gebhart/patrepeval huggingface dataset:
Injectable Microbubbles as Contrast Agents for Diagnostic Ultrasound Imaging: The Key Role of Perfluorochemicals (2003)

Ultrasonography has, until recently, lacked effective contrast-enhancing agents. Micrometer-sized gas bubbles that resonate at a diagnostic frequency are ideal reflectors for ultrasound. However, simple air bubbles, when injected into the blood stream, disappear within seconds through the combined effects of Laplace pressure, blood pressure, and exposure to ultrasound energy. Use of fluorocarbon vapor, by extending the persistence of microbubbles in vivo from seconds to minutes, propelled contrast ultrasonography into clinical practice. Imaging techniques that selectively suppress tissue, but not microbubble signal, further increase image contrast. Approved products consist of C3F8 or SF6 microbubbles, and N2 microbubbles osmotically stabilized with C6F14. These agents allow the detection and characterization of cardiovascular abnormalities and solid organ lesions, such as tumors. By providing higher quality images, they improve the accuracy and confidence of disease diagnosis, and can play a decisive role in clinical decision making. New objectives include agents that target specific cells for the molecular imaging of disease, and drug and gene delivery, including ultrasound-triggered delivery.
Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode α1,4- N -acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis (2001)

The tumor suppressors EXT1 and EXT2 are associated with hereditary multiple exostoses and encode bifunctional glycosyltransferases essential for chain polymerization of heparan sulfate (HS) and its analog, heparin (Hep). Three highly homologous EXT-like genes, EXTL1-EXTL3, have been cloned, and EXTL2 is an alpha1,4-GlcNAc transferase I, the key enzyme that initiates the HS/Hep synthesis. In the present study, truncated forms of EXTL1 and EXTL3, lacking the putative NH2-terminal transmembrane and cytoplasmic domains, were transiently expressed in COS-1 cells and found to harbor alpha-GlcNAc transferase activity. EXTL3 used not only N-acetylheparosan oligosaccharides that represent growing HS chains but also GlcAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl (Cbz), a synthetic substrate for alpha-GlcNAc transferase I that determines and initiates HS/Hep synthesis. In contrast, EXTL1 used only the former acceptor. Neither EXTL1 nor EXTL3 showed any glucuronyltransferase activity as examined with N-acetylheparosan oligosaccharides. Heparitinase I digestion of each transferase-reaction product showed that GlcNAc had been transferred exclusively through an alpha1,4-configuration. Hence, EXTL3 most likely is involved in both chain initiation and elongation, whereas EXTL1 possibly is involved only in the chain elongation of HS and, maybe, Hep as well. Thus, their acceptor specificities of the five family members are overlapping but distinct from each other, except for EXT1 and EXT2 with the same specificity. It now has been clarified that all of the five cloned human EXT gene family proteins harbor glycosyltransferase activities, which probably contribute to the synthesis of HS and Hep.
Gene Transfer into Hematopoietic Stem Cells of Nonhuman Primates (1996)

Nonhuman primates provide an appropriate preclinical large-animal model to test the efficacy of bone marrow gene therapy procedures. Successful retroviral vector-mediated gene transfer into monkey pluripotent hematopoietic stem cells (PHSC) has closed the gap between gene transfer experiments in mouse models and clinical application of bone marrow gene therapy. After initial bone marrow transplant failures, ex vivo bone marrow culture conditions were found that sufficiently supported maintenance of the long-term repopulating ability of genetically modified autologous monkey grafts. The efficiency of gene transfer into primate PHSC has, however, remained at least one order of magnitude lower than has been achieved in mice. Similar gene transfer efficiencies have been obtained with total bone marrow grafts, CD34+ bone marrow grafts, and mobilized peripheral blood progenitor cell grafts; however, various attempts to increase the transduction efficiency have been without significant success. Primate PHSC seem to require quite different culture conditions for their maintenance and transduction than mouse PHSC, in particular regarding hematopoietic growth factor addition. In contrast to observations in other species, some form of conditioning appeared essential for engraftment of transduced PHSC in monkeys. Although it has been shown that mouse retroviruses can replicate in monkeys and are capable of inducing neoplasms, experiments in monkeys have sufficiently confirmed the safety of current gene transfer procedures to allow their clinical application.
Penile erection: possible role for vasoactive intestinal polypeptide as a neurotransmitter. (1984)

Concentrations of vasoactive intestinal polypeptide were measured in blood drawn from the cavernous spaces of corpus cavernosum of the human penis during tumescence and erection, and the effect of injecting the polypeptide into the cavernous spaces was studied. A significant release of the polypeptide was shown during tumescence and erection. Injection of exogenous vasoactive intestinal polypeptide induced erection. These findings support the concept of vasoactive intestinal polypeptide as a neurotransmitter in penile erection and suggest that it might have a clinical use in patients suffering from erectile dysfunction.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes (2009)

Hematogenous metastasis is promoted by interactions of tumor cells with leukocytes, platelets, and the endothelium in the local intravascular microenvironment. Here we show that the activation of the microvascular endothelium results in recruitment of monocytes to metastatic tumor cells and promotes the establishment of the metastatic microenvironment. This inflammatory-like endothelial response was observed in microvascular endothelial cells only. Microarray analysis of microvascular endothelial cells cocultured with tumor cells in the presence of leukocytes and platelets revealed a specific gene expression profile. Selectin-mediated interactions of tumor cells with platelets and leukocytes activated endothelial cells and induced production of C-C chemokine ligand 5 (CCL5). Inhibition of CCL5-dependent monocyte recruitment during the early phase of metastasis by a CCL5 receptor antagonist strongly reduced tumor cell survival and attenuated metastasis. Collectively, these findings demonstrate that the endothelial expression of CCL5 contributes to the formation of a permissive metastatic microenvironment.
Living ring-opening metathesis polymerization catalyzed by well-characterized transition-metal alkylidene complexes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLiving ring-opening metathesis polymerization catalyzed by well-characterized transition-metal alkylidene complexesRichard R. SchrockCite this: Acc. Chem. Res. 1990, 23, 5, 158–165Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://pubs.acs.org/doi/10.1021/ar00173a007https://doi.org/10.1021/ar00173a007research-articleACS PublicationsRequest reuse permissionsArticle Views4059Altmetric-Citations744LEARN 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
Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma (2004)

A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.
Monodisperse Polymer Capsules: Tailoring Size, Shell Thickness, and Hydrophobic Cargo Loading via Emulsion Templating (2010)

Abstract The preparation of monodisperse polymer (polydopamine, PDA) capsules by a one‐step interfacial polymerization of dopamine onto dimethyldiethoxysilane (DMDES) emulsion droplets and removal of the DMDES templates with ethanol is reported. The diameters of the PDA capsules can be tailored from 400 nm to 2.4 µm by varying either the DMDES emulsion condensation time or the emulsion concentration used for templating. Further, capsules with defined nanometer‐scale shell thicknesses (ranging from ∼10 to 30 nm) can be prepared by adjusting the emulsion concentration. This shell thickness can be increased by repeated interfacial polymerization of dopamine, with three cycles yielding capsules with a shell thickness of up to 140 nm (for a 0.6% v/v suspension). Functional substances, such as organically stabilized magnetic (Fe 3 O 4 ) nanoparticles, quantum dots (CdSe/CdS), and hydrophobic drugs (thiocoraline), can be preloaded in the emulsion droplets, and following PDA coating and DMDES removal, these materials remain encapsulated in the polymer capsules. All of the unloaded and loaded PDA capsules are monodisperse and do not aggregate. This work provides new avenues for the preparation of polymer capsules with defined size and shell thickness and for the encapsulation of a range of hydrophobic substances.
In vitro and in vivo uptake of azithromycin (CP-62,993) by phagocytic cells: possible mechanism of delivery and release at sites of infection (1989)

Azithromycin, a novel azalide antibiotic, concentrated in human and mouse polymorphonuclear leukocytes (PMNs), murine peritoneal macrophages, and mouse and rat alveolar macrophages, attaining intracellular concentrations up to 226 times the external concentration in vitro. In murine peritoneal macrophages, azithromycin achieved concentration gradients (internal to external) up to 26 times higher than erythromycin. The cellular uptake of azithromycin was dependent on temperature, viability, and pH and was decreased by 2,4-dinitrophenol. Azithromycin did not decrease phagocyte-mediated bactericidal activity or affect PMN or macrophage oxidative burst activity (H2O2 release or Nitro Blue Tetrazolium reduction, respectively). Azithromycin remained in cells for several hours, even after extracellular drug was removed. However, its release was significantly enhanced by phagocytosis of Staphylococcus aureus (82 versus 23% by 1.5 h). In vivo, 0.05 micrograms of azithromycin was found in peritoneal fluids of mice 20 h after oral treatment with a dose of 50 mg/kg. Following caseinate-induced PMN infiltration, there was a sixfold increase in peritoneal cavity azithromycin to 0.32 micrograms, most of which was intracellular. Therefore, the uptake, transport, and later release of azithromycin by these cells demonstrate that phagocytes may deliver active drug to sites of infection.
Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles (2014)

Recent findings suggest that tau oligomers, which form before neurofibrillary tangles (NFTs), are the true neurotoxic tau entities in neurodegenerative tauopathies, including Alzheimer's disease (AD). Studies in animal models of tauopathy suggest that tau oligomers play a key role in eliciting behavioral and cognitive impairments. Here, we used a novel tau oligomer-specific monoclonal antibody (TOMA) for passive immunization in mice expressing mutant human tau. A single dose of TOMA administered either intravenously or intracerebroventricularly was sufficient to reverse both locomotor and memory deficits in a mouse model of tauopathy for 60 d, coincident with rapid reduction of tau oligomers but not phosphorylated NFTs or monomeric tau. Our data demonstrate that antibody protection is mediated by extracellular and rapid peripheral clearance. These findings provide the first direct evidence in support of a critical role for tau oligomers in disease progression and validate tau oligomers as a target for the treatment of AD and other neurodegenerative tauopathies.
In vivoproliferation of naïve and memory influenza-specific CD8+T cells (1999)

The virus-specific CD8(+) T cell response has been analyzed through the development, effector, and recovery phases of primary and secondary influenza pneumonia. Apparently, most, if not all, memory T cells expressing clonotypic receptors that bind a tetrameric complex of influenza nucleoprotein (NP)(366-374) peptide+H-2D(b) (NPP) are induced to divide during the course of this localized respiratory infection. The replicative phase of the recall response ends about the time that virus can no longer be recovered from the lung, whereas some primary CD8(+)NPP(+) T cells may proliferate for a few more days. The greatly expanded population of CD8(+)NPP(+) memory T cells in the lymphoid tissue of secondarily challenged mice declines progressively in mean prevalence over the ensuing 100 days, despite the fact that at least some of these lymphocytes continue to cycle. The recall of cell-mediated immunity thus is characterized by massive proliferation of the antigen-specific CD8(+) set, whereas the extent of lymphocyte turnover in the absence of cognate peptide is variable, at a low level, and can be influenced by intercurrent infection.
Isolation of the GSY1 gene encoding yeast glycogen synthase and evidence for the existence of a second gene. (1990)

Glycogen synthase preparations from Saccharomyces cerevisiae contained two polypeptides of molecular weights 85,000 and 77,000. Oligonucleotides based on protein sequence were utilized to clone a S. cerevisiae glycogen synthase gene, GSY1. The gene would encode a protein of 707 residues, molecular mass 80,501 daltons, with 50% overall identity to mammalian muscle glycogen synthases. The amino-terminal sequence obtained from the 85,000-dalton species matched the NH2 terminus predicted by the GSY1 sequence. Disruption of the GSY1 gene resulted in a viable haploid with glycogen synthase activity, and purification of glycogen synthase from this mutant strain resulted in an enzyme that contained the 77,000-dalton polypeptide. Southern hybridization of genomic DNA using the GSY1 coding sequence as a probe revealed a second weakly hybridizing fragment, present also in the strain with the GSY1 gene disrupted. However, the sequences of several tryptic peptides derived from the 77,000-dalton polypeptide were identical or similar to the sequence predicted by the GSY1 gene. The data are explained if S. cerevisiae has two glycogen synthase genes encoding proteins with significant sequence similarity The protein sequence predicted by the GSY1 gene lacks the extreme NH2-terminal phosphorylation sites of the mammalian enzymes. The COOH-terminal phosphorylated region of the mammalian enzyme over-all displayed low identity to the yeast COOH terminus, but there was homology in the region of the mammalian phosphorylation sites 3 and 4. Three potential cyclic AMP-dependent protein kinase sites are located in this region of the yeast enzyme. The region of glycogen synthase likely to be involved in covalent regulation are thus more variable than the catalytic center of the molecule.
Functional vision and corneal changes after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography (1999)

Functional vision changes do occur after LASIK. The optical quality of the cornea is reduced and the asphericity becomes oblate. Changes in functional vision worsen as the target contrast diminishes and the pupil size increases. These findings indicate that the oblate shape of the cornea following LASIK is the predominant factor in the functional vision decrease.
Role of innate immunity in a murine model of histidyl–transfer RNA synthetase (Jo‐1)–mediated myositis (2010)

Collectively, the findings of these experiments support a model in which HisRS can trigger both innate and adaptive immune responses that culminate in severe muscle inflammation that is the hallmark of idiopathic inflammatory myopathy.
Compression treatment of hypertrophic scars in burned children. (1978)

The formation of hypertrophic scars is common following healing of the burn wound, particularly in children. The control of scar formation is an important part of overall treatment in these cases and this paper describes a newer method that applies compression to the burn scar in an attempt to improve the ultimate appearance. The 35 patients treated by this method included some with partial-thickness and others with full-thickness burns. The results of treatment with compression garments were assessed at 6 months and at 12 months, using a grading system based on colour, consistency and thickness of the scar. The design of facial moulages and their use in compression of facial scars are dealt with. Overall there was a 75% to 80% improvement in the state of burn scars. The reasons for this improvement are discussed.
The Phosphate Carrier from Yeast Mitochondria (1998)

Wild type phosphate carrier (PIC) from Saccharomyces cerevisiae and recombinant PIC proteins with different C-terminal extensions were expressed in Escherichia coli as inclusion bodies. From these, PIC was isolated with the detergent sodium lauroyl sarcosinate in a form, partially monomeric and unfolded. This PIC associates to stable dimers after exchanging the detergent to the polyoxyethylene detergent C12E8 and dialysis. Combining two differently tagged monomers of PIC and following this with affinity chromatography yields defined homo- and heterodimeric forms of PIC, which are all fully active after reconstitution. As a member of the mitochondrial carrier family PIC is supposed to function as a homodimer. We investigated its dimeric nature in the functionally active state after reconstitution. When reconstituting PIC monomers a sigmoidal dependence of transport activity on the amount of inserted protein is observed, whereas insertion of PIC dimers leads to a linear dependence. Heterodimeric PIC constructs consisting of both an active and an inactivated subunit do not catalyze phosphate transport. In contrast, reconstitution of a mixture of active and inactive monomeric subunits led to partially active carrier. These experiments prove (i) that PIC does not function in monomeric form, (ii) that PIC dimers are stable both in the solubilized state and after membrane insertion, and (iii) that transport catalyzed by PIC dimers involves functional cross-talk between the two monomers.
Substrate recognition and identification of splice sites by the tRNA-splicing endonuclease and ligase from Saccharomyces cerevisiae. (1987)

We have examined the substrate requirements for efficient and accurate splicing of tRNA precursors in Saccharomyces cerevisiae. The effects of Schizosaccharomyces pombe tRNASer gene mutations on the two steps in splicing, intron excision and joining of tRNA halves, were determined independently by using partially purified splicing endonuclease and tRNA ligase from S. cerevisiae. Two mutations (G14 and A46) reduced the efficiency of excision and joining in parallel, whereas two others (U47:7 and C33) produced differential effects on these two steps; U47:7 affected primarily the excision reaction, and C33 had a greater impact on ligation. These data indicate that endonuclease and ligase recognize both common and unique features of their substrates. Another two mutations (Ai26 and A37:13) induced miscutting, although with converse effects on the two splice sites. Thus, the two cutting events appear to be independent. Finally, we suggest that splice sites may be determined largely through their position relative to sites within the tRNA-like domain of the precursors. Several of these important sites were identified, and others are proposed based on the data described here.
Electromyographic Analysis of Single-Leg, Closed Chain Exercises: Implications for Rehabilitation After Anterior Cruciate Ligament Reconstruction. (2002)

OBJECTIVE: Many knee rehabilitation studies have examined open and closed kinetic chain exercises. However, most studies focus on 2-legged, closed chain exercise. The purpose of our study was to characterize 1-legged, closed chain exercise in young, healthy subjects. SUBJECTS: Eighteen normal subjects (11 men, 7 women; age, 24.6 +/- 1.6 years) performed unsupported, 1-legged squats and step-ups to approximately tibial height. MEASUREMENTS: Knee angle data and surface electromyographic activity from the thigh muscles were recorded. RESULTS: The maximum angle of knee flexion was 111 +/- 23 degrees for squats and 101 +/- 16 degrees for step-ups. The peak quadriceps activation was 201 +/- 66% maximum voluntary isometric contraction, occurring at an angle of 96 +/- 16 degrees for squats. Peak quadriceps activation was 207 +/- 50% maximum voluntary isometric contraction and occurred at 83 +/- 12 degrees for step-ups. CONCLUSIONS: The high and sustained levels of quadriceps activation indicate that 1-legged squats and step-ups would be effective in muscle rehabilitation. As functional, closed chain activities, they may also be protective of anterior cruciate ligament grafts. Because these exercises involve no weights or training equipment, they may prove more cost effective than traditional modes of rehabilitation.
P[acman]: A BAC Transgenic Platform for Targeted Insertion of Large DNA Fragments in D. melanogaster (2006)

We describe a transgenesis platform for Drosophila melanogaster that integrates three recently developed technologies: a conditionally amplifiable bacterial artificial chromosome (BAC), recombineering, and bacteriophage PhiC31-mediated transgenesis. The BAC is maintained at low copy number, facilitating plasmid maintenance and recombineering, but is induced to high copy number for plasmid isolation. Recombineering allows gap repair and mutagenesis in bacteria. Gap repair efficiently retrieves DNA fragments up to 133 kilobases long from P1 or BAC clones. PhiC31-mediated transgenesis integrates these large DNA fragments at specific sites in the genome, allowing the rescue of lethal mutations in the corresponding genes. This transgenesis platform should greatly facilitate structure/function analyses of most Drosophila genes.
Silver free III-nitride flip chip light-emitting-diode with wall plug efficiency over 70% utilizing a GaN tunnel junction (2016)

A molecular beam epitaxy regrowth technique was demonstrated on standard industrial patterned sapphire substrate light-emitting diode (LED) epitaxial wafers emitting at 455 nm to form a GaN tunnel junction. By using an HF pretreatment on the wafers before regrowth, a voltage of 3.08 V at 20 A/cm2 was achieved on small area devices. A high extraction package was developed for comparison with flip chip devices which utilize an LED floating in silicone over a BaSO4 coated header and produced a peak external quantum efficiency (EQE) of 78%. A high reflectivity mirror was designed using a seven-layer dielectric coating backed by aluminum which has a calculated angular averaged reflectivity over 98% between 400 and 500 nm. This was utilized to fabricate a flip chip LED which had a peak EQE and wall plug efficiency of 76% and 73%, respectively. This flip chip could increase light extraction over a traditional flip chip LED due to the increased reflectivity of the dielectric based mirror.