gebhart/patrepeval huggingface dataset:
Protection of transplant-induced renal ischemia-reperfusion injury with carbon monoxide (2004)

Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against oxidative stress. We hypothesized that CO would protect ischemia-reperfusion (I/R) injury of transplanted organs, and the efficacy of CO was studied in the rat kidney transplantation model. A Lewis rat kidney graft, preserved in University of Wisconsin solution at 4 degrees C for 24 h, was orthotopically transplanted into syngeneic rats. Recipients were maintained in room air or exposed to CO (250 ppm) in air for 1 h before and 24 h after transplantation. Animals were killed 1, 3, 6, and 24 h after transplantation to assess efficacy of inhaled CO. Rapid upregulation of mRNA for IL-6, IL-1beta, TNF-alpha, ICAM-1, heme oxygenase-1, and inducible nitric oxide synthase was observed within 3 h after transplantation in the control grafts of air-exposed recipients, associating with histopathological evidences of acute tubular necrosis, interstitial hemorrhage, and edema. In contrast, the increase of inflammatory mediators was markedly inhibited in kidney grafts of CO-treated recipients, which correlated with improved renal cortical blood flow. Further detailed morphological analyses revealed that CO preserved the glomerular vascular architecture and podocyte viability with less apoptosis of tubular epithelial cells and less ED1(+) macrophage infiltration. CO inhalation resulted in improved serum creatinine levels and clearance, and animal survival was significantly improved with CO to 60.5 from 25 days in untreated controls. The study demonstrates that exposure of kidney graft recipients to CO at a low concentration can impart significant protective effects against renal I/R injury and improve function of renal grafts.
Presentation on class II MHC molecules of endogenous lysozyme targeted to the endocytic pathway (1997)

We compared the processing and presentation of the model Ag, hen-egg white lysozyme (HEL) expressed in C3.F6 APC as a fusion protein to three different acid hydrolases: cathepsin D, to an unglycosylated form of cathepsin D, and to pepsinogen. As expected from the biology of mannose 6-phosphate (Man-6-P)-containing enzyme, cathepsin D-HEL was delivered to the endosomal/lysosomal system. In contrast, the unglycosylated cathepsin D-HEL was retained in ER/Golgi and some was found in lysosomes. Most of pepsinogen-HEL was rapidly secreted from the APC. All transfectants presented HEL epitopes to T cell hybridomas. Regardless of the main route of traffic of the proteins, the strong I-Ak binding epitope HEL 48-62 was well presented by all. The biochemical forms of this epitope were identical for all. Three other epitopes of HEL that bind I-Ak with less affinity were processed equally well by unglycosylated cathepsin D-HEL and HEL-Ld. The glycosylated cathepsin D-HEL was less efficient in generating the 114-129 epitope. Pepsinogen-HEL was the less efficient of all transfectants in presenting these subdominant epitopes. Soluble cathepsin D-HEL recovered from culture supernatant was strongly immunogenic when added to C3.F6. The uptake was inhibited by free Man-6-P, indicating that the surface Man-6-P receptor can effectively deliver proteins to the class II MHC system.
Correction of β‐thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients (2010)

Beta-thalassemia is a common monogenic disorder due to mutations in the beta-globin gene and gene therapy, based on autologous transplantation of genetically corrected haematopoietic stem cells (HSCs), holds the promise to treat patients lacking a compatible bone marrow (BM) donor. We recently showed correction of murine beta-thalassemia by gene transfer in HSCs with the GLOBE lentiviral vector (LV), expressing a transcriptionally regulated human beta-globin gene. Here, we report successful correction of thalassemia major in human cells, by studying a large cohort of pediatric patients of diverse ethnic origin, carriers of different mutations and all candidates to BM transplantation. Extensive characterization of BM-derived CD34(+) cells before and following gene transfer shows the achievement of high frequency of transduction, restoration of haemoglobin A synthesis, rescue from apoptosis and correction of ineffective erythropoiesis. The procedure does not significantly affect the differentiating potential and the relative proportion of haematopoietic progenitors. Analysis of vector integrations shows preferential targeting of transcriptionally active regions, without bias for cancer-related genes. Overall, these results provide a solid rationale for a future clinical translation.
Nutrigenomics, Rumen-Derived Bioactive Fatty Acids, and the Regulation of Milk Fat Synthesis (2011)

Mammary synthesis of milk fat continues to be an active research area, with significant advances in the regulation of lipid synthesis by bioactive fatty acids (FAs). The biohydrogenation theory established that diet-induced milk fat depression (MFD) in the dairy cow is caused by an inhibition of mammary synthesis of milk fat by specific FAs produced during ruminal biohydrogenation. The first such FA shown to affect milk fat synthesis was trans-10, cis-12 conjugated linoleic acid, and its effects have been well characterized, including dose-response relationships. During MFD, lipogenic capacity and transcription of key mammary lipogenic genes are coordinately down-regulated. Results provide strong evidence for sterol response element-binding protein-1 (SREBP1) and Spot 14 as biohydrogenation intermediate responsive lipogenic signaling pathway for ruminants and rodents. The study of MFD and its regulation by specific rumen-derived bioactive FAs represents a successful example of nutrigenomics in present-day animal nutrition research and offers several potential applications in animal agriculture.
A fast algorithm suitable for DCT implementation with integer multiplication (2002)

The discrete cosine transform (DCT) has wide applications in speech and image data compression. We propose a novel fast DCT algorithm. The proposed algorithm is based on the symmetric property of the DCT kernel matrix. This decomposes an N-point DCT into an N/2-point DCT and can be iterated further. Because it has fewer multiplication steps, when converting the algorithm into hardware implementation with integer computation, we can reduce the error.
Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism (2009)

Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes.
Axotomy-Induced Expression of Calcium-Activated Chloride Current in Subpopulations of Mouse Dorsal Root Ganglion Neurons (2003)

Whole cell patch-clamp recordings of calcium-activated chloride current [ICl(Ca)] were made from adult sensory neurons of naive and axotomized mouse L4-L6 lumbar dorsal root ganglia after 1 day of culture in vitro. A basal ICl(Ca) was specifically expressed in a subset of naive medium-diameter neurons (30-40 microm). Prior nerve injury, induced by sciatic nerve transection 5 days before experiments, increased both ICl(Ca) amplitude and its expression in medium-diameter neurons. Moreover, nerve injury also induced ICl(Ca) expression in a new subpopulation of neurons, the large-diameter neurons (40-50 microm). Small-diameter neurons (inferior to 30 microm) never expressed ICl(Ca). Regulated ICl(Ca) expression was strongly correlated with injury-induced regenerative growth of sensory neurons in vitro and nerve regeneration in vivo. Cell culture on a substrate not permissive for growth, D,L-polyornithine, prevented both elongation growth and ICl(Ca) expression in axotomized neurons. Regenerative growth and the induction of ICl(Ca) expression take place 2 days after injury, peak after 5 days of conditioning in vivo, slowly declining thereafter to control values. The selective expression of ICl(Ca) within medium- and large-diameter neurons conditioned for rapid, efficient growth suggests that these channels play a specific role in postinjury behavior of sensory neuron subpopulations such as neuropathic pain and/or axonal regeneration.
Structure‐activity studies of analogs of β, γ‐methylene‐ATP at P2X‐purinoceptors in the rabbit ear central artery (1995)

Abstract Structure‐activity studies using naphthylmethyl analogs of β, γ‐methylene‐ATP were conducted at the P 2X ‐purinoceptor that mediates contraction of the rabbit ear central artery by ATP, α, β‐m‐ATP. On the adenine base, substitution at the C 2 ‐position (WRC‐0440) increased the agonist potency 2‐fold and substitution at the C 8 ‐position (WRC‐0431) did not change agonist potency, and both compounds had the same maximal response as β, γ‐m‐ATP, whereas substitution at the N 6 ‐position (WRC‐0416) abolished activity. On the D‐ribose sugar, substitution on the 2′‐hydroxyl generated a partial agonist (WRC‐0479), which had a maximal effect of only 39% of that of β‐γ‐m‐ATP. Attempts to substitute the 3′‐hydroxyls by naphthylmethyl failed, but substitution by p‐methoxybenzyl (WRC‐0617) did not change potency or the maximal response. Cyclic substitution of both the 2′‐ and 3′‐hydroxyls by naphthylmethylidine (WRC‐0498) had no effect on the agonist potency or the maximal response relative to β‐γ‐m‐ATP. On the β, γ‐methylenetriphosphonate chain, substitution on the methylene linkage by naphthylmethyl (WRC‐0433) had no effect on agonist potency, but the maximal response increased to 122% that of β‐γ‐ATP. However, the contractile response to WRC‐0433 was not desensitized by α, β‐γ‐ATP (contractile responses to all other agonists were abolished by α‐β‐γ‐ATP pretreatment), but was blocked by the α 1 antagonist prazosin (10 −6 M). WRC‐0433 appears to act at a prejunctional site that mediates ATP‐induced release of norepinephrine. Purine nucleotides with substituents at the 2′‐position of the ribose sugar could provide a lead to the generation of P 2X ‐purinoceptor antagonists. © 1995 Wiley‐Liss, Inc.
Structural characteristics and possible horizontal transfer of group I introns between closely related plant pathogenic fungi (1999)

We have characterized structural features and the distribution pattern of nuclear group I introns found in ribosomal DNA (rDNA) of closely related plant pathogenic fungi of the family Sclerotiniaceae. Sixteen introns, at two distinct positions in the small-subunit (SSU) and large-subunit (LSU) rDNA, were sequenced and analyzed among the 29 taxa included in the initial screening. Genera found to contain introns were Botrytis, Dumontinia, Encoelia, Grovesinia, Myriosclerotinia, and Sclerotinia. Secondary-structure analyses of the group I introns concluded that all belong to the common IC1 subclass. Interestingly, the SSU rDNA intron from Myriosclerotinia caricisampullacea contains an insertion-like sequence extension which may be a relic of an open reading frame. Incongruent branching patterns of intron-based and rDNA-based (internal transcribed spacer) phylogenetic trees suggest that the fungal host genomes and the group I introns do not share a common evolutionary history. A model to explain how horizontal intron transfers may have occurred among the closely related fungal taxa is proposed.
Approximating a data stream for querying and estimation: algorithms and performance evaluation (2003)

Obtaining fast and good-quality approximations to data distributions is a problem of central interest to database management. A variety of popular database applications, including approximate querying, similarity searching and data mining in most application domains, rely on such good-quality approximations. Histogram-based approximation is a very popular method in database theory and practice to succinctly represent a data distribution in a space-efficient manner. In this paper, we place the problem of histogram construction into perspective and we generalize it by raising the requirement of a finite data set and/or known data set size. We consider the case of an infinite data set in which data arrive continuously, forming an infinite data stream. In this context, we present single-pass algorithms that are capable of constructing histograms of provable good quality. We present algorithms for the fixed-window variant of the basic histogram construction problem, supporting incremental maintenance of the histograms. The proposed algorithms trade accuracy for speed and allow for a graceful tradeoff between the two, based on application requirements. In the case of approximate queries on infinite data streams, we present a detailed experimental evaluation comparing our algorithms with other applicable techniques using real data sets, demonstrating the superiority of our proposal.
Mirror Therapy for Phantom Limb Pain (2012)

Phantom limb pain is a painful sensation that is perceived in a body part that no longer exists. To control this pain, many methods have been used such as medication, physical treatment, nerve block, neuromodulation, surgical treatment and mirror therapy. However, until now, there effects have been uncertain. We report the successful reduction of phantom limb pain using mirror therapy when other treatments initially failed to control the pain.
Metal-Containing Compounds of the Anion (C2H5)2NN2O2 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal-Containing Compounds of the Anion (C2H5)2NN2O2Raymond Longhi and Russell S. DragoCite this: Inorg. Chem. 1963, 2, 1, 85–88Publication Date (Print):February 1, 1963Publication History Published online1 May 2002Published inissue 1 February 1963https://doi.org/10.1021/ic50005a024RIGHTS & PERMISSIONSArticle Views56Altmetric-Citations7LEARN 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 (458 KB) Get e-Alerts Get e-Alerts
Role of matrix protein in cytopathogenesis of vesicular stomatitis virus (1990)

The matrix (M) protein of vesicular stomatitis virus (VSV) plays an important structural role in viral assembly, and it also has a regulatory role in viral transcription. We demonstrate here that the M protein has an additional function. It causes visible cytopathic effects (CPE), as evidenced by the typical rounding of polygonal cells after VSV infection. We have analyzed a temperature-sensitive mutant of the M protein of VSV (tsG33) which is defective in viral assembly and which fails to cause morphological changes of the cells after infection at the nonpermissive temperature (40 degrees C). Interestingly, this defect in viral assembly as well as the CPE were reversible. Microinjection of antisense oligonucleotides which specifically inhibit M protein translation also inhibited the occurrence of CPE. Most importantly, when cells were transfected with a cDNA encoding the temperature-sensitive M protein of tsG33, no CPE was observed at the nonpermissive temperature. However, when these cells were shifted to the permissive temperature (32 degrees C), they rounded up and detached from the dish. These results demonstrate that M protein in the absence of the other viral proteins causes rounding of the cells, probably through a disorganization of the cytoskeleton. The absence of CPE at the nonpermissive temperature is correlated with an abnormal dotted staining pattern of M in these cells, suggesting that the mutant M protein may self-aggregate or associate with membranes rather than interact with cytoskeletal elements.
Thin, high atomic weight refractory film deposition for diffusion barrier, adhesion layer, and seed layer applications (1996)

Thin, nearly conformal films are required for semiconductor applications to function as diffusion barriers, adhesion layers and seed layers within trenches and vias. The deposition of high mass refractory films with conventional, noncollimated magnetron sputtering at low pressures shows better-than-expected conformality which is dependent on the degree of directionality of the depositing atoms: the conformality increases as the directionality increases. The primary cause appears to be a strongly angle-dependent reflection coefficient for the depositing metal atoms. As the deposition is made more directional by increasing the cathode-to-sample distance, the depositing atoms are more likely to reflect from the steep sidewalls, leading to better conformality as well as a less columnar film structure.
Lipoxygenase and Hydroperoxide Lyase in Germinating Watermelon Seedlings (1976)

Lipoxygenase (EC 1.13.1.13) was found in seedlings of Citrullus lanatus (Thunb.) Matsum. and Nakai (watermelon). The enzyme has pH optima of 4.4 and 5.5 and is inhibited by 0.2 mM nordihydroguaiaretic acid. It is present in two functional units with estimated molecular weights of 120,000 and 240,000, respectively.A new enzyme, tentatively termed hydroperoxide lyase, has been partially purified from watermelon seedlings. The enzyme, located principally in the region of the hypocotyl-root junction, catalyzes the conversion of 13-l-hydroperoxy-cis-9-trans-11-octadecadienoic acid to 12-oxo-trans-10-dodecenoic acid and hexanal. The hydroperoxide lyase enzyme from watermelon has a molecular weight in excess of 250,000, a pH optimum in the range of 6 to 6.5, and is inhibited by p-chloromercuribenzoic acid. Its presence has also been demonstrated in other cucurbits.The maximum activity of both enzymes occurs on the 6th day of germination. The identification of the products of the hydroperoxide lyase reaction suggests that lipoxygenase and hydroperoxide lyase may be involved in the conversion of certain polyunsaturated fatty acids to traumatic acid (trans-2-dodecenedioic acid).
Transcoronary chemical ablation of arrhythmias. (1992)

Chemical ablation is a technique that may be of enormous value and even lifesaving for patients with an incessant form of tachycardia not responding to any form of medical therapy. Transcoronary ablation of AV conduction should be considered in patients with a right dominant coronary circulation in whom radiofrequency ablation has failed.
Combinatorial TGF-β signaling blockade and anti-CTLA-4 antibody immunotherapy in a murine BRAFV600E-PTEN-/- transgenic model of melanoma. (2014)

3011 Background: T cell-targeted checkpoint inhibitor immunotherapy for melanoma and other solid tumor malignancies only benefits a subpopulation of patients. Our work has shown that melanoma-expressed factors including TGF-β can generate an immune privileged site by suppressing the function of critical dendritic cell populations within the local immune microenvironment. We hypothesized that inhibiting TGF-β signaling in the tumor microenvironment could augment the efficacy of anti-CTLA-4 antibody therapy in a murine transgenic model of melanoma. Methods: Upon primary melanoma development in Tyr::CreER;BrafCA/+;PTENlox/loxmice, the LY2157299 type I TGF-β receptor serine/threonine kinase inhibitor was administered daily by oral gavage accompanied by intra-peritoneal delivery of anti-CTLA-4 monoclonal antibody (mAb) every three days. Tumor development was monitored by caliper and photodocumentation/imaging analysis. After 14 days, tumor tissue, tumor-draining lymph node (TDLN) tissue, and lung tissue was resected for whole tissue Western blot analysis, T cell flow cytometry, immunohistochemistry, and indoleamine 2,3-dioxygenase (IDO) enzymatic activity assays. Results: While LY2157299 and anti-CTLA-4 mAb monotherapy failed to suppress melanoma progression, LY2152799-anti-CTLA-4 mAb combination therapy synergistically suppressed both primary melanoma tumor growth as well as melanoma metastasis in this physiologically-relevant transgenic melanoma model. These observations correlated with significant increases in the CD8+ T cell/CD4+FoxP3+regulatory T (Treg) cell ratio in melanoma tissues. In addition, LY2152799 effectively suppressed TDLN-derived dendritic cell IDO enzyme activity and this was found to correlate with diminished levels of Tregs in both TDLN and primary melanoma tissues. Conclusions: TGF-β signaling inhibition is a promising strategy for augmenting the anti-tumor efficacy of immune checkpoint blockade in melanoma. The pharmacological manipulation of the tumor microenvironment to reverse local immune evasion mechanisms and enhance anti-tumor immune responses represents an important avenue for future studies.