SLF acts on hematopoietic progenitors synergistically with other growth factors. Here we review the effect of these mutations on mouse hematopoiesis, and show that SLF acts on HSCs and other myeloerythroid progenitors, but that it, in our hands, does not play a critical role in HSC generation or self-renewal. Rather, SLF is the most potent co-mitogen (with IL-1, IL-3, IL-6, G-CSF, GM-CSF, or M-CSF) found that acts on these cells, but the effect of such treatments is the rather specific and massive expansion of myeloerythropoiesis, not lymphopoiesis, and perhaps at the expense of HSC self-renewal.
Visual space perception and visually directed action. (1992)

The results of two types of experiments are reported. In 1 type, Ss matched depth intervals on the ground plane that appeared equal to frontal intervals at the same distance. The depth intervals had to be made considerably larger than the frontal intervals to appear equal in length, with this physical inequality of equal-appearing intervals increasing with egocentric distance of the intervals (4 m-12 m). In the other type of experiment, Ss viewed targets lying on the ground plane and then, with eyes closed, attempted either to walk directly to their locations or to point continuously toward them while walking along paths that passed off to the side. Performance was quite accurate in both motoric tasks, indicating that the distortion in the mapping from physical to visual space evident in the visual matching task does not manifest itself in the visually open-loop motoric tasks.
Magnetic Nanocarriers of Doxorubicin Coated with Poly(ethylene glycol) and Folic Acid: Relation between Coating Structure, Surface Properties, Colloidal Stability, and Cancer Cell Targeting (2011)

We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure-activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics.
High resolution NMR for screening ligand/protein binding. (1999)

High resolution NMR spectroscopy has provided a versatile tool for assessing ligand/receptor interactions. NMR-based methods are currently being investigated which may prove valuable for compound screening. These techniques include the use of chemical shift perturbations, the monitoring of translational diffusion and the observation of NOEs. Novel experiments like TROSY and NOE pumping will play significant roles in looking at proteins larger than 30 kDa. New probe technology such as the Cryoprobe could have a significant impact on NMR-based screening for drug discovery by lowering the necessary amount of (15)N-labled protein.
Plasma levels in sepsis patients of annexin A1, lipoxin A4, macrophage inflammatory protein-3a, and neutrophil gelatinase-associated lipocalin (2013)

AnxA1 and LXA4 plasma levels were found to be decreased in sepsis patients, whereas the levels of MIP-3a and NGAL were found to be elevated. This warrants further study in order to determine the clinical implications of these changes.
Incidence and Severity of Huanglongbing and Candidatus Liberibacter asiaticus Titer among Field-infected Citrus Cultivars (2011)

Incidence and severity of Huanglongbing (HLB) disease were assessed in Apr. 2010 among eight citrus cultivars representing diverse scion types growing in commercial groves in Florida's Indian River region, an area with a high incidence of HLB. In each grove, 20 trees of each cultivar were rated for visual HLB symptoms and leaves were collected for quantitative polymerase chain reaction quantification of Candidatus Liberibacter asiaticus (CLas), the presumptive causal agent of HLB. There was a strong correlation between HLB rating and CLas titer (titer represented by Ct, r 2 = 0.37 and 0.40, for whole tree and leaf sample, respectively, both with P &lt; 0.0001) across all cultivars and groves. Although incidence and severity of HLB varied considerably among the groves, scion-specific differences were apparent, even when analyses excluded potentially confounding grove effects. ‘Temple’ tangor showed the most consistently low incidence of HLB symptoms and CLas titer; in contrast, ‘Murcott’ tangor and ‘Minneola’ tangelo had the highest incidence of HLB symptoms and highest CLas titer. These results suggest useful resistance to HLB with reduced symptoms and reduced CLas titer may be found in conventional scion cultivars and further work is needed to assess this potential and its commercial value.
Southern Sudan Before the 'Referendum for Freedom' (2010)

Southern Sudan’s historic referendum on whether to stay in or secede from a united Sudan is rapidly approaching. The political tide is flowing toward an independent country but the politics of Sudan’s North-South political transition remain beset with challenges. Southern Sudan is on the threshold of becoming an independent state, according to widespread popular Southern sentiment and the terms of Sudan’s North-South peace agreement that allow the right to self-determination through a referendum. The sense of historic inevitability about this outcome, which would be achieved through the ‘referendum for freedom’, is set against an intensely political atmosphere. There are myriad risks of this vision being derailed, including problems derived from the second referendum on the future status of the special administrative area of Abyei. The outstanding challenge today lies in managing the probable break-up of Sudan in such a way as to best ensure peace. Providing war does no return, any such achievement, in itself considerable, will be followed by the formidable challenges of sustaining peace.
685. Efficient Targeted Gene Modification in Primary Human Hematopoietic Cells Using Co-Delivery of Nuclease mRNA and AAV Donors (2015)

Current clinical HIV treatment strategies applying gene-editing technologies to disrupt the HIV co-receptor CCR5 via nuclease delivery are limited by inefficient bi-allelic disruption and the lack of a combinatorial approach to control HIV infection. The ability to target additional factors conferring HIV resistance to the CCR5 locus with efficient bi-allelic disruption has the potential to translate to improved clinical outcomes. Here we demonstrate a novel method in which RNA-based nuclease expression is paired with AAV-mediated delivery of a homologous gene-targeting donor template to achieve highly efficient targeted recombination in primary human T-cells. This method consistently achieves an average of 60% rates of homology directed recombination into the CCR5 locus in T-cells (>20 experiments with multiple donors); with up to 90% of the gene-modified population exhibiting bi-allelic modification. T-cells modified with this protocol maintain a diverse repertoire and engraft in immune deficient, NOD/SCID/gc-/- (NSG) mice as efficiently as unmodified control T-cells. Using this method, we have integrated chimeric antigen receptors (CARs) into the CCR5 locus; and show that the resulting “targeted CAR” or tCAR T-cells exhibit anti-tumor activities indistinguishable from those generated using lentiviral random integration. Alternatively, we introduced the C46 HIV fusion inhibitor by targeted recombination generating T cell populations with very high-rates of bi-allelic CCR5 disruption paired with protection from HIV with CXCR4 co-receptor tropism. Next, as proof of principle, we utilized the CCR5 site as a ‘safe harbor’ locus for targeted gene addition of the human Wiskott-Aldrich syndrome (WAS) gene. Finally, this novel protocol was also successfully applied to adult human mobilized CD34+ cells, resulting in 10-20% homologous gene targeting, the first such report in adult human CD34+ cells at the CCR5 locus. Our results demonstrate that high-efficiency targeted integration is feasible in primary human cells, and highlight the potential of gene editing technologies to engineer CAR T-cells or other T cell products with myriad novel functional properties.
New Synthetic Routes to 3-, 5-, and 6-Aryl-2-chloropyridines (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Synthetic Routes to 3-, 5-, and 6-Aryl-2-chloropyridinesRobert Church, Ronald Trust, J. Donald Albright, and Dennis PowellCite this: J. Org. Chem. 1995, 60, 12, 3750–3758Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/jo00117a029https://doi.org/10.1021/jo00117a029research-articleACS PublicationsRequest reuse permissionsArticle Views1435Altmetric-Citations39LEARN 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