bluuebunny/crossref_metadata_2025 huggingface dataset:
Intellectual disability nursing in Ireland: Identifying its development and future
Authors: Doody Owen , Slevin Eamonn , Taggart Laurence
Published: February 2012

As a profession, intellectual disability nursing has often come under scrutiny and been called into question. Since its inception as an individual nursing profession in 1959 in Ireland, both education and service provision philosophies have changed over time. These changes have been in response to national and international reports and changing attitudes. The changes have led to the current position where intellectual disability nurse education in Ireland is a four-year undergraduate course. As the discipline of intellectual disability nursing is unique to Ireland and the United Kingdom, there is a responsibility on intellectual disability nurses to identify their unique identity and their responses to the demands of changing services. This article traces the development of intellectual disability nursing in Ireland and identifies implications for the future.
Lyn kinase controls TLR4-dependent IKK and MAPK activation modulating the activity of TRAF-6/TAK-1 protein complex in mast cells
Authors: Avila Martin , Martinez-Juarez Adriana , Ibarra-Sanchez Alfredo , Gonzalez-Espinosa Claudia
Published: February 2012

Mast cells (MCs) control allergic reactions and contribute to protective innate immune responses through TLR4 activation. The tyrosine kinase Lyn is important to the high affinity IgE receptor (FcεRI) signal transduction system in MCs, but its role on the TLR4 signalling cascade is still elusive. Here, we characterized several TLR4-triggered responses in bone marrow-derived mast cells (BMMCs) from wild-type (WT) and Lyn−/− mice. We found that Lyn−/− MCs secreted lower amounts of TNF-α after LPS challenge when compared with WT cells. Lyn−/− BMMCs showed less MAPK, IκB phosphorylation and NF-κB nuclear translocation after TLR-4 triggering than WT cells. LPS-induced MAPK and inhibitor of IκB kinase (IKK) phosphorylation were importantly reduced in the absence of Lyn. A constitutive interaction between TNF receptor associated factor 6 (TRAF-6) and phosphorylated TGF-β-activated kinase (TAK-1) was observed in Lyn−/− BMMCs and this complex was insensitive to LPS addition. Lyn kinase was activated and associated to TRAF-6 shortly after LPS addition in WT MCs. Analyzing two local MC-dependent innate immune responses in vivo, we found that Lyn positively controls early TNF-α production and immune cell recruitment after an intraperitoneal injection of LPS. Our results indicate that Lyn plays a positive role in TLR4-induced production of TNF-α in MCs controlling the activity of the TRAF-6/TAK-1 protein complex.
Design of the Grand Touring sports car wing: geometric and aerodynamic twist
Authors: Marqués-Bruna Pascual
Published: February 2012

Wing twist gives the Grand Touring sports car an eye-catching ‘aerodynamic shape’. From the functional viewpoint, wing twist may improve downforce, provide stall control and enhance aerodynamic efficiency if the twist is optimised. This study aims, first, to explore the influence of linear geometric and aerodynamic twist upon spanwise upwash velocity, downforce and induced drag distributions and, second, to evaluate the use of optimum twist in achieving minimum induced drag while preserving high downforce, in wings with linear taper for the Grand Touring car. Baseline wing prototypes were designed and fitted, subsequently, with a Gurney flap and endplates to obtain complete wings. Aerodynamics for straight wings and wings with geometric, aerodynamic and optimised twist were computed using modified versions of the Prandtl’s Lifting-line Theory. Straight and geometrically-twisted wings with constituent NACA 651-412 airfoils present superior aerodynamic efficiency at angles of attack ≤ 1° and may be used as stabilisers on high-speed circuits. Geometric twisting elicits a partial, rather than complete, wing stall that contributes to safety in motor racing. A geometrically-twisted wing constructed with a NASA LS(1)-0413 airfoil yields high downforce at the expense of large induced drag via a double-peaked induced drag distribution, and it is suitable for high-downforce racing circuits. Nonetheless, the analysis suggests that a twist-optimised wing for the Grand Touring car very nearly duplicates the ideal aerodynamic performance of an elliptic wing and yields high downforce and minimum possible induced drag. The findings support the implementation of optimum wing twist at the conceptual stages of Grand Touring sports car design.
Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity
Authors: Marks Jonathan L. , Edwards Christopher J.
Published: February 2012

Rheumatoid arthritis (RA) is associated with an increased risk of premature mortality, predominantly due to increased cardiovascular disease (CVD). Systemic inflammation has been established as one of the primary drivers of accelerated atherosclerosis in RA, though other traditional and disease-specific risk factors also contribute. There is evidence that methotrexate, considered a mainstay of therapy for RA, can ameliorate some of this excess CVD risk, an effect that has not been seen consistently with other disease-modifying antirheumatic drugs. The cardioprotective action of methotrexate may occur through reducing systemic inflammation and by directly affecting some of the cellular mechanisms that lead to atherosclerosis. On the basis of this evidence, there are ongoing trials of low-dose methotrexate in patients from the general population with CVD but who do not have RA. Methotrexate reduces the overall CVD burden in patients with RA. With earlier treatment of RA and earlier use of methotrexate it is possible that we may have the capability to radically change patients’ long-term CVD risk.
The Skinny on Celebrities
Authors: Young Ariana F. , Gabriel Shira , Sechrist Gretchen B.
Published: February 2012

Much research demonstrates that exposure to thin media ideals has a negative effect on women’s body image. The present research suggests a notable and important exception to this rule. The authors propose the parasocial relationship-moderation hypothesis—that parasocial, or one-sided, relationships (PSRs) moderate the effects of thin media figures on body image. Specifically, the authors propose that having a PSR with a media figure increases the likelihood of assimilating, rather than contrasting, the PSR’s body to the self. Study 1 found that women who perceived similarity with a thin model felt better about their bodies than those who did not perceive similarity. Study 2 found that women were more satisfied with their bodies after exposure to a favorite celebrity they perceived as thin than a control celebrity they perceived as thin. Finally, Study 3 suggests that assimilation was the underlying mechanism of increased body satisfaction after exposure to a thin favorite celebrity.
Do Ideal Partner Preferences Predict Divorce? A Tale of Two Metrics
Authors: Eastwick Paul W. , Neff Lisa A.
Published: February 2012

Though people report idiosyncratic desires for particular traits in an ideal romantic partner, few studies have examined whether these ideals predict important long-term relationship outcomes. The present 3.5-year longitudinal study of newlywed couples used survival analysis to investigate whether the match between participants’ ideal preferences and the traits they perceive in their partner predict the likelihood of divorce. Results depended entirely on whether the match was conceptualized as a match in level (e.g., high ideal preference for a trait with the presence of the trait in the partner) or in pattern (e.g., the within-person correlation of ideals with a partner’s traits across all traits). The match between the pattern of ideals and traits negatively predicted divorce with an effect size larger than most established divorce risk factors. However, the match in level was unrelated to divorce, suggesting that perspectives emphasizing ideals for the level of traits may encounter predictive validity problems.
Valuable Therefore Not Threatening
Authors: Kauff Mathias , Wagner Ulrich
Published: February 2012

Previous findings demonstrate that believing in the value of diverse groups is related to positive attitudes toward immigrants. Based on these results, we hypothesized that pro-diversity beliefs are negatively related to discrimination of immigrants. In a representative multinational survey study (Study 1; N = 6,500), we demonstrate that diversity beliefs of nonimmigrant citizens from seven different European countries are negatively related to their discriminatory behavioral tendencies against immigrants. Moreover, it is revealed that this relationship is mediated by reduced realistic and symbolic threat. These findings are replicated in an experimental study (Study 2; N = 64), which confirms that diversity beliefs causally influence discriminatory behavioral tendencies. However, in the economic context of Study 2, the relationship is mediated by realistic but not by symbolic threat.
Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource
Authors: Williams Tim , van Staa Tjeerd , Puri Shivani , Eaton Susan
Published: February 2012

Since its inception in the mid-1980s, the General Practice Research Database (GPRD) has undergone many changes but remains the largest validated and most utilised primary care database in the UK. Its use in pharmacoepidemiology stretches back many years with now over 800 original research papers. Administered by the Medicines and Healthcare products Regulatory Agency since 2001, the last 5 years have seen a rebuild of the database processing system enhancing access to the data, and a concomitant push towards broadening the applications of the database. New methodologies including real-world harm–benefit assessment, pharmacogenetic studies and pragmatic randomised controlled trials within the database are being implemented. A substantive and unique linkage program (using a trusted third party) has enabled access to secondary care data and disease-specific registry data as well as socio-economic data and death registration data. The utility of anonymised free text accessed in a safe and appropriate manner is being explored using simple and more complex techniques such as natural language processing.
Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan
Authors: Tokunaga Takashi , Shimada Kazuyuki , Yamamoto Kazuhito , Chihara Dai , Ichihashi Takuji , Oshima Rika , Tanimoto Mitsune , Iwasaki Toshihiro , Isoda Atsushi , Sakai Akira , Kobayashi Hikaru , Kitamura Kunio , Matsue Kosei , Taniwaki Masafumi , Tamashima Sadahiro , Saburi Yoshio , Masunari Taro , Naoe Tomoki , Nakamura Shigeo , Kinoshita Tomohiro
Published: February 2012

Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.
Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings
Authors: Chiofalo Maria Grazia , Losito Nunzia Simona , Fulciniti Franco , Setola Sergio Venanzio , Tommaselli Antonio , Marone Ugo , Di Cecilia Maria Luisa , Pezzullo Luciano
Published: February 2012

Background

Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.

Case presentation

Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.

Discussion and Conclusion

Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.
Suppressive effects of liquid crystal compounds on the growth of U937 human leukemic monocyte lymphoma cells
Authors: Ishikawa Junya , Takahashi Yuuka , Hazawa Masaharu , Fukushi Yukako , Yoshizawa Atsushi , Kashiwakura Ikuo
Published: February 2012

Background

The aim of this study was to evaluate the biological and pharmaceutical activities of 14 amphiphilic liquid-crystalline compounds (LCs), i.e, phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit.

Results

The cytotoxic properties of the LCs on the cell growth, cell cycle distribution, and cell signaling pathway of U937 human leukemic monocyte lymphoma cells were assessed by flow cytometry and western blot analysis. Some LCs showed cytostatic effects, suppressing cell growth via S-phase arrest and without apoptosis in U937 cells. To investigate the mechanisms of the LC-induced S-phase arrest, proteins relevant to cell cycle regulation were investigated by western blot analysis. The rate of LC-induced S-phase arrest was congruent with the decreased expression of MCM2, cyclin A, cyclin B, CDK2, phospho-CDK1 and Cdc25C. Observed changes in cell cycle distribution by LC treated might be caused by insufficient preparation for G2/M transition. Considering the structure of the LCs, the rod-like molecules displaying cytotoxicity against U937 cells possessed flexible spacers with no bulky polar group attached via the flexible spacer.

Conclusions

Our results revealed that some LCs showed cytotoxic properties against non-solid type tumor human leukemic cells via LC-induced S-phase arrest and decreasing expression of several cell cycle related proteins.
Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen
Authors: Lin Chen-Si , Kao Shih-Han , Chen Yu-Cheng , Li Chi-Han , Hsieh Yuan-Ting , Yang Shang-Chih , Wu Chang-Jer , Lee Ru-Ping , Liao Kuang-Wen
Published: February 2012

Background

It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development.

Results

To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone.

Conclusion

The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.
Phenylketonuria: nutritional advances and challenges
Authors: Giovannini Marcello , Verduci Elvira , Salvatici Elisabetta , Paci Sabrina , Riva Enrica
Published: February 2012

Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.

In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients.
Comparison of cement pressurisation in flanged and unflanged acetabular cups
Authors: Bhattacharya Rajarshi , Attar Fahad G , Green Sarah , Port Andrew
Published: February 2012

Background

This biomechanical study examined difference in cement pressures generated by flanged and unflanged acetabular cups in hip arthroplasty.

Method

Using a model acetabulum, cement was inserted and pressurised followed by cup insertion and pressurisation. Pressures were recorded using transducers in the acetabulum. We compared Charnley Ogee (flanged), Exeter contemporary (flanged) and Exeter low profile (unflanged) cups using Simplex and CMW1 cements in turn.

Results

Using Simplex, Charnley Ogee cup generated highest initial peak pressure and overall mean pressure. Exeter unflanged cup generated higher initial and mean pressures compared to Exeter flanged cup. With CMW, there was no significant difference between the pressures generated by the cups.

Conclusions

Our experiment suggests that flanged cups do not consistently generate significantly higher cement pressures compared to unflanged cups.
Chondroitin sulfates in the developing rat hindbrain confine commissural projections of vestibular nuclear neurons
Authors: Kwok Jessica CF , Yuen Ying-Lai , Lau Wai-Kit , Zhang Fu-Xing , Fawcett James W , Chan Ying-Shing , Shum Daisy KY
Published: February 2012

Background

Establishing correct neuronal circuitry is crucial to proper function of the vertebrate nervous system. The abundance of chondroitin sulfate (CS) proteoglycans in embryonic neural environments suggests that matrix proteoglycans regulate axonal projections when fiber tracts have not yet formed. Among the early-born neurons, the vestibular nucleus (VN) neurons initiate commissural projections soon after generation at E12.5 and reach the contralateral target by E15.5 in the rat hindbrain. We therefore exploited 24-hour cultures (1 day in vitro (DIV)) of the rat embryos and chondroitinase ABC treatment of the hindbrain matrix to reveal the role of CS moieties in axonal initiation and projection in the early hindbrain.

Results

DiI tracing from the VN at E12.5(+1 DIV) showed contralaterally projecting fibers assuming fascicles that hardly reached the midline in the controls. In the enzyme-treated embryos, the majority of fibers were unfasciculated as they crossed the midline at 90°. At E13.5(+1 DIV), the commissural projections formed fascicles and crossed the midline in the controls. Enzyme treatment apparently did not affect the pioneer axons that had advanced as thick fascicles normal to the midline and beyond, towards the contralateral VN. Later projections, however, traversed the enzyme-treated matrix as unfasciculated fibers, deviated from the normal course crossing the midline at various angles and extending beyond the contralateral VN. This suggests that CSs also limit the course of the later projections, which otherwise would be attracted to alternative targets.

Conclusions

CS moieties in the early hindbrain therefore control the course and fasciculation of axonal projections and the timing of axonal arrival at the target.
Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut
Authors: Macedo Selma E , Moretzsohn Márcio C , M Leal-Bertioli Soraya C , Alves Dione MT , Gouvea Ediene G , Azevedo Vânia CR , Bertioli David J
Published: February 2012

Background

Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm.

Findings

A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties.

Conclusions

The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop.
Use of glucocorticoids and risk of breast cancer: a Danish population-based case-control study
Authors: Sørensen Gitte Vrelits , Cronin-Fenton Deirdre P , Sørensen Henrik Toft , Ulrichsen Sinna Pilgaard , Pedersen Lars , Lash Timothy L
Published: February 2012

Introduction

Glucocorticoids are widely prescribed drugs. In the human body, glucocorticoid is the main stress hormone and controls a variety of physiological and cellular processes, including metabolism and immune response. It belongs to the same steroid superfamily as estrogens, which are known to play a role in breast cancer. However, the effect of glucocorticoid use on the risk of breast cancer is not clear.

Methods

We conducted a case-control study using population-based medical databases from Northern Denmark (1.8 million inhabitants) to investigate the association between glucocorticoid prescriptions and breast cancer risk. The study included 9,488 incident breast cancer cases diagnosed between 1994 and 2008 and 94,876 population controls. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating glucocorticoid use with breast cancer occurrence, controlling for prescriptions of postmenopausal hormone replacement therapy, anti-diabetics, immunosuppressive drugs, and hospital diagnosis of obesity, diabetes, chronic pulmonary diseases and autoimmune diseases.

Results

We found no effect on breast cancer risk in ever users (> 2 prescriptions) of any glucocorticoids (adjusted odds ratio (aOR) = 1.0; 95% CI: 0.96, 1.1), systemic glucocorticoids (aOR = 1.0; 95% CI: 0.96, 1.1), or inhaled glucocorticoids (aOR = 1.0; 95% CI: 0.95, 1.1), each compared to never users of any glucocorticoids. Associations for recent use (preceding two years) and former use (more than two years earlier) were near null in all dose categories (low, medium and high number of prescriptions). Intensity of systemic glucocorticoid use (cumulative prednisolone equivalent doses), regardless of duration (< 1, 1 to 5, 5+ years), was also not associated with breast cancer risk.

Conclusions

Overall, our study provides no evidence that glucocorticoid use affects the risk of breast cancer.
Bayesian inversion of CSEM and magnetotelluric data
Authors: Buland Arild , Kolbjørnsen Odd
Published: February 2012

We have developed a Bayesian methodology for inversion of controlled source electromagnetic (CSEM) data and magnetotelluric (MT) data. The inversion method provided optimal solutions and also the associated uncertainty for any sets of electric and magnetic components and frequencies from CSEM and MT data. The method is based on a 1D forward modeling method for the electromagnetic (EM) response for a plane-layered anisotropic earth model. The inversion method was also designed to invert common midpoint (CMP)-sorted data along a 2D earth profile assuming locally horizontal models in each CMP position. The inversion procedure simulates from the posterior distribution using a Markov chain Monte Carlo (McMC) approach based on the Metropolis-Hastings algorithm. The method that we use integrates available geologic prior knowledge with the information in the electromagnetic data such that the prior model stabilizes and constrains the inversion according to the described knowledge. The synthetic examples demonstrated that inclusion of more data generally improves the inversion results. Compared to inversion of the inline electric component only, inclusion of broadside and magnetic components and an extended set of frequency components moderately decreased the uncertainty of the inversion. The results were strongly dependent on the prior knowledge imposed by the prior distribution. The prior knowledge about the background resistivity model surrounding the target was highly important for a successful and reliable inversion result.
Focused inversion of vertical radar profile (VRP) traveltime data
Authors: Vignoli Giulio , Deiana Rita , Cassiani Giorgio
Published: February 2012

The reconstruction of the GPR velocity vertical profile from vertical radar profile (VRP) traveltime data is a problem with a finite number of measurements and imprecise data, analogous to similar seismic techniques, such as the shallow down-hole test used for S-wave velocity profiling or the vertical seismic profiling (VSP) commonly used in deeper exploration. The uncertainty in data accuracy and the error amplification inherent in deriving velocity estimates from gradients of arrival times make this an example of an ill-posed inverse problem. In the framework of Tikhonov regularization theory, ill-posedness can be tackled by introducing a regularizing functional (stabilizer). The role of this functional is to stabilize the numerical solution by incorporating the appropriate a priori assumptions about the geometrical and/or physical properties of the solution. One of these assumptions could be the existence of sharp boundaries separating rocks with different physical properties. We apply a method based on the minimum support stabilizer to the VRP traveltime inverse problem. This stabilizer makes it possible to produce more accurate profiles of geological targets with compact structure. We compare more traditional inversion results with our proposed compact reconstructions. Using synthetic examples, we demonstrate that the minimum support stabilizer allows an improved recovery of the profile shape and velocity values of blocky targets. We also study the stabilizer behavior with respect to different noise levels and different choices of the reference model. The proposed approach is then applied to real cases where VPRs have been used to derive moisture content profiles as a function of depth. In these real cases, the derived sharper profiles are consistent with other evidence, such as GPR zero-offset profiles, GPR reflections and known locations of the water table.
Comparison of reproductive traits of regular and irradiated male desert locust Schistocerca gregaria (Orthoptera: Acrididae): Evidence of last-male sperm precedence
Authors: Dushimirimana Severin , Hance Thierry , Damiens David
Published: February 2012

The sterile insect technique (SIT) is increasingly used to control pest insect populations. The success of SIT control programs depends on the ability to release sterile males and on the capacity of sterile males to compete with wild males to inseminate wild females. In this study, we evaluated the mating performance of Schistocerca gregaria (Försk.) males irradiated with 4 Gray. We compared reproductive traits, such as duration of precopulation time, mating duration, quantity of sperm stored by females after copulation, number of females mated successively and postmating competition of irradiated males with non-irradiated males. Irradiated males were able to mate but the resulting number of offspring was dramatically reduced compared to the average number of offspring observed during a regular mating. During a single copulation, irradiated males transferred fewer sperm than regular males but, theoretically, this quantity is enough to fertilize all the eggs produced by a female during its reproductive life. Irradiated males also had the ability to remove sperm from a previous mating with unirraditated males. This new information on the mating strategies helps explain the post-copulation guarding behaviour of S. gregaria.
Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling
Authors: Sakane Hiroshi , Yamamoto Hideki , Matsumoto Shinji , Sato Akira , Kikuchi Akira
Published: February 2012

Glypicans are members of the heparan sulfate proteoglycans (HSPGs) and are involved in various growth factor signaling mechanisms. Although HSPGs affect the β-catenin-dependent and -independent pathways of Wnt signaling, how they regulate distinct Wnt pathways is not clear. It has been suggested that the β-catenin-dependent pathway is initiated through receptor endocytosis in lipid raft microdomains and the independent pathway is activated through receptor endocytosis in non-lipid raft microdomains. Here, evidence is presented that glypican-4 (GPC4) is localized to both membrane microdomains and that the localization affects its ability to regulate distinct Wnt pathways. GPC4 bound to Wnt3a and Wnt5a, which activate the β-catenin-dependent and -independent pathways, respectively, and colocalized with Wnts on the cell surface. LRP6, one of Wnt3a coreceptors, was present in lipid raft microdomains, whereas Ror2, one of Wnt5a coreceptors, was localized to non-lipid raft microdomains. Expression of GPC4 enhanced the Wnt3a-dependent β-catenin pathway and the Wnt5a-dependent β-catenin-independent pathway, and knockdown of GPC4 suppressed both pathways. A GPC4 mutant that was localized to only non-lipid raft microdomains inhibited the β-catenin-dependent pathway but enhanced the β-catenin-independent pathway. These results suggest that GPC4 concentrates Wnt3a and Wnt5a to the vicinity of their specific receptors in different membrane microdomains, thereby regulating distinct Wnt signaling.
Assembly of Bazooka polarity landmarks through a multifaceted membrane-association mechanism
Authors: McKinley R. F. Andrew , Yu Cao Guo , Harris Tony J. C.
Published: February 2012

Epithelial cell polarity is essential for animal development. The scaffold protein Bazooka (Baz/PAR-3) forms apical polarity landmarks to organize epithelial cells. However, it is unclear how Baz is recruited to the plasma membrane and how this is coupled with downstream effects. Baz contains an oligomerization domain, three PDZ domains, and binding regions for the protein kinase aPKC and phosphoinositide lipids. With a structure–function approach, we dissected the roles of these domains in the localization and function of Baz in the Drosophila embryonic ectoderm. We found that a multifaceted membrane association mechanism localizes Baz to the apical circumference. Although none of the Baz protein domains are essential for cortical localization, we determined that each contributes to cortical anchorage in a specific manner. We propose that the redundancies involved might provide plasticity and robustness to Baz polarity landmarks. We also identified specific downstream effects, including the promotion of epithelial structure, a positive-feedback loop that recruits aPKC, PAR-6 and Crumbs, and a negative-feedback loop that regulates Baz.
GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis
Authors: Wang Shuoshuo , Meyer Heiko , Ochoa-Espinosa Amanda , Buchwald Ulf , Önel Susanne , Altenhein Benjamin , Heinisch Jürgen J. , Affolter Markus , Paululat Achim
Published: February 2012

Here we report on the generation and in vivo analysis of a series of loss-of-function mutants for the Drosophila ArfGEF, Gartenzwerg. The Drosophila gene gartenzwerg (garz) encodes the orthologue of mammalian GBF1. garz is expressed ubiquitously in embryos with substantially higher abundance in cells forming diverse tubular structures such as salivary glands, trachea, proventriculus or hindgut. In the absence of functional Garz protein, the integrity of the Golgi complex is impaired. As a result, both vesicle transport of cargo proteins and directed apical membrane delivery are severely disrupted. Dysfunction of the Arf1–COPI machinery caused by a loss of Garz leads to perturbations in establishing a polarized epithelial architecture of tubular organs. Furthermore, insufficient apical transport of proteins and other membrane components causes incomplete luminal diameter expansion and deficiencies in extracellular matrix assembly. The fact that homologues of Garz are present in every annotated metazoan genome indicates that secretion processes mediated by the GBF-type ArfGEFs play a universal role in animal development.
Neuropilin-2 regulates α6β1 integrin in the formation of focal adhesions and signaling
Authors: Goel Hira Lal , Pursell Bryan , Standley Clive , Fogarty Kevin , Mercurio Arthur M.
Published: February 2012

The neuropilins (NRPs) contribute to the function of cancer cells in their capacity as VEGF receptors. Given that NRP2 is induced in breast cancer and correlates with aggressive disease, we examined the role of NRP2 in regulating the interaction of breast cancer cells with the ECM. Using epithelial cells from breast tumors, we defined NRP2high and NRP2low populations that differed in integrin expression and adhesion to laminin. Specifically, the NRP2high population adhered more avidly to laminin and expressed high levels of the α6β1 integrin than the NRP2low population. The NRP2high population formed numerous focal adhesions on laminin that were not seen in the NRP2low population. These results were substantiated using breast carcinoma cell lines that express NRP2 and α6β1 integrin. Depletion experiments revealed that adhesive strength on laminin but not collagen is dependent on NRP2, and that VEGF is needed for adhesion on laminin. A specific interaction between NRP2 and α6β1 integrin was detected by co-immunoprecipitation. NRP2 is necessary for focal adhesion formation on laminin and for the association of α6β1 integrin with the cytoskeleton. NRP2 also facilitates α6β1-integrin-mediated activation of FAK and Src. Unexpectedly, we discovered that NRP2 is located in focal adhesions on laminin. The mechanism by which NRP2 regulates the interaction of α6β1 integrin with laminin to form focal adhesions involves PKC activation. Together, our data reveal a new VEGF–NRP2 signaling pathway that activates the α6β1 integrin and enables it to form focal adhesions and signal. This pathway is important in the pathogenesis of breast cancer.
Src-mediated phosphorylation of mammalian Abp1 (DBNL) regulates podosome rosette formation in transformed fibroblasts
Authors: Boateng Lindsy R. , Cortesio Christa L. , Huttenlocher Anna
Published: February 2012

Podosomes are dynamic actin-based structures that mediate adhesion to the extracellular matrix and localize matrix degradation to facilitate cell motility and invasion. Drebrin-like protein (DBNL), which is homologous to yeast mAbp1 and is therefore known as mammalian actin-binding protein 1 (mAbp1), has been implicated in receptor-mediated endocytosis, vesicle recycling and dorsal ruffle formation. However, it is not known whether mAbp1 regulates podosome formation or cell invasion. In this study, we found that mAbp1 localizes to podosomes and is necessary for the formation of podosome rosettes in Src-transformed fibroblasts. Despite their structural similarity, mAbp1 and cortactin play distinct roles in podosome regulation. Cortactin was necessary for the formation of podosome dots, whereas mAbp1 was necessary for the formation of organized podosome rosettes in Src-transformed cells. We identified specific Src phosphorylation sites, Tyr337 and Tyr347 of mAbp1, which mediate the formation of podosome rosettes and degradation of the ECM. In contrast to dorsal ruffles, the interaction of mAbp1 with WASP-interacting protein (WIP) was not necessary for the formation of podosome rosettes. Finally, we showed that depletion of mAbp1 increased invasive cell migration, suggesting that mAbp1 differentially regulates matrix degradation and cell invasion. Collectively, our findings identify a role for mAbp1 in podosome rosette formation and cell invasion downstream of Src.
Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study
Authors: Heil Sandra G , de Jonge Robert , de Rotte Maurits C F J , van Wijnen Merel , Heiner-Fokkema Rebecca M R , Kobold Anneke C Muller , Pekelharing J Maurits M , Adriaansen Henk J , Sanders Edward , Trienekens Paul H , Rammeloo Ton , Lindemans Jan
Published: February 2012

Background

Vitamin B12 deficiency occurs frequently, especially among the elderly. However, screening for vitamin B12 deficiency is hampered by poor sensitivity of the existing total vitamin B12 assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B12 deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B12 deficiency in a mixed patient population.

Methods

Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B12 and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS).

Results

Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B12 in detecting vitamin B12 deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B12 and holoTC did not improve diagnostic accuracy at this cut-off level.

Conclusions

HoloTC has a better diagnostic accuracy than vitamin B12 and can replace the existing vitamin B12 assay as a primary screening test in patients suspected of vitamin B12 deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B12 deficiency (defined by MMA > 0.45 μmol/L) in a mixed patient population.
Bioinformatic software for cerebrospinal fluid spectrophotometry in suspected subarachnoid haemorrhage
Authors: Collet Nicolas , Garcelon Nicolas , Robbe Valentin , Lucas-Clerc Catherine , Cuggia Marc , Bendavid Claude
Published: February 2012

Background

Diagnosis of subarachnoid haemorrhage (SAH) is firstly based on imaging and secondly on spectrophotometry. Bilirubin may be detected in the cerebrospinal fluid (CSF) for up to two weeks after SAH. CSF pigment analysis is commonly performed according to the Chalmers manual technique but may be prone to operator error. We propose an online software solution, based on the United Kingdom National External Quality Assessment Service (UKNEQAS) recommendations, to support the interpretation of CSF pigment analysis.

Methods

Based on the manual Chalmers technique, we have developed a web application (in Personal Home Page language including JpGraph module and an Oracle database®) that enables the calculation of net oxyhaemoglobin absorbance and net bilirubin absorbance. It uses data from the CSF spectrophotometry, CSF and serum protein concentrations, and serum bilirubin concentration to provide an interpretation based on the NEQAS decision tree. The application was retrospectively validated using the spectra from 350 patients, previously analysed by the manual method.

Results

In total, 91.1% interpretations from spectra analysed with the web application were in accordance with the results obtained manually. The 8.9% discordant results were mostly related to an incorrect interpretation using the manual technique.

Conclusions

The software developed in our laboratory to interpret CSF pigment analysis results is a precise, robust and useful tool that allows reproducible conclusions to be drawn. This software is available through a web interface.
Successful reduction of clinical relevant neovascularization with a modified crossectomy combined with a barrier technique after 10-year follow-up
Authors: Schnyder S , Gabler S , Meier T O , Thalhammer C , Magnetti F , Spring S , Amann-Vesti B R
Published: February 2012

Objective

The aim of this retrospective study was to assess the long-term results of stripping the insufficient great saphenous vein (GSV) with stump coagulation, closure of the cribriform fascia and some additional measures, which will be described in detail.

Methods

Patients treated from 1998 to 1999 for varicose veins had been invited in 2009 for follow-up colour-coded duplex sonography and had been asked to answer a quality-of-life questionnaire. In 2009, the examinations for the study were conducted at a clinic of angiology by an independent and experienced sonographer.

Results

From a total of 165 patients, 91 (136 limbs) had been willing to participate in the study. Duplex ultrasound after a mean follow-up of 10.7 years revealed only clinically non-relevant (Ø < 0.3 cm) neovascularizations in 1.5% of all treated legs. No clinical relevant varicosities from the groin had developed.

Conclusion

The crossectomy combined with stump coagulation and suture of the fossa ovalis, completed with some additional measures, is a successful method to reduce neovascularization and recurrent varicosities, even for redo-crossectomies, without increasing the risk of perioperative complications.
Operational Compliance Levers, Environmental Performance, and Firm Performance Under Cap and Trade Regulation
Authors: Kroes James , Subramanian Ravi , Subramanyam Ramanath
Published: February 2012

Cap and trade programs impose limits on industry emissions but offer individual firms the flexibility to choose among different operational levers toward compliance, including inputs, process changes, and the use of allowances to account for emissions. In this paper, we examine the relationships among (1) levers for compliance (at-source pollution prevention, end-of-pipe pollution control, and the use of allowances); (2) environmental performance; and (3) firm market performance for the context of stringent cap and trade regulation with allowance grandfathering (i.e., the allocation of allowances for free). To investigate these relationships, we use data on publicly traded utility firms operating coal-fired generating units regulated by the U.S. Acid Rain Program from three principal sources: the U.S. Energy Information Administration, the U.S. Environmental Protection Agency, and the Compustat database. Our results indicate a significant relationship between better environmental performance and lower firm market performance over at least a three-year period. From a regulatory perspective, our results show a negative association between allowance grandfathering and firm environmental performance. Overall, by explicitly considering the context of stringent regulation, we find a counter-example to the view that better environmental performance generally associates with better economic performance.