gebhart/patrepeval huggingface dataset:
Effect of high‐pressure processing on the migration of antioxidant Irganox 1076 from polypropylene film into a food simulant (2004)

Abstract The effect of high‐pressure processing (HPP) on the migration behaviour of a typical antioxidant, Irganox 1076, from polypropylene (PP) flexible structures was studied. Initial concentrations of Irganox 1076 in polypropylene (PP) were 2.0 and 5.0 mg g −1 . The migration experiments were carried out on high‐pressure treated and non‐treated polypropylene pouches containing either 95 or 10% ethanol aqueous food simulating liquids (FSL) for 20 days at 40 and 60 °C. After the contact period, concentrations of Irganox in PP and FSL were measured to determine migration behaviour. The results showed that there was no significant difference in the concentration of Irganox 1076 migrating from PP, and into the FSL for pressure‐treated vs non‐treated samples. No significant concentration differences were found in non‐treated (control) samples and those treated for 5 and 10 min. However, there was a storage time effect on the migration level. There was also a significant migration effect on the migration of Irganox between the two different food simulants, and an increase in the HPP temperature increased the rate of migration. Copyright © 2004 Society of Chemical Industry
Tiled polygon traversal using half-plane edge functions (2000)

Existing techniques for traversing a polygon generate fragments one (or more) rows or columns at a time. (A fragment is all the information needed to paint one pixel of the polygon.) This order is non-optimal for many operations. For example, most frame buffers are tiled into rectangular pages, and there is a cost associated with accessing a different page. Pixel processing is more efficient if all fragments of a polygon on one page are generated before any fragments on a different page. Similarly, texture caches have reduced miss rates if fragments are generated in tiles (and even tiles of tiles) whose size depends upon the cache organization.
Radio-immunoassay of atrial natriuretic peptide (ANP) and characterization of ANP immunoreactivity in human plasma and atrial tissue (1992)

A sensitive radio-immunoassay (RIA) was developed to determine the occurrence of atrial natriuretic peptide (ANP) in plasma and atrial extracts from patients undergoing open heart surgery. The immunoreactive ANP (irANP) was characterized by high-pressure liquid chromatography coupled with RIA. The plasma irANP response to releasing stimuli during the operation was determined in simultaneously sampled venous and arterial blood, in order to evaluate any differences. The antiserum recognized the intact ring-structure of alpha-humanANP (alpha-hANP) and its propeptide gamma-hANP, as well as beta-hANP, an anti-parallel dimer of alpha-hANP. Less bioactive N-or C-terminal fragments of alpha-hANP, or an N-terminal fragment of the propeptide, gamma-hANP 1-67, did not cross-react with the antiserum. Sep Pak C18-extraction of plasma resulted in an 80% recovery of synthetic alpha-hANP. The assay had a sensitivity of 1.9 pmol l-1, well below the venous plasma concentrations of irANP found in healthy volunteers (7.4 +/- 1.3 pmol l-1, mean +/- SEM, n = 19), and the local standard was identical to an international standard of alpha-hANP. In atrial extracts three major peaks of irANP were identified as alpha-, beta- and gamma-hANP, with gamma-hANP as the most abundant form. In plasma alpha-hANP dominated, but in two cases high plasma levels of beta-hANP were seen, reflecting the high atrial content in these patients. In peripheral arterial blood, irANP was on an average 56% +/- 20% (p less than 0.01, n = 18) higher than in venous blood; this was associated with more distinct arterial irANP responses to releasing stimuli during the operation.
Double targeted gene replacement for creating null mutants. (1991)

We have used double gene targeting to create homozygous gene replacements in the protozoan parasite Leishmania major, an asexual diploid. This method uses two independent selectable markers in successive rounds of gene targeting to replace both alleles of an endogenous gene. We developed an improved hygromycin B-resistance cassette encoding hygromycin phosphotransferase (HYG) for use as a selectable marker for Leishmania. HYG-containing vectors functioned equivalently to those containing the neomycin phosphotransferase (NEO) cassette previously used for extrachromosomal transformation or gene targeting. Drug resistances conferred by the NEO and HYG markers were independent, allowing simultaneous selection for both markers. A HYG targeting vector was utilized to replace the single dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene remaining in a line heterozygous for a NEO replacement at the dhfr-ts locus (+/neo), with a targeting efficiency comparable to that seen with wild-type recipients. The resultant dhfr-ts- line (hyg/neo) was auxotrophic for thymidine. The double targeted replacement method will enable functional genetic testing in a variety of asexual diploids, including cultured mammalian cells and fungi such as Candida albicans. Additionally, it may be possible to use Leishmania bearing conditionally auxotrophic gene replacements as safe, improved live vaccines for leishmaniasis.
Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data (2017)

Establishing the in vivo diagnosis of Alzheimer's disease (AD) or other dementias relies on clinical criteria; however, the accuracy of these criteria can be limited. The diagnostic accuracy is 77% for a clinical diagnosis of AD, even among experts. We performed a review through PubMed of articles related to specific diagnostic modalities, including APOE genotyping, cerebrospinal fluid (CSF) testing, fludeoxyglucose F 18 positron emission tomography (PET), amyloid PET, tau PET, computed tomography (CT), single-photon emission CT, magnetic resonance imaging (MRI), and B12 and thyroid-stimulating hormone screening, to determine the specificity and sensitivity of each test used in the clinical diagnosis of AD. We added a novel immunomagnetic reduction assay that provides ultrasensitivity for analyzing the levels of plasma tau and beta amyloid 42 (Aβ<sub>42</sub>). The sensitivity and specificity of the current diagnostic approach (structural CT or MRI with screening labs) remain low for clinical detection of AD and are primarily used to exclude other conditions. Because of limited diagnostic capabilities, physicians do not feel comfortable or skilled in rendering a clinical diagnosis of AD. Compounding this problem is the fact that inexpensive, minimally invasive diagnostic tests do not yet exist. Biomarkers (obtained through CSF testing or PET imaging), which are not routinely incorporated in clinical practice, correlate well with pathologic changes. While PET is particularly costly and difficult to assess, CSF measures of tau and beta amyloid are not costly, and these tests may be worthwhile when the tiered approach proposed here warrants further testing. There is a need for developing bloodborne biomarkers that can aid in the clinical diagnosis of AD. Here we present a streamlined questionnaire-enriched, biomarker-enriched approach that is more cost-effective than the current diagnosis of exclusion and is designed to increase clinical confidence for a diagnosis of dementia due to AD.
Refinement of Tools for Targeted Gene Expression in Drosophila (2010)

A wide variety of biological experiments rely on the ability to express an exogenous gene in a transgenic animal at a defined level and in a spatially and temporally controlled pattern. We describe major improvements of the methods available for achieving this objective in Drosophila melanogaster. We have systematically varied core promoters, UTRs, operator sequences, and transcriptional activating domains used to direct gene expression with the GAL4, LexA, and Split GAL4 transcription factors and the GAL80 transcriptional repressor. The use of site-specific integration allowed us to make quantitative comparisons between different constructs inserted at the same genomic location. We also characterized a set of PhiC31 integration sites for their ability to support transgene expression of both drivers and responders in the nervous system. The increased strength and reliability of these optimized reagents overcome many of the previous limitations of these methods and will facilitate genetic manipulations of greater complexity and sophistication.
Development Of RNAi Therapeutics Targeting The Complement Pathway (2013)

Abstract The complement system is a pivotal player in multiple hematological conditions. Antibody blockade of the C5 component of complement has been approved as a treatment for both paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS), validating C5 as an important therapeutic target. Recently, we developed a robust RNAi therapeutics platform for the delivery of siRNAs to the liver using trivalent GalNAc conjugates, enabling silencing of hepatocyte-expressed genes following subcutaneous (SC) injection. The liver is a major source of C5 and other complement pathway components. The GalNAc conjugate technology allows rapid development of siRNAs targeting multiple members of the complement cascade and evaluation of their silencing in pre-clinical models. To examine the utility of the siRNA approach for targeting complement pathway components we designed and synthesized GalNAc conjugated siRNAs targeting rodent, primate and human C5. Potent siRNA duplexes, showing greater than 95% silencing of C5 mRNA were selected using in vitro screening in human cell lines and mouse primary hepatocytes. C5 silencing and serum hemolytic activity inhibition were evaluated in rodents using single and multi-dose SC treatment regimens. A C5-targeting siRNA conjugate demonstrated a single dose ED50 of 0.625 mg/kg in the mouse with greater than 90% silencing of serum C5 achievable at higher doses. Serum C5 silencing was durable, with recovery starting two weeks after a single SC injection We went on to examine the efficacy of C5 silencing in the rat and observed robust lowering of serum C5 with 2.5 and 5 mg/kg multi-dose regimens, resulting in up to ∼90% inhibition of complement classical pathway hemolytic activity. Evaluation of the translation of this approach to higher species is in progress. Since PNH erythrocyte lysis is thought to be mediated by the activation of the alternative pathway of complement we initiated work on the development of siRNA conjugates targeting Factor B, an essential component of the alternative pathway C3 convertase. siRNAs targeting rodent, primate and human Factor B were identified by in vitro screening and demonstrate &gt;90% silencing of Factor B mRNA in human cell lines and primary mouse hepatocytes. Evaluation of Factor B silencing in rodent models is ongoing. siRNA-mediated silencing of liver-derived complement components is a promising novel therapeutic approach for inhibiting the activity of C5 and other complement pathway targets, with the potential to enable subcutaneous treatment for patients with PNH and related disorders. Disclosures: Borodovsky: Alnylam: Employment. Yucius:Alnylam: Employment. Sprague:Alnylam: Employment. Butler:Alnylam: Employment. Fishman:Alnylam: Employment. Nguyen:Alnylam: Employment. Vaishnaw:Alnylam: Employment. Maier:Alnylam: Employment. Kallanthottathil:Alnylam: Employment. Kuchimanchi:Alnylam: Employment. Manoharan:Alnylam: Employment. Meyers:Alnylam: Employment. Fitzgerald:Alnylam: Employment.
Molecular tools for a molecular medicine: analyzing genes, transcripts and proteins using padlock and proximity probes (2004)

Procedures and reagents are needed to specifically detect all the macromolecules that are being identified in the course of genome projects. We discuss how this challenge may be met using a set of ligation-based reagents termed padlock probes and proximity ligation probes. These probes include elements with affinity for specific nucleic acid and protein molecules, respectively, along with unique identifier DNA sequence elements that encode the identity of the recognized target molecules. The information content of DNA strands that form in the detection reactions are recorded after amplification, allowing the recognized target molecules to be identified. The procedures permit highly specific solution-phase or localized analyses of large sets of target molecules as required in future molecular analyses.
Two types of HKT transporters with different properties of Na+ and K+ transport in Oryza sativa (2001)

Summary It is thought that Na + and K + homeostasis is crucial for salt‐tolerance in plants. To better understand the Na + and K + homeostasis in important crop rice ( Oryza sativa L.), a cDNA homologous to the wheat HKT1 encoding K + ‐Na + symporter was isolated from japonica rice, cv Nipponbare (Ni‐ OsHKT1 ). We also isolated two cDNAs homologous to Ni‐ OsHKT1 from salt‐tolerant indica rice, cv Pokkali (Po‐ OsHKT1 , Po‐ OsHKT2 ). The predicted amino acid sequence of Ni‐OsHKT1 shares 100% identity with Po‐OsHKT1 and 91% identity with Po‐OsHKT2, and they are 66–67% identical to wheat HKT1. Low‐K + conditions (less than 3 m m ) induced the expression of all three OsHKT genes in roots, but mRNA accumulation was inhibited by the presence of 30 m m Na + . We further characterized the ion‐transport properties of OsHKT1 and OsHKT2 using an expression system in the heterologous cells, yeast and Xenopus oocytes. OsHKT2 was capable of completely rescuing a K + ‐uptake deficiency mutation in yeast, whereas OsHKT1 was not under K + ‐limiting conditions. When OsHKTs were expressed in Na + ‐sensitive yeast, OsHKT1 rendered the cells more Na + ‐sensitive than did OsHKT2 in high NaCl conditions. The electrophysiological experiments for OsHKT1 expressed in Xenopus oocytes revealed that external Na + , but not K + , shifted the reversal potential toward depolarization. In contrast, for OsHKT2 either Na + or K + in the external solution shifted the reversal potential toward depolarization under the mixed Na + and K + containing solutions. These results suggest that two isoforms of HKT transporters, a Na + transporter (OsHKT1) and a Na + ‐ and K + ‐coupled transporter (OsHKT2), may act harmoniously in the salt tolerant indica rice.
Precise register allocation for irregular architectures (1998)

This paper proposes a precise approach to register allocation for irregular-register architectures which is based on 0-1 integer programming (IP). Prior work shows that IP register allocation is feasible for RISC architectures, which have uniform registers and register usage. Extensions to the prior work are proposed that precisely model register irregularities including combined source/destination specifiers, memory operands, and variations in the cost of register usage. The x86 architecture is selected as a representative irregular-register architecture for experimental study. An IP register allocator is built for the x86 architecture within the Gnu C Compiler (GCC), and is compared experimentally with GCC's graph-coloring register allocator. Experimental results show that the IP allocator reduces register allocation overhead by 61% compared with the graph coloring allocator. The results also show that the x86 IP allocator is dramatically faster than the prior RISC IP allocator; because of the smaller number of registers in the x86 architecture and because of the register irregularities. These results suggest that IP register allocation is well suited for irregular-register architectures.
Sulfur amino acid metabolism and protein synthesis in young sheep fed ryegrass pasture and two Lotus cultivars containing condensed tannin (1995)

Groups of sheep were fed either fresh ryegrass pasture, a low condensed tannin (CT) diet (Lotus corniculatus; or a medium CT diet (L. pedunculatus) to compare the effects of these feeds on methionine and cysteine metabolism, because of their significance in wool production, and on phenylalanine as an indicator of general protein metabolism. Dry matter intake (DMI) among groups, ryegrass pasture, Lotus corniculatus, L. pedunculatus, were significantly different, therefore the treatment means for metabolic measurements and wool growth were adjusted by covariate analysis using DMI. Neither diet nor DM1 had any overall effect on phenylalanine concentrations in whole blood or phenylalanine irrevirible loss rate (IRL). However there were significant (P &amp;lt; 0.001) diet effects on cysteine blood concentrations. Methionine effects paralleled those of cysteine, with higher concentrations in sheep fed L. pedunculatus relative to pasture fed animals. Sheep fed L. pedunculatus had much higher cysteine and methionine ILRs compared with either the pasture or L. corniculatus groups. Sheep fed the highest level of condensed tannin in their diet (l. pedunculatus) had significantly greater rates of transsulfuration, cysteine and methionine oxidation. Overall the results show that CT in L. pedunculatus gives a greater degree of 'protection' during digestion for cysteine, methionine and phenylalanine, while L. corniculatus resulted in very little advantage. Condensed tannin effects on wool production are marginal and secondary to whole body metabolic influences.
Combination of Living Radical Polymerization and Click Chemistry for Surface Modification (2007)

A novel reversible addition fragmentation technique chain transfer agent (RAFT CTA) was synthesized which permits the possibility of using RAFT polymerization and click chemistry together for surface modification. Using this RAFT CTA, the surface of silica nanoparticles was modified with polystyrene and polyacrylamide brushes via the “grafting to” approach. A click reaction was used to attach polymers onto the surface which produced relatively high grafting density. Both tethered polystyrene and polyacrylamide chains were found in the brush regime. The combination of ATRP and click chemistry was also explored for surface modification. To our knowledge, this is first report of RAFT polymerization and click chemistry together for surface modification.
Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury (2012)

Ischemia-reperfusion injury (IRI) contributes to decreased allograft function and allograft rejection in transplanted kidneys. Thrombospondin-1 is a stress protein typically secreted in response to hypoxia and the ligand activator for the ubiquitously expressed receptor CD47. The function of activated CD47 in IRI remains completely unknown. Here, we found that both CD47 and its ligand thrombospondin-1 were upregulated after renal IRI in mice. CD47-knockout mice were protected against renal dysfunction and tubular damage, suggesting that the development of IRI requires intact CD47 signaling. Chimeric CD47-knockout mice engrafted with wild-type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild-type controls after IRI, suggesting that CD47 signaling in parenchymal cells predominantly mediates renal damage. Treatment with a CD47-blocking antibody protected mice from renal dysfunction and tubular damage compared with an isotype control. Taken together, these data imply that CD47 on parenchymal cells promotes injury after renal ischemia and reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent or suppress ischemia-reperfusion-mediated damage.
HERPES SIMPLEX VIRUS DNA REPLICATION (1997)

The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virustype-1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for originspecific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5'-3' DNA helicase and primase activities, and an origin-binding protein with 3'-5' DNA helicase activity. HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for viral replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase alpha-primase, DNA ligase I, and topoisomerase II, are probably also required. Following circularization of the linear viral genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
Altered Cytokine Responses of Dengue-Specific CD4+ T Cells to Heterologous Serotypes (2005)

The interplay of different inflammatory cytokines induced during a dengue (DEN) virus infection plays a role in either protection or increased disease severity. We measured the frequencies and characterized the cytokine responses of DEN virus-specific memory CD4+ T cells in PBMC of six volunteers who received experimental live attenuated monovalent DEN vaccines. IFN-gamma and TNF-alpha responses to inactivated DEN Ags were detected in up to 0.54 and 1.17% of total circulating CD4+ T cells, respectively. Ags from the homologous serotype elicited the highest IFN-gamma response. The ratio of TNF-alpha- to IFN-gamma-producing CD4+ T cells was higher after stimulation with Ags from heterologous DEN serotypes. Peptide-specific CD4+ T cell frequencies of up to 0.089% were detected by direct staining using HLA class II tetramers. IFN-gamma and TNF-alpha responses to individual HLA class II-restricted peptide epitopes were detected in up to 0.05 and 0.27% of CD4+ T cells, respectively. Peptide sequences from the homologous serotype elicited a variety of cytokine response patterns. TNF-alpha- to IFN-gamma-positive CD4+ T cell ratios varied between peptides, but the ratio of the sum of responses was highest against heterologous serotypes. These results demonstrate epitope sequence-specific differences in T cell effector function. These patterns of effector responses may play a role in the immunopathogenesis of DEN hemorrhagic fever.