gebhart/patrepeval huggingface dataset:
Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy (2005)

Adeno-associated virus 8 (AAV8), a new member of the AAV family isolated from nonhuman primates, is an attractive candidate for hepatic gene transfer applications because of 10- to 100-fold improved transduction efficiency in mouse liver models. Additionally, AAV8 has lesser frequency of pre-existing immunity in humans. These properties could solve some of the problems associated with AAV2 vectors. The benefits of AAV8 demonstrated in mouse models, however, have not been confirmed in larger animals. In this study, we evaluate the efficacy and safety of AAV2/8 vector in both naive and AAV2-pretreated hemophilia B dogs. Two naive hemophilia B dogs that received a single intraportal administration of AAV2/8 vector have achieved sustained expression of 10% and 26% of normal levels of canine factor IX (cFIX) for more than a year. In an AAV2-pretreated hemophilia B dog, cFIX expression increased from less than 1% to 16% of normal levels when treated with an AAV2/8 vector, and a high level of expression has lasted for more than 2 years. No significant liver toxicity or cFIX-specific antibodies have been detected in these animals. Studies here have demonstrated the safety and improved efficacy of AAV2/8 vector in large-animal models for liver-directed gene therapy.
Differences in ICAM‐1 and TNF‐α expression between large single fraction and fractionated irradiation in mouse brain (2003)

The molecular response of the brain to single-dose irradiation was rapid, while its response to fractionated irradiation was slow. This finding is consistent with clinical observations and could be of use when designing strategies to mitigate radiation sequelae.
Review of Layer Transfer Processes for Crystalline Thin-Film Silicon Solar Cells (2001)

Layer transfer processes provide a new and largely unexplored route for the fabrication of highly efficient monocrystalline thin-film Si solar cells. Monocrystalline Si wafers serve as a substrate for epitaxial growth. A special surface conditioning of the substrate permits the transfer of a thin epitaxial film to an arbitrary carrier substrate. The growth substrate is then re-used to fabricate further cells. The possibility to use different materials for growing the thin film and for carrying the devices broadens the design flexibility and opens a new path for cost reduction. We describe and discuss the various layer transfer processes that are currently being developed for Si. A particular important point to work on in the future is the demonstration of a frequent re-use of the substrate and the development of a large-area and low-cost epitaxy technique.
Oral Zinc in Macular Degeneration (1988)

Macular degeneration associated with age and drusen, an important cause of severe visual loss in older persons, is of unknown cause. The sensory retina and retinal pigment epithelium, which are cell layers in zinc, appear to be prominently involved in the disease process. Because zinc plays a role in the metabolic function of several important enzymes in the chorioretinal complex, we undertook a prospective, randomized, double-masked, placebo-controlled investigation of the effects of oral zinc administration on the visual acuity outcome in 151 subjects with drusen or macular degeneration. Although some eyes in the zinc-treated group lost vision, this group had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months. This is the first controlled oral intervention study to show a positive, if limited, treatment effect in macular degeneration, a major public health problem. Because of the pilot nature of the study and the possible toxic effects and complications of oral zinc administration, widespread use of zinc in macular degeneration is not now warranted.
Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted (2017)

Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of encapsulated islets. A strategy to combat PFO is the use of mesenchymal stem cells (MSC). MSC have anti-inflammatory properties and their potential can be enhanced by stimulation with proinflammatory cytokines. This study investigated whether co-encapsulation or co-transplantation of MSC with encapsulated islets would reduce PFO and improve graft survival. Stimulating MSC with a cytokine cocktail of IFN-γ and TNF-α enhanced their immunosuppressive potential by increasing nitric oxide production and secreting higher levels of immunomodulatory cytokines. In vitro, co-encapsulation with MSC did not affect islet viability but significantly enhanced glucose-induced insulin secretion. In vivo, normoglycemia was achieved in 100% mice receiving islets co-encapsulated with stimulated MSC as opposed to 71.4% receiving unstimulated MSC and only 9.1% receiving encapsulated islets alone. Microcapsules retrieved from both unstimulated and stimulated MSC groups had significantly less PFO with improved islet viability and function compared to encapsulated islets alone. Levels of peritoneal immunomodulatory cytokines IL-4, IL-6, IL-10 and G-CSF were significantly higher in MSC co-encapsulated groups. Similar results were obtained when encapsulated islets and MSC were co-transplanted. In summary, co-encapsulation or co-transplantation of MSC with encapsulated islets reduced PFO and improved the functional outcome of allotransplants.
Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia (2003)

Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well-defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT-PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease-free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor.
Heparan Sulfates Mediate the Binding of Basic Fibroblast Growth Factor to a Specific Receptor on Neural Precursor Cells (1995)

Heparan sulfate proteoglycans are thought to be obligatory for receptor binding and subsequent mitogenic activity of basic fibroblast growth factor (FGF-2). In a previous study (Nurcombe V., Ford, M. D., Wildschut, J., Bartlett, P. F. (1993) Science 260, 103-106) we have shown that primary cultures of mouse neuroepithelial cells and a cell line derived from then, 2.3D, secrete a heparan sulfate proteoglycan with a high affinity for FGF-2. In this study, a combination of affinity chromatography and gel chromatography was used to further isolate heparan sulfate side chains with high affinity for FGF-2. These active chains had an average molecular weight of 18,000-20,000. In order to determine whether heparan sulfate chains with specificity for FGF-2 also displayed selectivity for the different FGF receptors, peptides designed to the heparin-binding region of the receptors were used in competitive inhibition studies. The structure of the predicted heparin-binding domain of the FGF receptor 1 was modeled on the basis of its presumed secondary and tertiary structure homology with immunoglobulin loops. These results suggested that many of the basic residues within the second immunoglobulin loop of the FGF receptor 1 form a basic domain in the molecule and therefore form part of a heparin-binding site. Peptides homologous to this region of FGF receptor 1 were shown to inhibit mitogenesis in 2.3D cells, while those to FGF receptor types 2, 3, and 4 did not. A reverse transcriptase-polymerase chain reaction assay designed to detect expression of the four FGF receptors types demonstrated that FGF receptors 1 and 3 were present on the 2.3D cell line but that receptors 2 and 4 were not. These findings indicate that unique heparan sulfate domains interact with specific cell-surface receptors to direct cellular responses.
Anti-DLL4 Inhibits Growth and Reduces Tumor-Initiating Cell Frequency in Colorectal Tumors with Oncogenic KRAS Mutations (2010)

KRAS mutations are frequent in colorectal cancer (CRC) and are associated with clinical resistance to treatment with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies. Delta-like 4 ligand (DLL4) is an important component of the Notch signaling pathway and mediates stem cell self-renewal and vascular development. DLL4 inhibition in colon tumor cells reduces tumor growth and stem cell frequency. Considering the need for new drugs to treat colon cancers with oncogenic KRAS mutations, we examined in this study the efficacy of anti-DLL4 antibodies in KRAS mutant tumors in a panel of early passage colon tumor xenograft models derived from patients. Consistent with clinical findings, mutant KRAS colorectal xenograft tumors were insensitive to the EGFR therapeutic antibody cetuximab, whereas KRAS wild-type tumors responded to cetuximab. In contrast, anti-DLL4 was efficacious against both wild-type and mutant KRAS colon tumors as a single agent and in combination with irinotecan. Further analysis of mutant KRAS tumors indicated that the anti-DLL4/irinotecan combination produced a significant decrease in colon cancer stem cell frequency while promoting apoptosis in tumor cells. Our findings provide a rationale for targeting DLL4-Notch signaling for improved treatment of CRC patients with activating KRAS mutations.
Optofluidic microscopy—a method for implementing a high resolution optical microscope on a chip (2006)

We report a novel microfluidics-based lensless imaging technique, termed optofluidic microscopy (OFM), and demonstrate Caenorhabditis elegans imaging with an OFM prototype that gives comparable resolution to a conventional microscope and a measured resolution limit of 490 +/- 40 nm.
Synthesis, characterization, and properties of polyurethanes containing 1,4:3,6‐dianhydro‐D‐sorbitol (2009)

Abstract Two‐ and three‐component polyurethanes containing 1,4:3,6‐dianhydro‐ D ‐sorbitol (isosorbide) derived from glucose were synthesized using n ‐BuSn(O)OH·H 2 O as a catalyst, and the thermal properties ( T g , T d ) of the polymers were investigated by differential scanning calorimetry and thermogravimetric analysis. We carried out molds for polyurethanes, the molds of polyurethanes were obtained. The dynamic mechanical analyzes showed that the storage modulus values of the three‐component polymers were constant to a higher temperature than those of the two‐component polymers. The storage moduli ( E′ ), loss moduli ( E″ ), and values of tan δ for the polymers were obtained. The rigidity of three‐component polymers was increased by the introduction of bisphenol A and diphenylmethane group to two‐component polymer. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6025–6031, 2009
Biogeneration of Aromas (1986)

Many of the approximately 5000 known volatile flavoring substances are generated in biogenetic processes in natural foods, or during the subsequest processing of these foods. In both cases, they are perceived as natural flavorings by both consumer and legislator. Many of these same flavoring substances can be produced by chemical processes, in pure form. In that case they are perceived as artificial flavoring substances, both by consumer and legislator in the United States. It is, however, in many cases, also possible to manufacture exactly these same flavoring substances by biogenetic processes, at a usually much higher cost. We will review how the origin of flavoring materials influences their regulatory and safety status, and how it determines consumer perception of flavorful foods.
Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia (2015)

Plasmid-based Sleeping Beauty (SB) transposon vectors were developed and used to deliver genes for low-density lipoprotein and very-low-density lipoprotein receptors (LDLR and VLDLR, respectively) or lacZ reporter into liver of an LDLR-deficient mouse model of familial hypercholesterolemia (FH). SB transposase, SB100x, was used to integrate the therapeutic transposons into mice livers for evaluating the feasibility of the vectors in reducing high blood cholesterol and the progression of atherosclerosis. Hydrodynamic gene delivery of transposon-VLDLR into the livers of the mice resulted in initial 17-19% reductions in plasma cholesterol, and at the later time points, in a significant stabilization of the cholesterol level for the 6.5-month duration of the study compared to the control mice. Transposon-LDLR-treated animals also demonstrated a trend of stabilization in the cholesterol levels in the long term. Vector-treated mice had slightly less lipid accumulation in the liver and reduced aortic atherosclerosis. Clinical chemistry and histological analyses revealed normal liver function and morphology comparable to that of the controls during the follow-up with no safety issues regarding the vector type, transgenes, or the gene transfer method. The study demonstrates the safety and potential benefits of the SB transposon vectors in the treatment of FH.
N6-(2,2-diphenylethyl)adenosine, a novel adenosine receptor agonist with antipsychotic-like activity (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN6-(2,2-diphenylethyl)adenosine, a novel adenosine receptor agonist with antipsychotic-like activityAlexander J. Bridges, Walter H. Moos, Deedee L. Szotek, Bharat K. Trivedi, James A. Bristol, Thomas G. Heffner, Robert F. Bruns, and David A. DownsCite this: J. Med. Chem. 1987, 30, 10, 1709–1711Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/jm00393a003https://doi.org/10.1021/jm00393a003research-articleACS PublicationsRequest reuse permissionsArticle Views185Altmetric-Citations41LEARN 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
FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo (1996)

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface-expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA-IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.
Direct Demonstration of the Flexibility of the Glycosylated Proline-Threonine Linker in the Cellulomonas fimi Xylanase Cex through NMR Spectroscopic Analysis (2006)

The modular xylanase Cex (or CfXyn10A) from Cellulomonas fimi consists of an N-terminal catalytic domain and a C-terminal cellulose-binding domain, joined by a glycosylated proline-threonine (PT) linker. To characterize the conformation and dynamics of the Cex linker and the consequences of its modification, we have used NMR spectroscopy to study full-length Cex in its nonglycosylated ( approximately 47 kDa) and glycosylated ( approximately 51 kDa) forms. The PT linker lacks any predominant structure in either form as indicated by random coil amide chemical shifts. Furthermore, heteronuclear (1)H-(15)N nuclear Overhauser effect relaxation measurements demonstrate that the linker is flexible on the ns-to-ps time scale and that glycosylation partially dampens this flexibility. The catalytic and cellulose-binding domains also exhibit identical amide chemical shifts whether in isolation or in the context of either unmodified or glycosylated full-length Cex. Therefore, there are no noncovalent interactions between the two domains of Cex or between either domain and the linker. This conclusion is supported by the distinct (15)N relaxation properties of the two domains, as well as their differential alignment within a magnetic field by Pf1 phage particles. These data demonstrate that the PT linker is a flexible tether, joining the structurally independent catalytic and cellulose-binding domains of Cex in an ensemble of conformations; however, more extended forms may predominate because of restrictions imparted by the alternating proline residues. This supports the postulate that the binding-domain anchors Cex to the surface of cellulose, whereas the linker provides flexibility for the catalytic domain to hydrolyze nearby hemicellulose (xylan) chains.
Universal quantum gates for single cooper pair box based quantum computing (2001)

Key words: quantum gates, cooper pair box, quantum computing
Mycophenolate Mofetil in Islet Cell Transplant: Variable Pharmacokinetics but Good Correlation Between Total and Unbound Concentrations (2005)

The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC(0-12) mcg x h/mL before day 60 was 62.1-67.8, declining to 33.6-64.7 thereafter (P = .61). Median total trough concentrations were 1.16-2.90 mcg/mL. Unbound AUC(0-12) was 412-673 ng x h/mL and did not change over time (P = .30). Median percent unbound mycophenolic acid was 0.95% of total concentrations. Individual unbound and total mycophenolic acid concentrations were highly correlated (r2 = 0.94). Total mycophenolic acid trough concentration and total AUC(0-12) were modestly correlated (r2 = 0.65). Intra- and interpatient variability of systemic mycophenolic acid exposure was high. Six patients required dose reductions prior to day 60 due to adverse effects. All subjects achieved insulin independence; 3 later lost graft function. The trend toward higher exposure in the early periods followed by dose reductions suggests that lower initial doses and therapeutic drug monitoring may be necessary.
Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release (2000)

These data indicate that submaximal exercise followed by a bout of eccentric exercise results in similar amounts of myofibrillar injury with a larger neutrophil response and CK release.
Soft Computing for Human Spermatozoa Morphology (2005)

A fuzzy data fusion approach was used for human sperm morphology recognition analysis using 3-CCD camera image data. Fuzzy operators were used to create the relationship between abnormal sperm morphology and normal sperm aberrations after digitizing the images. The approaches have focused on frequencies of sperm with either abnormal morphology in semen analysis samples. In order to establish whether various shapes of membership functions, the authors would classify the morphology according to their head, tail, and neck shapes into symmetrical, asymmetrical, irregular and amorphous categories based on the fuzzy region. The images results demonstrated how these findings facilitated approaches on the 100 semen samples. The average probability of morphology recognition analysis was equal to 95% and the average probability of unknown parameter was equal to 4.5%. The fuzzy fusion morphology provided a unified and consistent framework to express different shapes of human spermatozoa.
A statistical approach to learning and generalization in layered neural networks (1990)

A general statistical description of the problem of learning from examples is presented. Learning in layered networks is posed as a search in the network parameter space for a network that minimizes an additive error function of a statistically independent examples. By imposing the equivalence of the minimum error and the maximum likelihood criteria for training the network, the Gibbs distribution on the ensemble of networks with a fixed architecture is derived. The probability of correct prediction of a novel example can be expressed using the ensemble, serving as a measure to the network's generalization ability. The entropy of the prediction distribution is shown to be a consistent measure of the network's performance. The proposed formalism is applied to the problems of selecting an optimal architecture and the prediction of learning curves.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Randomized, Prospective Study of Low-Dose Versus High-Dose Inhaled Nitric Oxide in the Neonate With Hypoxic Respiratory Failure (2001)

We did not find any significant difference in response to low- versus high-dose iNO. An initial exposure to low-dose iNO does not compromise the response to higher doses if required and may result in less toxicity.