bluuebunny/crossref_metadata_2025 huggingface dataset:
Tax disincentives and female employment in Organisation for Economic Co-operation and Development (OECD) countries
Authors: Schwarz Peter
Published: February 2012

This paper analyses whether favourable taxation of married couples distorts women’s employment decisions. In contrast to previous research concentrating on experiences in a single country, this paper investigates cross-country differences in female labour force participation. The paper shows that, for a panel of Organisation for Economic Co-operation and Development (OECD) countries during the period 1979–2002, distortions with respect to the taxation of single and married persons can account partly for differences in female labour market participation across countries. However, we find also strong evidence that unfavourable market conditions due to high unemployment as well as few income opportunities have a deterring effect on female labour force participation, indicating that the decision to work is also driven by market forces. With respect to different countries the results suggest that especially in Ireland and the UK tax distortions have played a crucial role in distorting incentives to work.
The southern European social model: familialism and the high rates of female employment in Portugal
Authors: Tavora Isabel
Published: February 2012

This paper focuses on the high rates of female full-time employment in Portugal and examines whether these are consistent with the familialistic features that typify the southern European social model. It employs a comparative methodology to investigate the extent to which recent policy developments and current social values in Portugal are aligned with the familialistic southern European tradition or whether they signal a departure from the model. The analysis reveals that the high rates of female employment are associated with particular features of the case of Portugal, namely, lower gender-based labour market segmentation and welfare state support for dual-earner families. However, this study also shows that the country still retains familialistic characteristics, which are particularly visible in the organization of care and in the persistence of traditional gender values. The article contributes to debates on the southern European social model and sheds light on how high female employment levels can be compatible with relatively high levels of familialism.
Statin-induced lupus: a case/non-case study in a nationwide pharmacovigilance database
Authors: Moulis G , Béné J , Sommet A , Sailler L , Lapeyre-Mestre M , Montastruc J-L ,   The French Association of PharmacoVigilance Centres
Published: February 2012

Statin use has been advocated to prevent atheromatous complications in lupus patients and may be widely prescribed for these patients in future. Statin-induced lupus has also been described, though the risk is not confirmed. The goal of this study was to detect a safety signal regarding statin-induced lupus. We conducted a case/non-case study in the French PharmacoVigilance Database from January 2000 until December 2010. Cases were drug-induced lupus reports. Non-cases were all reports of other adverse drug reactions (ADRs). Exposure to statins at the time of ADR was screened in each report. Among 235,147 ADR reports, 232 were drug-induced lupus. Exposure to statins was present in 17 (7.3%) cases and in 10,601 (4.7%) non-cases. Reporting odds ratio (ROR) for statin exposure associated with lupus erythematosus was 1.67 (95% confidence interval 1.02–2.74). The ROR was > 1 for each statin but fluvastatin. This pharmacoepidemiological study suggests a link between statin exposure and lupus induction. The benefit-to-risk ratio of statin therapy in lupus patients should be evaluated through randomized controlled trials.
National risk registers: Security scientism and the propagation of permanent insecurity
Authors: Hagmann Jonas , Cavelty Myriam Dunn
Published: February 2012

Aiming at the measurement, comparison and ranking of all kinds of public dangers, ranging from natural hazards to industrial risks and political perils, the preparation of national risk registers stands out as a novel and increasingly popular Western security practice. This article focuses on these registers and the analytical power politics in which they are complicit. We argue, first, that positing science as an objective determinant of security truth, national risk registers advance a modernist understanding of how knowledge of national dangers can be arrived at, discounting both sovereign and popular authorities; second, that by operationalizing a traditional risk-assessment formula, risk registers make possible seemingly apolitical decisions in security matters, taken on the basis of cost–benefit thinking; and, third, that risk registers’ focus on risk ‘themes’ tiptoes around the definition of referent objects, avoiding overt decisions about the beneficiaries of particular security decisions. Taking all these factors into account, we find that risk registers ‘depoliticize’ national security debates while transforming national insecurity into something permanent and inevitable.
The ambivalence of assassination: Biopolitics, culture and political violence
Authors: Grayson Kyle
Published: February 2012

This article begins by presenting a biopolitical account of assassination and targeted killing events carried out by liberal regimes. It argues that forms of political violence are understood and made meaningful beyond the administrative frameworks and technical rationalizations often privileged in biopolitical analyses. Deploying Alan Feldman’s (1991) argument that political violence is an ‘emplotted action’ alongside William Connolly’s (2005 ) notion of resonance, it provides a genealogical account of how forms of assassination have been positioned within Western cultural understandings of political violence. The focal point of examination is the biblical heroine Judith, whose story has resonated as a preferred narrative structure for understanding and (de)legitimating acts of assassination among Western publics. Through its reading of the book of Judith, the article highlights the importance of ambivalence for understanding assassination as a form of political violence. The legacy of the moral problematique enabled by Judith is then illustrated in relation to US President Barak Obama’s May 2011 speech announcing the killing of Osama Bin Laden. The article concludes by suggesting that although the story of Judith may underpin contemporary assassination practices, it also offers a means of critically engaging with them.
Cyclones in cyberspace: Information shaping and denial in the 2008 Russia–Georgia war
Authors: Deibert Ronald J. , Rohozinski Rafal , Crete-Nishihata Masashi
Published: February 2012

While the rhetoric of cyber war is often exaggerated, there have been recent cases of international conflict in which cyberspace has played a prominent role. In this article, we analyze the impact of cyberspace in the conflict between Russia and Georgia over the disputed territory of South Ossetia in August 2008. We examine the role of strategic communications, information operations, operations in and through cyberspace, and conventional combat to account for the political and military outcomes of the conflict. The August 2008 conflict reveals some emergent issues in cyber warfare that can be generalized for further comparative research: the importance of control over the physical infrastructure of cyberspace, the strategic and tactical importance of information denial, the emergence of cyber-privateering, the unavoidable internationalization of cyber conflicts, and the tendency towards magnifying unanticipated outcomes in cyber conflicts – a phenomenon we call ‘cyclones in cyberspace’.
Football history off the field: Utilising archived accounting reports to challenge “myths” about the history of an Australian football club
Authors: Halabi Abdel K. , Frost Lionel , Lightbody Margaret
Published: February 2012

The Australian Football League (AFL) is the largest professional sports competition in Australia. Most AFL clubs began as amateur bodies in the nineteenth century, but to survive they have had to adapt to changes in demand and production costs by adopting a commercial management approach. Because financial management is seen by most club members as secondary to the core business of winning games, accounting data is generally invisible in football histories. We use a range of accounting information from annual reports, committee Minute Books and media commentaries from 1910 to 1917 to demonstrate how financial data can be used to enhance our understanding of the history of one AFL club – Carlton. In particular, we show how previously overlooked accounting records can enrich the history of this sporting club as well as challenge long held “myths”, thus creating new understandings of Australian football history.
Barriers to Use of Workplace Personal Assistance Services to Support Employment in California
Authors: Neri Melinda T. , Wong Alice , Harrington Charlene
Published: February 2012

Providing personal assistance services (PAS) in the workplace (WPAS) is one approach to support the employment of individuals with disabilities. This descriptive study examined the implementation of Medicaid WPAS by collecting and analyzing telephone interview data from key informants selected from county and public authority officials in California in 2010. The results showed that less than a fraction of 1% of individuals with disabilities who used Medicaid personal care services used the services at work. The barriers to using WPAS included lack of consumer knowledge about the Medicaid buy-in program and about WPAS, lack of additional hours allocated for WPAS, lack of WPAS arrangements for intermittent services and transportation, negative attitudes of PAS staff, and uncertainty regarding PAS budget cuts. Policy recommendations include improving information about the buy-in program and WPAS, collecting WPAS information about client interest in working, establishing a WPAS client tracking system, increasing hours to cover PAS at work, addressing negative PAS staff attitudes, and increasing the flexibility of PAS hours and services.
From adaptive behavior to human cognition: a review of Enaction
Authors: Froese Tom
Published: February 2012

Critics of the paradigm of enaction have long argued that enactive principles will be unable to account for the traditional domain of orthodox cognitive science, namely “higher-level” cognition and specifically human cognition. Moreover, even many of the paradigm’s “lower-level” insights into embodiment and situatedness appear to be amenable to a functionalist reinterpretation. In this review, I show on the basis of the recently published collection of papers, Enaction, that the paradigm of enaction has (a) a unique foundation in the notion of sense-making that places fundamental limits on the scope of functionalist appropriation; (b) a unique perspective on higher-level cognition that sets important new research directions without the need for the concept of mental representation; (c) a new concept of specifically human cognition in terms of second-order sense-making; and (d) a rich variety of approaches to explain the evolutionary, historical, and developmental origins of this sophisticated human ability. I also indicate how studies of the role of embodiment for abstract human cognition can strengthen their position by reconceiving their notion of embodiment in enactive terms.
Systemic–Developmental Supervision
Authors: Carlson Ryan G. , Lambie Glenn W.
Published: February 2012

Supervision models for marriage and family counseling student interns primarily focus on the use of traditional systemic techniques. In addition, a supervisee’s level of development may not be considered when utilizing systemic tools. Furthermore, the supervisory relationship has been identified as a significant indicator of quality supervision, including characteristics such as warmth, empathy, and a nonjudgmental perspective from the supervisor. This article presents systemic–developmental supervision (SDS) to promote supervisees’ professional growth through self-awareness and skills acquisition. As such, a focus on the supervisory relationship through integration of two developmental models of supervision and systemic supervision techniques is discussed, along with the practical applications of SDS, strengths, limitations, and recommendations for future research.
Sexual Health Attitudes, Knowledge, and Clinical Behaviors
Authors: Russell Elizabeth B.
Published: February 2012

This article explores the impact of practitioners’ attitudes and knowledge of sexual health on clinical behaviors. Sexual health topics are often areas of concern for clients of any age in counseling. Thus, counselors must be trained and equipped to address sexual health across the life span. This study explored whether child and adolescent clinical mental health staff’s attitudes and knowledge of sexual health predicted their clinical behaviors. Results indicated that the practitioners’ attitudes about sexual health, not their sexual health knowledge level, predicted whether or not they addressed sexual health with clients. Implications and suggestions for counselors and counselor educators are provided.
Malignant Transformation in Mature Cystic Teratoma of the Ovary
Authors: Quadri Asif M. , Ganesan Raji , Hock Ye Lin , Karim Sabeeha Naheed , Hirschowitz Lynn
Published: February 2012

This study reports 3 unusual cases of malignant transformation in mature cystic teratoma of the ovary (dermoid cyst), namely carcinosarcoma, atypical choroid plexus papilloma, and papillary thyroid carcinoma, the last case involving both ovaries and with peritoneal dissemination. Adequate sampling is essential in such ovarian tumors to establish their teratomatous origin and avoid an erroneous diagnosis of primary ovarian or metastatic tumors. The authors present the clinicopathological findings in these 3 cases with a review of literature.
Significance of the Correlation Between the Expression of Interleukin 6 and Clinical Features in Patients With Non-Small Cell Lung Cancer
Authors: Koh Eitetsu , Iizasa Toshihiko , Yamaji Haruko , Sekine Yasuo , Hiroshima Kenzo , Yoshino Ichiro , Fujisawa Takehiko
Published: February 2012

Background. The aims of the study were to identify the significance of interleukin (IL)-6 production and to determine whether IL-6 production influences long-term survival in patients with non-small-cell lung cancer (NSCLC). Method. A series of 90 patients with NSCLC who underwent surgery between 2005 and 2007 was analyzed. Preoperative serum IL-6 was measured, and tumor samples were immunohistochemically stained for IL-6. Results. Serum IL-6 levels were elevated in 43 of 90 cases (47.7%), and 23 (25.5%) of 90 cases stained positively for IL-6 ( P = .00265). The prognosis of patients with NSCLC who had positive immunohistochemical staining was significantly worse than that for those who had negative staining, by univariate analysis ( P = .0027). Multivariate analysis indicated that tumor size, postoperative stage, and overexpression of IL-6 were independent prognostic factors. Conclusions. The expression of IL-6 in tumor correlated with the concentration of serum IL-6, tumor progression, and overall survival in patients with NSCLC.
On the linear finite element analysis of fully coupled point contact elastohydrodynamic lubrication problems
Authors: Ahmed Sarfraz , Goodyer Christopher E , Jimack Peter K
Published: February 2012

The fully coupled approach for the solution of elastohydrodynamic lubrication point contact problems requires the numerical solution of the elasticity problem on a large 3D domain. A sufficiently fine computational mesh is required to obtain the elastic deformation solution to the necessary accuracy, and hence, a sufficiently accurate elastohydrodynamic lubrication point contact solution. This article discusses the accuracy of an elastohydrodynamic lubrication point contact solution over different finite element meshes. We present a family of efficient 3D meshes which can be used to calculate accurate elastohydrodynamic lubrication point contact solutions at a minimal computational cost. This article also illustrates the fact that the unstructured hierarchical meshes can lead to a poor quality elastohydrodynamic lubrication solution unless an appropriate post-processing, smoothing technique is applied.
Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)
Authors: Parving Hans-Henrik , Brenner Barry M , McMurray John JV , de Zeeuw Dick , Haffner Steven M , Solomon Scott D , Chaturvedi Nish , Persson Frederik , Nicolaides Maria , Richard Alexia , Xiang Zhihua , Armbrecht Juergen , Pfeffer Marc A ,   (on behalf of the ALTITUDE investigators)
Published: February 2012

Introduction:

Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone.

Materials and methods:

ALTITUDE is a randomized, double-blind, placebo-controlled study in high risk type 2 diabetic patients receiving aliskiren 300 mg once daily or placebo added to recommended cardio-renal protective treatment including ACEi or ARB, but not both. The number of patients randomized was 8606.

Results:

Baseline characteristics (median, IQR) are: age 65 (58, 72) years, male 68%, BMI 29.1 (25.7, 32.2) kg/m2, cardiovascular disease 47.9%, blood pressure 134.7 (126, 150)/74.3 (67, 81) mmHg, HbA1c 7.5 (6.6, 8.6)%, LDL-cholesterol 2.4 (1.9, 3.0) mmol/L, haemoglobin 130 (119, 143) g/L, serum creatinine 115 (91, 137) µmol/L, eGFR 51.7 (42, 65) ml/min per 1.73 m2, geometric mean UACR 198.9 (52, 2886) mg/g and frequency of micro/macroalbuminuria 25.7% and 58.2%. ALTITUDE is an event-driven trial to continue until 1628 patients experience a primary cardiovascular-renal event.

Conclusions:

ALTITUDE will determine the potential cardio-renal benefit and safety of aliskiren in combination with ACEi or ARB in high risk patients with type 2 diabetes.
Aboriginal early childhood education in Canada: Issues of context
Authors: Preston Jane P , Cottrell Michael , Pelletier Terrance R , Pearce Joseph V
Published: February 2012

Herein we provide a literature synthesis pertaining to the state of Aboriginal early childhood education in Canada. We identify key features of quality Aboriginal early childhood programs. The background and significance of early childhood education for Aboriginal peoples is explicated. Cultural compatibility theory is employed as the philosophical basis to conceptualize quality Aboriginal early childhood education. Based on this theoretical premise, we suggest Aboriginal early childhood programs should incorporate Aboriginal pedagogy, be infused with Aboriginal language and culture, be adequately staffed by qualified Aboriginal educators, be structured to empower Aboriginal communities and incorporate full-day kindergarten. Prominent Aboriginal early childhood programs are featured within the article.
Diabetic Foot Screening
Authors: Spruce Michelle C. , Bowling Frank L.
Published: February 2012

The objective was to determine if new technology could provide feedback to the clinician when a 10 g force had been delivered. Using a novel electronic force sensor, clinical longevity and the potential for reduced force delivery were assessed under laboratory conditions. Subsequent inter- and intrareliability data were generated and compared with the existing World Health Organization clinical standard (10 g monofilament). A total of 20 subjects were trained in the use of the 10 g monofilament (Bailey Instruments, Salford Quays, UK) and prototype electronic force sensor (Exsensus, UK). A total of 2000 applications (n = 100 per subject) were administered to a calibrated target at a controlled rate, while time and force histories were captured on a digital storage oscilloscope and data recorder for statistical analysis. Engineering standards in accordance with the American Society for Testing and Materials were applied throughout the experiment. No significant differences in mean peak, median peak, interquartile range, and total range of pressure forces were observed for the electronic force sensor. Alternatively, significant differences for mean and median peak forces were present in the 10 g monofilament ( P < .05 and P < .01). Post hoc analysis further showed the monofilament to degrade significantly at ≤30 applications ( P = .013). Forces delivered by the electronic force sensor appear to be significantly less susceptible to mechanical variability than those provided by monofilaments, thus increasing longevity. Similarly, this new technology provides objective feedback as to when the device is functioning correctly and potentially negates the need for fiber rest periods.
Management of Neglected Femoral Neck Fractures and Nonunions using a Novel Triple Surgery Combination
Authors: Kapoor Amit , Deety Lakshmi Venkatesh , John Vinith Zachariah , Devadoss Sathish , Devadoss A.
Published: February 2012

This study describes a 2- to 13-year follow-up of a novel technique for osteosynthesis of neglected femoral neck fractures and nonunions that combines internal fixation with the benefits of fibular grafting and valgus angulation osteotomy. Twenty-three patients were treated by the “3-in-1” surgery, which consisted of osteosynthesis with a dynamic hip screw, nonvascularized fibular grafting, and valgus osteotomy, between January 1996 and June 2009. Union was achieved in all patients at an average of 5.4 months. The average shortening was 0.9 cm. Although avascular necrosis was seen in 4 patients, 2 of them still had good functional scores. Excellent and good hip functional scores were seen in 18 patients. Well-executed surgeries combining biomechanics and biology can ensure union in neglected femoral neck fractures and nonunions provided an adequate length of the neck and proximal fragment is present and there is no subchondral collapse.
Experimental characterization of the mechanical properties of the superior sagittal sinus: bridging vein complex
Authors: Baeck Katrien , Asiminei Aida G , Verbeken Erik , Goffin Jan , Sloten Jos Vander
Published: February 2012

Acute subdural hematoma is one of the most frequent head injuries observed in victims of bicycle-related accidents. For nearly one third of the acute subdural hematoma cases, the etiopathology directly relates to the rupture of a bridging vein. To gain a better insight into the biomechanical characteristics of acute subdural hematoma following a head impact, an accurate description of the bridging vein material behaviour is essential. This study focuses on describing the material failure characteristics of the bridging vein – superior sagittal sinus complex. The junction of these bridging veins to the superior sagittal sinus has been described in the literature as an area with distinct vein wall architecture, and this should be taken into account since it might play an important role in the biomechanical response of the bridging vein to a head impact. A total of 63 bridging vein units were dissected and tested under axial loading conditions at strain rates ranging from 2.7 s−1 to 20.9 s−1. From the obtained load and displacement data, the ultimate stress and strain, Young’s modulus and yield stress and strain were calculated. Next, a comparison is made with published bridging vein data at lower strain rates to investigate strain rate dependency. Based on the presented data, no strain rate sensitivity could be observed in the bridging vein material behaviour. However, a gender influence was seen in both the bridging vein’s geometry and failure characteristics.
IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses
Authors: Aloulou Meryem , Ben Mkaddem Sanae , Biarnes-Pelicot Martine , Boussetta Tarek , Souchet Hervé , Rossato Elisabetta , Benhamou Marc , Crestani Bruno , Zhu Zhou , Blank Ulrich , Launay Pierre , Monteiro Renato C.
Published: February 2012

Intravenous immunoglobulin (IVIg) has been used in the treatment of several autoimmune and inflammatory diseases. However, its mechanism of action remains incompletely understood. Here, we investigated the possibility that IVIg induces its anti-inflammatory effects through activating Fcγ receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM) in the FcRγ signaling adaptor. Recently, the concept of inhibitory ITAM (ITAMi) has emerged as a new means to negatively control the immune response. We found that interaction of FcRγ-associated mouse or human FcγRIII with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab′)2 reduced calcium responses, reactive oxygen species production, endocytosis, and phagocytosis, induced by heterologous activating receptors on monocyte/macrophages and FcγRIII+ transfectants. Inhibition required the ITAMi configuration of the FcγRIII-associated FcRγ subunit and SHP-1 recruitment involving formation of intracellular “inhibisome” clusters containing FcγRIII, and the targeted heterologous activating receptor. IVIg as well as anti-FcγRIII treatments controlled the development of nonimmune mediated inflammation in vivo independently of FcγRIIB. These results demonstrate that circulating immunoglobulins (Ig)Gs are not functionally inert but act through continuous interaction with FcγRIII-inducing ITAMi signaling to maintain immune homeostasis. These data support a new mechanism of action for IVIg and demonstrate the therapeutic potential of FcγRIIIA targeting in inflammation.
The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO
Authors: Chou Fu-Sheng , Griesinger Andrea , Wunderlich Mark , Lin Shan , Link Kevin A. , Shrestha Mahesh , Goyama Susumu , Mizukawa Benjamin , Shen Shuhong , Marcucci Guido , Mulloy James C.
Published: February 2012

AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL.
Evolutionary history of the recruitment of conserved developmental genes in association to the formation and diversification of a novel trait
Authors: Shirai Leila T , Saenko Suzanne V , Keller Roberto A , Jerónimo Maria A , Brakefield Paul M , Descimon Henri , Wahlberg Niklas , Beldade Patrícia
Published: February 2012

Background

The origin and modification of novel traits are important aspects of biological diversification. Studies combining concepts and approaches of developmental genetics and evolutionary biology have uncovered many examples of the recruitment, or co-option, of genes conserved across lineages for the formation of novel, lineage-restricted traits. However, little is known about the evolutionary history of the recruitment of those genes, and of the relationship between them -for example, whether the co-option involves whole or parts of existing networks, or whether it occurs by redeployment of individual genes with de novo rewiring. We use a model novel trait, color pattern elements on butterfly wings called eyespots, to explore these questions. Eyespots have greatly diversified under natural and sexual selection, and their formation involves genetic circuitries shared across insects.

Results

We investigated the evolutionary history of the recruitment and co-recruitment of four conserved transcription regulators to the larval wing disc region where circular pattern elements develop. The co-localization of Antennapedia, Notch, Distal-less, and Spalt with presumptive (eye)spot organizers was examined in 13 butterfly species, providing the largest comparative dataset available for the system. We found variation between families, between subfamilies, and between tribes. Phylogenetic reconstructions by parsimony and maximum likelihood methods revealed an unambiguous evolutionary history only for Antennapedia, with a resolved single origin of eyespot-associated expression, and many homoplastic events for Notch, Distal-less, and Spalt. The flexibility in the (co-)recruitment of the targeted genes includes cases where different gene combinations are associated with morphologically similar eyespots, as well as cases where identical protein combinations are associated with very different phenotypes.

Conclusions

The evolutionary history of gene (co-)recruitment is consistent with both divergence from a recruited putative ancestral network, and with independent co-option of individual genes. The diversity in the combinations of genes expressed in association with eyespot formation does not parallel diversity in characteristics of the adult phenotype. We discuss these results in the context of inferring homology. Our study underscores the importance of widening the representation of phylogenetic, morphological, and genetic diversity in order to establish general principles about the mechanisms behind the evolution of novel traits.
Sexual and asexual oogenesis require the expression of unique and shared sets of genes in the insect Acyrthosiphon pisum
Authors: Gallot Aurore , Shigenobu Shuji , Hashiyama Tomomi , Jaubert-Possamai Stéphanie , Tagu Denis
Published: February 2012

Background

Although sexual reproduction is dominant within eukaryotes, asexual reproduction is widespread and has evolved independently as a derived trait in almost all major taxa. How asexuality evolved in sexual organisms is unclear. Aphids, such asAcyrthosiphon pisum, alternate between asexual and sexual reproductive means, as the production of parthenogenetic viviparous females or sexual oviparous females and males varies in response to seasonal photoperiodism. Consequently, sexual and asexual development in aphids can be analyzed simultaneously in genetically identical individuals.

Results

We compared the transcriptomes of aphid embryos in the stages of development during which the trajectory of oogenesis is determined for producing sexual or asexual gametes. This study design aimed at identifying genes involved in the onset of the divergent mechanisms that result in the sexual or asexual phenotype. We detected 33 genes that were differentially transcribed in sexual and asexual embryos. Functional annotation by gene ontology (GO) showed a biological signature of oogenesis, cell cycle regulation, epigenetic regulation and RNA maturation.In situhybridizations demonstrated that 16 of the differentially-transcribed genes were specifically expressed in germ cells and/or oocytes of asexual and/or sexual ovaries, and therefore may contribute to aphid oogenesis. We categorized these 16 genes by their transcription patterns in the two types of ovaries; they were: i) expressed during sexual and asexual oogenesis; ii) expressed during sexual and asexual oogenesis but with different localizations; or iii) expressed only during sexual or asexual oogenesis.

Conclusions

Our results show that asexual and sexual oogenesis in aphids share common genetic programs but diverge by adapting specificities in their respective gene expression profiles in germ cells and oocytes.
IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme
Authors: Wurster Andrea L , Precht Patricia , Becker Kevin G , Wood William H , Zhang Yongqing , Wang Zhong , Pazin Michael J
Published: February 2012

Background

SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.

Results

Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.

Conclusions

These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.
Angiotensin converting enzyme DD genotype is associated with acute coronary syndrome severity and sudden cardiac death in Taiwan: a case-control emergency room study
Authors: Chen Ying-Hsin , Liu Jui-Ming , Hsu Ren-Jun , Hu Sheng-Chuan , Harn Horng-Jyh , Chen Shee-Ping , Jeng Jing-Ren , Wu Chieh-Lin , Ho Jar-Yi , Yu Cheng-Ping
Published: February 2012

Background

Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined.

Results

The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046).

Conclusions

This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.
Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development
Authors: To Kwong-Him , Pajovic Sanja , Gallie Brenda L , Thériault Brigitte L
Published: February 2012

Background

Most human cancers show inactivation of both pRB- and p53-pathways. While retinoblastomas are initiated by loss of the RB1 tumor suppressor gene, TP53 mutations have not been found. High expression of the p53-antagonist MDM2 in human retinoblastomas may compromise p53 tumor surveillance so that TP53 mutations are not selected for in retinoblastoma tumorigenesis. We previously showed that p14ARF protein, which activates p53 by inhibiting MDM2, is low in retinoblastomas despite high mRNA expression.

Methods

In human fetal retinas, adult retinas, and retinoblastoma cells, we determined endogenous p14

ARF
mRNA, ARF protein, and miR-24 expression, while integrity of p53 signalling in WERI-Rb1 cells was tested using an adenovirus vector expressing p14ARF. To study p14ARF biogenesis, retinoblastoma cells were treated with the proteasome inhibitor, MG132, and siRNA against miR-24.

Results

In human retinoblastoma cell lines, p14

ARF
mRNA was disproportionally high relative to the level of p14ARF protein expression, suggesting a perturbation of p14ARF regulation. When p14ARF was over-expressed by an adenovirus vector, expression of p53 and downstream targets increased and cell growth was inhibited indicating an intact p14ARF-p53 axis. To investigate the discrepancy between p14

ARF
mRNA and protein in retinoblastoma, we examined p14ARF biogenesis. The proteasome inhibitor, MG132, did not cause p14ARF accumulation, although p14ARF normally is degraded by proteasomes. miR-24, a microRNA that represses p14ARF expression, is expressed in retinoblastoma cell lines and correlates with lower protein expression when compared to other cell lines with high p14

ARF
mRNA. Transient over-expression of siRNA against miR-24 led to elevated p14ARF protein in retinoblastoma cells.

Conclusions

In retinoblastoma cells where high levels of p14

ARF
mRNA are not accompanied by high p14ARF protein, we found a correlation between miR-24 expression and low p14ARF protein. p14ARF protein levels were restored without change in mRNA abundance upon miR-24 inhibition suggesting that miR-24 could functionally repress expression, effectively blocking p53 tumor surveillance. During retinal tumorigenesis, miR-24 may intrinsically compromise the p53 response to RB1 loss.
Predicting sample size required for classification performance
Authors: Figueroa Rosa L , Zeng-Treitler Qing , Kandula Sasikiran , Ngo Long H
Published: February 2012

Background

Supervised learning methods need annotated data in order to generate efficient models. Annotated data, however, is a relatively scarce resource and can be expensive to obtain. For both passive and active learning methods, there is a need to estimate the size of the annotated sample required to reach a performance target.

Methods

We designed and implemented a method that fits an inverse power law model to points of a given learning curve created using a small annotated training set. Fitting is carried out using nonlinear weighted least squares optimization. The fitted model is then used to predict the classifier's performance and confidence interval for larger sample sizes. For evaluation, the nonlinear weighted curve fitting method was applied to a set of learning curves generated using clinical text and waveform classification tasks with active and passive sampling methods, and predictions were validated using standard goodness of fit measures. As control we used an un-weighted fitting method.

Results

A total of 568 models were fitted and the model predictions were compared with the observed performances. Depending on the data set and sampling method, it took between 80 to 560 annotated samples to achieve mean average and root mean squared error below 0.01. Results also show that our weighted fitting method outperformed the baseline un-weighted method (p < 0.05).

Conclusions

This paper describes a simple and effective sample size prediction algorithm that conducts weighted fitting of learning curves. The algorithm outperformed an un-weighted algorithm described in previous literature. It can help researchers determine annotation sample size for supervised machine learning.
Expression and extracellular release of a functional anti-trypanosome Nanobody® in Sodalis glossinidius, a bacterial symbiont of the tsetse fly
Authors: De Vooght Linda , Caljon Guy , Stijlemans Benoît , De Baetselier Patrick , Coosemans Marc , Van Den Abbeele Jan
Published: February 2012

Background

Sodalis glossinidius, a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as a potential in vivo drug delivery vehicle to control trypanosome parasite development in the fly, an approach known as paratransgenesis. Despite this interest of S. glossinidius as a paratransgenic platform organism in tsetse flies, few potential effector molecules have been identified so far and to date none of these molecules have been successfully expressed in this bacterium.

Results

In this study, S. glossinidius was transformed to express a single domain antibody, (Nanobody®) Nb_An33, that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of the parasite Trypanosoma brucei. Next, we analyzed the capability of two predicted secretion signals to direct the extracellular delivery of significant levels of active Nb_An33. We show that the pelB leader peptide was successful in directing the export of fully functional Nb_An33 to the periplasm of S. glossinidius resulting in significant levels of extracellular release. Finally, S. glossinidius expressing pelBNb_An33 exhibited no significant reduction in terms of fitness, determined by in vitro growth kinetics, compared to the wild-type strain.

Conclusions

These data are the first demonstration of the expression and extracellular release of functional trypanosome-interfering Nanobodies® in S. glossinidius. Furthermore, Sodalis strains that efficiently released the effector protein were not affected in their growth, suggesting that they may be competitive with endogenous microbiota in the midgut environment of the tsetse fly. Collectively, these data reinforce the notion for the potential of S. glossinidius to be developed into a paratransgenic platform organism.
Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon
Authors: Baumann Andreas , Magris Magda M , Urbaez Marie-Luz , Vivas-Martinez Sarai , Durán Rommy , Nieves Tahidid , Esen Meral , Mordmüller Benjamin G , Theisen Michael , Avilan Luisana , Metzger Wolfram G
Published: February 2012

Background

Malaria transmission in most of Latin America can be considered as controlled. In such a scenario, parameters of baseline immunity to malaria antigens are of specific interest with respect to future malaria eradication efforts.

Methods

A cross-sectional study was carried out in two indigenous population groups in Amazonas/Venezuela. Data from the regional malaria documentation system were extracted and participants from the ethnic groups of the Guahibo (n = 180) and Piaroa (n = 295) were investigated for the presence of Plasmodium parasites and naturally acquired antibodies to Plasmodium falciparum antigens in serum. The GMZ2 vaccine candidate proteins MSP3 and GLURP were chosen as serological markers.

Results

The incidence of P. falcip arum in both communities was found to be less than 2%, and none of the participants harboured P. falciparum at the time of the cross-sectional. Nearly a quarter of the participants (111/475; 23,4%) had positive antibody titres to at least one of the antigens. 53/475 participants (11.2%) were positive for MSP3, and 93/475 participants (19.6%) were positive for GLURP. High positive responses were detected in 36/475 participants (7.6%) and 61/475 participants (12.8%) for MSP3 and GLURP, respectively. Guahibo participants had significantly higher antibody titres than Piaroa participants.

Conclusions

Considering the low incidence of P. falciparum, submicroscopical infections may explain the comparatively high anti-P. falciparum antibody concentrations.
Graphical approximation of common solutions to generalized nonlinear relaxed cocoercive operator equation systems with (A, η)-accretive mappings
Authors: Li Fang , Lan Heng-you , Je Cho Yeol
Published: February 2012

In this paper, we develop a new perturbed iterative algorithm framework with errors based on the variational graphical convergence of operator sequences with (A, η)-accretive mappings in Banach space. By using the generalized resolvent operator technique associated with (A, η)-accretive mappings, we also prove the existence of solutions for a class of generalized nonlinear relaxed cocoercive operator equation systems and the variational convergence of the sequence generated by the perturbed iterative algorithm in q-uniformly smooth Banach spaces. The obtained results improve and generalize some well-known results in recent literatures.

2000 Mathematics Subject Classification: 47H05; 49J40
Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast
Authors: Lanthaler Karin , Bilsland Elizabeth , Dobson Paul D , Moss Harry J , Pir Pınar , Kell Douglas B , Oliver Stephen G
Published: February 2012

Background

The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers.

Results

To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells.

Conclusions

As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.