tbuckley/cabot-search huggingface dataset:
Representation: Emulation and anticipation
Authors: Georgi Stojanov, Mark H. Bickhard
Journal: Behavioral and Brain Sciences (2004)

We address the issue of the normativity of representation and how Grush might address it for emulations as constituting representations. We then proceed to several more detailed issues concerning the learning of emulations, a possible empirical counterexample to Grush's model, and the choice of Kalman filters as the form of model-based control.
Arterial Distensibility in Adolescents
Authors: P.H. Whincup, J.A. Gilg, A.E. Donald, M. Katterhorn, C. Oliver, D.G. Cook, J.E. Deanfield
Journal: Circulation (2005)

Atherosclerosis develops from childhood, but the determinants of this preclinical stage remain uncertain. We examined the relations of classic coronary risk factors, adiposity and its associated metabolic disturbances, to arterial distensibility (a marker of early arterial disease) in 13- to 15-year-olds, some of whom had previously been studied at ages 9 to 11 years.Brachial artery distensibility was measured by a noninvasive ultrasound technique in 471 British children in whom measures of adiposity, blood pressure, fasting blood lipids, and insulin had been made. All adiposity measures showed strong graded inverse relationships with distensibility. Inverse associations with distensibility were also observed for insulin resistance (homeostasis model assessment), diastolic pressure, C-reactive protein, and the number of metabolic syndrome components present, which had a graded relation to distensibility. Total and LDL cholesterol levels were also inversely related to distensibility, but less strongly than adiposity; homocysteine had no relation to distensibility. Although the relations of total and LDL cholesterol and diastolic pressure to distensibility had been present at 9 to 11 years of age, those of adiposity and insulin resistance were only apparent at 13 to 15 years.Adiposity and its metabolic consequences are associated with adverse changes in the arterial wall by the teenage years. The graded relation with increasing adiposity was stronger than that for cholesterol and was seen at body mass index levels well below those considered to represent "obesity." This emphasizes the importance of population-based strategies to control adiposity and its metabolic consequences in the young.
Transmission of Information From Cardiac Dihydropyridine Receptor to Ryanodine Receptor
Authors: Hideki Katoh, Klaus Schlotthauer, Donald M. Bers
Journal: Circulation Research (2000)

Abstract —Coupling between L-type Ca 2+ channels (dihydropyridine receptors, DHPRs) and ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction (E-C) coupling in cardiac myocytes, and Ca 2+ influx is generally accepted as the trigger of sarcoplasmic reticulum (SR) Ca 2+ release. The L-type Ca 2+ channel agonist BayK 8644 (BayK) has also been reported to alter RyR gating via a functional linkage between DHPR and RyR, independent of Ca 2+ influx. Here, the effect of rapid BayK application on resting RyR gating in intact ferret ventricular myocytes was measured as Ca 2+ spark frequency (CaSpF) by confocal microscopy and fluo 3. BayK increased resting CaSpF by 401±15% within 10 seconds in Ca 2+ -free solution, and depolarization had no additional effect. The effect of BayK on CaSpF was dose-dependent, but even 50 nmol/L BayK induced a rapid 245±12% increase in CaSpF. Nifedipine (5 μmol/L) had no effect by itself on CaSpF, but it abolished the BayK effect (presumably by competitive inhibition at the DHPR). The nondihydropyridine Ca 2+ channel agonist FPL-64176 (1 μmol/L) did not alter CaSpF (despite rapid and potent enhancement of Ca 2+ current, I Ca ). In striking contrast to the very rapid and depolarization-independent effect of BayK on CaSpF, BayK increased I Ca only slowly (τ=18 seconds), and the effect was greatly accelerated by depolarization. We conclude that in ferret ventricular myocytes, BayK effects on I Ca and CaSpF both require drug binding to the DHPR, but postreceptor pathways may diverge in transmission to the gating of the L-type Ca 2+ channel and RyR. (Circ Res. 2000;87:106-111.)
CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism
Authors: Maria Febbraio, David P. Hajjar, Roy L. Silverstein
Journal: Journal of Clinical Investigation (2001)

Multiligand receptorsCD36, identified more than a quarter of a century ago as a platelet integral membrane glycoprotein (glycoprotein IV), was until recently best known as a receptor for thrombospondin-1 (TSP-1).TSP-1 is found in ECMs and platelet α granules, and it participates in cell attachment, motility, and proliferation, as well as in modulation of protease activity, TGF-β activation, neurite outgrowth, and angiogenesis (1).Initially, this receptor-ligand pair was shown to mediate interactions between platelets and monocytes, tumor cells, and matrix.Since then, CD36 has been implicated in multiple biological processes that define it as a multiligand scavenger receptor (see ref. 2 for review).These ligands appear remarkably diverse: In addition to TSP-1, they include long-chain fatty acids, modified LDL, retinal photoreceptor outer segments, Plasmodium falciparum malaria-parasitized erythrocytes, sickle erythrocytes, anionic phospholipids, apoptotic cells, and collagens I and IV.The biology of CD36 can be broadly divided in terms of functions that it mediates with or without TSP-1, but it is probable that it acts in concert with other proteins, such as fatty acid-binding proteins, caveola-associated proteins, integrins, cytoskeletal proteins, and signaling molecules, to effect its diverse functions.
Phylogeny of the C3/C4/C5 complement-component gene family indicates that C5 diverged first.
Authors: A L Hughes
Journal: Molecular Biology and Evolution (1994)

A phylogenetic analysis of DNA sequences from the C3/C4/C5 complement-component family of vertebrates supported the hypothesis that the C5 gene diverged first from the common ancestor of C3 and C4 and that C3 and C4 diverged later. The close relationship of C3 and C4 was further supported by the fact that a hagfish complement-component gene showed evidence of being more closely related to both C3 and C4 than to C5. This phylogeny is most consistent with the hypothesis that the alternative complement pathway was the first to evolve, followed by the terminal pathway and then by the classical pathway.
Functional Characterization of EBV-Encoded Nuclear Antigen 1–Specific CD4+ Helper and Regulatory T Cells Elicited by<i>In vitro</i>Peptide Stimulation
Authors: Kui Shin Voo, Guangyong Peng, Zhong Guo, Tihui Fu, Yanchun Li, Lori Frappier, Rong-Fu Wang
Journal: Cancer Research (2005)

CD4(+) helper and regulatory T (Treg) cells play important but opposing roles in regulating host immune responses against cancer and other diseases. However, very little is known about the antigen specificity of CD4(+) Treg cells. Here we describe the generation of a panel of EBV-encoded nuclear antigen 1 (EBNA1)-specific CD4(+) T-cell lines and clones that recognize naturally processed EBNA1-P(607-619) and -P(561-573) peptides in the context of HLA-DQ2 and HLA-DR11, -DR12, and -DR13 molecules, respectively. Phenotypic and functional analyses of these CD4(+) T cells revealed that they represent EBNA1-specific CD4(+) T helper as well as Treg cells. CD4(+) Treg cells do not secrete interleukin (IL)-10 and transforming growth factor beta cytokines but express CD25, the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), and Forkhead Box P3 (Foxp3), and are capable of suppressing the proliferative responses of naive CD4(+) and CD8(+) T cells to stimulation with mitogenic anti-CD3 antibody. The suppressive activity of these CD4(+) Treg cells is mediated via cell-cell contact or in part by a cytokine-dependent manner. Importantly, these Treg cells suppress IL-2 secretion by CD4(+) effector T cells specific for either EBNA1 or a melanoma antigen, suggesting that these CD4(+) Treg cells induce immune suppression. These observations suggest that the success of peptide-based vaccines against EBV-associated cancer and other diseases may likely depend upon our ability to identify antigens/peptides that preferentially activate helper T cells and/or to design strategies to regulate the balance between CD4(+) helper and Treg cells.
Haemothorax after subclavian vein cannulation.
Authors: S Holt, N Kirkham, E Myerscough
Journal: Thorax (1977)

A patient in whom pulmonary arterial bleeding occurred during percutaneous supraclavicular puncture of the subclavian vein is described. A retrospective survey of over 600 subclavian venepunctures disclosed seven patients in whom serious traumatic complications occurred, six of them in the hands of inexperienced operators.
Genetic control of the immune response to staphylococcal nuclease. IV. H-2-linked control of the relative proportions of antibodies produced to different determinants of native nuclease.
Authors: J A Berzofsky, A N Schechter, G M Shearer, D H Sachs
Journal: The Journal of Experimental Medicine (1977)

The relative proportions of antibodies of different specificities within antisera raised to native staphylococcal nuclease have been studied in several strains of mice in which the antibody response has been shown to be under H-2-linked Ir-gene control. A method was developed in which binding to different radiolabeled fragments of nuclease was titrated against increasing fragment concentration until the binding capacity of the antiserum for that fragment was saturated. In comparing the low responder (H-2b) strain C57BL/10 with its congenic high responder counterpart B10.A (H-2a), it was found that the two strains made markedly and reproducibly different proportions of antibodies to different determinants on native nuclease. Since these two strains differ only at H-2, and therefore have identical immunoglobulin structural gene repertoires, we conclude that H-2-linked Ir genes can control the response to different determinants on the same antigen molecule independently of one another. This result suggests a possible role of H-2-linked genes in the selection of specific B cells.
SPECIFIC HETEROLOGOUS ENHANCEMENT OF IMMUNE RESPONSES
Authors: Arnold S. Rubin, Albert H. Coons
Journal: The Journal of Experimental Medicine (1972)

In short-term cultures of thymocytes from tetanus toxoid-immunized mice, the addition of 1 ng of toxoid generated the release of a soluble factor which was capable of enhancing the immune response to a heterologous immunogen. The addition of supernatants from such cultures to assay cultures of sheep erythrocyte-stimulated normal spleen cells produced a significant augmentation of the hemolytic plaque response. Culture fluid from similar cultures of normal thymocytes or primed thymocytes cultured without the priming antigen were inactive. The enhancing factor was nondialyzable, heat stable (56 degrees C, 30 min), resistant to DNAse and RNAse, but was inactivated by protease. A factor produced by specifically stimulated primed spleen cells had similar characteristics. In toxoid-stimulated, mixed cell cultures containing primed thymocytes or spleen cells and normal spleen cells, tenfold fewer thymocytes than spleen cells were needed to produce a comparable degree of enhancement of the anti-sheep erythrocyte plaque-forming cell response.
Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
Authors: D. Plant, E. Flynn, H. Mbarek, P. Dieude, F. Cornelis, L. Arlestig, S. R. Dahlqvist, G. Goulielmos, D. T. Boumpas, P. Sidiropoulos, J. S. Johansen, L. M. Ornbjerg, M. L. Hetland, L. Klareskog, A. Filer, C. D. Buckley, K. Raza, T. Witte, R. E. Schmidt, J. Worthington
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. <h3>Objectives</h3> To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. <h3>Methods</h3> 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a &gt;95% success rate and only those SNPs with a genotype success rate of &gt;95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. <h3>Results</h3> After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (<i>AFF3</i>), rs1678542 (<i>KIF5A</i>), rs2476601 (<i>PTPN22</i>), rs3087243 (<i>CTLA4</i>), rs4810485 (<i>CD40</i>), rs5029937 (6q23), rs10760130 (<i>TRAF1/C5</i>) and rs7574865 (<i>STAT4</i>)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. <h3>Conclusions</h3> In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.
Doctor, Does This Mean I'm Going to Starve to Death?
Authors: Melissa K. Whitworth, Andrea Whitfield, Søren Holm, John Shaffer, Wendy Makin, Gordon C. Jayson
Journal: Journal of Clinical Oncology (2003)

Here’s the Case “Shirley” is a 60-year-old woman who presented with abdominal pain and distension 10 years ago. Following a total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy she had been diagnosed with an International Federation of Gynecology and Obstetrics stage IC poorly differentiated endometrioid cancer of the ovary and had subsequently received six cycles of carboplatin, cyclophosphamide, doxorubicin, and ifosfamide. She was well until 3 years ago, when a computed tomography scan showed extensive disease in the omentum and pelvis. A laparotomy revealed inoperable intra-abdominal disease that was histologically consistent with recurrent ovarian cancer. She received six cycles of carboplatin and paclitaxel. A computed tomography scan confirmed a partial response, and Shirley remained well until 2 years ago. At that time, she developed abdominal distension, colic, and flatulence, due to progressive disease. She was treated with single agent carboplatin, but after two cycles, Shirley presented with the symptoms and signs of bowel obstruction. Surgical management was not an option, given the extent of the intra-abdominal disease. Nausea and abdominal discomfort were well controlled medically, and she reported a good quality of life, although she vomited after eating. Following a series of long discussions with Shirley, her relatives, nursing staff, and a number of physicians, a percutaneous venting jejunostomy was fashioned to permit her to eat and drink. This drained 2 L of fluid per day on average. At this point, Shirley and her medical team began to consider whether intravenous nutritional support should be initiated. Ovarian cancer is a common malignancy in the Western world, causing ap
Motor activity of the sigmoid colon in chronic constipation: comparative study with normal subjects.
Authors: P Meunier, A Rochas, R Lambert
Journal: Gut (1979)

Manometric studies of the sigmoid colon were performed on 17 healthy volunteers and on 49 constipated patients, after a long period of fasting (18--20 hours). Motility was recorded using perfused catheters at basal level during 45 minutes, then 60 minutes after a 0.5 mg intravenous injection of neostigmine, and, finally, 30 minutes during and after a meal. Motor activity was assessed by a motility index (per cent of activity x mean amplitude of waves). In both normal and constipated patients, the basal motility index was very low (respectively 82 +/- 16 and 110 +/- 113). This low level of activity was due to the long fasting period imposed on all the subjects. After neostigmine the motility index increased in both controls (347 +/- 256) and constipated patients (311 +/- 325); this test, however was found to be unreliable. The meal increased the motility index to significantly higher values than after neostigmine in controls (538 +/- 215). In constipated patients the mean meal motility index was comparable with that of controls (577 +/- 549) with a large distribution of individual values. Using the mean meal motility index +/- 2 SD of the control group as a term of comparison, the patients were segregated into three groups: 'hypomotor' patients (eight cases), 'normomotor' patients (33 cases), and 'hypermotor' patients (eight cases). From the evidence of this series of clinically well-defined constipated patients, it was concluded that only the meal test is able to segregate three significant patterns of sigmoid activity and that a large number (68%) of constipated patients exhibit normal sigmoid motor activity.
Factors governing the transepithelial potential difference across the proximal tubule of the rat kidney.
Authors: L J Barratt, F C Rector, J P Kokko, D W Seldin
Journal: Journal of Clinical Investigation (1974)

Previous measurements of the transepithelial potential difference (PD) of the proximal tubule have yielded widely conflicting values (range -20 to +3 mV). In a recent study, Kokko has demonstrated that the PD of the in vitro perfused isolated proximal tubule of the rabbit varies in a predictable way from -6 to +3 mV, depending on the concentration of chloride, bicarbonate, glucose, and amino acids in the perfusing solution. The present micropuncture study examines the effect of tubular fluid composition on the PD profile along the proximal tubule of the in vivo rat kidney. Low resistance measuring electrodes with large tips (3-5 microns OD) filled with 3 M KCl, were used to provide stable PD recordings. Experiments were performed to validate the use of these electrodes. Transepithelial PD measurements were made in immediate postglomerular segments identified by injection of dye into Bowman's space of accessible surface glomeruli and in randomly selected more distal segments of the proximal tubule. In the control state, the first loop was found to have a small but consistently negative PD which could be obliterated by an infusion of phloridzin. In contrast, the PD in later segments was consistently positive. Infusion of acetazolamide abolished the positive PD in the later segments. Acetazolamide and glucose infusion resulted in a negative PD which was abolished by the additional infusion of phloridzin. These data provide evidence that glucose reabsorption is electrogenic and can account for the small negative PD normally present in the early proximal tubule. The positive PD in later segments appears to be a passive chloride diffusion potential. This positive potential is discussed as an important electrochemical driving force for significant passive reabsorption of sodium in the proximal tubule.
CpG Oligodeoxynucleotide Enhances Tumor Response to Radiation
Authors: Luka Milas, Kathryn A. Mason, Hisanori Ariga, Nancy Hunter, Robert Neal, David Valdecanas, Arthur M. Krieg, John K. Whisnant
Journal: Cancer Research (2004)

Abstract CpG oligodeoxynucleotides (ODNs) are synthetic DNA sequences containing unmethylated cytosine-guanine motifs with potent immunomodulatory effects. Via Toll-like receptor 9 agonism of dendritic cells and B cells, CpG ODNs induce cytokines, activate natural killer cells, and elicit vigorous T-cell responses that lead to significant antitumor effects, including improved efficacy of chemotherapeutic agents. On the basis of these properties of CpG ODNs, we tested whether they also could enhance tumor response to radiotherapy. Using an immunogenic mouse tumor, designated FSa, the response to radiotherapy was assayed by tumor growth delay and tumor cure rate (TCD50, radiation dose yielding 50% tumor cure rate). Treatments were initiated when established tumors were either 6 or 8 mm in diameter. CpG ODN as a single agent given s.c. peritumorally had little effect on tumor growth; however, it dramatically enhanced tumor growth delay in response to single-dose radiation by a factor of 2.58–2.65. CpG ODN also dramatically improved tumor radiocurability, reducing the TCD50 by a factor of 1.93, from 39.6 (36.1–43.1) Gy to 20.5 (14.3–25.7) Gy. The CpG ODN-induced enhancement of tumor radioresponse was diminished in tumor-bearing mice immunocompromised by sublethal whole-body radiation. Tumors treated with CpG ODN and radiation showed histologic changes characterized by increased necrosis, heavy infiltration by host inflammatory cells (lymphocytes and granulocytes), and reduced tumor cell density. These results show that CpG ODNs are potent enhancers of tumor radioresponse and as such have potential to improve clinical radiotherapy.
NUTRITIONAL CONTROL OF GENE EXPRESSION: How Mammalian Cells Respond to Amino Acid Limitation
Authors: M.S. Kilberg, Y.-X. Pan, H. Chen, V. Leung-Pineda
Journal: Annual Review of Nutrition (2005)

The amino acid response (AAR) pathway in mammalian cells is designed to detect and respond to amino acid deficiency. Limiting any essential amino acid initiates this signaling cascade, which leads to increased translation of a "master regulator," activating transcription factor (ATF) 4, and ultimately, to regulation of many steps along the pathway of DNA to RNA to protein. These regulated events include chromatin remodeling, RNA splicing, nuclear RNA export, mRNA stabilization, and translational control. Proteins that are increased in their expression as targets of the AAR pathway include membrane transporters, transcription factors from the basic region/leucine zipper (bZIP) superfamily, growth factors, and metabolic enzymes. Significant progress has been achieved in understanding the molecular mechanisms by which amino acids control the synthesis and turnover of mRNA and protein. Beyond gaining additional knowledge of these important regulatory pathways, further characterization of how these processes contribute to the pathology of various disease states represents an interesting aspect of future research in molecular nutrition.