gebhart/patrepeval huggingface dataset:
Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice (2005)

Long-term cures of hemophilia B have been achieved using AAV2 delivering the factor IX gene to the liver of adeno-associated virus (AAV)-naive hemophilic animals. However, the clinical success of this approach requires overcoming pre-existing AAV neutralizing antibodies prevalent in humans. To better define the inhibition of neutralizing antibodies on AAV2-mediated liver transduction, we developed an in vivo passive immunity model. SCID mice were first reconstituted to a defined neutralizing titer with pooled plasma-derived human immunoglobulin. AAV2-FIX vectors then were administered to the liver, and the transduction efficiency was measured by plasma FIX levels. Unexpectedly, AAV2 neutralizing titers lower than 1:10 were sufficient to neutralize 4 to 20 x 10(12) vg/kg of AAV2 vectors in vivo, a capacity that was underestimated by in vitro neutralizing assays. We also evaluated strategies to evade neutralization, including the use of alternative delivery routes, infusion parameters, empty capsids, and alternative AAV serotypes 6 and 8. The results indicate that low AAV2 neutralizing titers can be inhibitory to the tested human and primate AAV vectors delivered into the circulatory system. Therefore, novel nonprimate AAV vectors or compartmentalized delivery may offer more consistent therapeutic effects in the presence of pre-existing AAV neutralizing antibodies.
The Insulin-Like Growth Factor-I Receptor Kinase Inhibitor, NVP-ADW742, Sensitizes Small Cell Lung Cancer Cell Lines to the Effects of Chemotherapy (2005)

Inhibition of IGF-IR signaling synergistically enhances the sensitivity of SCLC to etoposide and carboplatin. This enhancement in sensitivity to chemotherapy tightly correlates with inhibition of PI3K-Akt activation. Future SCLC clinical trials incorporating IGF-IR inhibitors alone or in combination with other kinase inhibitors should include assessment of PI3K-Akt activity as a pharmacodynamic end-point.
Growth-stimulatory effect of androgen-induced autocrine growth factor(s) secreted from Shionogi carcinoma 115 cells on androgen-unresponsive cancer cells in a paracrine mechanism. (1988)

Androgen-responsive (SC-3) and -unresponsive (SC-4) cloned cell lines in culture were established from an androgen-responsive mouse mammary tumor, Shionogi carcinoma 115. By using a serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], characteristics of androgen-induced and autonomous growth factors (GFs) were examined. Serum-free conditioned medium (CM) obtained from testosterone-stimulated (+T) SC-3 cells had remarkable growth-stimulatory effects on both SC-3 and SC-4 cells. To examine the molecular characteristics of GF, CM(+T) from SC-3 was fractioned by heparin-Sepharose affinity chromatography; two peaks, eluted at 0.5 M (GF-low) and 1.1 M NaCl (GF-high) were identified. GF-high had the ability to stimulate growth with a morphological change of both SC-3 and SC-4 cells; the GF-high was not found in CM from T-unstimulated (-T) SC-3 or CM from SC-4. GF-low stimulated the growth without the morphological change of only SC-4 cells; the GF-low was also present in CM(-T) from SC-3 and CM from SC-4. The present findings demonstrate that T-induced autocrine GF-high secreted from SC-3 cells can also stimulate the growth of progressed unresponsive SC-4 cells in a paracrine mechanism and that autonomous GF-low secreted from both SC-3 and SC-4 cells can stimulate the growth of only SC-4 cells.
Obesity induces a phenotypic switch in adipose tissue macrophage polarization (2007)

Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.
Surveillance of Childhood Influenza Virus Infection: What Is the Best Diagnostic Method To Use for Archival Samples? (2004)

Despite the clinical importance of influenza virus in pediatric respiratory infections, the optimal set of diagnostic tests to use when conducting studies using archival samples is not clear. In this study, we compared diagnostic tests for influenza virus in 75 children younger than 5 years of age who presented with symptomatic respiratory infection during one of four influenza seasons, had negative viral cultures for other respiratory pathogens, and had both an archival nasal aspirate obtained at the time of illness and serology spanning that influenza season. For all eligible children, we compared the results of viral culture performed at the time of collection with serology and PCR of archival nasal aspirates. Using real-time viral culture as the "gold standard," the test characteristics of PCR of archival nasal aspirates (sensitivity, 82%; specificity, 100%) and serology (sensitivity, 82%; specificity, 87%) were similar. The relatively low sensitivity of PCR of archival nasal samples in this study compared to that of PCR of fresh samples in a previous study suggests that RNA degradation occurred despite storage of the specimens at -70 degrees C. RNA degradation would also explain why only 11 (52%) of 21 archival nasal samples that had positive influenza virus cultures at the time of collection had positive repeat cultures in the summer of 2000. Thus, in archival specimens stored at -70 degrees C, PCR was more sensitive than viral culture. However, testing of fresh specimens had the highest yield in this study. Studies of optimal methods for specimen storage are needed.
Results of treatment changes in patients with apparently drug‐resistant chronic epilepsy (2007)

This study provides a quantitative estimate of the value of changing drug therapy in patients in whom seizures were previously uncontrolled by previous therapy. The application of a systematic protocol to the treatment of chronic epilepsy will improve seizure control in a substantial proportion of cases. The rather nihilistic view that intractability is inevitable if seizure control is not obtained within a few years of the onset of therapy is incorrect.
Optically Amplified RNA–Protein Detection Methods Using Light‐Harvesting Conjugated Polymers (2003)

A sensor is described that takes advantage of highly specific RNA–protein interactions and the light‐harvesting properties of conjugated polymers. Coordination between a cationic conjugated polymer (CP + ) and a negatively charged protein–RNA complex results in efficient Förster resonance energy transfer (FRET) from CP + to a protein‐bound chromophore (see Figure and inside cover). This sensor was used to detect the transactivation responsive RNA sequence of HIV‐1.
Intrinsic Response of Graphene Vapor Sensors (2009)

Graphene is a two-dimensional material with extremely favorable chemical sensor properties. Conventional nanolithography typically leaves a resist residue on the graphene surface, whose impact on the sensor characteristics has not yet been determined. Here we show that the contamination layer chemically dopes the graphene, enhances carrier scattering, and acts as an absorbent layer that concentrates analyte molecules at the graphene surface, thereby enhancing the sensor response. We demonstrate a cleaning process that verifiably removes the contamination on the device structure and allows the intrinsic chemical responses of the graphene monolayer to be measured. These intrinsic responses are surprisingly small, even upon exposure to strong analytes such as ammonia vapor.
THE TRANSITIVITY MISCONCEPTION OF PEARSON’S CORRELATION COEFFICIENT (2009)

Despite the relevance of correlational studies for most research domains, many students, teachers, and researchers alike hold misconceptions concerning the Pearson product-moment correlation coefficient. One of these, the transitivity misconception, has not yet been documented in a systematic way. This paper summarizes the first empirical study, using 279 university students, and examines the relationship between student-based and task-based factors and the appearance of this misconception. In particular, two task-based factors seemed to have a significant effect on its appearance. In addition, the respondents’ level of confidence in their answer to the transitivity item was significantly lower than for most other times. First published November 2009 at Statistics Education Research Journal: Archives
External control of reactions in microdroplets (2015)

Scale reduction of chemical reactions enables novel screening and synthesis approaches that facilitate a highly parallelized and combinatorial exploration of chemical space. Droplet-based microfluidics have evolved as a powerful platform to allow many chemical reactions within small volumes that each can be controlled and manipulated. A significant technical challenge is the ability to change the concentration of reactants inside a droplet. Here we describe a strategy that relies on the use of reactants that are soluble in both oil and water and allow a passive, diffusive exchange of reactants between the oil and aqueous phases to externally control composition of the droplets. We demonstrate the applicability of our approach by externally changing the pH inside microdroplets without the need for physical manipulation or droplet merging.
Fibroblast growth factor 23 and adverse clinical outcomes in chronic kidney disease (2012)

FGF23 is emerging as a novel risk factor in CKD. Future studies should determine whether interventions that lower FGF23 levels improve clinical outcomes in CKD.
Polymerase chain reaction and other methods to detect hot-spot and multiple gene mutations. (1992)

Gene mutations responsible for main genetic diseases as Duchenne/Becker muscular dystrophy or cystic fibrosis, and involved in more important diseases like cancer or cardiac diseases have been identified. Direct DNA tests can now be performed for these disorders. However, despite the knowledge of the exact alteration of the DNA sequence in these diseases, incorporating DNA analysis into large screening programs has been hindered by technical difficulties since each different mutation requires a different probe to be detected. To overcome these problems the polymerase chain reaction technique (PCR) has been proposed. Multiplex PCR procedure is possible and consists of simultaneously amplifying several separate DNA sequences (the upper limit of the number of multiplex reactions that can be executed at one time is not known; eight or nine separate DNA sequences amplified have already been described). Another approach is to directly sequence the gene mutations generally concentrated in 'hot-spot' regions. This way it is possible to identify numerous mutations using only one micro-sequencing reaction (50-100 nucleotides). New generations of very sophisticated systems like capillary electrophoresis or non-isotopic, but very sensitive, microsequencing systems should allow in a near future to withdraw the use of PCR for this purpose.
Growing Pains: Evo-Devo Researchers Straddle Cultures (1997)

For Kevin Peterson, a temporary job as a chauffeur turned out to be the start of a new career in science. As a Ph.D. student in paleobiology at the University of California, Los Angeles (UCLA), in 1992, Peterson was studying the evolution of animals with bilateral symmetry, which includes everything from insects to mammals. Then one day he was drafted to drive a prominent visiting paleontologist, Richard Jeffries, around Los Angeles to meet various local scientific luminaries. Peterson “sat meekly” on the sidelines as Jeffries and developmental geneticist Eric Davidson of the California Institute of Technology (Caltech) speculated about the genetics behind the five-sided symmetry of echinoderms such as starfish.
How Long After Laser Irradiation Should Cellular Responses be Measured to Determine the Laser Effect? (2007)

Background: Low level laser therapy (LLLT) is a type of photomodulation, which uses photons to modulate biological activity. This photobiological effect depends on the wavelength, dose, intensity, as well as cell culture conditions. One problem with most of the published data on low level laser irradiation is that most studies do not record the duration between the exposure and the evaluation. It has been established that a single dose of 5 J/cm2 stimulates cell proliferation and mitochondrial activity to normalize cell function and accelerate wound healing. This study investigates the cellular responses of irradiated human skin fibroblasts to establish if the duration after laser irradiation could influence the results. Methods: Normal and wounded human skin fibroblasts were exposed to helium-neon (632.8 nm) laser irradiation using a single dose of 5 J/cm2 on one day or 5 J/cm2 on two consecutive days. The cellular responses were measured 15 min, 1, or 3 h postirradiation. Responses evaluated included the effect on cell migration, changes in mitochondrial activity (cell viability), cell proliferation, and damage or stress caused by the irradiation. Results: The results indicate that a duration of between 1 and 3 h postirradiation is sufficient when measuring the direct effect of laser radiation on cells (cell viability, ATP mitochondrial activity, IL-6 activity, membrane integrity, and DNA damage), however, a longer duration of 24 h is required to demonstrate the indirect effect (cell proliferation and protein expression). Conclusion: This study indicates that the duration of effect should be included as one of the main parameters when reporting on the parameters used in LLLT.
Integrated chemical systems: photocatalysis at semiconductors incorporated into polymer (Nafion)/mediator systems (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntegrated chemical systems: photocatalysis at semiconductors incorporated into polymer (Nafion)/mediator systemsM. Krishnan, James R. White, Marye Anne Fox, and Allen J. BardCite this: J. Am. Chem. Soc. 1983, 105, 23, 7002–7003Publication Date (Print):November 1, 1983Publication History Published online1 May 2002Published inissue 1 November 1983https://pubs.acs.org/doi/10.1021/ja00361a064https://doi.org/10.1021/ja00361a064research-articleACS PublicationsRequest reuse permissionsArticle Views459Altmetric-Citations97LEARN 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-Alertsclose Get e-Alerts
Bacillus amyloliquefaciens GA1 as a source of potent antibiotics and other secondary metabolites for biocontrol of plant pathogens (2009)

The production of all of these antibiotic compounds highlights B. amyloliquefaciens GA1 as a good candidate for the development of biocontrol agents.
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells (2012)

Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues. Here, we show that exosomes can efficiently deliver microRNA (miRNA) to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved by engineering the donor cells to express the transmembrane domain of platelet-derived growth factor receptor fused to the GE11 peptide. Intravenously injected exosomes delivered let-7a miRNA to EGFR-expressing xenograft breast cancer tissue in RAG2(-/-) mice. Our results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.
Absence of transitive and systemic pathways allows cell-specific and isoform-specific RNAi in Drosophila (2003)

RNA interference (RNAi) designates the multistep process by which double-stranded RNA induces the silencing of homologous endogenous genes. Some aspects of RNAi appear to be conserved throughout evolution, including the processing of trigger dsRNAs into small 21-23-bp siRNAs and their use to guide the degradation of complementary mRNAs. Two remarkable features of RNAi were uncovered in plants and Caenorhabditid elegans. First, RNA-dependent RNA polymerase activities allow the synthesis of siRNA complementary to sequences upstream of or downstream from the initial trigger region in the target mRNA, leading to a transitive RNAi with sequences that had not been initially targeted. Secondly, systemic RNAi may cause the targeting of gene silencing in one tissue to spread to other tissues. Using transgenes expressing dsRNA, we investigated whether transitive and systemic RNAi occur in Drosophila. DsRNA-producing transgenes targeted RNAi to specific regions of alternative mRNA species of one gene without transitive effect directed to sequences downstream from or upstream of the initial trigger region. Moreover, specific expression of a dsRNA, using either cell-specific GAL4 drivers or random clonal activation of a GAL4 driver, mediated a cell-autonomous RNAi. Together, our results provide evidence that transitive and systemic aspects of RNAi are not conserved in Drosophila and demonstrate that dsRNA-producing transgenes allow powerful reverse genetic approaches to be conducted in this model organism, by knocking down gene functions at the resolution of a single-cell type and of a single isoform.
Characterization of Interactions between the Mammalian Polycomb-Group Proteins Enx1/EZH2 and EED Suggests the Existence of Different Mammalian Polycomb-Group Protein Complexes (1998)

In Drosophila melanogaster, the Polycomb-group (PcG) and trithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxG gene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog of eed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs (esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.
The transition in hydrogen sensing behavior in noncontinuous palladium films (2010)

The morphological transition in ultrathin palladium (Pd) films around the percolation threshold and the related transition in hydrogen sensing behavior is investigated. We find that besides the transition from continuous to discontinuous Pd, an intermediate - semicontinuous-state must be considered. It shows hydrogen sensing features of both continuous and discontinuous film types, simultaneously. This study focuses on the discontinuous-semicontinuous transition. Experimental evidence is supported by studying the evolution of the electrical resistance with temperature, under hydrogen exposure and after thermal annealing. The results are highly relevant for the optimization of nanogap based hydrogen sensors.
Clinical Study of Daunomycin and Prednisone for Induction of Remission in Children with Advanced Leukemia (1969)

Sixty-seven children with acute leukemia and with one or more previous relapses were treated with Daunomycin and prednisone to determine the effectiveness of this combination for inducing clinical and hematologic remissions. Sixty had acute lymphocytic, and seven acute myelocytic leukemia. Of the former, 39 attained complete, and 10 partial, bone-marrow remission. Of the latter, one had complete, and one partial remission. Median time to onset of remission marrow in the 51 children was 27 days. Maintenance of remission by Daunomycin was not studied. Limiting toxicity included leukopenia, thrombocytopenia, oral ulcerations, Cushingoid appearance and chemical cellulitis at the injection site. Daunomycin and prednisone are a highly effective drug combination for induction of remissions in children with leukemia refractory to conventional antileukemic drugs.
Preoperative Nomogram Predicting the 10-Year Probability of Prostate Cancer Recurrence After Radical Prostatectomy (2006)

An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.