gebhart/patrepeval huggingface dataset:
Eicosapentaenoic acid, but not docosahexaenoic acid, increases mitochondrial fatty acid oxidation and upregulates 2,4‐dienoyl‐CoA reductase gene expression in rats (1996)

The aim of the present study was to investigate whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was responsible for the triglyceride-lowering effect of fish oil. In rats fed a single dose of EPA as ethyl ester (EPA-EE), the plasma concentration of triglycerides was decreased at 8 h after acute administration. This was accompanied by an increased hepatic fatty acid oxidation and mitochondrial 2,4-dienoyl-CoA reductase activity. The steady-state level of 2,4-dienoyl-CoA reductase mRNA increased in parallel with the enzyme activity. An increased hepatic long-chain acyl-CoA content, but a reduced amount of hepatic malonyl-CoA, was obtained at 8 h after acute EPA-EE treatment. On EPA-EE supplementation, both EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) increased in the liver, whereas the hepatic DHA (22:6n-3) concentration was unchanged. On DHA-EE supplementation retroconversion to EPA occurred. No statistically significant differences were found, however, for mitochondrial enzyme activities, malonyl-CoA, long-chain acyl-CoA, plasma lipid levels, and the amount of cellular fatty acids between DHA-EE treated rats and their controls at any time point studied. In cultured rat hepatocytes, the oxidation of [1-14C]palmitic acid was reduced by DHA, whereas it was stimulated by EPA. In the in vivo studies, the activities of phosphatidate phosphohydrolase and acetyl-CoA carboxylase were unaffected after acute EPA-EE and DHA-EE administration, but the fatty acyl-CoA oxidase, the rate-limiting enzyme in peroxisomal fatty acid oxidation, was increased after feeding these n-3 fatty acids. The hypocholesterolemic properties of EPA-EE may be due to decreased 3-hydroxy-3-methylglutaryl-CoA reductase activity. Furthermore, replacement of the ordinary fatty acids, i.e., the monoenes (16:1n-7, 18:1n-7, and 18:1n-9) with EPA and some conversion to DPA concomitant with increased fatty acid oxidation is probably the mechanism leading to changed fatty acid composition. In contrast, DHA does not stimulate fatty acid oxidation and, consequently, no such displacement mechanism operates. In conclusion, we have obtained evidence that EPA, and not DHA, is the fatty acid primarily responsible for the triglyceride-lowering effect of fish oil in rats.
Chemistry of thienopyridines. XIII. Selective formation of sulfones in Bi‐ and tricyclic Systems. Thieno[2,3‐b]pyridine 1,1‐dioxide as a dienophile (1972)

Abstract Bicyclic and tricyclic thienopyridines are converted into sulfones in 13‐73% yield by means of acid‐hypochlorite. The sulfone thieno[2,3‐ b ]pyridine 1,1‐oxide (Ib) undergoes Diels‐Alder condensation with furan (both exo and endo products formed), anthracene, and naphthacene. Self‐condensation of Ib occurs with elimination of sulfur dioxide to give 8‐(3‐pyridyl)quinoline (XV). The structure of XV was established by means of pmr and a europium shift reagent. Ultraviolet, pmr, and mass spectral data for various compounds are presented and discussed.
ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains (1998)

Leukocyte chemoattractants act through a rapidly growing subfamily of G protein-coupled receptors. We report the cloning of a novel human gene encoding an orphan receptor (ChemR23) related to the C3a, C5a and formyl Met-Leu-Phe receptors, and more distantly to the subfamilies of chemokine receptors. ChemR23 transcripts were found to be abundant in monocyte-derived dendritic cells and macrophages, treated or not with LPS. Low expression could also be detected by reverse transcription-PCR in CD4+ T lymphocytes. The gene encoding ChemR23 was assigned by radiation hybrid mapping to the q21.2-21.3 region of human chromosome 12, outside the gene clusters identified so far for chemoattractant receptors. Given the increasing number of chemoattractant receptors used by HIV-1, HIV-2 and SIV as coreceptors, ChemR23 was tested in fusion assays for potential coreceptor activity by a range of viral strains. None of the tested HIV-2 strains made use of ChemR23 as a coreceptor, but several SIV strains (SIVmac316, SIVmac239, SIVmacl7E-Fr and SIVsm62A), as well as a primary HIV-1 strain (92UG024-2) used it efficiently. ChemR23 therefore appears as a coreceptor for immunodeficiency viruses that does not belong to the chemokine receptor family. It is also a putative chemoattractant receptor relatively specific for antigen-presenting cells, and it could play an important role in the recruitment or trafficking of these cell populations. Future work will be required to identify the ligand(s) of this new G protein-coupled receptor and to define its precise role in the physiology of dendritic cells and macrophages.
A robot with improved absolute positioning accuracy for CT guided stereotactic brain surgery (1988)

The use of a Unimation Puma 200 robot, properly interfaced with a computerized tomographic (CT) scanner and with a probe guide mounted at its end effector for CT-guided brain tumor biopsis is discussed. Once the target is identified on the CT picture, a simple command allows the robot to move to a position such that the end-effector probe guide points toward the target. This results in a procedure faster than one using a manually adjustable frame. Probably the most important advantage, as is shown, is the improved accuracy that can be achieved by proper calibration of the robot.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Quantitation of GD2 synthase mRNA by real‐time reverse transcription‐polymerase chain reaction (2002)

Tumor cell depletion quantified by real-time RT-PCR demonstrated efficacy of MoAb 3F8 in BM purging.
Heparin-induced release of extracellular superoxide dismutase to human blood plasma (1987)

Extracellular superoxide dismutase (SOD) has previously been shown to be the major SOD isoenzyme in extracellular fluids. Upon chromatography on heparin-Sepharose it was separated into three fractions: A, without affinity; B, with intermediate affinity; and C, with relatively strong heparin affinity. Intravenous injection of heparin leads to a prompt increase in plasma extracellular-superoxide-dismutase (EC-SOD) activity. Heparin induces no release of EC-SOD from blood cells, nor does it activate EC-SOD in plasma, indicating that the source of the released enzyme is the endothelial-cell surfaces. No distinct saturation could be demonstrated in a dose-response curve up to 200 i.u. of heparin per kg body weight, showing that the releasing potency of heparin is lower for EC-SOD than for previously investigated heparin-released factors. Chromatography of human plasma on heparin-Sepharose shows nearly equal amounts of EC-SOD fractions A, B and C. Heparin induces specifically the release of fraction C. The findings point to the existence of an equilibrium of EC-SOD fraction C between the plasma phase and endothelial-cell surfaces. The major part of EC-SOD in the vasculature seems to be located on endothelial-cell surfaces.
Generative replay with feedback connections as a general strategy for continual learning (2018)

A major obstacle to developing artificial intelligence applications capable of true lifelong learning is that artificial neural networks quickly or catastrophically forget previously learned tasks when trained on a new one. Numerous methods for alleviating catastrophic forgetting are currently being proposed, but differences in evaluation protocols make it difficult to directly compare their performance. To enable more meaningful comparisons, here we identified three distinct scenarios for continual learning based on whether task identity is known and, if it is not, whether it needs to be inferred. Performing the split and permuted MNIST task protocols according to each of these scenarios, we found that regularization-based approaches (e.g., elastic weight consolidation) failed when task identity needed to be inferred. In contrast, generative replay combined with distillation (i.e., using class probabilities as "soft targets") achieved superior performance in all three scenarios. Addressing the issue of efficiency, we reduced the computational cost of generative replay by integrating the generative model into the main model by equipping it with generative feedback or backward connections. This Replay-through-Feedback approach substantially shortened training time with no or negligible loss in performance. We believe this to be an important first step towards making the powerful technique of generative replay scalable to real-world continual learning applications.
Fetal Growth Restriction and Schizophrenia: A Swedish Twin Study (2005)

Abstract Obstetric complications increase the risk of schizophrenia. However, it is not known whether there is a causal relation or whether the association is mediated by genetic and/or shared environmental effects. The aim of this study was to investigate the associations between birthweight, other birth characteristics, and schizophrenia. Twin pairs discordant for schizophrenia will also control for unmeasured genetic and shared environmental effects. Prospectively filed obstetric records were used for a cohort analysis of 11,360 same-sexed twins, and within–twin pair analyses were conducted on 90 twin pairs discordant for schizophrenia. The results from the cohort study showed that low birthweight (less than or equal to 1999 grams; odds ratio [OR] 1.67, 95% confidence interval [CI] 0.88–3.14 and 2000–2299 grams; OR 1.79, 95% CI 1.07–3.01) and small head circumference (less than or equal to 31.5 cm; OR 1.61, 95% CI 1.03–2.51) were associated with later development of schizophrenia. The associations remained in the within-pair analyses. The association between low birthweight and schizophrenia is partly a function of reduced fetal growth. Fetal growth restriction seems to be associated with risk of schizophrenia independently of familial factors.
Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci. (1992)

In MRL mice, the mostly recessive lpr mutation results in both the accumulation of CD4-, CD8-, CD3+ T cells in lymphoid tissue and many features of generalized autoimmune disease, including immune complex glomerulonephritis. To positionally clone the lpr mutation and analyze the effects of background genes, backcross offspring were examined from the cross: (MRL/MpJ-lpr x CAST/Ei)F1 x MRL/MpJ-lpr. The lpr gene was found to be closely linked to a mouse chromosome 19 marker defined by a variation of a Fas gene restriction fragment. Our results identified differences in RNA expression and differences in the genomic organization of the Fas gene between normal and lpr mice, and confirm the recent report that a mutation in the Fas apoptosis gene is the lpr mutation. However, our results also indicate that the Fas gene is expressed in spleen cells from normal mice, and spleen and lymph node cells from mice with a second mutation at the lpr locus (lprcg). Together these results suggest that altered Fas transcription results in the failure of lymphocytes to undergo programmed cell death and may lead to an altered immune cell repertoire. This mechanism may explain certain central and peripheral defects in tolerance that are present in autoimmune disease. The current study also demonstrates the profound effect of background genes on the degree of nephritis, lymphadenopathy, and anti-DNA antibody production. Of major note, our studies suggest the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggests that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. Moreover, this study provides a model for dissecting the complex genetic interactions that result in manifestations of autoimmune disease.
Safety of a new transpulmonary echocontrast agent (albunex®) in repeated echocardiographic studies in patients (1997)

These results suggest that repeated exposures to intravenous Albunex induce no adverse effect on the cellular and humoral immune systems and on left and right heart hemodynamics in patients.
A predominance of the T cell receptor Vγ2/Vδ2 subset in human mycobacteria-responsive T cells suggests germline gene encoded recognition (1991)

Abstract Little is known about the nature of Ag recognition by the TCR-γδ. The recent observation that γδT cells preferentially recognize mycobacterial Ag provides a model to examine the molecular basis of γδ-TCR recognition. Here, examination of the Mycobacteria-stimulated peripheral blood T cells with TCR-specific mAb revealed a predominance of T cells bearing Vγ2/Vδ2 gene products. PCR cloning and sequence analysis of the TCR chains demonstrated extensive junctional diversity indicating that the response was polyclonal. The marked in vitro γδT cell response to Mycobacteria was also detected in newborns before encounters with foreign Ag and exclusively involved the same V-gene usage observed in adults. Together, these results suggest that a major mechanism of γδT cell reactivity involves recognition mediated by germline-encoded segments of the TCR.
Pure red-cell aplasia due to anti-erythropoietin antibodies (2003)

Biopharmaceuticals generated by expression of DNA in cell lines have great potential for the treatment of diseases, in which the endogenous production of a specific protein is inadequately low anduor its administration has beneficial modulating effects on disease processes. Although these drugs are designed as copies of endogenous molecules, immunogenicity is a recognized risk. Factors that have been associated with an immunogenic potential include subtle differences in protein structure and in glycosylation (which is inherently variable), contaminants of the production process, the formulation, storage conditions, patient associated variables and the mode of application, with the i.v. route usually carrying the lowest risk [1]. Erythropoietin (Epo) produced by recombinant DNA technology (epoetin) is probably the most successful biopharmaceutical to date. It was introduced for the treatment of renal anaemia in the late 1980s as an i.v. drug. A few years later when first attempts were made to administer it s.c. at least some investigators were concerned about an increased risk of antibody formation. However, the s.c. application proved to be feasible and safe. Due to a lower dose requirement it became the preferred route of administration in many countries. Epoetin-induced antibodies remained a very rare complication for many years. Recently, however, a significant increase in the frequency of this complication, which leads to severe inhibition of red cell production, was noted.
Receptor-mediated gene delivery and expression in vivo. (1988)

A soluble DNA carrier system was used to target a foreign gene specifically to liver in vivo via asialoglycoprotein receptors. The DNA carrier was prepared consisting of a galactose-terminal (asialo-)glycoprotein, asialoorosomucoid (AsOR), covalently linked to poly-L-lysine. The conjugate was complexed in a 2:1 molar ratio (based on AsOR content of the conjugate) to the plasmid, pSV2 CAT, containing the gene for the bacterial enzyme chloramphenicol acetyltransferase (CAT). Intravenous injection of [32P]plasmid DNA complexed to the carrier demonstrated specific hepatic targeting with 85% of the injected counts taken up by the liver in 10 min compared to only 17% of the counts when the same amount of [32P]DNA alone was injected under identical conditions. Targeted pSV2 CAT DNA was detected at a level of 1.0 ng/g liver by hybridization of a [32P]pSV2 CAT cDNA probe to rat liver DNA extracted 24 h after intravenous injection of AsOR-poly-L-lysine-DNA complex containing 1.0 mg of DNA. Homogenates of livers taken 24 h after injection of the complex revealed that the targeted CAT gene was functional as reflected by the detection of CAT activity (approximately 4 microunits/mg protein). Livers from control animals that received individual constituents of the complex produced no CAT activity. Simultaneous injection of excess AsOR to compete with the AsOR-poly-L-lysine-DNA complex for uptake by the liver inhibited CAT gene expression. Assays for CAT activity in other organs (spleen, kidney, lungs) failed to demonstrate any activity in these organs. This new soluble DNA carrier system can permit targeted delivery of foreign genes specifically to liver with resultant foreign gene expression in vivo.
Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis (2009)

Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology.
Exploring the implications of the NBN for education in Tasmania (2011)

In 2009 The Australian Government announced the development of a $40 billion National Broadband Network (NBN) with some of the first roll-out towns in Tasmania. The question of what the NBN rollout would mean for Education in the state led to the NBN in Education project, including interviews with experts in the field and a culminating forum. It became clear that the NBN in education is not a simple matter of connecting fibre to schools; rather it is a complex environment with many different perspectives and assumptions about learning, the value of learning technologies and the future of schools. This paper reports the research approach associated with the project that helped a group of e-learning, professional learning and ICT leaders to engage with the issues. The frameworks developed to help this process may be valuable for others involved in engaging stakeholders in conversations about the implications of the NBN.
Impact of Protein Shedding on Detection of Mycobacterium avium subsp. paratuberculosis by a Whole-Cell Immunoassay Incorporating Surface-Enhanced Raman Scattering (2007)

The etiological agent of Johne's disease is Mycobacterium avium subsp. paratuberculosis. Controlling the spread of this disease is hindered by the lack of sensitive, selective, and rapid detection methods for M. avium subsp. paratuberculosis. By using a recently optimized sandwich immunoassay (B. J. Yakes, R. J. Lipert, J. P. Bannantine, and M. D. Porter, Clin. Vaccine Immunol. 15:227-234, 2008), which incorporates a new monoclonal antibody for the selective capture and labeling of M. avium subsp. paratuberculosis and surface-enhanced Raman scattering for sensitive readout, detection limits of approximately 630 and approximately 740 M. avium subsp. paratuberculosis cells/ml are achieved in phosphate-buffered saline and whole milk samples, respectively, after spiking with heat-treated M. avium subsp. paratuberculosis. Surprisingly, these detection limits are 3 orders of magnitude lower than expected based on theoretical predictions. Experiments designed to determine the origin of the improvement revealed that the major membrane protein targeted by the monoclonal antibody was present in the sample suspensions as shed protein. This finding indicates that the capture and labeling of shed protein function as a facile amplification strategy for lowering the limit of detection for M. avium subsp. paratuberculosis that may also be applicable to the design of a wide range of highly sensitive assays for other cells and viruses.
Soluble Phenyl-Substituted PPVs—New Materials for Highly Efficient Polymer LEDs (1998)

A new class of soluble electroluminescent poly(p-phenylenevinylene)s (PPVs) is introduced here. Alkoxy-substituted 2-phenyl PPVs (see Figure for a schematic representation) are found to exhibit very good solubility in the conjugated state, good film-forming properties, high molecular weights, and excellent electroluminescence performance. With a simple device setup the researchers achieved very high efficiencies.
β‐Catenin splice variants and downstream targets as markers for neoplastic progression of esophageal cancer (2005)

This study characterizes the frequency of exon 3 CTNNB1 mutations and compares the expression of CTNNB1 transcript variants and downstream targets MYC and WAF1 (p21) across the neoplastic progression of esophageal squamous cell carcinomas (ESCCs). Mutational analysis was performed on 56 tumors and corresponding germline DNA, using primers to exon 3 of CTNNB1 and SSCP DNA sequencing gels. Quantitative Real Time RT-PCR was performed on 45 foci representing the histological spectrum from normal to invasive cancer, using specific primer sets for alternative splice variants that differ by the presence (16A) or absence (16B) of a 159-bp noncoding segment of exon 16 of CTNNB1, in conjunction with downstream targets MYC and WAF1. Two unique mutations were identified, S37F in the SxxxS repeat region, and a germline polymorphism, T59A. Thus, mutation of CTNNB1 exon 3 is a rare event in this population. RT-PCR analysis successfully confirmed the presence of both beta-catenin splice variants in histologically normal and preneoplastic squamous epithelium, and invasive tumors of the esophagus, and identified a significant reduction in the 16A/16B ratio (P = 0.014) and an accompanying significant increase in the MYC/WAF1 expression ratio (P = 0.001) with progression from normal mucosa to dysplasia. This represents the first identification of two CTNNB1 transcripts in histologically "normal" esophageal squamous cells, squamous dysplasia, and invasive ESCC. These results show an increase in the minor mRNA (16B) isoform and changes in the expression of downstream markers consistent with increased transcription during the histological progression from normal to squamous dysplasia.
The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. (1994)

Osteocalcin is the most abundant noncollagenous protein of bone. Here we report that the mouse genome contains an osteocalcin cluster composed of three genes arranged within a 23-kilobase span of genomic DNA. We named them osteocalcin gene 1 (OG1), osteocalcin gene 2 (OG2), and osteocalcin-related gene (ORG) in order from the 5' end to the 3' end of the cluster. Hybridization of polymerase chain reaction-amplified cDNAs with specific oligonucleotides and RNase protection assays showed that OG1 and OG2 are expressed only in bone, whereas ORG is transcribed in kidney but not in bone. Furthermore, during embryogenesis, OG1 and OG2 begin to be expressed at day 15.5, while ORG is transcribed as early as day 10.5. The protein encoded by ORG has a similar pattern of expression and identical structural features to nephrocalcin, a calcium-binding protein partially purified from kidney that plays a role in calcium reabsorption and in prevention of nephrolithiasis. The nephrocalcin gene has not been cloned in any species; we propose that ORG is the mouse nephrocalcin gene. The existence of several osteocalcin or osteocalcin-related sequences is not restricted to mouse but is present in every species we examined.
Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans (2003)

These data indicate that some individuals have BKV and/or JCV antibodies that cross-react with SV40, but they do not provide support for SV40 being a prevalent human pathogen.