1,270 research outputs found

    Three computer codes to read, plot and tabulate operational test-site recorded solar data

    Get PDF
    Computer programs used to process data that will be used in the evaluation of collector efficiency and solar system performance are described. The program, TAPFIL, reads data from an IBM 360 tape containing information (insolation, flowrates, temperatures, etc.) from 48 operational solar heating and cooling test sites. Two other programs, CHPLOT and WRTCNL, plot and tabulate the data from the direct access, unformatted TAPFIL file. The methodology of the programs, their inputs, and their outputs are described

    Constructing meaning about the delinquency of young girls in public-housing neighbourhoods

    Get PDF
    UID/SOC/04647/2013 SFRH/BPD/116119/2016Rooted in the theoretical approaches of social ecology and in childhood studies, the Ph.D. research project on which this paper is based aimed to achieve a better understanding of children’s socialization processes in multi-problematic spaces, particularly concerning their involvement in violence and delinquency. A case study based on ethnographic research and child-centred methods was carried out in six public-housing neighbourhoods in Portugal, which were chosen because they had relatively high levels of social deprivation, violence and crime. The specificity of the social group under study—children aged from 6 to 12 years old—and their living conditions, led us to extend the data collected by trying to learn, from the girls, the reasoning and the meanings they assign to their own actions in daily social practices. The intention was to study the features of girls’ socialization in the field through their own accounts of their lives and to examine their perspectives on offending behaviours. The genderized process of social learning in delinquency identified in the girls’ conversation is an important variable, as familial and social experiences tend to facilitate their entry into delinquency. The transmission of delinquent values takes place essentially within the female family circle or via female peers, rather than from the influence of male individuals.authorsversionpublishe

    Визначення понять «резидент» і «нерезидент»: проблеми теорії і практики

    Get PDF
    Досліджено практику застосування понять «резидент» та «нерезидент» у як в Україні так і окремих зарубіжних країнах, а також надано авторське бачення щодо визначення даних термінів. Автори статті визначають умови оподаткування операцій з нерезидентами з огляду на існуючі особливості правозастосовної діяльності і вно­сять окремі пропозиції щодо удосконалення процедури адміністрування податків, що стягуються з нерезидентів.Исследована практика применения понятий «резидент» и «нерезидент» как в Украине, так и отдельных зарубежных странах, а также предоставлено авторское виденье относительно определения данных терминов. Авторы статьи определяют условия налогообложения операций с нерезидентами, учитывая существующие особен­ности правоприменительной деятельности, вносят отдельные предложения относи­тельно усовершенствования процедуры администрирования налогов, которые удержи­ваются из нерезидентов.Іn this article practice of application of concepts «resident» and «non­resident» are explored both in Ukraine and some foreign countries, and granted the author’s view on the definition of these terms. The authors of the article determine the term of taxation of operations with non­residents, taking into account the existing features of legal activity and make some suggestions in relation to the improvement of procedure of administration of taxes which are tightened from non­residents

    The role of MYH and microsatellite instability in the development of sporadic colorectal cancer

    Get PDF
    Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathological features of MYH cancers, and determined whether inactivation of mismatch repair and base excision repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte DNA of 872 colorectal cancer patients and 478 controls. Two compound heterozygotes were identified in the cancer population and all three cancers from these individuals displayed a prominent infiltration of intraepithelial lymphocytes. In total, 11 heterozygotes were found in the cancer group and five in the control group. One tumour from an individual with biallelic germline mutation of MYH also demonstrated microsatellite instability (MSI) as a result of biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers are rare in a sporadic colorectal population, this study shows that these tumours can develop through either a chromosomal or MSI pathway. Tumours arising in the setting of BER or mismatch repair deficiency may share a biological characteristic, which promotes lymphocytic infiltration

    Investigation of pathogenic mechanisms in multiple colorectal adenoma patients without germline APC or MYH/MUTYH mutations

    Get PDF
    Patients with multiple (5–100) colorectal adenomas (MCRAs) often have no germline mutation in known predisposition genes, but probably have a genetic origin. We collected a set of 25 MCRA patients with no detectable germline mutation in APC, MYH/MUTYH or the mismatch repair genes. Extracolonic tumours were absent in these cases. No vertical transmission of the MCRA phenotype was found. Based on the precedent of MYH-associated polyposis (MAP), we searched for a mutational signature in 241 adenomatous polyps from our MCRA cases. Somatic mutation frequencies and spectra at APC, K-ras and BRAF were, however, similar to those in sporadic colorectal adenomas. Our data suggest that the genetic pathway of tumorigenesis in the MCRA patients' tumours is very similar to the classical pathway in sporadic adenomas. In sharp contrast to MAP tumours, we did not find evidence of a specific mutational signature in any individual patient or in the overall set of MCRA cases. These results suggest that hypermutation of APC does not cause our patients' disease and strongly suggests that MAP is not a paradigm for the remaining MCRA patients. Our MCRA patients' colons showed no evidence of microadenomas, unlike in MAP and familial adenomatous polyposis (FAP). However, nuclear β-catenin expression was significantly greater in MCRA patients' tumours than in sporadic adenomas. We suggest that, at least in some cases, the MCRA phenotype results from germline variation that acts subsequent to tumour initiation, perhaps by causing more rapid or more likely progression from microadenoma to macroadenoma

    Analogue peptides for the immunotherapy of human acute myeloid leukemia

    Get PDF
    Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

    A Pilot Study of IL-2Rα Blockade during Lymphopenia Depletes Regulatory T-cells and Correlates with Enhanced Immunity in Patients with Glioblastoma

    Get PDF
    Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells.To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete T(Regs) while permitting vaccine-stimulated immune responses.A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ).Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study.ClinicalTrials.gov NCT00626015

    Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

    Get PDF
    Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

    Torosaurus Is Not Triceratops: Ontogeny in Chasmosaurine Ceratopsids as a Case Study in Dinosaur Taxonomy

    Get PDF
    Background: In horned dinosaurs, taxonomy is complicated by the fact that the cranial ornament that distinguishes species changes with age. Based on this observation, it has been proposed that the genera Triceratops and Torosaurus are in fact synonymous, with specimens identified as Torosaurus representing the adult form of Triceratops. The hypothesis of synonymy makes three testable predictions: 1) the species in question should have similar geographic and stratigraphic distributions, 2) specimens assigned to Torosaurus should be more mature than those assigned to Triceratops, and 3) intermediates should exist that combine features of Triceratops and Torosaurus. The first condition appears to be met, but it remains unclear whether the other predictions are borne out by the fossil evidence. Methodology/Principal Findings: We assessed the relative maturity of Torosaurus and Triceratops specimens by coding skulls for characters that vary with maturity, and then using a clustering analysis to arrange them into a growth series. We found that a well-defined sequence of changes exists in horned dinosaurs: development of cranial ornament occurs in juveniles, followed by fusion of the skull roof in subadults, and finally, the epoccipitals, epijugals, and rostral fuse to the skull in adults. Using this scheme, we identified mature and immature individuals of both Torosaurus and Triceratops. Furthermore, we describe the ventral depressions on the frill of Triceratops, and show that they differ in shape and position from the parietal fenestrae of Torosaurus. Thus, we conclude that these structures are not intermediates between the soli

    Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

    Get PDF
    The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse
    corecore