Extending the applicability of the dose addition model to the assessment of chemical mixtures of partial agonists by using a novel toxic unit extrapolation method

This article has been made available through the Brunel Open Access Publishing Fund.Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past. © 2014 Scholze et al

Revealed Preferences with Plural Motives: Axiomatic Foundations of Normative Assessments in Non-Utilitarian Welfare Economics

This paper explores the possibility of defining a non-utilitarian normative standard for assessments of welfare and deprivation. The paper formalises a key aspect of Amartya Sen’s critique of the assumption of consistent utility-maximisation in the revealed preference theory and proposes a generalisation of the standard Samuelsonian choice model for the case in which choices are based on plural motives (here, self-interested and moral motives). Based on a set of intuitive assumptions about the way in which unobservable motives are linked to observable choices, we then construct an alternative normative ranking rule that can be used in non-utilitarian welfare economics to rank social outcomes or provide a normative basis for the construction of composite indices, for instance

Digital manufacturing on a shoestring: Low cost digital solutions for SMEs

One of the key findings in a number of recent studies has been that small and medium sized manufacturers (SMEs) have been slow in adopting digital solutions within their organisations. Cost is understood to be one of the key barriers to adoption. Digital Manufacturing on a Shoestring is an approach to increasing the digital capabilities of SMEs via a series of low cost solutions. The programme proposes using off-the-shelf, (possibly non-industrial) components and software to address a company’s (digital) solution needs, adding capabilities one step at a time with minimal a priori infrastructure required. This paper will introduce the Digital Manufacturing on a Shoestring programme as a whole and demonstrate the way in which it addresses the need for low cost digital solutions for SME Manufacturers. It will discuss challenges associated with integrating low cost technologies into industrial solutions and the style of IT architectures best suited for integrating such solutions into industrial environments

Propriétés psychométriques de l’échelle de satisfaction des cours académiques (ESCA) chez les étudiants universitaires brésiliens

Academic satisfaction has been studied from different perspectives that considerate distinct ways of measurement. However, the plurality of evaluated facets prevents a more parsimonious assessment of the general students’ academic satisfaction. In the article, we aimed to provide psychometric evidence of the validity and reliability for the AMSS in Brazil in two studies (N = 893). In Study 1, an exploratory factor analysis and item parameters (Item Response Theory) support the one-factor solution and the suitability of the six items. Moreover, evidence for factorial invariance across gender and convergent validity with the PANAS and with the SWLS was also presented in Study 2. In conclusion, the present paper provides evidence of the adequacy of the AMSS to evaluate global satisfaction with the academics course in Brazil.Propiedades psicométricas de la Escala de Satisfacción del Curso Académico (ESCA) en estudiantes universitarios brasileños La satisfacción académica ha sido estudiada bajo diferentes perspectivas, produciendo dife- rentes formas de medición. Sin embargo, la pluralidad de facetas evaluadas impide una evaluación más parsimoniosa de la satisfacción académica de los estudiantes en general. En este artículo, objetivamos proporcionar evidencias psicométricas de la validez y con- fiabilidad para el ESCA en Brasil en dos estudios (N = 893). En el Estudio 1, un análisis factorial exploratorio y los parámetros de los ítems (Teoría de Respuesta al Item) soportan la solución unifatorial y la adecuación de los seis ítems. Además, se presentaron evidencias de invariancia factorial entre género y validez convergente con el PANAS y con el ESV en el Estudio 2. En conclusión, este estudio proporciona evidencias de la adecuación de la ESCA para evaluar la satisfacción global con el curso académico en Brasil.A satisfação acadêmica tem sido estudada sob diferentes perspectivas que contemplam formas distintas de mensuração. Entretanto, a pluralidade de facetas avaliadas impede uma avaliação mais parcimoniosa da satisfação acadêmica dos estudantes em geral. O presente estudo tem por objetivo fornecer evidências psicométricas da validade e confiabilidade para o ESCA no Brasil em dois estudos (N = 893). No Estudo 1, uma análise fatorial exploratória e os parâmetros dos itens (Teoria de Resposta ao Item) suportam a solução unifatorial e a adequação dos seis itens. Além disso, foram apresentadas evidências de invariância fatorial entre gênero e validade convergente com o PANAS e com o ESV no Estudo 2. Em con- clusão, este estudo fornece evidências da adequação da ESCA para avaliar a satisfação global com o curso acadêmico na versão em português.La satisfaction académique a été étudiée sous différentes perspectives qui envisagent différentes formes de mesure. Cependant, la pluralité des facettes évaluées empêche une évaluation plus parcimonieuse de la satisfaction académique des étudiants en général. La pré- sente étude vise à fournir des preuves psychométriques de validité et de fiabilité pour ESCA au Brésil dans deux études (N = 893). Dans l’étude 1, une analyse factorielle exploratoire et les paramètres d’item (Théorie de la réponse à l’item) corroborent la solution à un facteur et l’adéquation des six items. En outre, nous avons présenté des preuves d’invariance factorielle entre le sexe et la validité convergentes avec PANAS et ESV dans l’étude 2. En conclusion, cette étude fournit des preuves de l’aptitude de l’ESCA à évaluer la satisfaction générale à l’égard du cours universitaire dans la version portugaise

Preliminary Limits on the WIMP-Nucleon Cross Section from the Cryogenic Dark Matter Search (CDMS)

We are conducting an experiment to search for WIMPs, or weakly-interacting massive particles, in the galactic halo using terrestrial detectors. This generic class of hypothetical particles, whose properties are similar to those predicted by extensions of the standard model of particle physics, could comprise the cold component of non-baryonic dark matter. We describe our experiment, which is based on cooled germanium and silicon detectors in a shielded low-background cryostat. The detectors achieve a high degree of background rejection through the simultaneous measurement of the energy in phonons and ionization. Using exposures on the order of one kilogram-day from initial runs of our experiment, we have achieved (preliminary) upper limits on the WIMP-nucleon cross section that are comparable to much longer runs of other experiments.Comment: 5 LaTex pages, 5 eps figs, epsf.sty, espcrc2dsa2.sty. Proceedings of TAUP97, Gran Sasso, Italy, 7-11 Sep 1997, Nucl. Phys. Suppl., A. Bottino, A. di Credico and P. Monacelli (eds.). See also http://cfpa.berkeley.ed

Confirmation of low genetic diversity and multiple breeding females in a social group of Eurasian badgers from microsatellite and field data

The Eurasian badger ( Meles meles ) is a facultatively social carnivore that shows only rudimentary co-operative behaviour and a poorly defined social hierarchy. Behavioural evidence and limited genetic data have suggested that more than one female may breed in a social group. We combine pregnancy detection by ultrasound and microsatellite locus scores from a well-studied badger population from Wytham Woods, Oxfordshire, UK, to demonstrate that multiple females reproduce within a social group. We found that at least three of seven potential mothers reproduced in a group that contained 11 reproductive age females and nine offspring. Twelve primers showed variability across the species range and only five of these were variable in Wytham. The microsatellites showed a reduced repeat number, a significantly higher number of nonperfect repeats, and moderate heterozygosity levels in Wytham. The high frequency of imperfect repeats and demographic phenomena might be responsible for the reduced levels of variability observed in the badger

PENGARUH PEMERIKSAAN PAJAK DAN PENAGIHAN PAJAK TERHADAP KEPATUHAN WAJIB PAJAK (Survei pada Kantor Pelayanan Pajak Pratama Cibeunying, Madya, Bojonagara, Cicadas, dan Tegalega)

ABSTRAK Penelitian ini bertujuan untuk mengetahui seberapa besar pengaruh Pemeriksaan Pajak, dan Penagihan Pajak Terhadap Kepatuhan Wajib Pajak pada Survei pada Kantor Pelayanan Pajak Pratama Cibeunying, Madya, Bojonagara, Cicadas, dan Tegalega. Metode yang digunakan dalam penelitian ini adalah metode penelitian kuantitatif dengan pendekatan deskriptif dan verifikatif. Sampel dalam penelitian ini diperoleh dengan metode sampel jenuh. Didapatkan 30 responden yang menjadi sampel penelitian. Data yang digunakan adalah data primer. Teknik analisis data yang digunakan adalah analisis deskriptif, analisis verifikatif yang terdiri dari uji asumsi klasik, dan uji hipotesis, dan uji simultan yang terdiri dari analisis linier berganda, analisis korelasi, uji signifikasi simultan (Uji statistik F), dan analisis koefisien determinasi (R2) dengan bantuan program SPSS 25. Hasil penelitian ini menunjukkan bahwa secara parsial maupun simultan, Pemeriksaan Pajak, dan Penagihan Pajak Terhadap Kepatuhan Wajib Pajak. Kemampuan variabel independen dalam menjelaskan variabel dependen sebesar 63%, sedangkan sisanya sebesar 37% dijelaskan oleh variabel lain di luar model penelitian ini. Kata Kunci : Kepatuhan Wajib Pajak, Pemeriksaan Pajak, Penagihan Paja

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

PENGARUH PEMERIKSAAN PAJAK DAN PENAGIHAN PAJAK TERHADAP KEPATUHAN WAJIB PAJAK (Survei pada Kantor Pelayanan Pajak Pratama Cibeunying, Madya, Bojonagara, Cicadas, dan Tegalega)

Penelitian ini bertujuan untuk mengetahui seberapa besar pengaruh Pemeriksaan Pajak, dan Penagihan Pajak Terhadap Kepatuhan Wajib Pajak pada Survei pada Kantor Pelayanan Pajak Pratama Cibeunying, Madya, Bojonagara, Cicadas, dan Tegalega. Metode yang digunakan dalam penelitian ini adalah metode penelitian kuantitatif dengan pendekatan deskriptif dan verifikatif. Sampel dalam penelitian ini diperoleh dengan metode sampel jenuh. Didapatkan 30 responden yang menjadi sampel penelitian. Data yang digunakan adalah data primer. Teknik analisis data yang digunakan adalah analisis deskriptif, analisis verifikatif yang terdiri dari uji asumsi klasik, dan uji hipotesis, dan uji simultan yang terdiri dari analisis linier berganda, analisis korelasi, uji signifikasi simultan (Uji statistik F), dan analisis koefisien determinasi (R2) dengan bantuan program SPSS 25. Hasil penelitian ini menunjukkan bahwa secara parsial maupun simultan, Pemeriksaan Pajak, dan Penagihan Pajak Terhadap Kepatuhan Wajib Pajak. Kemampuan variabel independen dalam menjelaskan variabel dependen sebesar 63%, sedangkan sisanya sebesar 37% dijelaskan oleh variabel lain di luar model penelitian ini. Kata Kunci : Kepatuhan Wajib Pajak, Pemeriksaan Pajak, Penagihan Paja