tbuckley/cabot-search huggingface dataset:
Navigation bicoded as functions of x-<i>y</i> and time?
Authors: James G. Phillips, Rowan P. Ogeil
Journal: Behavioral and Brain Sciences (2013)

Abstract Evidence from egocentric space is cited to support bicoding of navigation in three-dimensional space. Horizontal distances and space are processed differently from the vertical. Indeed, effector systems are compatible in horizontal space, but potentially incompatible (or chaotic) during transitions to vertical motion. Navigation involves changes in coordinates, and animal models of navigation indicate that time has an important role.
Molecular Profiling of Carcinoma of Unknown Primary and Correlation With Clinical Evaluation
Authors: Gauri R. Varadhachary, Dmitri Talantov, Martin N. Raber, Christina Meng, Kenneth R. Hess, Tim Jatkoe, Renato Lenzi, David R. Spigel, Yixin Wang, F. Anthony Greco, James L. Abbruzzese, John D. Hainsworth
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate the feasibility of a 10-gene reverse transcriptase polymerase chain reaction assay to identify the tissue of origin in patients with carcinoma of unknown primary (CUP) site. Patients and Methods Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 120 patients with CUP were collected retrospectively from Sarah Cannon Research Institute, Nashville, TN, and prospectively from The University of Texas M. D. Anderson Cancer Center, Houston, TX. Tissue of origin assignments by the assay were correlated with clinical and pathologic features and with response to therapy. Results The assay was successfully performed in 104 patients (87%), and a tissue of origin was assigned in 63 patients (61%). In the remaining 41 patients (39%), the molecular profiles were not specific for the six tumor types detectable by this assay. The tissues of origin most commonly identified were lung, pancreas, and colon; most of these patients had clinical and pathologic features consistent with these diagnoses. Patients with lung and pancreas profiles had poor response to treatment. Patients with colon cancer profiles had better response to colon cancer–specific therapies than they did to empiric CUP therapy with taxane/platinum regimens. Patients with ovarian cancer profiles were atypical, with widespread visceral metastases and a paucity of overt peritoneal involvement. Conclusion This gene expression profiling assay was feasible using FFPE biopsy specimens and identified a putative tissue of origin in 61% of patients with CUP. In most patients, the assigned tissue of origin was compatible with clinicopathologic features and response to treatment. Prospective studies in which assay results are used to direct therapy are indicated.
Bronchopulmonary Kaposi's sarcoma in patients with AIDS.
Authors: R F Miller, M C Tomlinson, C P Cottrill, J J Donald, M F Spittle, S J Semple
Journal: Thorax (1992)

Kaposi's sarcoma in HIV antibody positive patients may affect the lungs. This study describes the presentation, chest radiographic appearances, and pulmonary function test abnormalities in patients with AIDS who had tracheobronchial Kaposi's sarcoma.Twenty nine (8%) of 361 consecutive HIV antibody positive patients undergoing bronchoscopy for respiratory symptoms had tracheobronchial Kaposi's sarcoma. Eight patients had intercurrent infections and one had previously received chemotherapy for cutaneous Kaposi's sarcoma; these patients were excluded. Seven of the remaining 20 patients had localised Kaposi's sarcoma (lesions confined to the trachea or the subsegments of one lobe) and 13 had widespread Kaposi's sarcoma (affecting the trachea and one lobe or the subsegments of more than one lobe); 19 patients also had cutaneous and palatal Kaposi's sarcoma. Seven patients, four with widespread disease, had a normal radiograph. All patients had reduced transfer factor (TLCO) and transfer coefficient (KCO) but only those with widespread disease had reductions in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Follow up pulmonary function testing in seven patients (median three months later) showed further reductions in TLCO. All four patients who received no treatment had progressive radiographic abnormalities; bronchoscopy in two patients showed progressive tracheobronchial disease, and two patients had further reductions in FEV1 and FVC. In three patients treated with chemotherapy palliation of symptoms was achieved but two had further reductions in FEV1 and FVC and the radiograph deteriorated. Bronchoscopy showed regression of disease in only one patient.Pulmonary Kaposi's sarcoma produces abnormalities of TLCO even in patients with localised disease; airflow obstruction may occur in patients with widespread disease. Bronchoscopic reassessment of the extent of disease may not accurately reflect response to chemotherapy.
Heterogeneity of intracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations.
Authors: P Openshaw, E E Murphy, N A Hosken, V Maino, K Davis, K Murphy, A O'Garra
Journal: The Journal of Experimental Medicine (1995)

CD4+ T helper (Th) cells can be classified into different types based on their cytokine profile. Cells with these polarized patterns of cytokine production have been termed Th1 and Th2, and can be distinguished functionally by the production of IFN-gamma and IL-4, respectively. These phenotypes are crucial in determining the type of immune response that develops after antigen priming. There are no surface markers that define them, and cytokine immunoassay or mRNA analysis both have limitations for characterization of single cells. Using immunofluorescent detection of intracellular IFN-gamma and IL-4, we have studied the emergence of Th1 and Th2 cells in response to antigen exposure and the patterns of cytokine synthesis in established T cell clones. IFN-gamma production by Th1 clones was detectable in almost all cells by 4 h, and it continued in most cells for &amp;gt; 24 h. IL-4 production in Th2 cells peaked at 4 h, but declined rapidly. In Th0 cells containing both cytokines, fewer cells produced IFN-gamma, which did not appear until IL-4 synthesis declined. Cocultivation of clones showed no such cross-regulation. Antigen stimulation of transgenic T cells expressing an ovalbumin-specific T cell receptor generated Th2 cells, probably as a result of endogenous IL-4 production. Addition of IL-12 and/or anti-IL-4 caused Th1 cells to develop, while some Th0 cells were seen when IL-12 alone was added. These results show that stimulation in the presence of polarizing stimuli results in cells producing either IFN-gamma or IL-4, but that coproduction can occur in rare cells under defined conditions.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: K. Marilyn Smart, Edwin D. Kilbourne
Journal: The Journal of Experimental Medicine (1966)

A comparative study was undertaken of the pathogenesis of infection of the allantoic sac of the chick embryo with three influenza viruses of differing virulence, and of the influence of hydrocortisone on the course of infection. Judged on the basis of earlier onset and greater degree of inflammatory response and diminished survival time of infected embryos, Mel. and Lee viruses were markedly more virulent than PR8, despite the earlier appearance of virus in PR8-infected embryos. Interferon appeared first and in greater quantity in the allantoic fluid of Lee-infected embryos and latest with PR8 infection. Thus, there was no correlation of avirulence and better interferon production with the viruses under study in the present system. Furthermore, evidence obtained suggested that Lee virus ("virulent") was most susceptible to interferon action, and also that viral synthesis in the chorioallantoic membrane with PR8 ("avirulent") persisted after the appearance of interferon. The injection of hydrocortisone within 2 hr of the initiation of infection delayed the synthesis of all three viruses; had no significant effect upon the inflammatory response; and transiently inhibited the synthesis of interferon, while prolonging the survival of Lee- and Mel.-infected embryos. Late administration of hydrocortisone suppresses both the inflammatory response and the production of interferon. Only in the case of Lee virus infection did hydrocortisone administration lead to augmentation of final yields of virus with the low infection multiplicity employed in the present experiments. It is postulated that Lee virus is a better inducer of interferon because its infectivity in vivo is more rapidly inactivated. As a consequence synthesis of Lee virus is more under the control of endogenous interferon than is the case with PR8 or Mel. virus. Therefore, inhibition of interferon synthesis with hydrocortisone has a greater influence on final yields of Lee virus.
Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial
Authors: Fernando D Martinez, Vernon M Chinchilli, Wayne J Morgan, Susan J Boehmer, Robert F Lemanske, David T Mauger, Robert C Strunk, Stanley J Szefler, Robert S Zeiger, Leonard B Bacharier, Elizabeth Bade, Ronina A Covar, Noah J Friedman, Theresa W Guilbert, Hengameh Heidarian-Raissy, H William Kelly, Jonathan Malka-Rais, Michael H Mellon, Christine A Sorkness, Lynn Taussig
Journal: The Lancet (2011)
The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila
Authors: Tobias Kockmann, Moritz Gerstung, Tommy Schlumpf, Zhu Xhinzhou, Daniel Hess, Niko Beerenwinkel, Christian Beisel, Renato Paro
Journal: Genome biology (2013)

Abstract Background The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription. Results and discussion Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters. Conclusions Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes.
Generation of anti-type III pneumococcal polysaccharide hybridomas from mice with an X-linked B-lymphocyte defect.
Authors: K R Schroer, K J Kim, B Prescott, P J Baker
Journal: The Journal of Experimental Medicine (1979)

(CBA/N X BALB/c male)F1 mice bear on X-linked defect making them totally unresponsive to T-independent (TI), TI-2 antigens such as type III pneumococcal polysaccharide (SSS-III). We found that somatic cell hybrids between CB nonresponder spleen cells and NS1 plasmacytoma cells secreted antibody specific for SSS-III. The solid-phase binding of such antibody was completely inhibited by the addition of free antigen (SSS-III) and the amount of antibody detected in culture fluids ranged from 10 ng/ml to 10 micrograms/ml. Eight hybridoma clones were identified; all make antibody of the IgM class. These results indicate that the X-linked defect does not result in a deletion of a B-cell subset which responds to TI-2 antigens.
Specifically Targeting Angiopoietin-2 Inhibits Angiogenesis, Tie2-Expressing Monocyte Infiltration, and Tumor Growth
Authors: Hanhua Huang, Jing-Yu Lai, Janet Do, Dingguo Liu, Lingna Li, Joselyn Del Rosario, Venkata R. Doppalapudi, Steven Pirie-Shepherd, Nancy Levin, Curt Bradshaw, Gary Woodnutt, Rodney Lappe, Abhijit Bhat
Journal: Clinical Cancer Research (2011)

Angiopoietin-1 (Ang1) plays a key role in maintaining stable vasculature, whereas in a tumor Ang2 antagonizes Ang1's function and promotes the initiation of the angiogenic switch. Specifically targeting Ang2 is a promising anticancer strategy. Here we describe the development and characterization of a new class of biotherapeutics referred to as CovX-Bodies, which are created by chemical fusion of a peptide and a carrier antibody scaffold.Various linker tethering sites on peptides were examined for their effect on CovX-Body in vitro potency and pharmacokinetics. Ang2 CovX-Bodies with low nmol/L IC(50)s and significantly improved pharmacokinetics were tested in tumor xenograft studies alone or in combination with standard of care agents. Tumor samples were analyzed for target engagement, via Ang2 protein level, CD31-positive tumor vasculature, and Tie2 expressing monocyte penetration.Bivalent Ang2 CovX-Bodies selectively block the Ang2-Tie2 interaction (IC(50) < 1 nmol/L) with dramatically improved pharmacokinetics (T(½) > 100 hours). Using a staged Colo-205 xenograft model, significant tumor growth inhibition (TGI) was observed (40%-63%, P < 0.01). Ang2 protein levels were reduced by approximately 50% inside tumors (P < 0.01), whereas tumor microvessel density (P < 0.01) and intratumor proangiogenic Tie2(+)CD11b(+) cells (P < 0.05) were significantly reduced. When combined with sunitinib, sorafenib, bevacizumab, irinotecan, or docetaxel, Ang2 CovX-Bodies produced even greater efficacy (∼80% TGI, P < 0.01).CovX-Bodies provide an elegant solution to overcome the pharmacokinetic-pharmacodynamic problems of peptides. Long-acting Ang2 specific CovX-Bodies will be useful as single agents and in combination with standard-of-care agents.
Fungal endocarditis after homograft valve replacement: difficulties in diagnosis and treatment.
Authors: R M Rudd, P R Hill, P Kopelman, D J Parker
Journal: Thorax (1980)

Fungal endocarditis is an uncommon but important problem after cardiac surgery. Two cases of fungal endocarditis after homograft valve replacement are reported. In both patients prolonged periods of antifungal chemotherapy with apparently satisfactory clinical responses ultimately failed to eradicate the infection. Both patients remain free of infection two years after excision of the infected valves and further chemotherapy. The value of serial estimations of fungal antibody titres in diagnosis and treatment is demonstrated and the necessity for early operation is emphasised.
Bioactive Suture
Authors: Terry Y. Shibuya, Sanghun Kim, Kevin Nguyen, Johnny Do, Christine E. McLaren, Kuo-Tung Li, Wen-Pin Chen, Parag Parikh, Ashish Wadhwa, Xiaolin Zi, Vincent Y. Chen, Hau-Sin Wong, William B. Armstrong, George H. Yoo
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a TH1 immune response and to define the immune-stimulating half-life of the sutures. Experimental Design: Bioactive sutures of interferon γ (IFNγ), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor κB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. Results: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNγ generated a prolonged TH1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-κB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. Conclusions: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged TH1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.
Oligonucleotide-protamine-albumin nanoparticles: Protamine sulfate causes drastic size reduction
Authors: Gottfried Mayer, Vitali Vogel, Jörg Weyermann, Dirk Lochmann, Jacomina A. van den Broek, Christos Tziatzios, Winfried Haase, Daan Wouters, Ulrich S. Schubert, Andreas Zimmer, Jörg Kreuter, Dieter Schubert
Journal: Journal of Controlled Release (2005)
Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort
Authors: Maryam Kavousi, Maarten J. G. Leening, David Nanchen, Philip Greenland, Ian M. Graham, Ewout W. Steyerberg, M. Arfan Ikram, Bruno H. Stricker, Albert Hofman, Oscar H. Franco
Journal: JAMA (2014)

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines introduced a prediction model and lowered the threshold for treatment with statins to a 7.5% 10-year hard atherosclerotic cardiovascular disease (ASCVD) risk. Implications of the new guideline's threshold and model have not been addressed in non-US populations or compared with previous guidelines.To determine population-wide implications of the ACC/AHA, the Adult Treatment Panel III (ATP-III), and the European Society of Cardiology (ESC) guidelines using a cohort of Dutch individuals aged 55 years or older.We included 4854 Rotterdam Study participants recruited in 1997-2001. We calculated 10-year risks for "hard" ASCVD events (including fatal and nonfatal coronary heart disease [CHD] and stroke) (ACC/AHA), hard CHD events (fatal and nonfatal myocardial infarction, CHD mortality) (ATP-III), and atherosclerotic CVD mortality (ESC).Events were assessed until January 1, 2012. Per guideline, we calculated proportions of individuals for whom statins would be recommended and determined calibration and discrimination of risk models.The mean age was 65.5 (SD, 5.2) years. Statins would be recommended for 96.4% (95% CI, 95.4%-97.1%; n = 1825) of men and 65.8% (95% CI, 63.8%-67.7%; n = 1523) of women by the ACC/AHA, 52.0% (95% CI, 49.8%-54.3%; n = 985) of men and 35.5% (95% CI, 33.5%-37.5%; n = 821) of women by the ATP-III, and 66.1% (95% CI, 64.0%-68.3%; n = 1253) of men and 39.1% (95% CI, 37.1%-41.2%; n = 906) of women by ESC guidelines. With the ACC/AHA model, average predicted risk vs observed cumulative incidence of hard ASCVD events was 21.5% (95% CI, 20.9%-22.1%) vs 12.7% (95% CI, 11.1%-14.5%) for men (192 events) and 11.6% (95% CI, 11.2%-12.0%) vs 7.9% (95% CI, 6.7%-9.2%) for women (151 events). Similar overestimation occurred with the ATP-III model (98 events in men and 62 events in women) and ESC model (50 events in men and 37 events in women). The C statistic was 0.67 (95% CI, 0.63-0.71) in men and 0.68 (95% CI, 0.64-0.73) in women for hard ASCVD (ACC/AHA), 0.67 (95% CI, 0.62-0.72) in men and 0.69 (95% CI, 0.63-0.75) in women for hard CHD (ATP-III), and 0.76 (95% CI, 0.70-0.82) in men and 0.77 (95% CI, 0.71-0.83) in women for CVD mortality (ESC).In this European population aged 55 years or older, proportions of individuals eligible for statins differed substantially among the guidelines. The ACC/AHA guideline would recommend statins for nearly all men and two-thirds of women, proportions exceeding those with the ATP-III or ESC guidelines. All 3 risk models provided poor calibration and moderate to good discrimination. Improving risk predictions and setting appropriate population-wide thresholds are necessary to facilitate better clinical decision making.
Modal Codon Usage: Assessing the Typical Codon Usage of a Genome
Authors: J. J. Davis, G. J. Olsen
Journal: Molecular Biology and Evolution (2009)

Most genomes are heterogeneous in codon usage, so a codon usage study should start by defining the codon usage that is typical to the genome. Although this is commonly taken to be the genomewide average, we propose that the mode—the codon usage that matches the most genes—provides a more useful approximation of the typical codon usage of a genome. We provide a method for estimating the modal codon usage, which utilizes a continuous approximation to the number of matching genes and a simplex optimization. In a survey of bacterial and archaeal genomes, as many as 20% more of the genes in a given genome match the modal codon usage than the average codon usage. We use the mode to examine the evolution of the multireplicon genomes of Agrobacterium tumefaciens C58 and Borrelia burgdorferi B31. In A. tumefaciens, the circular and linear chromosomes are characterized by a common "chromosome-like" codon usage, whereas both plasmids share a distinct "plasmid-like" codon usage. In B. burgdorferi, in addition to different codon-usage biases on the leading and lagging strands of DNA replication found by McInerney (McInerney JO. 1998. Replicational and transcriptional selection on codon usage in Borrelia burgdorferi. Proc Natl Acad Sci USA. 95:10698–10703), we also detect a codon-usage similarity between linear plasmid lp38 and the leading strand of the chromosome and a high similarity among the cp32 family of plasmids.
Does Coffee Consumption Reduce the Risk of Type 2 Diabetes in Individuals With Impaired Glucose?
Authors: Besa Smith, Deborah L. Wingard, Tyler C. Smith, Donna Kritz-Silverstein, Elizabeth Barrett-Connor
Journal: Diabetes Care (2006)

The purpose of this study was to investigate the association between coffee intake and incident diabetes based on an oral glucose tolerance test (OGTT) and examine coffee habits in those with impaired glucose separately from those with normal glucose at baseline.In this prospective study, 910 adults aged >/=50 years without diabetes at baseline in 1984-1987 were followed to 1992-1996, an average of 8 years after assessment of coffee intake. Logistic regression models were adjusted for sex, age, physical activity, BMI, smoking, alcohol, hypertension, and baseline fasting plasma glucose.Past and current coffee drinkers had a reduced risk of incident diabetes (odds ratio 0.38 [95% CI 0.17-0.87] and 0.36 [0.19-0.68], respectively) compared with those who never drank coffee. The 317 participants with baseline impaired glucose who were past or current coffee drinkers were also at reduced risk for incident diabetes (0.31 [0.11-0.87] and 0.36 [0.16-0.83], respectively).This study confirms a striking protective effect of caffeinated coffee against incident diabetes and extends these findings to incident diabetes based on OGTT independent of multiple plausible confounders.