bluuebunny/crossref_metadata_2025 huggingface dataset:
The OSCE contribution to democratization in North African countries
Authors: Wohlfeld Monika
Published: December 2011

The article focuses on a possible assistance of the OSCE to North African countries in political transition following the events of the so called 'Arab Spring'. The OSCE has extensive experience in relevant realms. It also has a long-standing institutionalized dialogue and co-operation with a number of North African states.

The discussion within the Organization itself on what the OSCE could offer and with states such as Tunisia on their needs has began in January 2011, and is ongoing. The OSCE has also implemented first hands-on projects aimed at supporting the transitions processes in those countries, and linked to the on-going election processes there. But the OSCE Mediterranean dialogue suffers from the institutional context in which the Mediterranean Partners have the status akin to that of observers, and a certain lack of vision.
The Adolescence of Family Firm Research
Authors: Gedajlovic Eric , Carney Michael , Chrisman James J. , Kellermanns Franz W.
Published: January 2012

Through its rapid growth during the past decade, family business research has reached its adolescence as a field of study, and family business scholars now regularly contribute interesting and thought-provoking work to top-tier management, entrepreneurship, and finance journals. In this review article, the authors seek to document the growing maturity of family business research and to promote its integration into broader streams of inquiry in the organizational sciences. To do so, the authors describe recent family business research that addresses two fundamental questions: “How do firms differ in terms of their financial performance?” and “How do institutional conditions moderate performance differences between firms?” Based on their review, the authors describe the past and potential future contributions of family business research and conclude that it holds great promise to “give back” and provide meaningful contributions to the general field of management.
Regulatory T-Cells: Diverse Phenotypes Integral to Immune Homeostasis and Suppression
Authors: Peterson Richard A.
Published: January 2012

Regulatory T-cells (TREG) are diverse populations of lymphocytes that regulate the adaptive immune response in higher vertebrates. TREG delete autoreactive T-cells, induce tolerance, and dampen inflammation. TREG cell deficiency in humans (i.e., IPEX [Immunodysregulation, Polyendocrinopathy and Enteropathy, X-linked syndrome]) and animal models (e.g., “Scurfy” mouse) is associated with multisystemic autoimmune disease. TREG in humans and laboratory animal species are similar in type and regulatory function. A molecular marker of and the cell lineage specification factor for TREG is FOXP3, a forkhead box transcription factor. CD4+ TREG are either natural (nTREG), which are thymus-derived CD4+CD25+FOXP3+ T-cells, or inducible (i.e., Tr1 cells that secrete IL-10, Th3 cells that secrete TGF-β and IL-10, and Foxp3+ Treg). The proinflammatory Th17 subset has been a major focus of research. TH17 CD4+ effector T-cells secrete IL-17, IL-21, and IL-22 in autoimmune and inflammatory disease, and are dynamically balanced with TREG cell development. Other lymphocyte subsets with regulatory function include: inducible CD8+ TREG, CD3+CD4−CD8− TREG (double-negative), CD4+Vα14+ (NKTREG), and γδ T-cells. TREG have four regulatory modes of action: secretion of inhibitory cytokines (e.g., IL-10 and TGF-β), granzyme-perforin-induced apoptosis of effector lymphocytes, depriving effector T-cells of cytokines leading to apoptosis, or inhibition of dendritic cell function. The role of TREG in mucosal sites, inflammation/infection, pregnancy, and cancer as well as a review of TREG as a modulatory target in drug development will be covered.
Entrepreneurial activity in the venture creation and development process
Authors: Wright Mike , Marlow Susan
Published: January 2012

This special edition editorial notes the complex and dynamic nature of the new venture creation process. Although the growing body of work which explores discrete elements of this process is acknowledged, in-depth analyses of the ‘black box’ of new venture creation remain scarce. Thus, this special edition features articles that recognize and explore how entrepreneurial actors and their ventures progress within and between the various phases necessary to establish viable new firms within differing and uncertain contexts. Three articles are featured offering a diverse range of perspectives upon the challenges encountered during new venture creation and the strategies adopted to address these issues. Drawing from these articles, a more nuanced processual view of entrepreneurial activity in the venture creation and development process is presented and in addition, pathways are suggested for future research to develop this debate.
Autonomous vehicle collision avoidance system using path planning and model-predictive-control-based active front steering and wheel torque control
Authors: Shim Taehyun , Adireddy Ganesh , Yuan Hongliang
Published: January 2012

Autonomous vehicles have attracted more attention in recent years as vehicle applications are evolving to a more intelligent and autonomous stage. This paper presents the development of a collision avoidance system for an autonomous vehicle application which consists of a motion planner and model-predictive-control-based active vehicle steering and active wheel torque control. A motion planner, based on polynomial parameterization, determines a collision-free trajectory when a vehicle collision with obstacles is likely to happen. Then an MPC-based control system controls the front steering and individual wheel torques to track the desired collision-free reference trajectory. The proposed system is evaluated through simulation, using an eight-degrees-of-freedom vehicle model with a ‘magic formula’ tire model, active front steering, and active wheel torque distribution systems. The simulation results show that it effectively performs collision avoidance maneuvers.
Putting the World as Classroom
Authors: Racine Louise , Proctor Peggy , Jewell Lisa M.
Published: January 2012

This article focuses on the description of an educational initiative, the Interdisciplinary Population Health Project (IPHP) conducted in the academic year of 2006-2007 with a group of nursing and health care students. Inspired by population health, community development, critical pedagogy, and the inequalities imagination model, students participated in diverse educational activities to become immersed in the everyday life of an underserved urban neighborhood. A sample of convenience composed of 158 students was recruited from 4 health disciplines in a Western Canadian university. Data were collected using a modified version of the Parsell and Bligh’s Readiness of Health Care Students for Interprofessional Learning Scale. A one group pretest–posttest design was used to assess the outcomes of the IPHP. Paired t tests and one-way analyses of variance were used to compare the responses of students from different academic programs to determine if there were differences across disciplines. Findings suggest that students’ readiness to work in interprofessional teams did not significantly change over the course of their participation in the IPHP. However, the inequalities imagination model may be useful to enhance the quality and the effectiveness of fieldwork learning activities as a means of educating culturally and socially conscious nurses and other health care professionals of the future.
When HIV-Positive Children Grow Up
Authors: Persson Asha , Newman Christy
Published: January 2012

Young people with perinatally acquired HIV are routinely problematized in the research literature as inadequately equipped to manage transition to adolescent sexuality and adult clinical care without comprehensive interventions, partly because of challenges associated with adolescence itself, and partly because of neurocognitive and psychosocial dysfunctions commonly attributed to these children. However, little is actually known about this population, given their recent emergence in the HIV epidemic. Using critical discourse analysis, we argue that several problematic assumptions operate in this literature, hampering the objective of understanding these young people. Our analysis can contribute to a reframing of future research on HIV-positive adolescents, by encouraging greater attunement to the experiences of the adolescents themselves and to the discursive meanings that underpin research agendas, so that different and more productive questions can be asked and answered.
Dancing Into the Desert
Authors: Collins Christopher C.
Published: January 2012

This article addresses concerns of being and becoming between father and son. The article uses performative and autoethnographic approaches to examine the poetics of memory and family construction. The piece centers on disability, fatherhood, and masculinity. The author produces a narrative engagement with his father that imagines a reflexive approach to the poetics of memory. The text spreads across various memories culminating in a recent journey to Sedona, Arizona. The memories and the journey demonstrate the growing distance between father and son and the process of mending such gaps through the recognition of the self in the other.
Geometrical design parameters for journal bearings with flexure pads and compliant liners
Authors: Thomsen Kim , Klit Peder
Published: January 2012

A hydrodynamic journal bearing utilizing flexure pads with a compliant liner is studied and its performance enhanced through a parametric study. The main geometrical dimensions are varied and the affect on pad performance is analyzed. This will put more knowledge into the design and function of flexure pads. Guidelines are given to the design of the pads and are also covering the polymer liner. It is found that the use of flexure pads is an attractive alternative to pivoted pads. Pivot contact-related failure modes are eliminated and load capacity is not restricted by the force that can be transferred through the pivot contact. When combined with a polymer liner, the pad performance is enhanced further, especially when operating at thin lubricant films.
The Importance of Being Trustworthy
Authors: Gilstrap J. Bruce , Collins Brian J.
Published: January 2012

In this study, the authors examined the relationship between leader behaviors and subordinate job satisfaction by adopting the theoretical perspective of the integrative model of trust. The authors hypothesized that one’s trust in their supervisor mediates the relationships of procedural and informational justice and transformational leadership behavior with subordinate job satisfaction. Results from a field sample suggest that trust fully mediates the effects of procedural and informational fairness and transformational leadership on employee job satisfaction. The implications for practice and potential areas of future research are also discussed.
The Need for Office Systems to Improve Colorectal Cancer Screening
Authors: Levy Barcey T. , Daly Jeanette M. , Schmidt Erin J. , Xu Yinghui
Published: January 2012

Patients generally access colorectal cancer (CRC) screening through primary care physicians. National guidelines recommend CRC screening for adults beginning at age 50, yet one-third of Americans are not up to date. Methods: A self-administered questionnaire was administered to family physicians from 16 practices in a Midwestern state who attended an information session for a randomized study to improve CRC screening. The questionnaire assessed CRC screening practices, knowledge of CRC screening guidelines, and office strategies for improving screening. Results: Of 131 health care providers, 85 (65%) completed the questionnaire. Two-thirds were aware of the CRC screening guidelines; 91% knew that the follow-up interval for screening depends on the test chosen. Twenty-five percent incorrectly stated that a single-sample in-office fecal occult blood test is an acceptable screening test. Only 8% had a written policy regarding CRC screening; 18% had offices that used chart reminders; and 32% had charts organized to easily identify patient screening status. Regarding perceptions, those who agreed that they encourage their office staff to participate in screening estimated that they offer screening to more patients than those who disagreed (82.8% vs 70.2%, P < .0001); in addition, those who agreed with and tried to follow the guidelines estimated that they offer screening to more patients than those who disagreed (77.4% vs 60.5%, P = .004). Conclusion: Although physicians were knowledgeable about CRC screening guidelines, 25% mistakenly believed that single-sample in-office fecal testing was appropriate. There was a striking lack of office systems for identifying eligible patients and facilitating CRC screening.
Beyond Randomized Controlled Trials
Authors: Golden Isaac
Published: January 2012

Complementary and alternative medicine is criticized by some as lacking evidence to support the effectiveness of its methods and medicines. Such critics typically point to mixed results from using randomized controlled trials to test complementary and alternative medicine. Randomized controlled trials have been held to be the “gold standard” in pharmaceutical research, but a growing body of evidence in orthodox journals has identified their limitations. Here, 5 fundamental flaws in the randomized controlled trial–based model are discussed as well as the impact on its relevance for testing complementary and alternative medicine therapies. A better way to evaluate complementary and alternative medicine therapies is also proposed. A 7-item checklist is suggested to quantify the strength of an area of complementary and alternative medicine research.
Multi-tyrosine kinase inhibitors in preclinical studies for pediatric CNS AT/RT: Evidence for synergy with Topoisomerase-I inhibition
Authors: Jayanthan Aarthi , Bernoux Delphine , Bose Pinaki , Riabowol Karl , Narendran Aru
Published: December 2011

Background

Currently, Atypical Teratoid Rhabdoid Tumor (AT/RT) constitutes one of the most difficult to treat malignancies in pediatrics. Hence, new knowledge of potential targets for therapeutics and the development of novel treatment approaches are urgently needed. We have evaluated the presence of cytokine pathways and the effects of two clinically available multi-tyrosine kinase inhibitors for cytotoxicity, target modulation and drug combinability against AT/RT cell lines.

Results

AT/RT cell lines expressed measurable quantities of VEGF, FGF, PDGF and SDF-1, although the absolute amounts varied between the cell lines. The targeted receptor tyrosine kinase inhibitor sorafenib inhibited the key signaling molecule Erk, which was activated following the addition of own conditioned media, suggesting the existence of autocrine/paracrine growth stimulatory pathways. The multi-tyrosine kinase inhibitors sorafenib and sunitinib also showed significant growth inhibition of AT/RT cells and their activity was enhanced by combination with the topoisomerase inhibitor, irinotecan. The loss of cytoplasmic NF-kappa-B in response to irinotecan was diminished by sorafenib, providing evidence for a possible benefit for this drug combination.

Conclusions

In addition to previously described involvement of insulin like growth factor (IGF) family of cytokines, a multitude of other growth factors may contribute to the growth and survival of AT/RT cells. However, consistent with the heterogeneous nature of this tumor, quantitative and qualitative differences may exist among different tumor samples. Multi-tyrosine kinase inhibitors appear to have effective antitumor activity against all cell lines studied. In addition, the target modulation studies and drug combinability data provide the groundwork for additional studies and support the evaluation of these agents in future treatment protocols.
Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi) in southern Tanzania: evaluation of impact on survival
Authors: Schellenberg Joanna RM Armstrong , Maokola Werner , Shirima Kizito , Manzi Fatuma , Mrisho Mwifadhi , Mushi Adiel , Alonso Pedro , Mshinda Hassan , Tanner Marcel , Schellenberg David M
Published: December 2011

Background

Intermittent Preventive Treatment for malaria control in infants (IPTi) consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204].

Methods

After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12) or not (n = 12). Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived.

Results

Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P < 0.0001). Over the three years of the study there was a marked improvement in survival in both groups. Between 2001-4 and 2005-7, mortality rates in two-11 month olds fell from 34.1 to 23.6 per 1,000 person-years in intervention areas and from 32.3 to 20.7 in comparison areas. In 2007, divisions implementing IPTi had a 14% (95% CI -12%, 49%) higher mortality rate in two-11 month olds in comparison with non-implementing divisions (P = 0.31).

Conclusion

The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.
Health effects of dietary phospholipids
Authors: Küllenberg Daniela , Taylor Lenka A , Schneider Michael , Massing Ulrich
Published: January 2012

Beneficial effects of dietary phospholipids (PLs) have been mentioned since the early 1900's in relation to different illnesses and symptoms, e.g. coronary heart disease, inflammation or cancer. This article gives a summary of the most common therapeutic uses of dietary PLs to provide an overview of their approved and proposed benefits; and to identify further investigational needs.

From the majority of the studies it became evident that dietary PLs have a positive impact in several diseases, apparently without severe side effects. Furthermore, they were shown to reduce side effects of some drugs. Both effects can partially be explained by the fact that PL are highly effective in delivering their fatty acid (FA) residues for incorporation into the membranes of cells involved in different diseases, e.g. immune or cancer cells. The altered membrane composition is assumed to have effects on the activity of membrane proteins (e.g. receptors) by affecting the microstructure of membranes and, therefore, the characteristics of the cellular membrane, e.g. of lipid rafts, or by influencing the biosynthesis of FA derived lipid second messengers. However, since the FAs originally bound to the applied PLs are increased in the cellular membrane after their consumption or supplementation, the FA composition of the PL and thus the type of PL is crucial for its effect. Here, we have reviewed the effects of PL from soy, egg yolk, milk and marine sources. Most studies have been performed in vitro or in animals and only limited evidence is available for the benefit of PL supplementation in humans. More research is needed to understand the impact of PL supplementation and confirm its health benefits.
Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities
Authors: Khosroushahi Ahmad Yari , Naderi-Manesh Hossein , Yeganeh Hamid , Barar Jaleh , Omidi Yadollah
Published: January 2012

Background

Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells.

Results

The amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether) glycol (PTMEG) and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI). The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43) and high loading efficiency (80%) with low level of critical micelle concentration (CMC). In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA fragmentation in the treated cells.

Conclusions

Based upon these findings, we propose that the bioactive waterborne polyurethane nanomicelles can be used as an effective nanocarrier for delivery of anticancer chemotherapies such as paclitaxel.
Ga-doped ZnO transparent electrodes with TiO2 blocking layer/nanoparticles for dye-sensitized solar cells
Authors: Kim Ji-Hong , Lee Kyung-Ju , Roh Ji-Hyung , Song Sang-Woo , Park Jae-Ho , Yer In-Hyung , Moon Byung-Moo
Published: January 2012

Ga-doped ZnO [GZO] thin films were employed for the transparent electrodes in dye-sensitized solar cells [DSSCs]. The electrical property of the deposited GZO films was as good as that of commercially used fluorine-doped tin oxide [FTO]. In order to protect the GZO and enhance the photovoltaic properties, a TiO2 blocking layer was deposited on the GZO surface. Then, TiO2 nanoparticles were coated on the blocking layer, and dye was attached for the fabrication of DSSCs. The fabricated DSSCs with the GZO/TiO2 glasses showed an enhanced conversion efficiency of 4.02% compared to the devices with the normal GZO glasses (3.36%). Furthermore, they showed better characteristics even than those using the FTO glasses, which can be attributed to the reduced charge recombination and series resistance.
Enhanced electrochemical properties of fluoride-coated LiCoO2 thin films
Authors: Lee Hye Jin , Kim Seuk Buom , Park Yong Joon
Published: January 2012

The electrochemical properties of fluoride-coated lithium cobalt oxide [LiCoO2] thin films were characterized. Aluminum fluoride [AlF3] and lanthanum fluoride [LaF3] coating layers were fabricated on a pristine LiCoO2 thin film by using a spin-coating process. The AlF3- and LaF3-coated films exhibited a higher rate capability, cyclic performance, and stability at high temperature than the pristine film. This indicates that the AlF3 and LaF3 layers effectively protected the surface of the pristine LiCoO2 film from the reactive electrolyte.
Non-stem cancer cell kinetics modulate solid tumor progression
Authors: Morton Charles I , Hlatky Lynn , Hahnfeldt Philip , Enderling Heiko
Published: December 2011

Background

Solid tumors are heterogeneous in composition. Cancer stem cells (CSCs) are believed to drive tumor progression, but the relative frequencies of CSCs versus non-stem cancer cells span wide ranges even within tumors arising from the same tissue type. Tumor growth kinetics and composition can be studied through an agent-based cellular automaton model using minimal sets of biological assumptions and parameters. Herein we describe a pivotal role for the generational life span of non-stem cancer cells in modulating solid tumor progression in silico.

Results

We demonstrate that although CSCs are necessary for progression, their expansion and consequently tumor growth kinetics are surprisingly modulated by the dynamics of the non-stem cancer cells. Simulations reveal that slight variations in non-stem cancer cell proliferative capacity can result in tumors with distinctly different growth kinetics. Longer generational life spans yield self-inhibited tumors, as the emerging population of non-stem cancer cells spatially impedes expansion of the CSC compartment. Conversely, shorter generational life spans yield persistence-limited tumors, with symmetric division frequency of CSCs determining tumor growth rate. We show that the CSC fraction of a tumor population can vary by multiple orders of magnitude as a function of the generational life span of the non-stem cancer cells.

Conclusions

Our study suggests that variability in the growth rate and CSC content of solid tumors may be, in part, attributable to the proliferative capacity of the non-stem cancer cell population that arises during asymmetric division of CSCs. In our model, intermediate proliferative capacities give rise to the fastest-growing tumors, resulting in self-metastatic expansion driven by a balance between symmetric CSC division and expansion of the non-stem cancer population. Our results highlight the importance of non-stem cancer cell dynamics in the CSC hypothesis, and may offer a novel explanation for the large variations in CSC fractions reported in vivo.
Modularity detection in protein-protein interaction networks
Authors: Narayanan Tejaswini , Gersten Merril , Subramaniam Shankar , Grama Ananth
Published: December 2011

Background

Many recent studies have investigated modularity in biological networks, and its role in functional and structural characterization of constituent biomolecules. A technique that has shown considerable promise in the domain of modularity detection is the Newman and Girvan (NG) algorithm, which relies on the number of shortest-paths across pairs of vertices in the network traversing a given edge, referred to as the betweenness of that edge. The edge with the highest betweenness is iteratively eliminated from the network, with the betweenness of the remaining edges recalculated in every iteration. This generates a complete dendrogram, from which modules are extracted by applying a quality metric called modularity denoted by Q. This exhaustive computation can be prohibitively expensive for large networks such as Protein-Protein Interaction Networks. In this paper, we present a novel optimization to the modularity detection algorithm, in terms of an efficient termination criterion based on a target edge betweenness value, using which the process of iterative edge removal may be terminated.

Results

We validate the robustness of our approach by applying our algorithm on real-world protein-protein interaction networks of Yeast, C.Elegans and Drosophila, and demonstrate that our algorithm consistently has significant computational gains in terms of reduced runtime, when compared to the NG algorithm. Furthermore, our algorithm produces modules comparable to those from the NG algorithm, qualitatively and quantitatively. We illustrate this using comparison metrics such as module distribution, module membership cardinality, modularity Q, and Jaccard Similarity Coefficient.

Conclusions

We have presented an optimized approach for efficient modularity detection in networks. The intuition driving our approach is the extraction of holistic measures of centrality from graphs, which are representative of inherent modular structure of the underlying network, and the application of those measures to efficiently guide the modularity detection process. We have empirically evaluated our approach in the specific context of real-world large scale biological networks, and have demonstrated significant savings in computational time while maintaining comparable quality of detected modules.
PTPN22 polymorphisms may indicate a role for this gene in atopic dermatitis in West Highland white terriers
Authors: Roque Joana Barros , O'Leary Caroline A , Kyaw-Tanner Myat , Duffy David L , Gharahkhani Puya , Vogelnest Linda , Mason Kenneth , Shipstone Michael
Published: December 2011

Background

Canine atopic dermatitis is an allergic inflammatory skin disease common in West Highland white terriers. A genome-wide association study for atopic dermatitis in a population of West Highland white terriers identified a 1.3 Mb area of association on CFA17 containing canine protein tyrosine phosphatase non-receptor type 22 (lymphoid) PTPN22. This gene is a potential candidate gene for canine atopic dermatitis as it encodes a lymphoid-specific signalling mediator that regulates T-cell and possibly B-cell activity.

Findings

Sequencing of PTPN22 in three atopic and three non-atopic West Highland white terriers identified 18 polymorphisms, including five genetic variants with a bioinformatically predicted functional effect. An intronic polymorphic repeat sequence variant was excluded as the cause of the genome-wide association study peak signal, by large-scale genotyping in 72 West Highland white terriers (gene-dropping simulation method, P = 0.01).

Conclusions

This study identified 18 genetic variants in PTPN22 that might be associated with atopic dermatitis in West Highland white terriers. This preliminary data may direct further study on the role of PTPN22 in this disease. Large scale genotyping and complementary genomic and proteomic assays would be required to assess this possibility.
Developing criteria and data to determine best options for expanding the core CODIS loci
Authors: Ge Jianye , Eisenberg Arthur , Budowle Bruce
Published: January 2012

Background

Recently, the Combined DNA Index System (CODIS) Core Loci Working Group established by the US Federal Bureau of Investigation (FBI) reviewed and recommended changes to the CODIS core loci. The Working Group identified 20 short tandem repeat (STR) loci (composed of the original CODIS core set loci (minus TPOX), four European recommended loci, PentaE, and DYS391) plus the Amelogenin marker as the new core set. Before selecting and finalizing the core loci, some evaluations are needed to provide guidance for the best options of core selection.

Method

The performance of current and newly proposed CODIS core loci sets were evaluated with simplified analyses for adventitious hit rates in reasonably large datasets under single-source profile comparisons, mixture comparisons and kinship searches, and for international data sharing. Informativeness (for example, match probability, average kinship index (AKI)) and mutation rates of each locus were some of the criteria to consider for loci selection. However, the primary factor was performance with challenged forensic samples.

Results

The current battery of loci provided in already validated commercial kits meet the needs for single-source profile comparisons and international data sharing, even with relatively large databases. However, the 13 CODIS core loci are not sufficiently powerful for kinship analyses and searching potential contributors of mixtures in larger databases; 19 or more autosomal STR loci perform better. Y-chromosome STR (Y-STR) loci are very useful to trace paternal lineage, deconvolve female and male mixtures, and resolve inconsistencies with Amelogenin typing. The DYS391 locus is of little theoretical or practical use. Combining five or six Y-chromosome STR loci with existing autosomal STR loci can produce better performance than the same number of autosomal loci for kinship analysis and still yield a sufficiently low match probability for single-source profile comparisons.

Conclusion

A more comprehensive study should be performed to provide the necessary information to decision makers and stakeholders about the construction of a new set of core loci for CODIS. Finally, selection of loci should be driven by the concept that the needs of casework should be supported by the processes of CODIS (or for that matter any forensic DNA database).
A phenomenological model of seizure initiation suggests network structure may explain seizure frequency in idiopathic generalised epilepsy
Authors: Benjamin Oscar , Fitzgerald Thomas HB , Ashwin Peter , Tsaneva-Atanasova Krasimira , Chowdhury Fahmida , Richardson Mark P , Terry John R
Published: January 2012

We describe a phenomenological model of seizure initiation, consisting of a bistable switch between stable fixed point and stable limit-cycle attractors. We determine a quasi-analytic formula for the exit time problem for our model in the presence of noise. This formula--which we equate to seizure frequency--is then validated numerically, before we extend our study to explore the combined effects of noise and network structure on escape times. Here, we observe that weakly connected networks of 2, 3 and 4 nodes with equivalent first transitive components all have the same asymptotic escape times. We finally extend this work to larger networks, inferred from electroencephalographic recordings from 35 patients with idiopathic generalised epilepsies and 40 controls. Here, we find that network structure in patients correlates with smaller escape times relative to network structures from controls. These initial findings are suggestive that network structure may play an important role in seizure initiation and seizure frequency.
Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells
Authors: Sprowl Jason A , Reed Kerry , Armstrong Stephen R , Lanner Carita , Guo Baoqing , Kalatskaya Irina , Stein Lincoln , Hembruff Stacey L , Tam Adam , Parissenti Amadeo M
Published: January 2012

Introduction

The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, and other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization of microtubules, the mechanisms by which tumor cells die remains unclear. Paclitaxel has been shown to induce soluble tumor necrosis factor alpha (sTNF-α) production in macrophages, but the involvement of TNF production in taxane cytotoxicity or resistance in tumor cells has not been established. Our study aimed to correlate alterations in the TNF pathway with taxane cytotoxicity and the acquisition of taxane resistance.

Methods

MCF-7 cells or isogenic drug-resistant variants (developed by selection for surviving cells in increasing concentrations of paclitaxel or docetaxel) were assessed for sTNF-α production in the absence or presence of taxanes by enzyme-linked immunosorbent assay (ELISA) and for sensitivity to docetaxel or sTNF-α by using a clonogenic assay (in the absence or presence of TNFR1 or TNFR2 neutralizing antibodies). Nuclear factor (NF)-κB activity was also measured with ELISA, whereas gene-expression changes associated with docetaxel resistance in MCF-7 and A2780 cells were determined with microarray analysis and quantitative reverse transcription polymerase chain reaction (RTqPCR).

Results

MCF-7 and A2780 cells increased production of sTNF-α in the presence of taxanes, whereas docetaxel-resistant variants of MCF-7 produced high levels of sTNF-α, although only within a particular drug-concentration threshold (between 3 and 45 nM). Increased production of sTNF-α was NF-κB dependent and correlated with decreased sensitivity to sTNF-α, decreased levels of TNFR1, and increased survival through TNFR2 and NF-κB activation. The NF-κB inhibitor SN-50 reestablished sensitivity to docetaxel in docetaxel-resistant MCF-7 cells. Gene-expression analysis of wild-type and docetaxel-resistant MCF-7, MDA-MB-231, and A2780 cells identified changes in the expression of TNF-α-related genes consistent with reduced TNF-induced cytotoxicity and activation of NF-κB survival pathways.

Conclusions

We report for the first time that taxanes can promote dose-dependent sTNF-α production in tumor cells at clinically relevant concentrations, which can contribute to their cytotoxicity. Defects in the TNF cytotoxicity pathway or activation of TNF-dependent NF-κB survival genes may, in contrast, contribute to taxane resistance in tumor cells. These findings may be of strong clinical significance.
The p65 subunit of NF-κB and PARP1 assist Snail1 in activating fibronectin transcription
Authors: Stanisavljevic Jelena , Porta-de-la-Riva Montserrat , Batlle Raquel , de Herreros Antonio García , Baulida Josep
Published: January 2012

Snail1 is a transcriptional repressor of E-cadherin that triggers epithelial–mesenchymal transition (EMT). Here, we report assisted Snail1 interaction with the promoter of a typical mesenchymal gene, fibronectin (FN1), both in epithelial cells undergoing EMT and in fibroblasts. Together with Snail1, the p65 subunit of NF-κB and PARP1 bound to the FN1 promoter. We detected nuclear interaction of these proteins and demonstrated the requirement of all three for FN1 transcription. Moreover, other genes involved in cell movement mimic FN1 expression induced by Snail1 or TGF-β1 treatment and recruit p65NF-κB and Snail1 to their promoters. The molecular cooperation between Snail1 and NF-κB in transcription activation provides a new insight into how Snail1 can modulate a variety of cell programs.
Molecular Recognition of Chiral Diporphyrin Receptor with a Macrocyclic Cavity for Intercalation of Aromatic Compounds
Authors: Ema Tadashi , Ura Norichika , Eguchi Katsuya , Sakai Takashi
Published: December 2011

Chiral diporphyrin receptor 1, which has a macrocyclic cavity for the intercalation of aromatic guest molecules, was designed and synthesized from pyrrole in five steps. The binding constants (Ka) revealed the greater affinity of 1 for more electron-deficient aromatic guests. The complexation between 1 and 1,3,5-trinitrobenzene (G8) (Ka = 1850 M−1) was much stronger than that between porphyrin monomer 3 and G8 (Ka = 50 M−1). This result strongly suggests that G8 was intercalated into the cavity of 1 via cooperative double π–π stacking. Interestingly, 1 enabled the naked-eye detection of an aromatic explosive G8; a dark-red solution of 1 in CHCl3 turned into a colloidal suspension upon addition of G8, and the light was scattered. Fluorescence spectroscopy was also useful for the selective detection of G8; fluorescence of 1 was quenched by complexation with G8, which was visible with the naked eye. Despite modest binding constants for dinitrobenzene derivatives, 1 showed a good ability to discriminate the enantiomers of twelve chiral compounds bearing a dinitrophenyl group by NMR spectroscopy. The MM calculations with the MM3 force field reproduced inclusion complexes between 1 and nitroaromatic compounds. The mechanism of chiral discrimination is proposed.
Synthesis of Non-Steroidal Estrogen Receptor Antagonists R1128 A, B, C, and D via an Oxazoline-Promoted Iterative ortho-Lithiation Strategy
Authors: Fukuda Tsutomu , Fukushima Koichiro , Sanai Susumu , Iwao Masatomo
Published: December 2011

A concise total synthesis of non-steroidal estrogen receptor antagonists R1128 A–D (1a–1d) has been achieved using iterative ortho-lithiation of 2-(4-methoxyphenyl)-4,4-dimethyloxazoline (3) as the key reaction.
Pathways and Kinetics of Anisole Pyrolysis Studied by NMR and Selective 13C Labeling. Heterolytic Carbon Monoxide Generation
Authors: Tsujino Yasuo , Yasaka Yoshiro , Matubayasi Nobuyuki , Nakahara Masaru
Published: December 2011

By applying 13C and 1H NMR spectroscopy the pyrolysis of site-selectively 13C-enriched (H313CO12C6H5) and normal anisole compounds was studied in the dark at 0.001–1.0 M (M, mol dm−3) and at 400–600 °C (supercritical conditions). Conversion of the 13C-labeled methyl group was confined to the methoxy-originated fragments, 13CO and 13CH4, and the reactive intermediate, H13CHO*. The normal phenyl group, 12C6H5– was converted to benzene, 12C6H6 and phenol, 12C6H5OH without ring disintegration. The pyrolysis consists of two elementary steps: (1) the rate-determining unimolecular ether-bond fission (k1) to generate the fragmented product C6H6 and energized intermediate H13CHO* through the intramolecular proton transfer from the methoxy group to the phenyl, and (2) the fast bimolecular disproportionation (k2) through the intermolecular proton/hydride transfer from H13CHO* to H313COC6H5 to produce 13CO, 13CH4, and C6H5OH. CO is generation by the heterolytic (ionic) mechanism in contrast to the homolytic (radical) one via the phenoxy radical intermediate (C6H5O•) in the literature despite the agreement of the rate constant (k1) and the activation energy.
The Risk of Partner Aggression Research: Impact of Laboratory Couples Conflict Protocols on Participants
Authors: Owen Daniela J. , Heyman Richard E. , Smith Slep Amy M.
Published: December 2011

The impact of male-to-female intimate partner violence (IPV) research on participants is unknown. A measure of impact was given to participants in an IPV study to assess systematically the impact of completing questionnaires, engaging in conflict conversations, and being interviewed individually about anger escalation and de-escalation during the conversations. Participants completed a six-question, Likert-scaled impact measure. Both male and female participants rated the impact of the study as helpful to them personally and to their relationships. Female participants rated different segments of the study as more helpful to themselves and their relationships, while male participants did not find any segment of the study to have a different impact than other segments.
Reaction Time and Item Presentation Factors in the Self-Report of Partner Aggression
Authors: Vega Edward M. , O’Leary Daniel K.
Published: December 2011

The Conflict Tactics Scales (CTS) have used different formats intended to maximize the accuracy and disclosure of relationship aggression. The original CTS presented items in a hierarchical order, seeking to establish a “context of legitimation.” The CTS2 presented items in an interspersed order to reduce denial response sets. The current study used computer administration of the CTS and sought to determine whether the two presentation formats described above result in differing self-reports of aggression and to explore possible causes of such an effect, such as differences in reaction time. Results indicated that item order did not significantly affect reports of aggression, but increasing participants’ reaction times by experimental manipulation of the minimum item display duration resulted in increased self-reports of aggression.
Efficacy and Safety of Paricalcitol Therapy for Chronic Kidney Disease
Authors: Cheng Jun , Zhang Wen , Zhang Xiaohui , Li Xiayu , Chen Jianghua
Published: January 2012

Background and objectives

Observational data indicate that newer vitamin D compounds such as paricalcitol can suppress serum intact parathyroid hormone (iPTH) and reduce proteinuria in patients with CKD. To systematically evaluate the efficacy and safety of paricalcitol for CKD, we conducted a meta-analysis of the published randomized controlled trials (RCTs).

Design, setting, participants, & measurements

MEDLINE, Embase, the Cochrane Library, and article reference lists were searched for RCTs that compared paricalcitol with placebo in the treatment of patients with stage 2–5 CKD. The quality of the studies was evaluated using the Jadad method. The results are summarized as risk ratios (RRs) for dichotomous outcomes or mean differences for continuous outcomes.

Results

Nine studies (832 patients) were included. Compared with placebo, paricalcitol suppressed serum iPTH (RR, 6.37; 95% confidence interval [95% CI], 4.64–8.74; P<0.001) and reduced proteinuria (RR, 1.68; 95% CI, 1.25–2.25; P<0.001). Compared with the control group, the RR for hypercalcemia associated with paricalcitol use was 2.25 (95% CI, 0.81–6.26; P=0.12). Patients receiving paricalcitol therapy did not have an increased risk of endocrine system and cardiovascular system adverse effects (RR, 1.07; 95% CI, 0.84–1.36; P=0.58).

Conclusions

We conﬁrm that paricalcitol suppresses iPTH and lowers proteinuria in patients with stage 2–5 CKD without an increased risk of adverse events. A trend toward increased hypercalcemia did not reach statistical signiﬁcance, but may be clinically relevant. A randomized trial is needed to determine if paricalcitol affects the development of ESRD or mortality.
Solar-Assisted Hemodialysis
Authors: Agar John W. M. , Perkins Anthony , Tjipto Alwie
Published: January 2012

Background and objectives

Hemodialysis resource use—especially water and power, smarter processing and reuse of postdialysis waste, and improved ecosensitive building design, insulation, and space use—all need much closer attention. Regarding power, as supply diminishes and costs rise, alternative power augmentation for dialysis services becomes attractive. The first 12 months of a solar-assisted dialysis program in southeastern Australia is reported.

Design, setting, participants, & measurements

A 24-m2, 3-kWh rated solar array and inverter—total cost of A$16,219—has solar-assisted the dialysis-related power needs of a four-chair home hemodialysis training service. All array-created, grid-donated power and all grid-drawn power to the four hemodialysis machines and minireverse osmosis plant pairings are separately metered. After the grid-drawn and array-generated kilowatt hours have been billed and reimbursed at their respective commercial rates, financial viability, including capital repayment, can be assessed.

Results

From July of 2010 to July of 2011, the four combined equipment pairings used 4166.5 kWh, 9% more than the array-generated 3811.0 kWh. Power consumption at 26.7 c/kWh cost A$1145.79. Array-generated power reimbursements at 23.5 c/kWh were A$895.59. Power costs were, thus, reduced by 76.5%. As new reimbursement rates (60 c/kWh) take effect, system reimbursements will more than double, allowing both free power and potential capital pay down over 7.7 years. With expected array life of ∼30 years, free power and an income stream should accrue in the second and third operative decades.

Conclusions

Solar-assisted power is feasible and cost-effective. Dialysis services should assess their local solar conditions and determine whether this ecosensitive power option might suit their circumstance.
Kurzweil integral for Riesz space-valued functions: Uniform convergence theorem
Authors: Monteiro G. , Fernandez R.
Published: December 2011

Our objective here is to prove that the uniform convergence of a sequence of Kurzweil integrable functions implies the convergence of the sequence formed by its corresponding integrals.