bluuebunny/crossref_metadata_2025 huggingface dataset:
Church Attendance, Implicit Religion and Belief in Luck
Authors: Francis Leslie J. , Williams Emyr , Robbins Mandy
Published: November 2009

This study was designed to examine the complex pattern of relationships between conventional religious practice (in the sense of church attendance), implicit religion (in the sense of persisting Christian beliefs and values, unsupported by church attendance), and alternative spirituality (in the sense of non-conventional beliefs). In this context implicit religion was operationalized in terms of attitude toward the explicit religion of Christianity, and alternative spirituality was operationalized in terms of belief in luck. Data were provided by a sample of 1,133 13- to 15-year-old adolescents in South Wales who completed the Belief in Luck Index (BILI) and the Francis Scale of Attitude toward Christianity (FSAC), alongside information about frequency of church attendance. These data demonstrate that among non-churchgoers there is a significant positive correlation between attitude toward Christianity and belief in luck. Among churchgoers, however, these two variables were uncorrelated. These findings support the view that a general eclectic belief system is underpinning the spirituality of the unchurched rather than a widespread rejection of transcendence in favour of secularity.
Translation of “Présentation” from La Religion Implicite
Authors: Menard Guy
Published: November 2009

Edward Bailey’s book, Implicit Religion: An Introduction, was published in 1998 by Middlesex University Press (London). This translation is part of a broader project to introduce an area of study which has been developing in Great Britain and in other English-speaking countries for about thirty years, to the French-speaking world. In 1996, Religiologiques, the journal of the Department of Religious Studies at the University of Quebec in Montreal, devoted an issue to this field of study by publishing a “selection” of ten articles by British authors illustrating the fertile diversity of this approach to the phenomenon of religion. Unfortunately, despite some incursion into French speaking territory, this approach remains largely unknown here. Yet even today, more than ten years later, the prospects opened up by this line of research are by their nature capable of contributing to the renewal of our understanding of the phenomenon of religion and its current evolution. So it seemed important to me to translate this short treatise which introduces the origins and the broader themes of the concept of implicit religion, together with some of the principal results of the research it has inspired.
Religious Musings on Francis Bacon
Authors: Arya Rina
Published: November 2009

Francis Bacon is arguably the most well-known British artist after J.M.W. Turner, and his centenary in 2009 has been well documented in both the art world and the mass media. The BBC archive contains a comprehensive range of interviews and footage of the artist. To commemorate the centenary, the Tate has put together the third retrospective on Bacon (the previous ones were in 1962 and 1985 and were also held at the Tate), which has brought together some of his best works from different periods of his life. This extensive exhibition then moves to the Prado (Madrid) from 3 February–19 April 2009, and on to the Metropolitan Museum in New York from 18 May–6 August 2009.
Modelos de atenção à saúde de usuários de álcool e outras drogas: discursos políticos, saberes e práticas
Authors: Alves Vânia Sampaio
Published: November 2009

O presente artigo tem por objetivo caracterizar os modelos de atenção à saúde de usuários de álcool e outras drogas existentes no contexto brasileiro. Para tanto, realizou-se uma análise do discurso de políticas públicas de drogas no Brasil a partir da década de 1970. Tal análise foi contextualizada por uma breve digressão sobre os principais posicionamentos políticos identificados entre países do mundo para o enfrentamento de questões relacionadas ao consumo de substâncias psicoativas. As políticas públicas brasileiras de drogas apresentam-se, a partir da presente década, permeáveis ao enfoque da redução de danos, repercutindo na reorientação do modelo de atenção à saúde. Conclui-se que a estruturação e o fortalecimento de uma rede de atenção integral aos usuários de álcool e outras drogas e às suas famílias, centrada na atenção comunitária, orientada pela concepção ampliada de redução de danos e articulada com outras redes de serviços sociais e de saúde constitui, na atualidade, um importante desafio à saúde pública.
Recovery Behaviour of a Partly Illitized Sandstone Gas Reservoir
Authors: Uwaga Anthony O.
Published: November 2009

Diagenesis is defined as any chemical, physical or biological change undergone by a sediment (rock) after its initial deposition and during and after its lithification, exclusive of surface alteration (weathering) and metamorphism. The diagenetic changes that occur in the rock result in the alteration of some of the original petrophysical properties of the rock. Porosity and permeability, amongst others, have been established to be altered by diagenesis.

It is common knowledge in the industry that the amount of hydrocarbon recovered from a reservoir is dependent, amongst other factors, on the hydrocarbon initially-in-place in the reservoir and the intra reservoir rock pore space connectivity. The hydrocarbon initially-in-place is a function of the reservoir rock porosity and the pore space connectivity is a measure of the permeability of the reservoir rock. Thus the recovery from a reservoir rock affected by diagenesis, based on the aforementioned effects of diagenesis on reservoir rock porosity and permeability, is largely dependent on the extent of diagenesis that took place in the reservoir rock.

While reservoir performance behaviour is well established in sandstone reservoirs with diagenetic clays occurring throughout the reservoir, though may be scattered here and there in the reservoir rock, the case of a reservoir rock with a clay-affected layer directly below a clay-free layer, but is one sand pack, is unique.

This paper discusses the recurring increases in gas recovery in a partly illitized sandstone reservoir using the North Morecambe field in the East Irish Sea Basin as case study. Illite, a diagenetic clay mineral, has the characteristic of lining the pores of the reservoir rock. Its main effect is reservoir permeability alteration.

The North Morecambe field is a sandstone reservoir with two flow zones: an illite-affected zone overlain by an illite-free zone. More than half of the gas-in-place in the field is located in the illite-free zone. Reservoir dynamic simulation and historical production data analysis carried out on the field indicates differential draining of the flow zones: the illite-free zone producing much better than the illite-affected zonecrossflow from the illite-affected zone to the illite-free zonethat though the illite-free zone of the reservoir is being preferentially drained, in comparison to the illite-affected zone, the illite-affected zone is nonetheless being efficiently drained through crossflow into the illite-free zone

The study carried out and presented in this paper highlights best practise approach in completion strategy for efficient draining of the illitized part of a partly illitized sandstone reservoir. It further establishes a cubic, not a linear, behaviour as the reservoir performance behaviour to be expected from a partly illitized sandstone reservoir.
Acetate uptake efficiency of polyphosphate-accumulating organisms under exposure to surfactants
Authors: Tsuji K. , Fujita M. , Furumai H.
Published: November 2009

We investigated the influence of surfactants such as linear alkylbenzene sulfonates (LAS) and alcohol ethoxylates (AE) on acetate uptake by polyphosphate-accumulating organisms (PAOs) under anaerobic conditions, using the phosphate requirement for acetate uptake (+ΔP/−ΔAc ratio). In order to estimate the +ΔP/−ΔAc ratio, anaerobic batch tests were conducted using activated sludge collected from an anaerobic/oxic sequencing batch reactor used to treat municipal wastewater continuously supplemented with a detergent containing LAS and AE. We demonstrated that LAS and AE have both positive and negative impacts on acetate uptake by PAOs. The disadvantage is that long-term exposure to the detergent inhibits acetate uptake by PAOs, thus deteriorating the efficiency, even if the surfactants are no longer present during the tests. Furthermore, the existence of LAS and/or AE with acetate further diminishes the efficiency. The advantage is that LAS and AE are potential sources of polyhydroxyalkanoate for PAOs, because acetate is produced from the surfactants under anaerobic conditions.
Phosphate removal from source separated urine by electrocoagulation using iron plate electrodes
Authors: Zheng Xiang-yong , Kong Hai-Nan , Wu De-yi , Wang Chong , Li Yan , Ye Hai-ren
Published: November 2009

The aim of this study was to investigate the effects of current density, gap between electrodes, urine dosage, dilution and hydrolysis on phosphate removal from human urine by electrocoagulation technique using iron as electrodes. It was shown that, although a high current density and a long electrolysis time favored the removal of phosphate, an appropriate value for these two parameters can be obtained by taking into account the consumption of energy and iron in addition to P removal. In this study, current density 40 mA/cm2 and electrolysis time 20 min were shown to be optimal for 1.0 L pure urine to achieve nearly a complete removal (98%) efficiency of phosphate under the conditions of electrode area 160 cm2, the stirring speed 150 rpm, and the gap between electrodes 5 mm. Increase of gap between electrodes had little effect on phosphate removal, although it increased the energy consumption dramatically. The use of a high urine dosage reduced the efficiency of phosphate removal but increased the amount of removed phosphate. When pure urine was diluted with tap water, use of a higher tap water proportion for dilution expedited the electrolysis to achieve a nearly complete removal of phosphate in solution, but dilution caused the increase in energy consumption. It was also revealed that the hydrolysis of urine prior to electrocoagulation treatment impeded phosphate removal.
Three advanced oxidation processes for the treatment of the wastewater from acrylonitrile production
Authors: Yan-yang Chu , Yi Qian , Mao-juan Bai
Published: November 2009

A new advanced oxidation processes: electrochemical oxidation with iron promoting (EOIP) was presented and the treatment of an actual industrial wastewater from acrylonitrile production by three advanced oxidation processes (AOPs) has been studied: Fenton oxidation (FO), electro-Fenton oxidation (EFO), and electrochemical oxidation with iron promoting (EOIP). It was found that all the three processes were able to treat this wastewater, but different results in terms of efficiency and different behaviors were obtained. When the same dosage of H2O2 was added to the wastewater, the oxidation power of three AOPs increased in the order: FO < EFO < EOIP. Under the condition of higher dosage of H2O2, the three AOPs applied could achieve the better color removal. When the dosage of H2O2 was lower than 1,500 mg l−1, the color of the wastewater after treated increased from FO and EFO due to the formation of Fe (III) complexes, but this was not found in EOIP. The results of this work indicate that EOIP is a promising alternative for COD and color removal from organic wastewater.
Risk in the mist? Deriving data to quantify microbial health risks associated with aerosol generation by water-efficient devices during typical domestic water-using activities
Authors: O'Toole J. , Keywood M. , Sinclair M. , Leder K.
Published: November 2009

The aim of this study was to address existing data gaps and to determine the size distribution of aerosols associated with water-efficient devices during typical domestic activities. This information is important to assist in understanding infection spread during water-using activities and in designing water regulations. Three water-using scenarios were evaluated: i) showering using a water-efficient showerhead; ii) use of a high pressure spray unit for cleaning cars and iii) toilet flushing using a dual flush low volume flush device. For each scenario a control condition (conventional lower efficiency device) was selected for benchmarking purposes. Shower module results highlighted the complexity of particle generation and removal processes and showed that more than 90% of total particle mass in the breathing zone was attributed to particle diameters greater than 6 μm. Conversely, results for car washing experiments showed that particle diameters up to 6 μm constituted the major part of the total mass generated by both water-efficient and conventional devices. Even under worse case scenario conditions for toilet flushing, particle measurements were at or below the level of detection of the measuring instrumentation. The data provide information that assists in health risk assessment and in determining future research directions, including methodological aspects.
Effect of Intruded Exit on Riser Type Circulating Fluidized Beds
Authors: Daga Sudarshan K. , Kumar Vineet
Published: November 2009

The present work attempts to study the flow dynamics of Geldart group A and group B particles in a circulating fluidized bed (CFB) riser with intruded exits using computational fluid dynamics (CFD) techniques. In this work, three different designs of riser exit geometries were studied using a 2D transient Eulerian approach with kinetic theory of granular flow in a commercial CFD simulation package. The three exits geometries, namely conventional exit, intruded curved and straight exits were designed and simulated. The various factors like solid volume fraction, pressure drop, and solid velocity were studied for both group A and group B particles. Results indicate that intruded exits have certain advantages like low riser pressure, uniform particle distribution, etc., over the conventional design because fluid and particle comes out from the core of the riser where there is no wall effect and particles have higher momentum concentration.
Forensic importance of homicide
Authors: Novakovic Milan
Published: November 2009

Introduction. This study encompassed the total number of homicides in Bosnia and Herzegovina (B&H) in the period from 1st January 1997 to 31st December 2006 and then analyzed homicidal behaviour. The aim is to assess the differences between the people who committed violent and those who committed accidental homicide in Bosnia and Herzegovina. Material and methods. In a multicentric, retrospective study of comparing the groups with equal number of respondents we analysed the individuals who had committed violent (n=135) and accidental homicides (n=135). The homicides were tested by using socio-demographic and psychosocial items. Measurement instruments were: General data list, Eysenck Personality Questionnaire (EPQ), Hamilton Depression Rating Scale (HDRS), Emotions Profile Index (EPI). The descriptive and multivariable logistic analysis was done statistically. Results. In the descriptive analysis the socio-demographically violent murderers were: male gender (c2=3.340, P=0.009), more workers than officials (c2=7.340, P=0.011), fathers were more often workers/farmers (c2=1.430, P=0.046), gambling (c2 =13.100,P=0.001) and possible recidivism (c2 = 6.770, a P = 0.001). The accidental murderers were family people (c2 =4.100, P =0.041), with more frequent drug abuse (c2 =3.190, P= 0.012) and they would not repeat the delict. In the multivariate analysis the violent murderers were highly discriminated (P=0.001) from accidental ones by: war involvement r =0.1148, OR =2.971 (95%), CI=1.040-7.890; age, father's education, psychoticism (EPQ) r =-0.1085, OR= 0.291(95%), CI= 0.110-0870, HDRS-total r= -0.1797, OR= 0.830 (95%), CI=0.710 - 0.930, destructiveness r = 0.1270, OR =1.560 (95%), CI=1.197-2.032, and deprivation in the P. I. E. tests. Conclusion. By the violence of their acts murderers confirm micro-social model of transferring the violence, and transition and heredity confirm the ecological-developmental trans-generation model of violence. Accidental murderers commit homicide in anomy, with intoxications and prolonged psycho-traumatism.
Empirical soot formation and oxidation model
Authors: Boussouara Karima , Kadja Mahfoud
Published: November 2009

Modelling internal combustion engines can be made following different approaches, depending on the type of problem to be simulated. A diesel combustion model has been developed and implemented in a full cycle simulation of a combustion, model accounts for transient fuel spray evolution, fuel-air mixing, ignition, combustion, and soot pollutant formation. The models of turbulent combustion of diffusion flame, apply to diffusion flames, which one meets in industry, typically in the diesel engines particulate emission represents one of the most deleterious pollutants generated during diesel combustion. Stringent standards on particulate emission along with specific emphasis on size of emitted particulates have resulted in increased interest in fundamental understanding of the mechanisms of soot particulate formation and oxidation in internal combustion engines. A phenomenological numerical model which can predict the particle size distribution of the soot emitted will be very useful in explaining the above observed results and will also be of use to develop better particulate control techniques. A diesel engine chosen for simulation is a version of the Caterpillar 3406. We are interested in employing a standard finite-volume computational fluid dynamics code, KIVA3V-RELEASE2.
Critical review of thermoelectrics in modern power generation applications
Authors: Saqr Khalid , Musa Mohd
Published: November 2009

The thermoelectric complementary effects have been discovered in the nineteenth century. However, their role in engineering applications has been very limited until the first half of the twentieth century, the beginning of space exploration era. Radioisotope thermoelectric generators have been the actual motive for the research community to develop efficient, reliable and advanced thermoelectrics. The efficiency of thermoelectric materials has been doubled several times during the past three decades. Nevertheless, there are numerous challenges to be resolved in order to develop thermoelectric systems for our modern applications. This paper discusses the recent advances in thermoelectric power systems and sheds the light on the main problematic concerns which confront contemporary research efforts in that field.
Transesterification for the preparation of biodiesel from crude-oil of Pongamia pinnata
Authors: Babu Veeresh , Rao Appa , Kumar Ravi
Published: November 2009

Biodiesel was prepared from the non-edible oil of Pongamia pinnata L. by transesterification of the crude-oil with methanol in the presence of NAOH as catalyst. Vegetable oils can be transesterified by heating them with a large excess of anhydrous methanol and an acidic or basic reagent as catalyst. Both the acid as well as alkaline esterifications were subsequently performed to get the final product. A catalyst is usually used to improve the reaction rate and yield. NaOH was found to be a better catalyst than KOH in terms of yield. In a transesterification reaction, a larger amount of methanol was used to shift the reaction equilibrium to the right side and produce more methyl esters as the proposed product. Several aspects including the type of catalyst (alkaline, acid, or enzyme), alcohol/vegetable oil molar ratio, temperature, purity of the reactants (mainly water content) and free fatty acid content have an influence on the course of the transesterification. A maximum conversion of 94% (oil to ester) was achieved using a 1:10 molar ratio of oil to methanol at 60 to 65 ?C. Important fuel properties of methyl esters of pongamia oil (biodiesel) compare well with ASTM standards.
Jatropha oil methyl ester and its blends used as an alternative fuel in diesel engine
Authors: Yarrapathruni Rao , Voleti Sudheer , Pereddy Reddy , Alluru Raju
Published: November 2009

Biomass derived vegetable oils are quite promising alternative fuels for agricultural diesel engines. Use of vegetable oils in diesel engines leads to slightly inferior performance and higher smoke emissions due to their high viscosity. The performance of vegetable oils can be improved by modifying them through the transesterification process. In this present work, the performance of single cylinder water-cooled diesel engine using methyl ester of jatropha oil as the fuel was evaluated for its performance and exhaust emissions. The fuel properties of biodiesel such as kinematic viscosity, calorific value, flash point, carbon residue, and specific gravity were found. Results indicate that B25 has closer performance to diesel and B100 has lower brake thermal efficiency mainly due to its high viscosity compared to diesel. The brake thermal efficiency for biodiesel and its blends was found to be slightly higher than that of diesel fuel at tested load conditions and there was no difference of efficiency between the biodiesel and its blended fuels. For jatropha biodiesel and its blended fuels, the exhaust gas temperature increased with the increase of power and amount of biodiesel. However, its diesel blends showed reasonable efficiency, lower smoke, and CO2 and CO emissions.
Adverse Section 404 Opinions and Shareholder Dissatisfaction toward Auditors
Authors: Hermanson Dana R. , Krishnan Jagan , Ye Zhongxia (Shelly)
Published: November 2009

SYNOPSIS: Auditors issuing adverse Section 404 internal control opinions may be viewed as too conservative, or they may be blamed for being partly responsible for the existence of the internal control material weaknesses. Using a sample of 240 companies with adverse internal control opinions and 240 matched “clean” companies in their first year of Section 404 compliance, we examine how shareholder dissatisfaction with the auditors varies depending on material weakness existence/type (company-level versus noncompany-level) and the presence of recent accounting restatements. In the full sample, we find a significant positive interaction between restatement and company-level material weakness—company-level material weaknesses have a greater effect on shareholder dissatisfaction when a restatement has occurred. To provide insight, we partition our sample based on whether test companies have had recent accounting restatements. In the nonrestatement sample, we find that shareholders are less likely to vote for auditor ratification if the company received an adverse Section 404 internal control opinion because of noncompany-level material weaknesses. Shareholders may view the auditor as being too conservative when no company-level material weaknesses are cited and no recent accounting restatements have been issued. In the restatement sample, we find that shareholders are less likely to vote for auditor ratification if the company received an adverse Section 404 opinion with or without company-level material weaknesses cited—but with shareholder dissatisfaction greater for companies with company-level material weaknesses. Hence, in companies with recent accounting restatements, shareholders may blame the auditor for being partly responsible for the existence of material weaknesses (i.e., low audit quality). Overall, the results provide insights into shareholders’ perceptions of auditing and suggest that existing shareholders may sometimes prefer less conservative auditors. We encourage additional research on the role of auditors in protecting current versus prospective shareholders.
Examination of All Type 2 Diabetes GWAS Loci Reveals HHEX-IDE as a Locus Influencing Pediatric BMI
Authors: Zhao Jianhua , Bradfield Jonathan P. , Zhang Haitao , Annaiah Kiran , Wang Kai , Kim Cecilia E. , Glessner Joseph T. , Frackelton Edward C. , Otieno F. George , Doran James , Thomas Kelly A. , Garris Maria , Hou Cuiping , Chiavacci Rosetta M. , Li Mingyao , Berkowitz Robert I. , Hakonarson Hakon , Grant Struan F.A.
Published: November 2009

OBJECTIVE

A number of studies have found that BMI in early life influences the risk of developing type 2 diabetes later in life. Our goal was to investigate if any type 2 diabetes variants uncovered through genome-wide association studies (GWAS) impact BMI in childhood.

RESEARCH DESIGN AND METHODS

Using data from an ongoing GWAS of pediatric BMI in our cohort, we investigated the association of pediatric BMI with 20 single nucleotide polymorphisms at 18 type 2 diabetes loci uncovered through GWAS, consisting of ADAMTS9, CDC123-CAMK1D, CDKAL1, CDKN2A/B, EXT2, FTO, HHEX-IDE, IGF2BP2, the intragenic region on 11p12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and TSPAN8-LGR5. We randomly partitioned our cohort exactly in half in order to have a discovery cohort (n = 3,592) and a replication cohort (n = 3,592).

RESULTS

Our data show that the major type 2 diabetes risk–conferring G allele of rs7923837 at the HHEX-IDE locus was associated with higher pediatric BMI in both the discovery (P = 0.0013 and survived correction for 20 tests) and replication (P = 0.023) sets (combined P = 1.01 × 10−4). Association was not detected with any other known type 2 diabetes loci uncovered to date through GWAS except for the well-established FTO.

CONCLUSIONS

Our data show that the same genetic HHEX-IDE variant, which is associated with type 2 diabetes from previous studies, also influences pediatric BMI.
Cytokines Interleukin-1β and Tumor Necrosis Factor-α Regulate Different Transcriptional and Alternative Splicing Networks in Primary β-Cells
Authors: Ortis Fernanda , Naamane Najib , Flamez Daisy , Ladrière Laurence , Moore Fabrice , Cunha Daniel A. , Colli Maikel L. , Thykjaer Thomas , Thorsen Kasper , Ørntoft Torben F. , Eizirik Decio L.
Published: November 2009

OBJECTIVE

Cytokines contribute to pancreatic β-cell death in type 1 diabetes. This effect is mediated by complex gene networks that remain to be characterized. We presently utilized array analysis to define the global expression pattern of genes, including spliced variants, modified by the cytokines interleukin (IL)-1β + interferon (IFN)-γ and tumor necrosis factor (TNF)-α + IFN-γ in primary rat β-cells.

RESEARCH DESIGN AND METHODS

Fluorescence-activated cell sorter–purified rat β-cells were exposed to IL-1β + IFN-γ or TNF-α + IFN-γ for 6 or 24 h, and global gene expression was analyzed by microarray. Key results were confirmed by RT-PCR, and small-interfering RNAs were used to investigate the mechanistic role of novel and relevant transcription factors identified by pathway analysis.

RESULTS

Nearly 16,000 transcripts were detected as present in β-cells, with temporal differences in the number of genes modulated by IL-1β + IFNγ or TNF-α + IFN-γ. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression of genes involved in the maintenance of β-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-α, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine-induced changes in alternative splicing of >50% of the cytokine-modified genes.

CONCLUSIONS

The present study doubles the number of known genes expressed in primary β-cells, modified or not by cytokines, and indicates the biological role for several novel cytokine-modified pathways in β-cells. It also shows that cytokines modify alternative splicing in β-cells, opening a new avenue of research for the field.
TCF7L2 Variant rs7903146 Affects the Risk of Type 2 Diabetes by Modulating Incretin Action
Authors: Villareal Dennis T. , Robertson Heather , Bell Graeme I. , Patterson Bruce W. , Tran Hung , Wice Burton , Polonsky Kenneth S.
Published: November 2009

OBJECTIVE

Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk.

RESEARCH DESIGN AND METHODS

Eight subjects with risk-conferring TCF7L2 genotypes (TT or TC at rs7903146) and 10 matched subjects with wild-type genotype (CC) underwent 5-h oral glucose tolerance test (OGTT), isoglycemic intravenous glucose infusion, and graded glucose infusion (GGI). Mathematical modeling was used to quantify insulin-secretory profiles during OGTT and glucose infusion protocols. The incretin effect was assessed from ratios of the insulin secretory rates (ISR) during oral and isoglycemic glucose infusions. Dose-response curves relating insulin secretion to glucose concentrations were derived from the GGI.

RESULTS

β-cell responsivity to oral glucose was 50% lower (47 ± 4 vs. 95 ± 15 × 109 min−1; P = 0.01) in the group of subjects with risk-conferring TCF7L2 genotypes compared with control subjects. The incretin effect was also reduced by 30% (32 ± 4 vs. 46 ± 4%; P = 0.02) in the at-risk group. The lower incretin effect occurred despite similar glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses to oral glucose. The ISR response to intravenous glucose over a physiologic glucose concentration range (5–9 mmol/l) was similar between groups.

CONCLUSIONS

The TCF7L2 variant rs7903146 appears to affect risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion. This is not due to reduced secretion of GLP-1 and GIP but rather due to the effect of TCF7L2 on the sensitivity of the β-cell to incretins. Treatments that increase incretin sensitivity may decrease the risk of type 2 diabetes.
E2F-1-Deficient NOD/SCID Mice Developed Showing Decreased Saliva Production
Authors: Matsui-Inohara Hikaru , Uematsu Hiroshi , Narita Takanori , Satoh Keitaro , Yonezawa Hideo , Kuroda Koichiro , Ito Tatsuro , Yoneda Saori , Kawarai Taketo , Sugiya Hiroshi , Watanabe Haruo , Senpuku Hidenobu
Published: November 2009

The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjoögren’s syndrome (SS). In a previous report, we found NOD. E2f1−/−mice show a greater progressive development to IDDM and SS compared to NOD mice. Our previous data indicated a progressive decrease in regulatory T cells (CD4+CD25+) and a decrease in the systemic secretion systems for insulin, and saliva was associated with the progression of IDDM and SS. Therefore, to define the mechanism of early-onset IDDM SS in E2F-1 deficient NOD mice required further investigation by producing E2F-1 deficient NOD/SCID mice in which the T and B cells do not develop. The purpose here was to analyze the essential function of the E2F-1 molecule in the development of IDDM and SS; and the dysfunction of the pancreas islet and salivary gland in the NOD background using NOD/SCID mice. We produced NOD/SCID. E2f1−/−mice using homologous recombination; determined diabetes development; measured saliva and insulin production; and performed a histological analysis. The deficient mice showed a decreasing volume of saliva; no infiltration of lymphocytes into salivary glands; no development of diabetes; and no protein localization of FGFR-2b in the ducts of the salivary gland that regulates submandibular gland proliferation and morphogenesis. Therefore, we considered a deficiency in E2F-1 induces a decrease in regulatory T cells and an increase in auto-reactive T cells; however, the E2F-1 deficiency is not associated with T and B cells-independent dysfunction of pancreatic β cell in insulin secretion. Further, the E2F-1 deficiency is associated with T and B cells-independent dysfunction of the salivary gland exhibits a decrease in saliva production volume. We suggest E2F-1 may be also associated with the differentiation of exocrine cells in the duct where FGFR-2b is expressed in the salivary gland. The E2F-1 deficient NOD/SCID mouse model is useful for showing the development of the salivary gland; and is also useful for various experiments in humanized mice.
Pollination biology of Harrisia portoricensis (Cactaceae), an endangered Caribbean species
Authors: Rojas‐Sandoval Julissa , Meléndez‐Ackerman Elvia
Published: November 2009

Traits associated with self‐pollination are common features of island plant communities. In this work, we studied the pollination biology and the breeding system of Harrisia portoricensis, an island columnar cactus, to test for the presence of inbreeding and inbreeding depression. For H. portoricensis, which bears flowers with typical outcrossing morphology, the results from 322 h of direct observations and videotaping showed that visits to flowers by animals were uncommon. Controlled pollinations demonstrated that H. portoricensis has a partially self‐compatible breeding system that it is not autogamous and thus requires an external mechanism for the movement of pollen to set fruit. We detected differences in seed size, seed mass, germination success, and multiplicative fitness estimates between self‐ and cross‐pollination treatments. We found that progeny resulting from natural and self‐pollination treatments showed signs of inbreeding depression compared with progeny resulting from cross‐pollination; however, the magnitude of the inbreeding depression was less than 50%. Our combined results suggest that for this species an endogamous breeding system should be favored by natural selection.
Early inbreeding depression in the sexually polymorphic plant Dianthus sylvestris (Caryophyllaceae): Effects of selfing and biparental inbreeding among sex morphs
Authors: Collin Carine L. , Penet Laurent , Shykoff Jacqui A.
Published: November 2009

Predominantly outcrossing plant species are expected to accumulate recessive deleterious mutations, which can be purged when in a homozygous state following selfing. Individuals may vary in their genetic load because of different selfing histories, which could lead to differences in inbreeding depression among families. Lineage‐dependent inbreeding depression can appear in gynodioecious species if obligatory outcrossed females are more likely to produce female offspring and if partially selfing hermaphrodites are more likely to produce hermaphrodites. We investigated inbreeding depression at the zygote, seed, and germination stages in the gynomonoecious‐gynodioecious Dianthus sylvestris, including pure‐sexed plants and a mixed morph. We performed hand‐pollinations on 56 plants, belonging to the three morphs, each receiving 2–3 cross treatments (out‐, sib‐ and self‐pollination) on multiple flowers. Effects of cross treatments varied among stages and influenced seed provisioning, with sibling competition mainly occurring within outcrossed fruits. We found significant inbreeding depression for seed mass and germination and cumulative early inbreeding depression varied greatly among families. Among sex morphs, we found that females and hermaphrodites differed in biparental inbreeding depression, whereas uniparental was similar for all. Significant inbreeding depression levels may play a role in female maintenance in this species, and individual variation in association with sex‐lineages proclivity is discussed.
Sublingual Immunization with Nonreplicating Antigens Induces Antibody-Forming Cells and Cytotoxic T Cells in the Female Genital Tract Mucosa and Protects against Genital Papillomavirus Infection
Authors: Çuburu Nicolas , Kweon Mi-Na , Hervouet Catherine , Cha Hye-Ran , Pang Yuk-Ying S. , Holmgren Jan , Stadler Konrad , Schiller John T. , Anjuère Fabienne , Czerkinsky Cecil
Published: November 2009

We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8+ cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8+ cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.
B7-1/2 (CD80/CD86) Direct Signaling to B Cells Enhances IgG Secretion
Authors: Rau Friederike C. , Dieter Jacquelyn , Luo Zhang , Priest Stephen O. , Baumgarth Nicole
Published: November 2009

B cell responses are regulated by Ag recognition, costimulatory signals provided by interaction with helper T cells, and by innate signals. We recently provided evidence for a link between the effects of innate and costimulatory signals on B cells during influenza virus infection, by demonstrating that most B cells in the regional lymph nodes of the respiratory tract enhance surface expression of the costimulator B7-2 (CD86) within 24–48 h following infection via a type I IFNR-dependent mechanisms, a finding we are confirming here. While the role of B7-1/2 for helper T cell activation is well documented, its role in direct B cell regulation is poorly understood. Here, our in vivo studies with mixed bone marrow irradiation chimeric mice, lacking B7-1/2 only on B cells, demonstrated that B7-1/2 expression is crucial for induction of maximal local, but to a lesser extent systemic, IgG Ab responses following influenza virus infection. In contrast to mice that completely lack B7-1/2 expression, loss of B7-1/2 on B cells alone did not significantly affect germinal center formation or the extent of CD4+ T cell activation and IFN-γ secretion. Instead, our in vitro studies identify a dramatic effect of B7-2 engagement on IgG, but not IgM secretion by already class-switched B cells. Concomitantly, B7-2 engagement induced expression of X-box binding protein 1 (XBP-1) and spliced XBP1, evidence for increased protein synthesis by these cells. Taken together, these results identify direct signaling through B7-1/2 as a potent regulator of IgG secretion by previously activated B cells.
Activation, Immune Polarization, and Graft-versus-Leukemia Activity of Donor T Cells Are Regulated by Specific Subsets of Donor Bone Marrow Antigen-Presenting Cells in Allogeneic Hemopoietic Stem Cell Transplantation
Authors: Li Jian-Ming , Southerland Lauren T. , Lu Ying , Darlak Kataryna A. , Giver Cynthia R. , McMillin Douglas W. , Harris Wayne A. C. , Jaye David L. , Waller Edmund K.
Published: November 2009

We investigated the roles of specific subsets of donor APCs purified from bone marrow in donor T cell activation and graft-vs-leukemia (GvL) activity in murine models of hemopoietic stem cell transplantation. Lineage−CD11c+ APC precursors were separated from donor bone marrow based on expression of CD11b. Transplanting lineage−CD11c+CD11b− APC (CD11b− APC) in combination with c-kit+Sca-1+lineage− hemopoietic stem cells (HSC) and congenic donor T cells led to increased donor CD4+ and CD8+ T cell proliferation and higher donor T cell chimerism than with transplanting grafts containing HSC, T cells, and lineage−CD11c+CD11b+ APCs (CD11b+ APC), or grafts containing only HSC and T cells. Transplanting CD11b− APCs induced Th1/type 1 cytotoxic T lymphocyte donor T cell immune polarization and enhanced GvL activity of donor T cells without increased graft-vs-host disease in both MHC- and minor histocompatibility Ag-mismatched murine hemopoietic stem cell transplantation models, whereas CD11b+ APCs led to Th2/type 2 cytotoxic T lymphocyte donor T cell immune polarization. Donor CD11b− APCs were plasmacytoid dendritic cell progenitors (>90% CD317; PDCA-1+) and up-regulated CD80, CD86, and IL-12 during alloantigen presentation, whereas CD11b+ APCs expressed Gr-1 and up-regulated expression of programmed death ligands-1 and 2 after activation. These results are the first to show that manipulation of the content of donor APCs in allogeneic HSC grafts can regulate donor T cell immunity and enhance GvL without increasing graft-vs-host disease activity.
Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance
Authors: Godin-Ethier Jessica , Pelletier Sandy , Hanafi Laïla-Aïcha , Gannon Philippe O. , Forget Marie-Andrée , Routy Jean-Pierre , Boulassel Mohamed-Rachid , Krzemien Urszula , Tanguay Simon , Lattouf Jean-Baptiste , Arbour Nathalie , Lapointe Réjean
Published: November 2009

Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-γ. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.
RasGRP1 Is Required for Human NK Cell Function
Authors: Lee Suk Hyung , Yun Sohyun , Lee Jiwon , Kim Mi Jeong , Piao Zheng-Hao , Jeong Mira , Chung Jin Woong , Kim Tae-Don , Yoon Suk Ran , Greenberg Philip D. , Choi Inpyo
Published: November 2009

Cross-linking of NK activating receptors activates phospholipase-γ and subsequently induces diacylglycerol and Ca2+ as second messengers of signal transduction. Previous studies reported that Ras guanyl nucleotide-releasing protein (RasGRP) 1, which is activated by diacylglycerol and Ca2+, is crucial for TCR-mediated Ras-ERK activation. We now report that RasGRP1, which can also be detected in human NK cells, plays an essential role in NK cell effector functions. To examine the role of RasGRP1 in NK cell functions, the expression of RasGRP1 was suppressed using RNA interference. Knockdown of RasGRP1 significantly blocked ITAM-dependent cytokine production as well as NK cytotoxicity. Biochemically, RasGRP1-knockdown NK cells showed markedly decreased ability to activate Ras, ERK, and JNK. Activation of the Ras-MAPK pathway was independently shown to be indispensable for NK cell effector functions via the use of specific pharmacological inhibitors. Our results reveal that RasGRP1 is required for the activation of the Ras-MAPK pathway leading to NK cell effector functions. Moreover, our data suggest that RasGRP1 might act as an important bridge between phospholipase-γ activation and NK cell effector functions via the Ras-MAPK pathway.
Bim-Mediated Apoptosis Is Not Necessary for Thymic Negative Selection to Ubiquitous Self-Antigens
Authors: Hu Qian , Sader Alyssa , Parkman Julia C. , Baldwin Troy A.
Published: November 2009

T cell education in the thymus is critical for establishing a functional, yet self-tolerant, T cell repertoire. Negative selection is a key process in enforcing self-tolerance. There are many questions that surround the mechanism of negative selection, but it is currently held that apoptosis initiated by Bim and/or Nur77 is critical for negative selection. Recent studies, however, have questioned the necessity of Bim in maintaining both central and peripheral T cell tolerance. To reconcile these apparently contradictory findings, we examined the role of Bim in negative selection in the well-characterized, physiological HYcd4 mouse model. We found that while Bim expression was required for CD4+CD8+ double-positive thymocyte apoptosis, it was not required for negative selection. Furthermore, Bim deficiency did not alter the frequency or affinity of male reactive cells that escape negative selection in an oligoclonal repertoire. Collectively, these studies indicate that negative selection occurs efficiently in the absence of apoptosis and suggest that the current paradigm of negative selection requiring apoptosis be revisited.
Thymus-Blood Protein Interactions Are Highly Effective in Negative Selection and Regulatory T Cell Induction
Authors: Atibalentja Danielle F. , Byersdorfer Craig A. , Unanue Emil R.
Published: November 2009

Using hen egg-white lysozyme, the effect of blood proteins on CD4 thymic cells was examined. A small fraction of i.v. injected hen egg-white lysozyme rapidly entered the thymus into the medulla. There it was captured and presented by dendritic cells (DCs) to thymocytes from two TCR transgenic mice, one directed to a dominant peptide and a second to a poorly displayed peptide, both presented by MHC class II molecules I-Ak. Presentation by DC led to negative selection and induction of regulatory T cells, independent of epithelial cells. Presentation took place at very low levels, less than 100 peptide-MHC complexes per DC. Such low levels could induce negative selection, but even lower levels could induce regulatory T cells. The anatomy of the thymus-blood barrier, the highly efficient presentation by DC, together with the high sensitivity of thymic T cells to peptide-MHC complexes, results in blood protein Ags having a profound effect on thymic T cells.
Tracking the Total CD8 T Cell Response to Infection Reveals Substantial Discordance in Magnitude and Kinetics between Inbred and Outbred Hosts
Authors: Rai Deepa , Pham Nhat-Long L. , Harty John T. , Badovinac Vladimir P.
Published: November 2009

Determining the magnitude and kinetics, together with the phenotypic and functional characteristics of responding CD8 T cells, is critical for understanding the regulation of adaptive immunity as well as in evaluating vaccine candidates. Recent technical advances have allowed tracking of some CD8 T cells responding to infection, and a body of information now exists describing phenotypic changes that occur in CD8 T cells of known Ag-specificity during their activation, expansion, and memory generation in inbred mice. In this study, we demonstrate that Ag but not inflammation-driven changes in expression of CD11a and CD8α can be used to distinguish naive from Ag-experienced (effector and memory) CD8 T cells after infection or vaccination. Interestingly and in contrast to inbred mice, tracking polyclonal CD8 T cell responses with this approach after bacterial and viral infections revealed substantial discordance in the magnitude and kinetics of CD8 T cell responses in outbred hosts. These data reveal limitations to the use of inbred mouse strains as preclinical models at vaccine development and suggest the same dose of infection or vaccination can lead to substantial differences in the magnitude and timing of Ag-specific CD8 expansion as well in differences in protective memory CD8 T cell numbers in outbred individuals. This concept has direct relevance to development of vaccines in outbred humans.