bluuebunny/crossref_metadata_2025 huggingface dataset:
A spatial decision support tool for estimating population catchments to aid rural and remote health service allocation planning
Authors: Schuurman Nadine , Randall Ellen , Berube Myriam
Published: December 2011

There is mounting pressure on healthcare planners to manage and contain costs. In rural regions, there is a particular need to rationalize health service allocation to ensure the best possible coverage for a dispersed population. Rural health administrators need to be able to quantify the population affected by their allocation decisions and, therefore, need the capacity to incorporate spatial analyses into their decision-making process. Spatial decision support systems (SDSS) can provide this capability. In this article, we combine geographical information systems (GIS) with a web-based graphical user interface (webGUI) in a SDSS tool that enables rural decision-makers charged with service allocation, to estimate population catchments around specific health services in rural and remote areas. Using this tool, health-care planners can model multiple scenarios to determine the optimal location for health services, as well as the number of people served in each instance.
An empowerment-based approach to developing innovative e-health tools for self-management
Authors: Alpay Laurence , van der Boog Paul , Dumaij Adrie
Published: December 2011

E-health is seen as an important technological tool in achieving self-management; however, there is little evidence of how effective e-health is for self-management. Example tools remain experimental and there is limited knowledge yet about the design, use, and effects of this class of tools. By way of introducing a new view on the development of e-health tools dedicated to self-management we aim to contribute to the discussion for further research in this area. Our assumption is that patient empowerment is an important mechanism of e-health self-management and we suggest incorporating it within the development of self-management tools. Important components of empowerment selected from literature are: communication, education and health literacy, information, self-care, decision aids and contact with fellow patients. All components require skills of both patients and the physicians. In this discussion paper we propose how the required skills can be used to specify effective self-management tools.
Not 2 old 2 TXT: There is potential to use email and SMS text message healthcare reminders for rheumatology patients up to 65 years old
Authors: Hughes Lyndsay D , Done John , Young Adam
Published: December 2011

Short message service (SMS) and email reminders have the potential to improve adherence to appointments and medication taking. Within the UK, information and communication technology (ICT) is widely used with a very high proportion of people having access to the internet and mobile phones. Little is known about ICT use by older adults and those with chronic illness. A feasibility survey was carried out with 112 rheumatology patients in Hertfordshire, UK to determine their current use of the internet, email and SMS and their willingness to receive electronic reminders in the future. A high proportion of patients up to age 65 are successfully using ICT despite older age or functional disability caused by rheumatic disease. Forty-four percent would be willing to receive an electronic appointment reminder and 25% a medication reminder. The results suggest that reminders would be welcomed by some patients and extensive patient training would not be needed before implementation.
Emergency department triaging of admitted stroke patients—A Bayesian Network analysis
Authors: Nadathur Shyamala G , Warren James R
Published: December 2011

This study uses hospital administrative data to ascertain the differences in the patient characteristics, process and outcomes of care between the Emergency Department (ED) triage categories of patients admitted from an ED presentation into a large metropolitan teaching hospital with a Stroke Care Unit. Bayesian Networks (BNs) derived from the administrative data were used to provide the descriptive models. Nearly half the patients in each stroke subtype were triaged as ‘Urgent’ (to be seen within 30 minutes). With a decrease in the urgency of triage categories, the proportion admitted within 8 hours decreased dramatically and the proportion of formal discharge increased. Notably, 45% of transient ischaemic attacks (TIAs) were categorized as ‘Semi-urgent’ (to be attended within 60 minutes), indicating an opportunity to improve emergency assessment of TIAs. The results illustrate the utility of hospital administrative data and the applicability of BNs for review of the current triage practices and subsequent impact.
Jurisdictional protectionism in online news: Am erican journalists and their perceptions of hyperlinks
Authors: Chang Tsan-Kuo , Southwell Brian G. , Lee Hyung-Min , Hong Yejin
Published: December 2011

Because of their widespread use on the internet, hyperlinks have become a useful tool in information sharing and knowledge distribution in online communication, particularly in the realm of journalism. Their importance has received little scholarly attention, however. Against the backdrop of the sociology of professions, the purpose of this study is to determine how journalists approach hyperlinks and what they perceive to be their functions in online news. A national survey of newspaper editors and TV news directors in the United States shows that American journalists exhibit a sense of jurisdictional protectionism in online news. They appear to privilege US hyperlinks over foreign ones, especially internal links to their own websites. They are also predominantly against linking to foreign news media that cover the same events or issues. Financial consideration seems to be the main reason behind the journalistic preference.
Dead meat: Feeding at the anatomy table of Gunther von Hagens' Body Worlds
Authors: Deller Rosemary
Published: December 2011

Whether in the growing awareness of the origins of supermarket meat or the emergence of meat art, carnality appears to be something increasingly under question. Yet, despite meat carrying connotations that offer provocative connection with feminist concerns regarding the body, consumption and the cultural representation of women, meat consciousness has been only sporadically explored in existing feminist theory. Struck, however, by the comparisons between the dissected Body Worlds corpse and the filleted flesh of meat that are levelled most particularly at female bodies on display, I examine in my article the bodily relations constructed in the Body Worlds exhibition by positioning the Body Worlds cadaver as a grotesque ‘meaty’ body under the broader rubric of the Bakhtinian carnivalesque. Within such webs of alimentary exchange, pleats of meaty matter may bring about localised eruptions of traditional and bodily engagements – including that of the gendered gaze – that entwine the possibility of pleasure, wonder and fascination into each act of inter-bodily engagement. Through this entrance into the very bowels of Body Worlds, my article ultimately asks what, as a feminist, it means to become meat conscious.
The Z-Poisson distribution with application to the modelling of soccer score probabilities
Authors: Lillestøl Jostein , Andersson Jonas
Published: December 2011

This paper presents a non-standard multivariate Poisson-type distribution, here named as Z-Poisson distribution. Some details on the bivariate case are worked out in the context of modeling soccer (football) scores, and the distribution is fitted to score data from the top league in the 2007–08 season for 10 European countries.
Evaluating Life: Working with Ethical Dilemmas in Education for Sustainable Development
Authors: De Lucia Dahlbeck Moa , Dahlbeck Johan
Published: December 2011

Codifications of human rights are widely understood as politically established instruments for evaluating human life. The call for such an apparatus emerges as a response to the age-old problem of social organization, constituting – in extension – a means by which to cope with the overall problem of survival. However, evaluating life is inherently problematic. It is problematic as it presupposes an already existing framework by which to judge all instances of life. In a way then, the impartial evaluation of life seems impossible from a human point of view. Nevertheless, as the problem of survival is one of continuous relevance, attempts to formulate reasonable variables may be viewed as a necessary strategy for organizing a viable society. We aim at investigating the problem of codifying evaluations of life by looking at paradigmatic examples from the discourse of education for sustainable development, using a theoretical framework drawing on the ethics of Nietzsche and Deleuze in particular.
Clinical Outcomes of Characterized Chondrocyte Implantation
Authors: Vanlauwe Johan , Huylebroek José , Van Der Bauwhede Jan , Saris Daniël , Veeckman Geert , Bobic Vladimir , Victor Jan , Almqvist Karl Fredrik , Verdonk Peter , Fortems Yves , Van Lommel Nel , Haazen Ludo
Published: December 2011

Objective:

To assess the clinical outcome of patients treated with autologous chondrocyte implantation using ChondroCelect in daily practice.

Methods:

The study is a cross-sectional analysis of an open-label, noninterventional cohort. The setting was a compassionate use program, involving 43 orthopaedic centers in 7 European countries. The participants were patients treated with ChondroCelect between October 13, 2004 and July 2, 2008. The measurements used were Clinical Global Impression–Improvement and –Efficacy and solicited adverse event reports.

Results:

Safety data were collected from 334 patients (90.3%), and effectiveness data were from 282 (76.2%) of the 370 patients treated. Mean age at baseline was 33.6 years (range, 12-57 years), 57% were male, and mean body mass index was 25 kg/m2. Mean follow-up was 2.2 years (range, 0.4-4.1 years). A femoral condyle lesion was reported in 66% (288/379) and a patellar lesion in 19% (84/379). Mean lesion size was 3.5 cm2; a collagen membrane was used in 92.4% (328/355). A therapeutic effect was reported in 89% (234/264) of patients overall and in 87% (40/46) of patellar lesion patients. Rates of much or very much improved patients were similar in patients with short- (<18 months: 71% [115/163]) and long-term follow-up (>18 months: 68% [70/103]) ( P = 0.68) and were independent of lesion size (>4 cm2: 75.5% [37/49]; ≤4 cm2: 67.7% [111/164]) ( P = 0.38). Adverse events were similar to those reported in the randomized trial with the same product, with more arthrofibrosis, more reduced joint mobility, and more crepitations reported in patellar lesions. Overall, less cartilage hypertrophy was noted, probably due to the use of a biological membrane cover.

Conclusions:

Implantation of ChondroCelect appeared to result in a positive benefit/risk ratio when used in an unselected heterogenous population, irrespective of the follow-up period, lesion size, and type of lesion treated.
The Role of Transabdominal Sonography in Facilitating Successful Brachytherapy Outcomes in Cervical Cancer
Authors: Phelps Christina K. , Petereit Daniel G.
Published: December 2011

Radiation is a standard of care in the treatment of locally advanced cervical cancer. Radiation consists of external beam radiation and brachytherapy to optimize local control and cure. High-dose-rate (HDR) brachytherapy is most commonly used in the United States. Advantages of HDR are outpatient treatment, elimination of exposure to medical staff, patient convenience, and the ability to modify the treatment because multiple fractions are used. Accurate placement of the tandem in the uterus is critical to maximize tumor control and minimize complications. Transabdominal sonography offers real-time imaging of the tandem placement, which allows the radiation oncologist to adjust the tandem position, thus ensuring correct dosimetry and treatment. This article discusses the etiology, diagnosis, and treatment of cervical cancer. This article further explains the importance of the brachytherapy technique, the role of transabdominal sonography, and how both can lead to a successful outcome for the patient.
Some exponential inequalities for acceptable random variables and complete convergence
Authors: Shen Aiting , Hu Shuhe , Volodin Andrei , Wang Xuejun
Published: December 2011

Some exponential inequalities for a sequence of acceptable random variables are obtained, such as Bernstein-type inequality, Hoeffding-type inequality. The Bernstein-type inequality for acceptable random variables generalizes and improves the corresponding results presented by Yang for NA random variables and Wang et al. for NOD random variables. Using the exponential inequalities, we further study the complete convergence for acceptable random variables.

MSC(2000): 60E15, 60F15.
"Antelope": a hybrid-logic model checker for branching-time Boolean GRN analysis
Authors: Arellano Gustavo , Argil Julián , Azpeitia Eugenio , Benítez Mariana , Carrillo Miguel , Góngora Pedro , Rosenblueth David A , Alvarez-Buylla Elena R
Published: December 2011

Background

In Thomas' formalism for modeling gene regulatory networks (GRNs), branching time, where a state can have more than one possible future, plays a prominent role. By representing a certain degree of unpredictability, branching time can model several important phenomena, such as (a) asynchrony, (b) incompletely specified behavior, and (c) interaction with the environment. Introducing more than one possible future for a state, however, creates a difficulty for ordinary simulators, because infinitely many paths may appear, limiting ordinary simulators to statistical conclusions. Model checkers for branching time, by contrast, are able to prove properties in the presence of infinitely many paths.

Results

We have developed Antelope ("Analysis of Networks through TEmporal-LOgic sPEcifications", http://turing.iimas.unam.mx:8080/AntelopeWEB/), a model checker for analyzing and constructing Boolean GRNs. Currently, software systems for Boolean GRNs use branching time almost exclusively for asynchrony. Antelope, by contrast, also uses branching time for incompletely specified behavior and environment interaction. We show the usefulness of modeling these two phenomena in the development of a Boolean GRN of the Arabidopsis thaliana root stem cell niche.

There are two obstacles to a direct approach when applying model checking to Boolean GRN analysis. First, ordinary model checkers normally only verify whether or not a given set of model states has a given property. In comparison, a model checker for Boolean GRNs is preferable if it reports the set of states having a desired property. Second, for efficiency, the expressiveness of many model checkers is limited, resulting in the inability to express some interesting properties of Boolean GRNs.

Antelope tries to overcome these two drawbacks: Apart from reporting the set of all states having a given property, our model checker can express, at the expense of efficiency, some properties that ordinary model checkers (e.g., NuSMV) cannot. This additional expressiveness is achieved by employing a logic extending the standard Computation-Tree Logic (CTL) with hybrid-logic operators.

Conclusions

We illustrate the advantages of Antelope when (a) modeling incomplete networks and environment interaction, (b) exhibiting the set of all states having a given property, and (c) representing Boolean GRN properties with hybrid CTL.
H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast
Authors: Shieh Grace S , Pan Chin-Hua , Wu Jia-Hong , Sun Yun-Ju , Wang Chia-Chang , Hsiao Wei-Chun , Lin Chia-Yeh , Tung Luh , Chang Tien-Hsien , Fleming Alastair B , Hillyer Cory , Lo Yi-Chen , Berger Shelley L , Osley Mary Ann , Kao Cheng-Fu
Published: December 2011

Background

The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.

Results

Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality.

Conclusion

These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.
Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis
Authors: Guida Alessandro , Lindstädt Claudia , Maguire Sarah L , Ding Chen , Higgins Desmond G , Corton Nicola J , Berriman Matthew , Butler Geraldine
Published: December 2011

Background

Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored.

Results

We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5' and 3' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3' UTR of one gene. This is the first report of 3' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia.

Conclusion

We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor Upc2 role has a conserved role as a major regulator of the hypoxic response in C. parapsilosis and C. albicans.
FReDoWS: a method to automate molecular docking simulations with explicit receptor flexibility and snapshots selection
Authors: Machado Karina S , Schroeder Evelyn K , Ruiz Duncan D , Cohen Elisângela ML , Norberto de Souza Osmar
Published: December 2011

Background

In silico molecular docking is an essential step in modern drug discovery when driven by a well defined macromolecular target. Hence, the process is called structure-based or rational drug design (RDD). In the docking step of RDD the macromolecule or receptor is usually considered a rigid body. However, we know from biology that macromolecules such as enzymes and membrane receptors are inherently flexible. Accounting for this flexibility in molecular docking experiments is not trivial. One possibility, which we call a fully-flexible receptor model, is to use a molecular dynamics simulation trajectory of the receptor to simulate its explicit flexibility. To benefit from this concept, which has been known since 2000, it is essential to develop and improve new tools that enable molecular docking simulations of fully-flexible receptor models.

Results

We have developed a Flexible-Receptor Docking Workflow System (FReDoWS) to automate molecular docking simulations using a fully-flexible receptor model. In addition, it includes a snapshot selection feature to facilitate acceleration the virtual screening of ligands for well defined disease targets. FReDoWS usefulness is demonstrated by investigating the docking of four different ligands to flexible models of Mycobacterium tuberculosis’ wild type InhA enzyme and mutants I21V and I16T. We find that all four ligands bind effectively to this receptor as expected from the literature on similar, but wet experiments.

Conclusions

A work that would usually need the manual execution of many computer programs, and the manipulation of thousands of files, was efficiently and automatically performed by FReDoWS. Its friendly interface allows the user to change the docking and execution parameters. Besides, the snapshot selection feature allowed the acceleration of docking simulations. We expect FReDoWS to help us explore more of the role flexibility plays in receptor-ligand interactions. FReDoWS can be made available upon request to the authors.
Inhibition of N-linked glycosylation impairs ALK phosphorylation and disrupts pro-survival signaling in neuroblastoma cell lines
Authors: Del Grosso Federica , De Mariano Marilena , Passoni Lorena , Luksch Roberto , Tonini Gian Paolo , Longo Luca
Published: December 2011

Background

The Anaplastic Lymphoma Kinase (ALK) is an orphan receptor tyrosine kinase, which undergoes post-translational N-linked glycosylation. The catalytic domain of ALK was originally identified in the t(2;5) translocation that produces the unglycosylated oncogenic protein NPM-ALK, which occurs in Anaplastic Large Cell Lymphoma (ALCL). Recently, both germline and somatic activating missense mutations of ALK have been identified in neuroblastoma (NB), a pediatric cancer arising from neural crest cells. Moreover, we previously reported that ALK expression is significantly upregulated in advanced/metastatic NB. We hypothesized that ALK function may depend on N-linked glycosylation and that disruption of this post-translational modification would impair ALK activation, regardless the presence of either gene mutations or overexpression.

Methods

We employed tunicamycin to inhibit N-linked glycosylation. The following ALK-positive NB cell lines were used: SH-SY5Y and KELLY (ALK mutation F1174L), UKF-NB3 (ALK mutation R1275Q) and NB1 (ALK amplification). As a control, we used the NB cell lines LA1-5S and NB5 (no ALK expression), and the ALCL cell line SU-DHL1 (NPM-ALK).

Results

Tunicamycin treatment of ALK-positive NB cells resulted in a hypoglycosylated ALK band and in decreased amounts of mature full size receptor. Concomitantly, we observed a marked reduction of mature ALK phosphorylation. On the contrary, tunicamycin had no effects on NPM-ALK phosphorylation in SU-DHL1 cells. Moreover, phosphorylation levels of ALK downstream effectors (AKT, ERK1/2, STAT3) were clearly impaired only in ALK mutated/amplified NB cell lines, whereas no significant reduction was observed in both ALK-negative and NPM-ALK-positive cell lines. Furthermore, inhibition of N-linked glycosylation considerably impaired cell viability only of ALK mutated/amplified NB cells. Finally, the cleavage of the Poly-ADP-ribose-polymerase (PARP) suggested that apoptotic pathways may be involved in cell death.

Conclusions

In this study we showed that inhibition of N-linked glycosylation affects ALK phosphorylation and disrupts downstream pro-survival signaling, indicating that inhibition of this post-translational modification may be a promising therapeutic approach. However, as tunicamycin is not a likely candidate for clinical use other approaches to alter N-linked glycosylation need to be explored. Future studies will assess whether the efficacy in inhibiting ALK activity might be enhanced by the combination of ALK specific small molecule and N-linked glycosylation inhibitors.
Optimizing of preoperative computed tomography for diagnosis in patients with peritoneal carcinomatosis
Authors: Duhr Carolin D , Kenn Werner , Kickuth Ralph , Kerscher Alexander G , Germer Christoph-Thomas , Hahn Dietbert , W Pelz Joerg O
Published: December 2011

Background and Objective

This study evaluates whether Computer Tomography is an effective procedure for preoperative staging of patients with Peritoneal Carcinomatosis.

Method

A sample of 37 patients was analyzed with contrast enhanced abdominal Computer Tomography, followed by surgical staging. All Computer Tomography scans were evaluated 3 times by 2 radiologists with one radiologist reviewing 2 times. The efficacy of Computer Tomography was evaluated using the Spearman correlation coefficient. Correlations were analyzed by abdominopelvic region to assess results of the Peritoneal Carcinomatosis Index (PCI) aggregating the 13 regions. Surgical findings were compared to radiological findings.

Results

Results indicate high correlations between the surgical and radiological Peritoneal Carcinomatosis Indices. Analyses of the intra-class correlation between the first and second reading of one radiologist suggest high intra-observer reliability. Correlations by abdominopelvic region show higher values in the upper and middle regions and relatively lower values in the lower regions and the small bowel (correlation coefficients range between 0.418 and 0.726, p < 0.010; sensitivities range between 50% and 96%; and specificities range between 62% and 100%).

Conclusion

Computer Tomography represents an effective procedure in the preoperative staging of patients with PC. However, results by abdominopelvic region show lower correlation, therefore suggest lower efficacy. These results are supported by analyses of sensitivity and accuracy by lesion size. This suggests that Computer Tomography is an effective procedure for pre-operative staging but less for determining a tumor's accurate extent.
Skull base metastases from a malignant solitary fibrous tumor of the liver. A case report and literature review
Authors: Peng Lu , Liu Yang , Ai Yongbiao , Liu Zhisu , He Yueming , Liu Quanyan
Published: December 2011

Solitary fibrous tumors (SFTs) of the liver are rarely described; only 38 cases have been reported in literature, most of which have shown benign clinical characteristics, and only 3 of these cases exhibited malignant variants. In this study, we present a 24-year-old woman with a 1-month history of a rapidly enlarging abdominal mass and a CT showing an exophytic heterogeneous liver mass with a firm parietal bone mass. The patient underwent a transcatheter arterial chemoembolization (TACE) before operation, and an extended right hepatectomy and craniectomy with a negative margin was performed under general anesthesia. The masses showed histological features of oval spindle cells haphazardly arranged in the classic short-storiform or so-called patternless pattern of solitary fibrous tumors. The tumor cells showed positive immunohistochemical reactions to CD34 and bcl-2. The tumor recurred in the residual liver 2 months after operation, metastatic osteoblastic lesions in the thoracic and lumbar vertebrae were identified 3 months after the operation, and lumbar vertebrae metastasis 7 months after operation paralyzed the patient. The patient underwent percutaneous ethanol injection therapy (PEI) and chemotherapy, but the patient died because of the uncontrolled tumor 16 months after the initial operation. To our knowledge, this is the first case of malignant solitary fibrous liver tumors with skeletal metastasis.
Comparative evaluation of extraction methods for apoplastic proteins from maize leaves
Authors: Witzel Katja , Shahzad Muhammad , Matros Andrea , Mock Hans-Peter , Mühling Karl H
Published: December 2011

Proteins in the plant apoplast are essential for many physiological processes. We have analysed and compared six different infiltration solutions for proteins contained in the apoplast to recognize the most suitable method for leaves and to establish proteome maps for each extraction. The efficiency of protocols was evaluated by comparing the protein patterns resolved by 1-DE and 2-DE, and revealed distinct characteristics for each infiltration solution. Nano-LC-ESI-Q-TOF MS analysis of all fractions was applied to cover all proteins differentially extracted by infiltration solutions and led to the identification of 328 proteins in total in apoplast preparations. The predicted subcellular protein localisation distinguished the examined infiltration solutions in those with high or low amounts of intracellular protein contaminations, and with high or low quantities of secreted proteins. All tested infiltration solution extracted different subsets of proteins, and those implications on apoplast-specific studies are discussed.
Microplate-based high throughput screening procedure for the isolation of lipid-rich marine microalgae
Authors: Pereira Hugo , Barreira Luísa , Mozes André , Florindo Cláudia , Polo Cristina , Duarte Catarina V , Custódio Luísa , Varela João
Published: December 2011

We describe a new selection method based on BODIPY (4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) staining, fluorescence activated cell sorting (FACS) and microplate-based isolation of lipid-rich microalgae from an environmental sample. Our results show that direct sorting onto solid medium upon FACS can save about 3 weeks during the scale-up process as compared with the growth of the same cultures in liquid medium. This approach enabled us to isolate a biodiverse collection of several axenic and unialgal cultures of different phyla.
“Othering” the health worker: self‐stigmatization of HIV/AIDS care among health workers in Swaziland
Authors: de Vries Daniel H , Galvin Shannon , Mhlanga Masitsela , Cindzi Brian , Dlamini Thabsile
Published: December 2011

Background

HIV is an important factor affecting healthcare workforce capacity in high‐prevalence countries, such as Swaziland. It contributes to loss of valuable healthcare providers directly through death and absenteeism and indirectly by affecting family members, increasing work volume and decreasing performance. This study explored perceived barriers to accessing HIV/AIDS care and prevention services among health workers in Swaziland. We asked health workers about their views on how HIV affects Swaziland's health workforce and what barriers and strategies health workers have for addressing HIV and using healthcare treatment facilities.

Methods

Thirty‐four semi‐structured, in‐depth interviews, including a limited set of quantitative questions, were conducted among health workers at health facilities representing the mixture of facility type, level and location found in the Swaziland health system. Data were collected by a team of Swazi nurses who had received training in research methods. Study sites were selected using a purposive sampling method while health workers were sampled conveniently with attention to representing a mixture of different cadres. Data were analyzed using Nvivo qualitative analysis software and Excel.

Results

Health workers reported that HIV had a range of negative impacts on their colleagues and identified HIV testing and care as one of the most important services to offer health workers. They overwhelmingly wanted to know their own HIV status. However, they also indicated that in general, health workers were reluctant to access testing or care as they feared stigmatization by patients and colleagues and breaches of confidentiality. They described a self‐stigmatization related to a professional need to maintain a HIV‐free status, contrasting with the HIV‐vulnerable general population. Breaching of this boundary included feelings of professional embarrassment and fear of colleagues' and patients' judgements.

Conclusions

While care is available and relatively accessible, Swaziland health workers still face unique usage barriers that relate to a self‐stigmatizing process of boundary maintenance ‐ described here as a form of “othering” from the HIV‐vulnerable general population ‐ and a lack of trust in privacy and confidentiality. Interventions that target health workers should address these issues.
IL-10 signaling in CD4+ T cells is critical for the pathogenesis of collagen-induced arthritis
Authors: Tao Jian , Kamanaka Masahito , Hao Jianlei , Hao Zhifang , Jiang Xi , Craft Joe E , Flavell Richard A , Wu Zhenzhou , Hong Zhangyong , Zhao Liqing , Yin Zhinan
Published: December 2011

Introduction

IL-10 is a very important anti-inflammatory cytokine. However, the role of this cytokine in T cells in the pathogenesis of collagen-induced arthritis is unclear. The purpose of this study was to define the role of IL-10 signaling in T cells in the pathogenesis of collagen-induced arthritis.

Methods

IL-10 receptor dominant-negative transgenic (Tg) and control mice were immunized with bovine type II collagen to induce arthritis. The severity of arthritis was monitored and examined histologically. T-cell activation and cytokine production were analyzed using flow cytometry. T-cell proliferation was examined by [3H]thymidine incorporation. Antigen-specific antibodies in serum were measured by ELISA. Foxp3 expression in CD4+ regulatory T cells (Tregs) was determined by intracellular staining or Foxp3-RFP reporter mice. The suppressive function of Foxp3+CD4+ Tregs was determined in vitro by performing a T-cell proliferation assay. The level of IL-17 mRNA in joints was measured by real-time PCR. A two-tailed nonparametric paired test (Wilcoxon signed-rank test) was used to calculate the arthritis and histological scores. Student's paired or unpaired t-test was used for all other statistical analyses (InStat version 2.03 software; GraphPad Software, San Diego, CA, USA).

Results

Blocking IL-10 signaling in T cells rendered mice, especially female mice, highly susceptible to collagen-induced arthritis. T-cell activation and proliferation were enhanced and produced more IFN-γ. The suppressive function of CD4+Foxp3+ regulatory T cells was significantly impaired in Tg mice because of the reduced ability of Tregs from Tg mice to maintain their levels of Foxp3. This was further confirmed by transferring Foxp3-RFP cells from Tg or wild-type (Wt) mice into a congenic Wt host. The higher level of IL-17 mRNA was detected in inflammatory joints of Tg mice, probably due to the recruitment of IL-17+γδ T cells into the arthritic joints.

Conclusion

IL-10 signaling in T cells is critical for dampening the pathogenesis of collagen-induced arthritis by maintaining the function of Tregs and the recruitment of IL-17+γδ T cells.
Mammographic density and breast cancer risk: the role of the fat surrounding the fibroglandular tissue
Authors: Lokate Mariëtte , Peeters Petra HM , Peelen Linda M , Haars Gerco , Veldhuis Wouter B , van Gils Carla H
Published: December 2011

Introduction

Both the percent of mammographic density and absolute dense (fibroglandular) area are strong breast cancer risk factors. The role of non-dense (fat) breast tissue is not often investigated, but we hypothesize that this also influences risk. In this study we investigated the independent effects of dense and fat tissue, as well as their combined effect on postmenopausal breast cancer risk.

Methods

We performed a nested case-control study within the EPIC-NL cohort (358 postmenopausal breast cancer cases and 859 postmenopausal controls). We used multivariate logistic regression analyses to estimate breast cancer odds ratios adjusted for body mass index and other breast cancer risk factors.

Results

Large areas of dense (upper (Q5) vs lower quintile (Q1): OR 2.8 95% CI 1.7 to 4.8) and fat tissue (Q5 vs Q1: OR 2.4; 95% CI 1.3 to 4.2) were independently associated with higher breast cancer risk. The combined measure showed that the highest risk was found in women with both a large (above median) area of dense and fat tissue.

Conclusions

Fibroglandular and breast fat tissue have independent effects on breast cancer risk. The results indicate that the non-dense tissue, which represents the local breast fat, increases risk, even independent of body mass index (BMI). When studying dense breast tissue in relation to breast cancer risk, adjustment for non-dense tissue seems to change risk estimates to a larger extent than adjustment for BMI. This indicates that adjustment for non-dense tissue should be considered when studying associations between dense areas and breast cancer risk.
Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh
Authors: Wang Weiguang , Lian Na , Ma Yun , Li Lingzhen , Gallant Richard C. , Elefteriou Florent , Yang Xiangli
Published: December 2011

Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes. The relative contribution of Atf4 in chondrocytes and osteoblasts to the regulation of skeletal development and bone formation is poorly understood. Investigations of the Atf4–/–;Col2a1-Atf4 mouse model, in which Atf4 is selectively overexpressed in chondrocytes in an Atf4-null background, demonstrate that chondrocyte-derived Atf4 regulates osteogenesis during development and bone remodeling postnatally. Atf4 overexpression in chondrocytes of the Atf4–/–;Col2a1-Atf4 double mutants corrects the reduction in stature and limb in Atf4–/– embryos and rectifies the decrease in Ihh expression, Hh signaling, proliferation and accelerated hypertrophy that characterize the Atf4–/– developing growth plate cartilages. Unexpectedly, this genetic manipulation also restores the expression of osteoblastic marker genes, namely Ocn and bone sialoprotein, in Atf4–/– developing bones. In Atf4–/–;Col2a1-Atf4 adult mice, all the defective bone parameters found in Atf4–/– mice, including bone volume, trabecular number and thickness, and bone formation rate, are rescued. In addition, the conditioned media of ex vivo cultures from wild-type or Atf4–/–;Col2a1-Atf4, but not Atf4–/– cartilage, corrects the differentiation defects of Atf4–/– bone marrow stromal cells and Ihh-blocking antibody eliminates this effect. Together, these data indicate that Atf4 in chondrocytes is required for normal Ihh expression and for its paracrine effect on osteoblast differentiation. Therefore, the cell-autonomous role of Atf4 in chondrocytes dominates the role of Atf4 in osteoblasts during development for the control of early osteogenesis and skeletal growth.
The genomic regulatory control of skeletal morphogenesis in the sea urchin
Authors: Rafiq Kiran , Cheers Melani S. , Ettensohn Charles A.
Published: December 2011

A central challenge of developmental and evolutionary biology is to understand how anatomy is encoded in the genome. Elucidating the genetic mechanisms that control the development of specific anatomical features will require the analysis of model morphogenetic processes and an integration of biological information at genomic, cellular and tissue levels. The formation of the endoskeleton of the sea urchin embryo is a powerful experimental system for developing such an integrated view of the genomic regulatory control of morphogenesis. The dynamic cellular behaviors that underlie skeletogenesis are well understood and a complex transcriptional gene regulatory network (GRN) that underlies the specification of embryonic skeletogenic cells (primary mesenchyme cells, PMCs) has recently been elucidated. Here, we link the PMC specification GRN to genes that directly control skeletal morphogenesis. We identify new gene products that play a proximate role in skeletal morphogenesis and uncover transcriptional regulatory inputs into many of these genes. Our work extends the importance of the PMC GRN as a model developmental GRN and establishes a unique picture of the genomic regulatory control of a major morphogenetic process. Furthermore, because echinoderms exhibit diverse programs of skeletal development, the newly expanded sea urchin skeletogenic GRN will provide a foundation for comparative studies that explore the relationship between GRN evolution and morphological evolution.
In vivo imaging of basement membrane movement: ECM patterning shapesHydrapolyps
Authors: Aufschnaiter Roland , Zamir Evan A. , Little Charles D. , Özbek Suat , Münder Sandra , David Charles N. , Li Li , Sarras Michael P. , Zhang Xiaoming
Published: December 2011

Growth and morphogenesis during embryonic development, asexual reproduction and regeneration require extensive remodeling of the extracellular matrix (ECM). We used the simple metazoan Hydra to examine the fate of ECM during tissue morphogenesis and asexual budding. In growing Hydra, epithelial cells constantly move towards the extremities of the animal and into outgrowing buds. It is not known, whether these tissue movements involve epithelial migration relative to the underlying matrix or whether cells and ECM are displaced as a composite structure. Furthermore, it is unclear, how the ECM is remodeled to adapt to the shape of developing buds and tentacles. To address these questions, we used a new in vivo labeling technique for Hydra collagen-1 and laminin, and tracked the fate of ECM in all body regions of the animal. Our results reveal that Hydra ‘tissue movements’ are largely displacements of epithelial cells together with associated ECM. By contrast, during the evagination of buds and tentacles, extensive movement of epithelial cells relative to the matrix is observed, together with local ECM remodeling. These findings provide new insights into the nature of growth and morphogenesis in epithelial tissues.
European Integration at the Crossroads: A Review Essay on the 50th Anniversary of Bela Balassa'sTheory of Economic Integration
Authors: Sapir André
Published: December 2011

Bela Balassa's Theory of Economic Integration, published fifty years ago, is a remarkable, yet little known book. This essay reviews developments in the economic literature and in the process of European integration since the book's publication, showing that it was incredibly prescient. It anticipated by more than twenty years the modern literature on economic integration that emphasizes scale economies, imperfect competition, and economic geography. It also predicted that monetary union cannot function properly without political unification, a condition well illustrated by the recent euro-debt crisis that is likely to be a watershed in the history of European integration. (JEL B31, F15, F36, G01)
TEAM ASPAR Uses Binary Optimization to Obtain Optimal Gearbox Ratios in Motorcycle Racing
Authors: Amorós Javier , Escudero Laureano F. , Monge Juan F. , Segura José V. , Reinoso Oscar
Published: December 2011

In this paper, we present a binary integer linear program for obtaining the optimal combination of gears to install on a competitive racing motorcycle. Our objective is to meet the requirements of both the rider and track at a set of points on the racing circuit. This requires determining the best transmission (gearbox) for each circuit and rider. We discuss a solution for a rider in the World Motorcycling Racing Championship.
Spectroscopic studies on U(VI)-salicylate complex formation with multiple equilibria
Authors: Cha W. , Cho Hye-Ryun , Jung E. C. , Park K. K. , Kim W. H. , Song K.
Published: December 2011

This study investigates multiple equilibria related to the formation of the U(VI)-salicylate complex in a pH range of 3.0–5.5 using UV-Vis absorption and fluorescence measurement techniques. The absorbance changes at the characteristic charge-transfer bands of the complex were monitored, and the results indicated the presence of multiple equilibria and the formation of both 1:1 and 1:2 (U(VI):salicylate) complexes possessing bi-dentate chelate structures. The determined step-wise formation constants (log K
1:1 and log K
1:2) are as follows: 12.5 ± 0.1 and 11.4 ± 0.2 for salicylate, 11.2 ± 0.1 and 10.1 ± 0.2 for 5-sulfosalicylate, and 12.4 ± 0.1 and 11.4 ± 0.1 for 2,6-dihydroxybenzoate, respectively. The molar absorptivities of the complexes are also provided. Furthermore, time-resolved laser-induced luminescence spectra of U(VI) species demonstrate the presence of both a dynamic and static quenching process upon the addition of a salicylate ligand. Particularly for the luminescent hydroxouranyl species, a strong static quenching effect is observed. The results suggest that both the UO2(HSal)+ and the U(VI)–Sal chelate complexes serve as ground-state complexes that induce static quenching. The Stern–Volmer parameters were derived based on the measured luminescent intensity and lifetime data. The static quenching constants (log K
S) obtained are 3.3 ± 0.1, 4.9 ± 0.1, and 4.4 ± 0.1 for UO2
2+, (UO2)2(OH)2
2+ and (UO2)3(OH)5
+, respectively.
GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls
Authors: Zirilli Lucia , Orlando Gabriella , Carli Federica , Madeo Bruno , Cocchi Stefania , Diazzi Chiara , Carani Cesare , Guaraldi Giovanni , Rochira Vincenzo
Published: December 2011

Objective

GH secretion is impaired in lipodystrophic human immunodeficiency virus (HIV) patients and inversely related to lipodystrophy-related fat redistribution in men. Less is known about the underlying mechanisms involved in reduced GH secretion in HIV-infected women.

Design

A case–control, cross-sectional study comparing GH/IGF1 status, body composition, and metabolic parameters in 92 nonobese women with HIV-related lipodystrophy and 63 healthy controls matched for age, ethnicity, sex, and body mass index (BMI).

Methods

GH, IGF1, IGF binding protein 3 (IGFBP3), GH after GHRH plus arginine (GHRH+Arg), several metabolic variables, and body composition were evaluated.

Results

GH response to GHRH+Arg was lower in HIV-infected females than in controls. Using a cutoff of peak GH ≤7.5 μg/l, 20.6% of HIV-infected females demonstrated reduced peak GH response after GHRH+Arg. In contrast, none of the control subjects demonstrated a peak GH response ≤7.5 μg/l. Bone mineral density (BMD), quality of life, IGF1, and IGFBP3 were lowest in the HIV-infected females with a GH peak ≤7.5 μg/l. BMI was the main predictive factor of GH peak in stepwise multiregression analysis followed by age, with a less significant effect of visceral fat in the HIV-infected females.

Conclusions

This study establishes that i) GH response to GHRH+Arg is lower in lipoatrophic HIV-infected women than in healthy matched controls, ii) BMI more than visceral adipose tissue or trunk fat influences GH peak in this population, and iii) HIV-infected women with a GH peak below or equal to 7.5 μg/l demonstrate reduced IGF1, IGFBP3, BMD, and quality of life.