gebhart/patrepeval huggingface dataset:
Pro- and antiarrhythmic properties of a diet rich in fish oil (2006)

Increased consumption of fish rich in omega-3 polyunsaturated fatty acids (omega3-PUFAs) is associated with decreased incidence of sudden cardiac death in post-myocardial infarction patients, but is also related to increased incidence of sudden death and arrhythmias in patients with acute myocardial ischemia. This review discusses the possible pro- and antiarrhythmic mechanisms of omega3-PUFAs in relation to various cardiac pathologies. Differences between circulating and incorporated omega3-PUFAs with respect to electrophysiology are emphasized. We conclude that omega3-PUFAs alter cardiac electrophysiology and thereby may be pro- or antiarrhythmic, dependent on the mechanism of arrhythmia. As omega3-PUFAs may be antiarrhythmic under conditions that favour triggered activity, they may facilitate re-entrant arrhythmias. This may explain the contradictory outcomes of increased intake of fish oil on sudden death and arrhythmias in clinical trials. Advice to increase intake of omega3-PUFA supplements or fatty fish should be tailored to individual patients with respect to the arrhythmogenic mechanisms associated with the underlying pathology.
Regional differences in composition of the perforatorium and outer periacrosomal layer of the rat spermatozoon as revealed by immunocytochemistry (1990)

The rat perforatorium is the part of the perinuclear theca that underlies the acrosomic system. It appears to be composed of several polypeptides. The main objective of this study was to determine the distribution of seven of these perforatorial polypeptides in the head of the rat spermatozoon. For this purpose, polyclonal antibodies were affinity purified from these polypeptides and tested 1) for their distribution on electron-microscope sections of late spermatids and spermatozoa by immunogold labeling and 2) for their specificity on Western blots of denatured perforatorial polypeptides by immunoblotting. Immunoblotting showed that all seven of the prominent perforatorial polypeptides had epitopes in common. Immunogold labeling of spermatozoa showed that antibodies against the 13, 13.4, and 16 kDa polypeptides were restricted in their localization to the thicker apical portion of the perforatorium and to the inner zone of the ventral spur. However, antibodies against the 34, 43, 57, and 63 kDa polypeptides reacted with the entire perforatorium but, in addition, reacted with the inner part of the ventral spur and with a portion of the "outer periacrosomal layer" lying between the plasma membrane and the outer acrosomal membrane. These results suggest 1) that there are regional differences in protein composition of the perforatorium, of the outer periacrosomal layer, and of the postacrosomal dense lamina; and 2) that perforatorial polypeptides may not necessarily be restricted to the subacrosomal region, but may also compose portions of the outer periacrosomal layer and postacrosomal dense lamina. Based on both immunoblotting and immunocytochemical results, using an antiactin monoclonal antibody that recognizes all known isoforms of actin, actin was not detected in the perforatorium of step 19 spermatids or spermatozoa. Actin, however, together with the seven perforatorial polypeptides tested, was present in the subacrosomal space of elongating spermatids before the process of condensation of the perforatorium takes place.
Highly Efficient Isothermal DNA Amplification System Using Three Elements of 5′-DNA-RNA-3′ Chimeric Primers, RNaseH and Strand-displacing DNA Polymerase (2007)

We developed an efficient method of isothermally amplifying DNA termed ICAN, Isothermal and Chimeric primer-initiated Amplification of Nucleic acids. This method allows the amplification of target DNA under isothermal conditions at around 55 degrees C using only a pair of 5'-DNA-RNA-3' chimeric primers, a thermostable RNaseH and a DNA polymerase with strong strand-displacing activity. ICAN is capable of amplifying DNA at least several times greater than the amount produced with PCR by increasing primer concentration. This method would be applicable for on-site DNA detection including gene diagnosis, and would also be suitable for 'real time' detection when combined with a cycling probe.
In senescence, age‐associated B cells secrete TNFα and inhibit survival of B‐cell precursors* (2013)

Aged mice exhibit ~ 5-10-fold increases in an ordinarily minor CD21/35(-) CD23(-) mature B-cell subset termed age-associated B cells (ABCs). ABCs from old, but not young, mice induce apoptosis in pro-B cells directly through secretion of TNFα. In addition, aged ABCs, via TNFα, stimulate bone marrow cells to suppress pro-B-cell growth. ABC effects can be prevented by the anti-inflammatory cytokine IL-10. Notably, CD21/35(+) CD23(+) follicular (FO) splenic and FO-like recirculating bone marrow B cells in both young and aged mice contain a subpopulation that produces IL-10. Unlike young adult FO B cells, old FO B cells also produce TNFα; however, secretion of IL-10 within this B-cell population ameliorates the TNFα-mediated effects on B-cell precursors. Loss of B-cell precursors in the bone marrow of old mice in vivo was significantly associated with increased ABC relative to recirculating FO-like B cells. Adoptive transfer of aged ABC into RAG-2 KO recipients resulted in significant losses of pro-B cells within the bone marrow. These results suggest that alterations in B-cell composition during old age, in particular, the increase in ABC within the B-cell compartments, contribute to a pro-inflammatory environment within the bone marrow. This provides a mechanism of inappropriate B-cell 'feedback' that promotes down-regulation of B lymphopoiesis in old age.
Nitrogen-containing compounds in tobacco and tobacco smoke (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNitrogen-containing compounds in tobacco and tobacco smokeIrwin. Schmeltz and Dietrich. HoffmannCite this: Chem. Rev. 1977, 77, 3, 295–311Publication Date (Print):June 1, 1977Publication History Published online1 May 2002Published inissue 1 June 1977https://pubs.acs.org/doi/10.1021/cr60307a001https://doi.org/10.1021/cr60307a001research-articleACS PublicationsRequest reuse permissionsArticle Views1634Altmetric-Citations253LEARN 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
Placebo‐Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome (2018)

Medically refractory, severe, cholestasis-induced pruritus in Alagille syndrome may be improved by surgical interruption of the enterohepatic circulation. This multicenter trial (NCT02057692) tested the hypothesis that the intestinal bile acid transport inhibitor maralixibat would similarly reduce pruritus in Alagille syndrome. Thirty-seven children with Alagille syndrome were randomly assigned to double-blinded administration of placebo, 70, 140, or 280 µg/kg/day of maralixibat for 13 weeks. Pruritus was assessed by caregiver (itch-reported outcome instrument [ItchRO]) and clinician report (range, 0-4 [severe]). Liver chemistries and serum bile acids were measured. The primary outcome was the change from baseline to week 13 in ItchRO relative to placebo. In the <i>a priori</i> first analysis of the primary efficacy endpoint, the mean adjusted difference between participants receiving 140 or 280 µg/kg/day and placebo was -0.47 (95% confidence interval [CI], -1.14, 0.20; <i>P =</i> 0.16). Statistically significant decreases were observed with doses of 70 and 140 µg/kg/day (mean adjusted difference, -0.89; 95% CI, -1.70, -0.08; <i>P =</i> 0.032; and mean adjusted difference, -0.91; 95% CI, -1.62, -0.19; <i>P =</i> 0.014) but not 280 µg/kg/day (mean adjusted difference, -0.04; 95% CI, -0.94, 0.86; <i>P =</i> 0.44) or all doses combined (mean adjusted difference, -0.61; 95% CI, -1.24, 0.20; <i>P =</i> 0.055). A 1-point reduction in pruritus was more common in maralixibat-treated versus placebo-treated participants (caregiver ItchRO, 65% versus 25%; <i>P =</i> 0.06; clinician score, 76% versus 25%; <i>P =</i> 0.01). There were no significant changes in liver chemistries or bile acids relative to placebo. Adverse and serious adverse events were similar between maralixibat and placebo. <i>Conclusion:</i> Although the prespecified primary analyses of ItchRO were not all statistically significant, the data suggest that maralixibat is safe and may reduce pruritus in Alagille syndrome.
Transcriptome dissection of gastric cancer: Identification of novel diagnostic and therapeutic targets from pathology specimens (2009)

Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. 'Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-alpha upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer.
Piezoelectric Biomaterials for Sensors and Actuators (2018)

Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead-based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.
High-Resolution Structural Analysis of a DNA Nanostructure by cryoEM (2009)

Many DNA nanostructures have been produced and a wide range of potential applications have been proposed. However, confirmation of accurate 3D construction is particularly challenging. Here, we demonstrate that cryoEM may be exploited to obtain structural information at sufficient resolution to visualize the DNA helix and reveal the absolute stereochemistry of a 7 nm self-assembled DNA tetrahedron. Structural analysis at such high resolution by cryoEM image analysis is unprecedented for any biological molecule of this size.
Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers (2015)

MicroRNAs (miRNAs) are involved in the progression and suppression of various diseases through translational inhibition of target mRNAs. Therefore, the alteration of miRNA biogenesis induces several diseases. The nuclear factor 90 (NF90)-NF45 complex is known as a negative regulator in miRNA biogenesis. Here, we showed that NF90-NF45 double-transgenic (dbTg) mice develop skeletal muscle atrophy and centronuclear muscle fibers in adulthood. Subsequently, we found that the levels of myogenic miRNAs, including miRNA 133a (miR-133a), which promote muscle maturation, were significantly decreased in the skeletal muscle of NF90-NF45 dbTg mice compared with those in wild-type mice. However, levels of primary transcripts of the miRNAs (pri-miRNAs) were clearly elevated in NF90-NF45 dbTg mice. This result indicated that the NF90-NF45 complex suppressed miRNA production through inhibition of pri-miRNA processing. This finding was supported by the fact that processing of pri-miRNA 133a-1 (pri-miR-133a-1) was inhibited via binding of NF90-NF45 to the pri-miRNA. Finally, the level of dynamin 2, a causative gene of centronuclear myopathy and concomitantly a target of miR-133a, was elevated in the skeletal muscle of NF90-NF45 dbTg mice. Taken together, we conclude that the NF90-NF45 complex induces centronuclear myopathy through increased dynamin 2 expression by an NF90-NF45-induced reduction of miR-133a expression in vivo.
Clinical Islet Transplantation — Registry Report, Accomplishments in the past and Future Research Needs (1993)

This review provides the results of a recent analysis of the Islet Transplant Registry on clinical adult islet transplants performed worldwide through June 30, 1992. Between December 12, 1893 and June 30, 1992, 167 adult islet transplants were performed at 25 institutions worldwide, including 104 at 9 institutions in North America, 62 at 15 institutions in Europe, and 1 elsewhere. The total number of diabetic patients reported to be insulin independent after adult islet allotransplantation through June 30, 1992, was 19. In an analysis by era, the percentage of patients that showed positive basal C-peptide levels (i.e., > or = 1 ng/mL at > or = 1 mo) posttransplant, and that became insulin independent (> 1 wk) in the 1985-1989 era (n = 35 cases) were 20% and 6%, and in the 1990-1992 era (n = 69 cases) were 64% and 20%, respectively, and thus have improved significantly (p < 0.001 and p < 0.05). For the 1990-1992 period, the percentage of patients who showed positive basal C-peptide levels post-transplant, and who became insulin independent in the single donor pancreas group (n = 31 cases) were 52% and 13%, and in the multiple donor pancreata group (n = 36 cases) were 75% and 28%, respectively. Islet graft function rates were nearly identical for grafts prepared from pancreata stored < or = 6 h (n = 27) and > 6 < or = 12 h (n = 29), so that 67% and 72% showed positive basal C-peptide levels, and 30% and 21% of the recipients became insulin independent, respectively. No single patient showed islet graft function sufficient to allow withdrawal from insulin, if the pancreata have been stored for more than 12 h. In regard to recipient category for the six groups, namely IAK (islet after kidney), SIK (simultaneous islet kidney transplantation), SIL (simultaneous islet liver transplantation), SIL(C) (simultaneous islet liver transplantation after cluster operation), SIKL (simultaneous islet kidney liver transplantation), and SIH-L (simultaneous islet heart-lung transplantation), the number of patients who showed positive basal C-peptide levels post-transplant was 11 (58%), 17 (57%), 5 (83%), 8 (80%), 1 (50%), and 0 (0%), and the number of insulin independent patients was 4 (21%), 4 (13%), 0 (0%), 6 (60%), 0 (0%), and 0 (0%), respectively. Comparing the two largest recipient categories, namely IAK and SIK, no difference in the outcome of these transplants was apparent.(ABSTRACT TRUNCATED AT 400 WORDS)
Registration of head volume images using implantable fiducial markers (1997)

In this paper, we describe an extrinsic-point-based, interactive image-guided neurosurgical system designed at Vanderbilt University, Nashville, TN, as part of a collaborative effort among the Departments of Neurological Surgery, Computer Science, and Biomedical Engineering. Multimodal image-to-image (II) and image-to-physical (IP) registration is accomplished using implantable markers. Physical space tracking is accomplished with optical triangulation. We investigate the theoretical accuracy of point-based registration using numerical simulations, the experimental accuracy of our system using data obtained with a phantom, and the clinical accuracy of our system using data acquired in a prospective clinical trial by six neurosurgeons at four medical centers from 158 patients undergoing craniotomies to resect cerebral lesions. We can determine the position of our markers with an error of approximately 0.4 mm in X-ray computed tomography (CT) and magnetic resonance (MR) images and 0.3 mm in physical space. The theoretical registration error using four such markers distributed around the head in a configuration that is clinically practical is approximately 0.5-0.6 mm. The mean CT-physical registration error for the phantom experiments is 0.5 mm and for the clinical data obtained with rigid head fixation during scanning is 0.7 mm. The mean CT-MR registration error for the clinical data obtained without rigid head fixation during scanning is 1.4 mm, which is the highest mean error that we observed. These theoretical and experimental findings indicate that this system is an accurate navigational aid that can provide real-time feedback to the surgeon about anatomical structures encountered in the surgical field.
The development of carboranyl nucleic acid precursors for use in neutron capture therapy of tumors (1991)

Abstract
The FLT3 ligand potently and directly stimulates the growth and expansion of primitive murine bone marrow progenitor cells in vitro: synergistic interactions with interleukin (IL) 11, IL-12, and other hematopoietic growth factors. (1995)

The recently cloned murine flt3 ligand (FL) was studied for its ability to stimulate the growth of primitive (Lin-Sca-1+) and more committed (Lin-Sca-1-) murine bone marrow progenitor cells, alone and in combination with other hematopoietic growth factors (HGFs). Whereas FL was a weak proliferative stimulator alone, it potently synergized with a number of other HGFs, including all four colony-stimulating factor (CSF), interleukin (IL) 6, IL-11, IL-12, and stem cell factor (SCF), to promote the colony formation of Lin-Sca-1+, but not Lin-Sca-1- or erythroid progenitor cells. The synergistic activity of FL was concentration dependent, with maximum stimulation occurring at 250 ng/ml, and was observed when cells were plated at a concentration of one cell per culture, suggesting that its effects are directly mediated. 2 wk of treatment with FL in combination with IL-3 or SCF resulted in the production of a high proportion of mature myeloid cells (granulocytes and macrophages), whereas the combination of FL with G-CSF, IL-11, or IL-12 resulted predominantly in the formation of cells with an immature blast cell appearance. Accordingly, FL in combination with G-CSF or IL-11 expanded the number of progenitors more than 40-fold after 2 wk incubation. Thus, FL emerges as a potent synergistic HGF, that in combination with numerous other HGFs, can directly stimulate the proliferation, myeloid differentiation, and expansion of primitive hematopoietic progenitor cells.
Autoimmune rheumatic disease (1987)

Setting the scene Immunological methodology Systemic lupus erythematosus Rheumatoid arthritis S J Gren's syndrome Polymyositis Scleroderma Overlap syndromes, undifferentiated diseases and vasculitis.
A nested set of six or seven subgenomic mRNAs is formed in cells infected with different isolates of porcine reproductive and respiratory syndrome virus (1996)

The subgenomic mRNAs (sg mRNA) of porcine reproductive and respiratory syndrome virus (PRRSV) were characterized. The number of sg mRNAs, which form a 3'-coterminal nested set in PRRSV-infected cells, varied from six to seven among PRRSV isolates with differing virulence. The additional species of sg mRNA in some isolates of PRRSV was designated as sg mRNA 3-1. The leader-mRNA junction sequences of sg mRNAs 3, 3-1 and 4 were found to contain a similar six nucleotide sequence motif, U(G)UA(G/C)ACC. By comparing the 5'-terminal sequence of sg mRNA 3-1 with the genomic sequence of two isolates, ISU79 and ISU1894, it was found that a point mutation, from U in isolate ISU1894 to C in isolate ISU79, led to the acquisition of a new leader-mRNA junction sequence (UUGACC) in isolate ISU79, and therefore an additional species of sg mRNA 3-1. A small ORF (3-1) was identified at the 5' end of sg mRNA 3-1.
AT7867 Is a Potent and Oral Inhibitor of AKT and p70 S6 Kinase That Induces Pharmacodynamic Changes and Inhibits Human Tumor Xenograft Growth (2010)

The serine/threonine kinase AKT plays a pivotal role in signal transduction events involved in malignant transformation and chemoresistance and is an attractive target for the development of cancer therapeutics. Fragment-based lead discovery, combined with structure-based drug design, has recently identified AT7867 as a novel and potent inhibitor of both AKT and the downstream kinase p70 S6 kinase (p70S6K) and also of protein kinase A. This ATP-competitive small molecule potently inhibits both AKT and p70S6K activity at the cellular level, as measured by inhibition of GSK3beta and S6 ribosomal protein phosphorylation, and also causes growth inhibition in a range of human cancer cell lines as a single agent. Induction of apoptosis was detected by multiple methods in tumor cells following AT7867 treatment. Administration of AT7867 (90 mg/kg p.o. or 20 mg/kg i.p.) to athymic mice implanted with the PTEN-deficient U87MG human glioblastoma xenograft model caused inhibition of phosphorylation of downstream substrates of both AKT and p70S6K and induction of apoptosis, confirming the observations made in vitro. These doses of AT7867 also resulted in inhibition of human tumor growth in PTEN-deficient xenograft models. These data suggest that the novel strategy of AKT and p70S6K blockade may have therapeutic value and supports further evaluation of AT7867 as a single-agent anticancer strategy.
Diversity of the biosynthesis of the isoprene units (2003)

This review covers the biosynthesis of the starter units of terpenoids, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) via the nonmevalonate pathway together with a new enzyme involved in the conversion of IPP and DMAPP, i.e type 2 IPP isomerase. The biosynthesis of terpenoids produced by actinomycetes is also reviewed. 117 references are cited.