bluuebunny/crossref_metadata_2025 huggingface dataset:
Drawing w/Digits_Painting w/Pixels: Selected Artworks of the Gesture over 50 Years
Authors: Nappi Maureen
Published: January 2013

This paper selectively traces the art history of the gesture in drawing and painting with electronic painting systems/programs. Beginning with Ivan Sutherland's Sketchpad (1963), which mechanized the hand gesture via light pen; Richard Shoup's SuperPaint system (1973), with the Summagraphics tablet and stylus; the Quantel Paintbox (1983); and the Macintosh (1984), the author concludes with a review of contemporary finger painting via capacitive touchscreens in the iPhone and iPad. A selection of nine classically trained visual artists who have sought to expand their work by creating art via the computer while heuristically inventing unique ways of working reveals the genesis of a hybrid vocabulary for the visual arts.
Can you enhance executive control without glucose? The effects of fructose on problem solving
Authors: Miller Holly C , Bourrasseau Camille , Blampain Justine
Published: January 2013

The consumption of glucose can enhance executive control by increasing blood glucose and providing energy for brain processes. However, a glucose mouth rinse also positively affects executive control in the absence of an effect on blood glucose. This observation suggests that glucose can enhance executive control via another mechanism, perhaps by increasing cortical activation in motivational reward pathways. This hypothesis was examined in the current study by having participants consume fructose, glucose or a placebo 10 minutes before solving word anagrams. Fructose was used because it does not affect blood glucose levels, inhibits cortical responding, and cannot entrain a taste preference post-ingestion. The latter evidences that fructose differs from glucose in its ability to elicit activation in motivational reward pathways. It was observed that consuming fructose and glucose resulted in the resolution of more anagrams than the placebo. These results suggest that at least some of the effects of glucose and fructose on problem solving operate through a common peripheral mechanism that is independent of motivational reward pathways.
Community-Based Conservation, Income Governance, and Poverty Alleviation in Tanzania
Authors: Mwakaje Agnes G. , Manyasa Emmanuel , Wawire Nelson , Muchai Muchane , Ongare David , Mugoya Charles , Masiga Clet Wandui , Nikundiwe Alfeo
Published: January 2013

Protected areas occupy about 27% of Tanzania’s land of 945,000 sq km and contribute 17.5% of its GDP. But who benefits from and pays for the cost of conservation? This study provides insights into these issues based on a survey conducted in the Serengeti ecosystem, involving 20 villages in Serengeti and Loliondo. The results show that villagers received insignificant benefits from conservation compared with the costs they are incurring. Governance of income at the village level was also a major challenge. There was a lack of capacity to handle large amounts of money and little or no planning, transparency, and accountability. It is recommended that income allocation to the communities is increased and external audits of village funds are conducted. Communities should furthermore be allowed to extract resources sustainably in protected areas. Youth should be encouraged to attend higher education and wildlife technical colleges to learn about the values of wildlife. Finally, the governance structures must be improved to make them gender equitable, participatory, transparent, and fully accountable to the communities and all citizens.
Effects of Statins on Serum n-3 to n-6 Polyunsaturated Fatty Acid Ratios in Patients With Coronary Artery Disease
Authors: Nozue Tsuyoshi , Yamamoto Shingo , Tohyama Shinichi , Fukui Kazuki , Umezawa Shigeo , Onishi Yuko , Kunishima Tomoyuki , Sato Akira , Nozato Toshihiro , Miyake Shogo , Takeyama Youichi , Morino Yoshihiro , Yamauchi Takao , Muramatsu Toshiya , Hibi Kiyoshi , Michishita Ichiro
Published: January 2013

Background:

A low n-3 to n-6 polyunsaturated fatty acids (PUFAs) ratio is reported to be associated with cardiovascular events. However, the effects of statins on this ratio have not been fully examined.

Methods:

A total of 101 patients with coronary artery disease, who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of pravastatin. Serum PUFA levels were measured at baseline and 8 months after treatment with statins.

Results:

Pitavastatin was used to treat 51 patients and the remaining 50 patients were treated using pravastatin. A significant positive correlation was observed between the percent change in low-density lipoprotein cholesterol and that in dihomogamma-linolenic acid ( r = .376, P = .007), arachidonic acid (AA; r = .316, P = .02), eicosapentaenoic acid (EPA; r = .408, P = .003), or docosahexaenoic acid (DHA; r = .270, P = .056) in the pitavastatin group. However, these correlations were not observed in the pravastatin group. The DHA/AA ratio decreased significantly in the pitavastatin group only (from 0.96 to 0.83, P = .0002) and the DHA/AA ratio was significantly lower in the pitavastatin group at 8 months (0.83 vs 0.96, P = .03). The EPA/AA ratio did not show significant changes in either group.

Conclusions:

Pitavastatin decreased the serum DHA/AA ratio, whereas pravastatin had no effect on this ratio. Neither pitavastatin nor pravastatin had an effect on the serum EPA/AA ratio in patients with coronary artery disease.
Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part I
Authors: Voss Joachim G. , Dobra Adrian , Morse Caryn , Kovacs Joseph A. , Danner Robert L. , Munson Peter J. , Logan Carolea , Rangel Zoila , Adelsberger Joseph W. , McLaughlin Mary , Adams Larry D. , Raju Raghavan , Dalakas Marinos C.
Published: January 2013

Purpose:

Human immunodeficiency virus (HIV)–related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs).

Methodology:

The authors compared gene expression profiles of CD14+ cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls ( n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved.

Relevance for nursing practice:

Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14+ cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients.

Implication for Practice:

The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction.
A proper wife, a proper marriage: Constructions of ‘us’ and ‘them’ in Dutch family migration policy
Authors: Bonjour Saskia , de Hart Betty
Published: January 2013

Migration policy is a product and producer of identities and values. This article argues that discourses and policies on family reunification participate in the politics of belonging, and that gender and family norms play a crucial role in this production of collective identities, i.e. in defining who ‘we’ are and what distinguishes ‘us’ from ‘the others’. Tracing the development of political debates and policy-making about ‘fraudulent’ and ‘forced’ marriages in the Netherlands since the 1970s, the authors examine how categories of gender and ethnicity interact with ‘other’ transnational marriages and the women who engage in them. These practices of ‘othering’ legitimize restrictive reforms of marriage migration policies. Also, and no less importantly, they serve the symbolic function of defining Dutch identity, and show that the government protects this identity.
Cruising through liquid modernity
Authors: Vogel Michael P , Oschmann Cristina
Published: January 2013

In this article, we try to make sense of the history of leisure cruising and of recent cruise product and marketing developments by interpreting them in the light of Zygmunt Bauman’s concepts of solid and liquid modernity. Our aim is to understand the influence of liquid modernity on the co-evolution of cruise demand and supply. We suggest that liquid modernity was a precondition for the cruise sector to grow out of its tiny elitist niche and to become the global business it is today, and that cruise tourism is a manifestation of liquid modernity.
The formal support experiences of family carers of people with an intellectual disability who also display challenging behaviour and/or mental health issues
Authors: James Neil
Published: January 2013

This article reports the findings of a literature review of research that has explored the support experiences of family carers of a person with an intellectual disability who displays challenging behaviour and/or has a mental health problem. The purpose of this review is to provide an overview of the reported experiences of family carers from recent research studies, about their own support. Having discussed the search strategy, definitions of challenging behaviour and mental health/illness are presented. Evidence concerning the needs of carers and the extent to which they are met is explored, and the need for consistency and good communication are highlighted. Conclusions are drawn and recommendations made for the development of future research and practice.
Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice
Authors: Llor Carl , Bjerrum Lars , Munck Anders , Hansen Malene P. , Córdoba Gloria Cristina , Strandberg Eva Lena , Ovhed Ingvar , Radzeviciene Ruta , Cots Josep M. , Reutskiy Anatoliy , Caballero Lidia
Published: January 2013

Background:

The aim of this study was to describe the antibiotic prescribing rate in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to analyse predictors for antibiotic prescribing and to explore the influence of the use C-reactive protein (CRP) rapid test.

Methods:

A cross-sectional study was carried out in January and February 2008 in primary care. General practitioners (GPs) from six countries (Denmark, Sweden, Lithuania, Russia, Spain and Argentina) registered all patients with AECOPD during a 3-week period. A multilevel logistic regression model was estimated using two hierarchical levels, (i) patients and (ii) physicians, and was used to analyse the association between antibiotic prescribing and potential predictors for antibiotic use: patients’ age and gender, duration and symptoms and signs of exacerbations (fever, cough, dyspnoea, sputum volume and purulence) and the results of the CRP test.

Results:

A total of 617 GPs registered 1233 patients with AECOPD. A total of 970 patients (79%) were prescribed antibiotics, varying from 49% (Denmark) to 93% (Russia). The presence of purulent sputum was the strongest predictor for antibiotic treatment (odds ratio [OR] 8.7; 95% confidence interval [CI] 5.9–12.8). CRP determination was carried out mainly in Denmark and Sweden and its use was the strongest protective factor for antibiotic therapy (OR 0.3; 95% CI 0.2-0.6). GPs that used CRP testing weighted purulent sputum lower than GPs who did not use CRP testing. CRP values had a strong influence on the antibiotic prescribing rate.

Conclusions:

Antibiotic treatment for AECOPD is very high. This study shows that GPs performing CRP rapid tests prescribe fewer antibiotics than those who do not.
Family Medicine Patients Who Use Retail Clinics Have Lower Continuity of Care
Authors: Rohrer James E. , Angstman Kurt B. , Garrison Gregory M. , Maxson Julie A. , Furst Joseph W.
Published: January 2013

Purpose: The purpose of this study was to compare continuity of care for family medicine patients using retail medicine clinics to continuity for patients not using retail clinics. Retail medicine clinics have become popular in some markets. However, their impact on continuity of care has not been studied. Methods: Electronic medical records of adult primary care patients seen in a large group practice in Minnesota in 2011 were analyzed for this study. Two randomly chosen groups of patients were selected (N = 400): those using 1 of 3 retail walk-in clinics staffed by nurse practitioners in addition to standard office care and a comparison group that only used standard office care. Continuity was measured as the percentage of visits that involved the primary care provider. We also compared patients who made zero visits to their primary care providers with those who made some visits to their primary care providers. Results: Continuity of care was lower for patients who used retail clinics than for patients who did not use retail clinics (0.17 vs 0.44, mean difference 0.27). The percentage of patients who made zero visits to their primary care providers was 54.5 for users of retail clinics versus 31.0 for those who did not use retail clinics. Conclusions: Continuity of care should be monitored as retail medicine continues to expand.
The Impact of Repeated Lying on Survey Results
Authors: Chesney Thomas , Penny Kay
Published: January 2013

We study the effects on results of participants completing a survey more than once, a phenomenon known as farming. Using data from a real social science study as a baseline, three strategies that participants might use to farm are studied by Monte Carlo simulation. Findings show that farming influences survey results and can cause both statistical hypotheses testing Type I (false positive) and Type II (false negative) errors in unpredictable ways.
Pharmacological inhibition of VIP signaling enhances antiviral immunity and improves survival in murine cytomegalovirus-infected allogeneic bone marrow transplant recipients
Authors: Li Jian-Ming , Hossain Mohammad S. , Southerland Lauren , Waller Edmund K.
Published: January 2013

Key Points

A small-molecule peptide inhibitor of VIP-signaling protected murine allo-BMT recipients from lethal mCMV infection without increasing GvHD. Treatment with the VIP inhibitor reduced viral loads, increased antigen-specific T-cells, and decreased PD-1 expression.
Comprehensive structural annotation of Pichia pastoris transcriptome and the response to various carbon sources using deep paired-end RNA sequencing
Authors: Liang Shuli , Wang Bin , Pan Li , Ye Yanrui , He Minghui , Han Shuangyan , Zheng Suiping , Wang Xiaoning , Lin Ying
Published: January 2013

Background

The methylotrophic yeast Pichia pastoris is widely used as a bioengineering platform for producing industrial and biopharmaceutical proteins, studying protein expression and secretion mechanisms, and analyzing metabolite synthesis and peroxisome biogenesis. With the development of DNA microarray and mRNA sequence technology, the P. pastoris transcriptome has become a research hotspot due to its powerful capability to identify the transcript structures and gain insights into the transcriptional regulation model of cells under protein production conditions. The study of the P. pastoris transcriptome helps to annotate the P. pastoris transcript structures and provide useful information for further improvement of the production of recombinant proteins.

Results

We used a massively parallel mRNA sequencing platform (RNA-Seq), based on next-generation sequencing technology, to map and quantify the dynamic transcriptome of P. pastoris at the genome scale under growth conditions with glycerol and methanol as substrates. The results describe the transcription landscape at the whole-genome level and provide annotated transcript structures, including untranslated regions (UTRs), alternative splicing (AS) events, novel transcripts, new exons, alternative upstream initiation codons (uATGs), and upstream open reading frames (uORFs). Internal ribosome entry sites (IRESes) were first identified within the UTRs of genes from P. pastoris, encoding kinases and the proteins involved in the control of growth. We also provide a transcriptional regulation model for P. pastoris grown on different carbon sources.

Conclusions

We suggest that the IRES-dependent translation initiation mechanism also exists in P. pastoris. Retained introns (RIs) are determined as the main AS event and are produced predominantly by an intron definition (ID) mechanism. Our results describe the metabolic characteristics of P. pastoris with heterologous protein production under methanol induction and provide rich information for further in-depth studies of P. pastoris protein expression and secretion mechanisms.
Hemiarthroplasties in young patients with osteonecrosis or a tumour of the proximal femur; an observational cohort study
Authors: van Egmond Pim W , Taminiau Antonie HM , van der Heide Huub JL
Published: January 2013

Background

The failure scenario in total hip arthroplasty (THA), in younger patients, is dependent on the fixation and wear of the acetabular component. In selected cases, where endoprosthetic replacement of the femoral head is unavoidable for limb salvage or functional recovery, hemiarthroplasty can be chosen as an alternative. The purpose of this study is to evaluate hemiarthroplasty as treatment strategy for young patients with osteonecrosis or a tumour of the proximal femur.

Methods

Between 1985 and 2008, 42 hemiarthroplasties (unipolar and bipolar) were performed in patients younger than 65 years with osteonecrosis (n=13) or a tumour of the proximal femur (n=29). All patients were seen at yearly follow-up examination and evaluated. Revision or conversion to a THA was regarded as a failure of the implant. A Kaplan Meier analysis was performed. To determine significant differences between categorical groups, the Pearson chi-square test was used. In numerical groups the independent T-test and One-way ANOVA were used.

Results

After a mean follow-up of 7.1 years, failure of the hemiarthroplasty occurred 6 times. The Kaplan Meier survival analysis with conversion to THA or revision as endpoint of the bipolar hemiarthroplasties (n=38) shows a 96% survival at 15, and 60% at 20 years. In the unipolar type (n=4) we found a conversion rate of 50% within 3 years.

Conclusions

Bipolar hemiarthroplasty is a reasonable alternative in a young patient with osteonecrosis or a tumour of the proximal femur as indication. Because of the high conversion rate after unipolar hemiarthroplasties, we would not recommend this type of prosthesis in the young patient.
Health service quality scale: Brazilian Portuguese translation, reliability and validity
Authors: Rocha Luiz Roberto Martins , Veiga Daniela Francescato , e Oliveira Paulo Rocha , Song Elaine Horibe , Ferreira Lydia Masako
Published: January 2013

Background

The Health Service Quality Scale is a multidimensional hierarchical scale that is based on interdisciplinary approach. This instrument was specifically created for measuring health service quality based on marketing and health care concepts. The aim of this study was to translate and culturally adapt the Health Service Quality Scale into Brazilian Portuguese and to assess the validity and reliability of the Brazilian Portuguese version of the instrument.

Methods

We conducted a cross-sectional, observational study, with public health system patients in a Brazilian university hospital. Validity was assessed using Pearson’s correlation coefficient to measure the strength of the association between the Brazilian Portuguese version of the instrument and the SERVQUAL scale. Internal consistency was evaluated using Cronbach’s alpha coefficient; the intraclass (ICC) and Pearson’s correlation coefficients were used for test-retest reliability.

Results

One hundred and sixteen consecutive postoperative patients completed the questionnaire. Pearson’s correlation coefficient for validity was 0.20. Cronbach's alpha for the first and second administrations of the final version of the instrument were 0.982 and 0.986, respectively. For test-retest reliability, Pearson’s correlation coefficient was 0.89 and ICC was 0.90.

Conclusions

The culturally adapted, Brazilian Portuguese version of the Health Service Quality Scale is a valid and reliable instrument to measure health service quality.
Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data
Authors: Emmert-Streib Frank , Abogunrin Funso , de Matos Simoes Ricardo , Duggan Brian , Ruddock Mark W , Reid Cherith N , Roddy Owen , White Lisa , O'Kane Hugh F , O'Rourke Declan , Anderson Neil H , Nambirajan Thiagarajan , Williamson Kate E
Published: January 2013

Background

Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods

On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results

Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with 'low cancer-risk' characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring 'high cancer-risk" characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest 'high cancer- risk' cluster were different than those contributing to the classifiers for the 'low cancer-risk' clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions

The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs.
Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits
Authors: Wang Jian Ben , Zhu Yali , McVoy Michael A , Parris Deborah S
Published: January 2013

Background

During herpesvirus replication, terminase packages viral DNA into capsids. The subunits of herpes simplex virus terminase, UL15, UL28, and UL33, assemble in the cytoplasm prior to nuclear import of the complex.

Methods

To detect similar interactions between human cytomegalovirus terminase subunits, the orthologous proteins UL89, UL56, and UL51 were expressed in HEK-293 T cells (via transfection) or insect cells (via baculovirus infection) and subcellular localizations were detected by cellular fractionation and confocal microscopy.

Results

In both cell types, UL56 and UL89 expressed alone were exclusively cytoplasmic, whereas UL51 was ~50% nuclear. Both UL89 and UL56 became ~50% nuclear when expressed together, as did UL56 when expressed with UL51. Nuclear localization of each protein was greatest when all three proteins were co-expressed.

Conclusions

These results support inclusion of UL51 as an HCMV terminase subunit and suggest that nuclear import of human cytomegalovirus terminase may involve nuclear import signals that form cooperatively upon subunit associations.
An unusual case of giant cell myocarditis missed in a Heartmate-2 left ventricle apical-wedge section: a case report and review of the literature
Authors: Anderson Kim , Carrier Michel , Romeo Philippe , Pelletier Guy B , Liszkowski Mark , Racine Normand , White Michel , Ducharme Anique
Published: January 2013

Herein we present a case of fulminant myocarditis in a woman previously treated for B-cell lymphoma. While the clinical context was suggestive of adriamycin-induced cardiomyopathy, the initial pathology of the Heartmate-2 apical core showed lymphocytic myocarditis. After 8 months of stability, the patient presented with progressive heart failure and recurrent ventricular arrhythmias. An endomyocardial biopsy revealed findings typical of giant cell myocarditis (GCM); poor response to immunosuppressive therapy and marked hemodynamic instability led to urgent transplantation. To our knowledge, this is the first reported case of GCM following an acute lymphocytic myocarditis and the second GCM case associated with B-cell lymphoma.
Fatty acid composition of lipids in pot marigold (Calendula officinalisL.) seed genotypes
Authors: Dulf Francisc V , Pamfil Doru , Baciu Adriana D , Pintea Adela
Published: January 2013

Background

Calendula officinalis L. (pot marigold) is an annual aromatic herb with yellow or golden-orange flowers, native to the Mediterranean climate areas. Their seeds contain significant amounts of oil (around 20%), of which about 60% is calendic acid. For these reasons, in Europe concentrated research efforts have been directed towards the development of pot marigold as an oilseed crop for industrial purposes.

Results

The oil content and fatty acid composition of major lipid fractions in seeds from eleven genotypes of pot marigold (Calendula officinalis L.) were determined. The lipid content of seeds varied between 13.6 and 21.7 g oil/100 g seeds. The calendic and linoleic acids were the two dominant fatty acids in total lipid (51.4 to 57.6% and 28.5 to 31.9%) and triacylglycerol (45.7 to 54.7% and 22.6 to 29.2%) fractions. Polar lipids were also characterised by higher unsaturation ratios (with the PUFAs content between 60.4 and 66.4%), while saturates (consisted mainly of palmitic and very long-chain saturated fatty acids) were found in higher amounts in sterol esters (ranging between 49.3 and 55.7% of total fatty acids).

Conclusions

All the pot marigold seed oils investigated contain high levels of calendic acid (more than 50% of total fatty acids), making them favorable for industrial use. The compositional differences between the genotypes should be considered when breeding and exploiting the pot marigold seeds for nutraceutical and pharmacological purposes.
c-Abl tyrosine kinase plays a critical role in β2 integrin-dependent neutrophil migration by regulating Vav1 activity
Authors: Tong Haibin , Zhao Bin , Shi Huifang , Ba Xueqing , Wang Xiaoguang , Jiang Yong , Zeng Xianlu
Published: January 2013

A central regulatory role of c-Abl kinase in controlling actin polymerization and membrane protrusion dynamics at leading edge, during β2 integrin-dependent neutrophil migration.

The recruitment and migration of neutrophils are critical for innate immunity and acute inflammatory responses. However, the mechanism that regulates the recruitment and migration of neutrophils has not been well characterized. We here reveal a novel function of c-Abl kinase in regulating neutrophil migration. Our results demonstrate that c-Abl kinase is required for neutrophil recruitment in vivo and migration in vitro, and the inhibition of c-Abl kinase activity has a significant impact on neutrophil migratory behavior. Moreover, c-Abl kinase activation depends on β2 integrin engagement, and the activated c-Abl kinase further regulates actin polymerization and membrane protrusion dynamics at the extended leading edges during neutrophil migration. In addition, we identify the Rho GEF Vav1 as a major downstream effector of c-Abl kinase. The C-terminal SH3-SH2-SH3 domain and proline-rich region of Vav1 are required for its interaction with c-Abl kinase, and c-Abl kinase probably regulates the activity of Vav1 by direct phosphorylation at Tyr-267 in the DH domain. Together, these results indicate that c-Abl kinase plays a critical role in β2 integrin-dependent neutrophil migration by regulating Vav1 activity.
Nick Cave: Meet Me at the Center of the Earth
Authors: Erickson Peter
Published: January 2013

This article on Nick Cave’s exhibition Meet Me at the Center of the Earth locates the center in Cave’s first soundsuits, made in response to the beating of Rodney King by Los Angeles police in 1991. Cave makes a connection between King’s flattened body on the ground and twigs that Cave found on the ground while sitting, emotionally deflated, on a park bench, twigs out of which he created protective suits that enable the artist to stand up and regain control. Overall, the power of this art expands the initial motion from prostration to gorgeous displays of newly clad bodies in standing position and moves outward into the cross-media trajectory of free-flowing, freewheeling gestures associated with the fluid mobility of dance.
Contested Terrains
Authors: Hynes NJ
Published: January 2013

This review examines Contested Terrains, an innovative show that presents the work of four “emerging” artists: Adolphus Opara, Michael MacGarry, Kader Attia, and Sammy Baloji. The exhibition plays with our notions of past and present, fracturing our sense of the contemporary and shattering any residual myth of Africa as a timeless continent. It is significant not only for its focus and framing but also for the institutional shift it represents. The show, cocurated by the Tate Modern in London and the Centre for Contemporary Arts in Lagos, was conceived as a joint exhibition that would travel to both venues.
Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme
Authors: Terriente-Felix Ana , Li Jinghua , Collins Stephanie , Mulligan Amy , Reekie Ian , Bernard Fred , Krejci Alena , Bray Sarah
Published: January 2013

The diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch. Functional studies of targets, such as klumpfuss (ERG/WT1 family) and pebbled/hindsight (RREB1 homologue), show that Notch acts both to prevent the cells adopting alternate cell fates and to promote morphological characteristics associated with crystal cell differentiation. Inappropriate activity of Klumpfuss perturbs the differentiation programme, resulting in melanotic tumours. Thus, by acting as a master regulator, Lz directs Notch to activate selectively a combination of target genes that correctly locks cells into the differentiation programme.
Axon tracts guide zebrafish facial branchiomotor neuron migration through the hindbrain
Authors: Wanner Sarah J. , Prince Victoria E.
Published: January 2013

Appropriate localization of neurons within the brain is a crucial component of the establishment of neural circuitry. In the zebrafish hindbrain, the facial branchiomotor neurons (FBMNs) undergo a chain-like tangential migration from their birthplace in rhombomere (r) 4 to their final destination in r6/r7. Here, we report that ablation of either the cell body or the trailing axon of the leading FBMN, or ‘pioneer’ neuron, blocks the migration of follower FBMNs into r5. This demonstrates that the pioneer neuron and its axon are crucial to the early migration of FBMNs. Later migration from r5 to r6 is not dependent on pioneer neurons but on the medial longitudinal fasciculus (MLF), a bundle of axons lying ventral to the FBMNs. We find that MLF axons enter r5 only after the pioneer neuron has led several followers into this region; the MLF is then contacted by projections from the FBMNs. The interactions between FBMNs and the MLF are important for migration from r5 to r6, as blocking MLF axons from entering the hindbrain can stall FBMN migration in r5. Finally, we have found that the adhesion molecule Cdh2 (N-cadherin) is important for interactions between the MLF and FBMNs, as well as for interactions between the trailing axon of the pioneer neuron and follower FBMNs. Interestingly, migration of pioneer neurons is independent of both the MLF and Cdh2, suggesting pioneer migration relies on independent cues.
Inducible mouse models illuminate parameters influencing epigenetic inheritance
Authors: Wan Mimi , Gu Honggang , Wang Jingxue , Huang Haichang , Zhao Jiugang , Kaundal Ravinder K. , Yu Ming , Kushwaha Ritu , Chaiyachati Barbara H. , Deerhake Elizabeth , Chi Tian
Published: January 2013

Environmental factors can stably perturb the epigenome of exposed individuals and even that of their offspring, but the pleiotropic effects of these factors have posed a challenge for understanding the determinants of mitotic or transgenerational inheritance of the epigenetic perturbation. To tackle this problem, we manipulated the epigenetic states of various target genes using a tetracycline-dependent transcription factor. Remarkably, transient manipulation at appropriate times during embryogenesis led to aberrant epigenetic modifications in the ensuing adults regardless of the modification patterns, target gene sequences or locations, and despite lineage-specific epigenetic programming that could reverse the epigenetic perturbation, thus revealing extraordinary malleability of the fetal epigenome, which has implications for ‘metastable epialleles’. However, strong transgenerational inheritance of these perturbations was observed only at transgenes integrated at the Col1a1 locus, where both activating and repressive chromatin modifications were heritable for multiple generations; such a locus is unprecedented. Thus, in our inducible animal models, mitotic inheritance of epigenetic perturbation seems critically dependent on the timing of the perturbation, whereas transgenerational inheritance additionally depends on the location of the perturbation. In contrast, other parameters examined, particularly the chromatin modification pattern and DNA sequence, appear irrelevant.
Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration
Authors: Pan Fong Cheng , Bankaitis Eric D. , Boyer Daniel , Xu Xiaobo , Van de Casteele Mark , Magnuson Mark A. , Heimberg Harry , Wright Christopher V. E.
Published: January 2013

Pancreatic multipotent progenitor cells (MPCs) produce acinar, endocrine and duct cells during organogenesis, but their existence and location in the mature organ remain contentious. We used inducible lineage-tracing from the MPC-instructive gene Ptf1a to define systematically in mice the switch of Ptf1a+ MPCs to unipotent proacinar competence during the secondary transition, their rapid decline during organogenesis, and absence from the mature organ. Between E11.5 and E15.5, we describe tip epithelium heterogeneity, suggesting that putative Ptf1a+Sox9+Hnf1β+ MPCs are intermingled with Ptf1aHISox9LO proacinar progenitors. In the adult, pancreatic duct ligation (PDL) caused facultative reactivation of multipotency factors (Sox9 and Hnf1β) in Ptf1a+ acini, which undergo rapid reprogramming to duct cells and longer-term reprogramming to endocrine cells, including insulin+ β-cells that are mature by the criteria of producing Pdx1HI, Nkx6.1+ and MafA+. These Ptf1a lineage-derived endocrine/β-cells are likely formed via Ck19+/Hnf1β+/Sox9+ ductal and Ngn3+ endocrine progenitor intermediates. Acinar to endocrine/β-cell transdifferentiation was enhanced by combining PDL with pharmacological elimination of pre-existing β-cells. Thus, we show that acinar cells, without exogenously introduced factors, can regain aspects of embryonic multipotentiality under injury, and convert into mature β-cells.
Aspirin for the Prophylaxis of Venous Thromboembolic Events in Orthopedic Surgery Patients: A Comparison of the AAOS and ACCP Guidelines with Review of the Evidence
Authors: Stewart David W , Freshour Jessica E
Published: January 2013

BACKGROUND

The American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) have both developed evidence-based guidelines to prevent venous thromboembolism (VTE) in high-risk orthopedic surgery patients. Recent changes to these documents have brought them into agreement as to the inclusion of aspirin as an appropriate option for VTE prophylaxis in this patient population.

OBJECTIVE

To evaluate the appropriateness of aspirin to prevent VTE in high-risk orthopedic surgery patients.

DATA SOURCES

Guidelines published by the AAOS in 2011 and the ACCP in 2012 were compared regarding their recommendations on the use of aspirin for the prevention of VTE. A literature search was also conducted to identify clinical trials that evaluated the use of aspirin for the prevention of VTE in this patient population. Search terms included the MeSH terms venous thromboembolism; venous thrombosis; pulmonary embolism; aspirin; arthroplasty, replacement, knee; arthroplasty, replacement, hip; and hip fractures/surgery.

STUDY SELECTION AND DATA EXTRACTION

Any study that evaluated aspirin, even in combination with another method of prophylaxis (such as pneumatic compression devices), and had been published during or after 1985 was included.

DATA SYNTHESIS

Randomized controlled trials, meta-analyses, and other large pooled and retrospective reviews have failed to consistently arrive at similar conclusions regarding the efficacy and safety of aspirin as an option for VTE prophylaxis in patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or hip fracture surgery (HFS). Disagreements in the appropriateness of surrogate markers for safety and efficacy have resulted in differing recommendations from the ACCP and AAOS. The primary argument lies in the appropriateness of deep vein thrombosis as a surrogate marker for more serious outcomes such as pulmonary emboli.

CONCLUSIONS

Recent changes to both the ACCP and AAOS guidelines are in agreement for those who choose to use aspirin for chemoprophylaxis of VTE. Current surgical care improvement project measures do not include aspirin as an appropriate sole option for the prevention of VTE, but in patients undergoing elective TKA or who have a contraindication to pharmacologic prophylaxis and undergo a THA or HFS, aspirin in conjunction with compression devices as part of a multimodal approach would meet these measures. Data do not support the hypothesis that aspirin is less likely to cause adverse bleeding events than more potent anticoagulants.
National Utilization Patterns of Warfarin Use in Older Patients with Atrial Fibrillation: A Population-Based Study of Medicare Part D Beneficiaries
Authors: Raji Mukaila A , Lowery Matthew , Lin Yu-Li , Kuo Yong-Fang , Baillargeon Jacques , Goodwin James S
Published: January 2013

BACKGROUND

Although warfarin therapy reduces stroke incidence in patients with atrial fibrillation (AF), the rate of warfarin use in this population remains low. In 2008, the Medicare Part D program was expanded to pay for medications for Medicare enrollees.

OBJECTIVE

To examine rates and predictors of warfarin use in Medicare Part D beneficiaries with AF.

METHODS

This population-based retrospective cohort study used claims data from 41,447 Medicare beneficiaries aged 66 and older with at least 2 AF diagnoses in 2007 and at least 1 diagnosis in 2008. All subjects had continuous Medicare Part D prescription coverage in 2008. Statistical analysis using χ2 was used to examine differences in warfarin use by patient characteristics (age, ethnicity, sex, Medicaid eligibility, comorbidities, contraindications to warfarin, and whether they visited a cardiologist or a primary care physician [PCP]), CHADS2 score (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack; higher scores indicate higher risks of stroke), and geographic regions. Using hierarchical generalized linear models restricted to subjects without warfarin contraindications (n = 34,947), we examined the effect of patient characteristics and geographic regions on warfarin use.

RESULTS

The overall warfarin use rate was 66.8%. The warfarin use rates varied between hospital referral regions, with highest rates in the Midwestern states and lowest rates in the South. The regional variation persisted even after adjustment for patient characteristics. Multivariable analysis showed that the odds of being on warfarin decreased significantly with age and increasing comorbidity, in blacks, and among those with low income. Seeing a cardiologist (OR 1.10; 95% CI 1.05–1.16), having a PCP (OR 1.23; 95% CI 1.17–1.29), and CHADS2 score of 2 or greater (OR 1.09; 95% CI 1.01–1.17) were associated with increased odds of warfarin use.

CONCLUSIONS

Warfarin use rates vary by patient characteristics and region, with higher rates among residents of the Midwest and among patients seen by cardiologists and PCPs. Preventing stroke-related disability in AF requires implementation of evidence-based initiatives to increase warfarin use.
A Computational Approach to Detect Gap Junction Plaques and Associate Them with Cells in Fluorescent Images
Authors: Goldberg Joshua S. , Vadakkan Tegy J. , Hirschi Karen K. , Dickinson Mary E.
Published: January 2013

Intercellular signaling is a fundamental requirement for complex biological system function and survival. Communication between adjoining cells is largely achieved via gap junction channels made up of multiple subunits of connexin proteins, each with unique selectivity and regulatory properties. Intercellular communication via gap junction channels facilitates transmission of an array of cellular signals, including ions, macromolecules, and metabolites that coordinate physiological processes throughout tissues and entire organisms. Although current methods used to quantify connexin expression rely on number or area density measurements in a field of view, they lack cellular assignment, distance measurement capabilities (both within the cell and to extracellular structures), and complete automation. We devised an automated computational approach built on a contour expansion algorithm platform that allows connexin protein detection and assignment to specific cells within complex tissues. In addition, parallel implementation of the contour expansion algorithm allows for high-throughput analysis as the complexity of the biological sample increases. This method does not depend specifically on connexin identification and can be applied more widely to the analysis of numerous immunocytochemical markers as well as to identify particles within tissues such as nanoparticles, gene delivery vehicles, or even cellular fragments such as exosomes or microparticles.
The modern miniature camera objective: an evolutionary design path from the landscape lens
Authors: Bates Rob
Published: January 2013

The modern miniature camera lens is the most prolific design manufactured today, yet its design form and origins are often not well understood. This paper illuminates the ancestry of the modern miniature camera lens by developing the lens form from ‘scratch.’ Starting with the Wollaston meniscus of 1812, the lens is designed progressively, employing incremental design decisions aimed at correcting limiting aberrations at each step. The result demonstrates an ancestry that is distinctly different than that of the common large-format objective lenses.
Compliance in the single market
Authors: Egan Michelle , Guimarães Maria Helena
Published: January 2013

This article focuses on the barriers faced by firms due to non-compliance with European law. Although there is an extensive literature on non-compliance in the European Union, there has not been any systematic assessment of the barriers faced by firms in trying to market their products across different national boundaries. We draw on a comprehensive database of over 2000 cases of business complaints about regulatory and administrative barriers encountered in the single market. Our empirical findings survey the range and type of barriers that affect different industrial sectors, the variation in compliance with European law among member states, and the different solutions used to address business complaints about the functioning of the single market. The data shows that firms continue to face considerable challenges in operating the single market, and that there are still trade and growth dividends to be harnessed from addressing the remaining barriers to trade.
Chemical and enzymatic characterization of recombinant rabbit muscle pyruvate kinase
Authors: Boehme Christian , Bieber Frank , Linnemann Julia , Breitling Reinhard , Lorkowski Stefan , Reissmann Siegmund
Published: January 2013

The stepwise synthesis of thymidine triphosphate (TTP) requires a kinase for phosphorylation in the last step. Because pyruvate kinase (PK) using phosphoenolpyruvate (PEP) as substrate can regenerate adenosine triphosphate and phosphorylate thymidine diphosphate as well, we chose this enzyme for the synthesis of TTP via an enzymatic cascade reaction. The metalloenzyme PK shows pronounced promiscuity and therefore fits well to the conditions of this reaction. PK commonly used today is isolated from rabbit muscle. We cloned and expressed the respective open reading frame in Escherichia coli, purified, and characterized the His-tagged recombinant enzyme. The enzyme has an activity optimum at 37°C and in the pH range from 7.4 to 7.8. K

m
constants conformed well with the isolated native enzyme for adenosine diphosphate (ADP) to 0.37±0.02 mm and for PEP to 0.07±0.01 mm. The recombinant enzyme shows the following range in its substrate specificity: ADP>dADP>dGDP>dCDP>thymidine diphosphate (TDP). It allows the phosphorylation of TDP to TTP in high yield (up to 95%). The metal ions Mg2+ and K+ are necessary for full enzymatic activity. The addition of transition metal ions such as Mn2+, Cu2+, Co2+, and Ni2+ reduces activity. Storage of the enzyme at -20°C retains full activity.