gebhart/patrepeval huggingface dataset:
High-level β-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells (2004)

Transplantation of genetically corrected autologous hematopoietic stem cells is an attractive approach for the cure of sickle-cell disease and beta-thalassemia. Here, we infected human cord blood cells with a self-inactivating lentiviral vector encoding an anti-sickling betaA-T87Q-globin transgene and analyzed the transduced progeny produced over a 6-month period after transplantation of the infected cells directly into sublethally irradiated NOD/LtSz-scid/scid mice. Approximately half of the human erythroid and myeloid progenitors regenerated in the mice containing the transgene, and erythroid cells derived in vitro from these in vivo-regenerated cells produced high levels of betaA-T87Q-globin protein. Linker-mediated PCR analysis identified multiple transgene-positive clones in all mice analyzed with 2.1 +/- 0.1 integrated proviral copies per cell. Genomic sequencing of vector-containing fragments showed that 86% of the proviral inserts had occurred within genes, including several genes implicated in human leukemia. These findings indicate effective transduction of very primitive human cord blood cells with a candidate therapeutic lentiviral vector resulting in the long-term and robust, erythroid-specific production of therapeutically relevant levels of beta-globin protein. However, the frequency of proviral integration within genes that regulate hematopoiesis points to a need for additional safety modifications.
In vivo notch reactivation in differentiating cochlear hair cells induces sox2 and prox1 expression but does not disrupt hair cell maturation (2012)

Our results suggest that the developmental program of cochlear differentiating HCs is refractory to Notch reactivation and that Notch is an upstream regulator of Sox2 and Prox1 in cochlear development. In addition, our results support that Sox2 and Prox1 should not be the main blockers for terminal differentiation of HCs newly regenerated from postnatal cochlear SCs that still maintain Sox2 and Prox1 expression.
Biomimetic Nanowire Coatings for Next Generation Adhesive Drug Delivery Systems (2009)

Without bioadhesive delivery devices, complex compounds are typically degraded or cleared from mucosal tissues by the mucous layer.While some chemically modified, microstructured surfaces have been studied in aqueous environments,adhesion due to geometry alone has not been investigated. Silicon nanowire-coated beads show significantly better adhesion than those with targeting agents under shear, and can increase the lift-off force 100-fold. We have shown that nanowire coatings, paired with epithelial physiology, significantly increase adhesion in mucosal conditions.
Guided self-assembly of Au nanocluster arrays electronically coupled to semiconductor device layers (2000)

We report the controlled deposition of close-packed monolayer arrays of ∼5-nm-diam Au clusters within patterned regions on GaAs device layers, thus demonstrating guided self-assembly on a substrate which can provide interesting semiconductor device characteristics. Uniform nanometer scale ordering of the clusters is achieved by a chemical self-assembly process, while micron scale patterning is provided by a soft lithographic technique. Scanning tunneling microscope imaging and current–voltage spectroscopy indicate the Au nanoclusters are strongly coupled electronically into the underlying semiconductor substrate while exhibiting only weak electronic coupling in the lateral plane.
Human ADP-ribosylation Factor-activated Phosphatidylcholine-specific Phospholipase D Defines a New and Highly Conserved Gene Family (1995)

Activation of phosphatidylcholine-specific phospholipase D (PLD) has been implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. We report here the identification of the first human PLD cDNA, which defines a new and highly conserved gene family. Characterization of recombinant human PLD1 reveals that it is membrane-associated, selective for phosphatidylcholine, stimulated by phosphatidylinositol 4,5-bisphosphate, activated by the monomeric G-protein ADP-ribosylation factor-1, and inhibited by oleate. PLD1 likely encodes the gene product responsible for the most widely studied endogenous PLD activity.
Feasibility of Relationships between Tablet Physical Quality Parameters and Mechanical Properties of Dry Powder Formulation (2013)

Compaction is a key unit operation in many particulate industries. Accordingly, this study addresses a research question of considerable importance concerning compact (or tablet) formation, i.e., the feasibility of using mechanical properties of powder formulations in low to medium pressure regime (<10 MPa) as predictors of tablet (i.e., compact) quality parameters. For the feasibility study, mechanical properties, i.e., elastic and elastoplastic, of dry powder formulations at three binder contents were determined using a flexible boundary cubical triaxial tester in low to medium pressure regime. For the same formulations, tablets formed at two pressing pressures (70 and 90 MPa) were tested for four physical quality parameters, i.e., diametral strength, axial penetration strength, indentation hardness, and friability. Some of the key findings were: bulk modulus increased with pressure and binder; shear modulus increased with confining pressure; tablet hardness increased with binder content upto a point and thereafter decreased or remained constant. All the powders' properties related with tablet qualities, i.e., had R2>0.80; i.e., demonstrating the feasibility of using powder properties as initial predictors of tablet quality for formulations tested. In particular, the spring-back index, compression index, and bulk modulus were found to be most correlated with tablets' diametral strength, axial penetration strength, indentation hardness, and friability. An elastic energy based hypothesis was proposed to provide a fundamental basis for mechanical properties of powder formulations vs. tablet quality relationships. The positive outcome of this feasibility study suggests that the approach could be used for other similar powder formulations.
STING Millennium: a web-based suite of programs for comprehensive and simultaneous analysis of protein structure and sequence (2003)

STING Millennium Suite (SMS) is a new web-based suite of programs and databases providing visualization and a complex analysis of molecular sequence and structure for the data deposited at the Protein Data Bank (PDB). SMS operates with a collection of both publicly available data (PDB, HSSP, Prosite) and its own data (contacts, interface contacts, surface accessibility). Biologists find SMS useful because it provides a variety of algorithms and validated data, wrapped-up in a user friendly web interface. Using SMS it is now possible to analyze sequence to structure relationships, the quality of the structure, nature and volume of atomic contacts of intra and inter chain type, relative conservation of amino acids at the specific sequence position based on multiple sequence alignment, indications of folding essential residue (FER) based on the relationship of the residue conservation to the intra-chain contacts and Calpha-Calpha and Cbeta-Cbeta distance geometry. Specific emphasis in SMS is given to interface forming residues (IFR)-amino acids that define the interactive portion of the protein surfaces. SMS may simultaneously display and analyze previously superimposed structures. PDB updates trigger SMS updates in a synchronized fashion. SMS is freely accessible for public data at http://www.cbi.cnptia.embrapa.br, http://mirrors.rcsb.org/SMS and http://trantor.bioc.columbia.edu/SMS.
Meta-analysis of intraoperative povidone–iodine application to prevent surgical-site infection (2010)

The meta-analysis results suggested that the use of intraoperative PVI reduced rates of SSI.
Luminescent Nanoparticle Probes for Bioimaging (2004)

Bioimaging with luminescent nanoparticle probes have recently attracted widespread interest in biology and medicine. In comparison with commonly used organic dyes, luminescent nanoparticles are better in terms of photostability and sensitivity. These optical features of nanoparticle probes are critical for real time tracking and monitoring of biological events in the cellular level, which may not be accomplished using regular fluorescent dyes. Nanoparticle probes are also shown highly suitable for immunoassay and other diagnostic and therapeutic applications. In this article, we describe a variety of optical nanoparticle probes such as quantum dots, metal nanoparticles, dye-doped nanoparticles etc. for bioimaging applications.
Validation of the Sonomat: A Contactless Monitoring System Used for the Diagnosis of Sleep Disordered Breathing (2014)

These data indicate that the Sonomat was reliable and accurate for the diagnosis of OSA. The provision of audible breath sound/snoring replay permits more accurate quantification of snoring. It requires no patient attachment and can be performed in the home with minimal training.
Alcohol Consumption and Risk of Stroke (2003)

These results indicate that heavy alcohol consumption increases the relative risk of stroke while light or moderate alcohol consumption may be protective against total and ischemic stroke.
Miniaturized optogenetic neural implants: a review (2015)

Optogenetics is an exciting new technology that allows targetable fast control and readout of specific neural populations in complex brain circuits. With the rapid development of light-sensitive microbial opsins, substantial gains in understanding the causal relationships between neural activity and behavior in both healthy and diseased brains have been achieved during the last decade. However, the intricate and complex interactions between different neural populations in mammalian brains require novel, implantable, neural interfaces that are capable of manipulating and probing targeted neurons at multiple sites and with high spatiotemporal resolution. Advanced microtechnology has offered the highest potential to meet these demands of optogenetic applications. In this paper, we review a variety of miniaturized optogenetic neural implants developed in recent years, based on different light sources, including lasers, laser diodes, and light-emitting diodes. We then summarize the specifications of these microimplants and their related microfabrication approaches and discuss the major challenges of current techniques and the vision for the future of the field.
Hypoxia-specific cytotoxins in cancer therapy (1996)

Hypoxic-specific cytotoxins are a new, and as yet clinically untested, mode of treatment of solid tumors. If they can be given at high enough concentrations and sufficiently often, they should prove extremely effective both in combination with standard radiotherapy and also with certain chemotherapeutic drugs. It is likely that their optimum use will turn hypoxic cells in solid tumors from a therapeutic disadvantage to an advantage. In this report, we review the rationale for the use of hypoxia- cytotoxins, including both the theoretical basis for combining them with fractionated radiation and the preclinical results that have been obtained to date combing these agents with fractionated radiation. We also discuss the three major classes of bioreductive drugs, including the quinones (mitomycin C, porfiromycin, and E09), notroaromatic compounds (including RB6145 and various deoxyribonucleic acid [DNA] targeted aromatics), and finally the n-oxides of which tirapazamine is the lead compound. We also briefly discuss new approaches to bioreductive drug development. The best ways to use these agents are also covered. These include using them in combination with radiation, in combination with chemotherapy, and in combination with agents that increase tumor hypoxia. Finally, the importance of the selection of patients for clinical trials is illustrated by showing how dramatically the number of patients for clinical trials is illustrated by showing how dramatically the number of patients in a clinical trial has to increase to obtain statistical significance for a procedure targeted towards hypoxic cells if some of the patients in the trials have well-oxygenated tumors.
Effect of Solvent on the Lithium−Bromine Exchange of Aryl Bromides:  Reactions of n-Butyllithium and tert-Butyllithium with 1-Bromo-4-tert-butylbenzene at 0 °C (2006)

The outcome of reactions of 1-bromo-4-tert-butylbenzene (1), a representative aryl bromide, with n-BuLi or t-BuLi at 0 degrees C in a variety of solvent systems has been investigated. The products of reactions of 1 with n-BuLi vary significantly with changes in solvent composition: 1 does not react with n-BuLi in pure heptane; the exchange reaction to give (4-tert-butylphenyl)lithium, which is slow in pure diethyl ether, is virtually quantitative in heptane containing a small quantity of THF; and the reaction of 1 with n-BuLi in THF leads to considerable coupling. Lithium-bromine exchange is the virtually exclusive outcome of reactions of 1 with t-BuLi in every solvent studied except pure heptane: the presence of a small quantity of any of a variety of structurally diverse ethers (Et(2)O, THF, THP, MTBE) in the predominantly hydrocarbon medium affords (4-tert-butylphenyl)lithium, assayed as tert-butylbenzene, in yields exceeding 97%. The only side products observed from reactions of 1 with t-BuLi are small amounts of benzyne-derived hydrocarbons.
Transmetalation and reverse transmetalation on ortho-activated aromatic compounds: a direct route to o,o'-disubstituted benzenes (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransmetalation and reverse transmetalation on ortho-activated aromatic compounds: a direct route to o,o'-disubstituted benzenesPhilip E. Eaton and Ronald M. MartinCite this: J. Org. Chem. 1988, 53, 12, 2728–2732Publication Date (Print):June 1, 1988Publication History Published online1 May 2002Published inissue 1 June 1988https://doi.org/10.1021/jo00247a013RIGHTS & PERMISSIONSArticle Views645Altmetric-Citations35LEARN 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 InReddit PDF (667 KB) Get e-Alerts Get e-Alerts
Interaction between Chitosan and Oil under Stomach and Duodenal Digestive Chemical Conditions (2005)

Chitosan, the N acetylated derivative of chitin, has an effect on the absorption of dietary lipids, but there is not enough scientific knowledge about the mechanism. To study the interaction between chitosan and oil, the action of this biopolymer has been evaluated through an experimental model of the stomach and duodenum tract, although the enzimatic activity had not been evaluated. We microscopically confirmed that chitosan in a hychloridic acid medium (pH 1.0-2.0) emulsified lipids and the emulsion was a water in oil in water type (w/o/w). When the pH value and speed of agitation were increased to mirror the duodenum medium conditions under which lipids are absorbed, the emulsion capacity was better with an increased number of droplets and the emulsion continued as the w/o/w type. At pH 6.2, chitosan precipitated and lipids were entrapped in the formed flocculus. The binding oil was quantitatively determined, and we also demonstrate that a larger oil quantity induced less retention, while the chitosan characteristics had no influence. These observations allow us to postulate that the interaction between chitosan and oil inhibited duodenal absorption and enhanced lipid excretion.
Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis (2004)

The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5VDeltaC) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5VDeltaC induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5VDeltaC, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5VDeltaC induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5VDeltaC was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5VDeltaC was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5VDeltaC-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5VDeltaC infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5VDeltaC can trigger cell death by inducing ER stress.
Regulation of TNF‐α and IFN‐γ induced CXCL10 expression: participation of the airway smooth muscle in the pulmonary inflammatory response in chronic obstructive pulmonary disease (2003)

The chemokine CXCL10 is produced by many inflammatory cells found in the diseased lung and has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The present study demonstrates elevated CXCL10 protein in the lungs of COPD patients, which appears histologically in airway smooth muscle (hASM). In primary cultured hASM cells taken from normal donors, CXCL10 protein expression was induced by IFN-gamma and TNF-alpha, cytokines reported as elevated in COPD, and a synergistic response was obtained when they were combined. TNF-alpha stimulation of hASM enhanced accumulation of CXCL10 mRNA, indicating regulation at the transcriptional level, while IFN-gamma stimulation resulted in a smaller accumulation of CXCL10 mRNA. When these cytokines were applied simultaneously, an additive effect was obtained. TNF-alpha-induced CXCL10 expression in hASM was dependent on NFkappaB activation, and a salicylanilide NFkappaB inhibitor blocked the CXCL10 expression. In contrast, IFN-gamma stimulation resulted in transient NFkappaB activation, and the inhibitor had little effect on CXCL10 expression. When these cytokines were added simultaneously, NFkappaB was activated earlier and lasted longer, and the effect was blocked by the inhibitor. These data demonstrate a potential active role for hASM in pulmonary inflammatory diseases such as COPD by producing CXCL10.
Accelerated A Deposition in APPswe/PS1 E9 Mice with Hemizygous Deletions of TTR (Transthyretin) (2007)

A cardinal pathological lesion of Alzheimer's disease (AD) is the deposition of amyloid beta (Abeta) in the brain. We previously reported that exposing transgenic mice harboring APPswe/PS1deltaE9 transgenes to an enriched environment resulted in reduced levels of Abeta peptides and deposition, findings that were correlated with an increase in the expression of TTR, encoding transthyretin (TTR). TTR is expressed at high levels in the choroid plexus and known to bind Abeta peptides and modulate their aggregation in vitro and in vivo. To explore the impact of TTR expression on Abeta levels and deposition in vivo, we crossed ceAPPswe/PS1deltaE9 transgenic mice to mice with genetic ablations of TTR. We now report that the levels of detergent-soluble and formic acid-soluble levels of Abeta and deposition are elevated in the brains of ceAPPswe/PS1deltaE9/TTR+/- mice compared with age-matched ceAPPswe/PS1deltaE9/TTR+/+ mice. Moreover, Abeta deposition is significantly accelerated in the hippocampus and cortex of ceAPPswe/PS1deltaE9/TTR+/- mice. Our results strongly suggest that TTR plays a critical role in modulating Abeta deposition in vivo.
Monolithic 77 K dc SQUID magnetometer (1991)

We report the first fabrication of a monolithic dc SQUID magnetometer that operates above 77 K. We have used bi-epitaxial grain boundary Josephson junctions in YBa2Cu3O7 (YBCO) to produce the SQUID itself while the flux transformer consists of heteroepitaxial layers of YBCO/SrTiO3/LaAlO3/SrTiO3/YBCO. In the circuit fabricated, the SQUID is built on top of the epitaxial layers of the flux transformer. We have used dry etching, ion-beam cleaning, and photolithographic processing to pattern all the layers. Via contacts and step coverage of the epitaxial wire layers have been achieved without significant degradation of the superconducting properties of any of the three YBCO layers. The magnetometer enhances the magnetic field sensitivity of the bare SQUID by a factor of 127, giving an effective area, dΦ/dB, of 1.9 mm2.
Identification of a Binding Site for Quaternary Amines in Factor Xa (2000)

In the process of characterizing the Na(+)-binding properties of factor Xa, a specific inhibition of this enzyme by quaternary amines was identified, consistent with previous observations. The binding occurs with K(i) in the low millimolar range, with trimethylphenylammonium (TMPA) showing the highest specificity. Binding of TMPA inhibits substrate hydrolysis in a competitive manner, does not inhibit the binding of p-aminobenzamidine to the S1 pocket, and is positively linked to Na(+) binding. Inhibition by TMPA is also seen in thrombin and tissue plasminogen activator (tPA), though to a lesser extent compared to factor Xa. Computer modeling using the crystal structure of factor Xa suggests that TMPA binds to the S2/S3 specificity sites, with its hydrophobic moiety making van der Waals interactions with the side chains of Y99, F174, and W215, and the charged amine coupling electrostatically with the carboxylates of E97. Site-directed mutagenesis of factor Xa, thrombin, and tPA confirms the predictions drawn by docking calculations and reveal a dominant role for residue Y99. Binding of TMPA to factor Xa is drastically (25-fold) reduced by the Y99T replacement. Likewise, the Y99L substitution compromises binding of TMPA to tPA. On the other hand, the affinity of TMPA is enhanced 4-fold in thrombin with the substitution L99Y. The identification of a binding site for quaternary amines in factor Xa has a bearing on the rational design of selective inhibitors of this clotting enzyme.