bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the prevalence and burden of major disorders of the brain in Nepal: methodology of a nationwide population-based study
Authors: Manandhar Kedar , Risal Ajay , Steiner Timothy J , Holen Are , Koju Rajendra , Linde Mattias
Published: August 2014

Background

The major disorders of the brain (MDBs), in terms of their prevalence and the burdens of ill health, disability and financial cost that they impose on individuals and society, are headache, depression and anxiety. No population-based studies have been conducted in Nepal.

Aim

Our purpose was to assess the prevalence and burden attributable to MDBs in Nepal in order to inform health policy. Here we report the methodology.

Methods

The unusual sociocultural diversity and extreme geographical variation of the country required adaptation of standard methodology. We ran pre-pilot and pilot studies before embarking on the main study. The study design was cross-sectional. The population of interest were adults aged 18–65 years who were Nepali speaking and living in Nepal. We selected, employed and trained groups of interviewers to visit randomly selected households by cold-calling. Households were selected from 15 representative districts out of 75 in the country through multistage cluster sampling. One participant was selected randomly from each household. We used structured questionnaires (the HARDSHIP questionnaire, Hospital Anxiety and Depression Scale, and Eysenck Personality Questionnaire -Neuroticism), culturally adapted and translated into Nepali. We recorded blood pressure, weight, height and waist circumference, and altitude of each household. We implemented various quality-assurances measures.

Results

We completed the survey in one month, prior to onset of the monsoon. Among 2,210 selected households, all were contacted, 2,109 were eligible for the study and, from these, 2,100 adults participated. The participation rate was 99.6%.

Conclusion

Standard methodology was successfully applied in Nepal, with some adaptations. The sociocultural and extraordinary geographic diversity were challenging, but did not require us to compromise the scientific quality of the study.
Engineering optical properties of gold-coated nanoporous anodic alumina for biosensing
Authors: Hernández-Eguía Laura P , Ferré-Borrull Josep , Macias Gerard , Pallarès Josep , Marsal Lluís F
Published: August 2014

The effect in the Fabry-Pérot optical interferences of nanoporous anodic alumina films coated with gold is studied as a function of the porosity and of the gold thickness by means of reflectance spectroscopy. Samples with porosities between 14 and 70% and gold thicknesses (10 and 20 nm) were considered. The sputtering of gold on the nanoporous anodic alumina (NAA) films results in an increase of the fringe intensity of the oscillations in the spectra resulting from Fabry-Pérot interferences in the porous layer, with a reduction in the maximum reflectance in the UV-visible region. For the thicker gold layer, sharp valleys appear in the near-infrared (IR) range that can be useful for accurate spectral shift measurements in optical biosensing. A theoretical model for the optical behavior has also been proposed. The model shows a very good agreement with the experimental measurements, what makes it useful for design and optimization of devices based on this material. This material capability is enormous for using it as an accurate and sensitive optical sensor, since gold owns a well-known surface chemistry with certain molecules, most of them biomolecules.
Probabilistic motion pixel detection for the reduction of ghost artifacts in high dynamic range images from multiple exposures
Authors: An Jaehyun , Ha Seong Jong , Cho Nam Ik
Published: August 2014

This paper presents an algorithm for compositing a high dynamic range (HDR) image from multi-exposure images, considering inconsistent pixels for the reduction of ghost artifacts. In HDR images, ghost artifacts may appear when there are moving objects while taking multiple images with different exposures. To prevent such artifacts, it is important to detect inconsistent pixels caused by moving objects in consecutive frames and then to assign zero weights to the corresponding pixels in the fusion process. This problem is formulated as a binary labeling problem based on a Markov random field (MRF) framework, the solution of which is a binary map for each exposure image, which identifies the pixels to be excluded in the fusion process. To obtain the ghost map, the distribution of zero-mean normalized cross-correlation (ZNCC) of an image with respect to the reference frame is modeled as a mixture of Gaussian functions, and the parameters of this function are used to design the energy function. However, this method does not well detect faint objects that are in low-contrast regions due to over- or under-exposure, because the ZNCC does not show much difference in such areas. Hence, we obtain an additional ghost map for the low-contrast regions, based on the intensity relationship between the frames. Specifically, the intensity mapping function (IMF) between the frames is estimated using pixels from high-contrast regions without inconsistent pixels, and pixels out of the tolerance range of the IMF are considered moving pixels in the low-contrast regions. As a result, inconsistent pixels in both the low- and high-contrast areas are well found, and thus, HDR images without noticeable ghosts can be obtained.
Early changes of muscle membrane properties in porcine faecal peritonitis
Authors: Ackermann Karin A , Bostock Hugh , Brander Lukas , Schröder Ralph , Djafarzadeh Siamak , Tuchscherer Daniel , Jakob Stephan M , Takala Jukka , Z’Graggen Werner J
Published: August 2014

Introduction

Sepsis-induced myopathy and critical illness myopathy (CIM) are possible causes of muscle weakness in intensive care patients. They have been attributed to muscle membrane dysfunction. The aim of this study was to investigate membrane properties in the early stage of experimental sepsis by evaluating muscle excitability.

Methods

In total, 20 anaesthetized and mechanically ventilated pigs were randomized to either faecal peritonitis (n = 10) or to non-septic controls (n = 10). Resuscitation with fluids and vasoactive drugs was started 3 hours after peritonitis induction. Muscle membrane properties were investigated by measuring muscle velocity recovery cycles before induction of peritonitis as well as 6, 18 and 27 hours thereafter. Muscle relative refractory period (MRRP) and early supernormality (ESN) were assessed.

Results

Peritonitis lasting 27 hours was associated with an increase of MRRP by 28% from 2.38 ± 0.18 ms (mean ± SD) to 3.47 ± 1.79 ms (P <0.01) and a decrease of ESN by 31% from 9.64 ± 2.82% to 6.50 ± 2.64% (P <0.01). ESN reduction was already apparent 6 hours after induction of peritonitis. Values in controls did not show any significant alterations.

Conclusions

Muscle membrane abnormalities consistent with membrane depolarization and/or sodium channel inactivation occurred within 6 hours of peritonitis induction. This indicates that changes that have been described in established sepsis-induced myopathy and/or CIM start early in the course of sepsis. Muscle excitability testing facilitates evaluation of the time course of these changes.
Relationships between computer-extracted mammographic texture pattern features and BRCA1/2mutation status: a cross-sectional study
Authors: Gierach Gretchen L , Li Hui , Loud Jennifer T , Greene Mark H , Chow Catherine K , Lan Li , Prindiville Sheila A , Eng-Wong Jennifer , Soballe Peter W , Giambartolomei Claudia , Mai Phuong L , Galbo Claudia E , Nichols Kathryn , Calzone Kathleen A , Olopade Olufunmilayo I , Gail Mitchell H , Giger Maryellen L
Published: August 2014

Introduction

Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.

Methods

We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject’s digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject’s belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model’s discriminatory capacity.

Results

In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density.

Conclusions

Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.
Genome-wide DNA methylation profiles in progression to in situand invasive carcinoma of the breast with impact on gene transcription and prognosis
Authors: Fleischer Thomas , Frigessi Arnoldo , Johnson Kevin C , Edvardsen Hege , Touleimat Nizar , Klajic Jovana , Riis Margit LH , Haakensen Vilde D , Wärnberg Fredrik , Naume Bjørn , Helland Åslaug , Børresen-Dale Anne-Lise , Tost Jörg , Christensen Brock C , Kristensen Vessela N
Published: August 2014

Background

Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development.

Results

We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma.

Conclusions

This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.
Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy?
Authors: van Baarsen Lisa GM , Lebre Maria C , van der Coelen Dennis , Aarrass Saïda , Tang Man W , Ramwadhdoebe Tamara H , Gerlag Daniëlle M , Tak Paul P
Published: August 2014

Introduction

Accumulating evidence suggests an important role for interleukin 17 (IL-17) in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Accordingly, clinical trials aimed at blocking IL-17 have been initiated, but clinical results between patients and across different diseases have been highly variable. The objective was to determine the variability in expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the synovia of patients with arthritis.

Methods

Synovial biopsies were obtained from patients with RA (n = 11), PsA (n = 15) and inflammatory osteoarthritis (OA, n = 14). For comparison, synovia from noninflamed knee joints (n = 7) obtained from controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. We used confocal microscopy to determine which cells in the synovium express IL-17A and IL-17F, double-staining with CD4, CD8, CD15, CD68, CD163, CD31, von Willebrand factor, peripheral lymph node address in, lymphatic vessel endothelial hyaluronan receptor 1, mast cell tryptase and retinoic acid receptor-related orphan receptor γt (RORγt).

Results

IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly expressed in synovial tissues of all patient groups. Whereas IL-17RA was present mostly in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant (P < 0.05) increase of only IL-17A in arthritis patients compared to noninflamed control tissues. The expression of IL-17A, IL-17F and their receptors was similar in the different patient groups, but highly variable between individual patients. CD4+ and CD8+ cells coexpressed IL-17A, and few cells coexpressed IL-17F. IL-17A and IL-17F were not expressed by CD15+ neutrophils. Mast cells were only occasionally positive for IL-17A or IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in macrophages, as well as in blood vessels and lymphatics. This staining probably reflects receptor-bound cytokine staining. Many infiltrated cells were positive for the transcription factor RORγt. Colocalisation between RORγt and IL-17A and IL-17F indicates local IL-17 production.

Conclusions

Increased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients; it is also observed in inflammatory OA. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patients.
Online social sports networks as crime facilitators
Authors: Stottelaar Bas , Senden Jeroen , Montoya Lorena
Published: August 2014

Emerging technologies such as broadband services and mobile and wireless technologies create not only benefits for the community but also risks (Choo, Smith, McCusker 78: iii, 2007). The implications of these developments should be evaluated to make any necessary changes to policing, policy and legislation. This study investigates the risk of disclosure of confidential information via online public exercise routes. The study identified in particular whether a) people inadvertently disclose their home address more often indirectly via online sports tracking networks than directly via other means and whether b) gender and age play a role in this disclosure. In addition, an analysis of the temporal characteristics of runs was performed to establish the window of opportunity for a home burglary and whether running is temporally predictable by hour of day or day of week. A total of 513 RunKeeper users were selected from the Dutch cities of Enschede and Nijmegen. 231 runners (45.03%) were located via RunKeeper and 122 (23.78%) via other Internet (i.e. non-social sports network) sources. It was found that a statistical difference exists between the indirect and direct disclosure of addresses; more runners disclose their home address via online sports tracking networks than via other sources. Furthermore, it was found that age played a role in the direct disclosure of addresses but not in the indirect disclosure. Older users more often disclosed their home address directly than younger ones. Conversely, gender plays a role in the indirect disclosure but not in the direct disclosure. Men more often disclosed their home address indirectly than women. Regarding temporal characteristics, it was found that the window of opportunity for a burglary is approximately 1 hour. Furthermore, the ‘within subject’ analysis suggests that the starting hour of the run is the most predictable temporal characteristic, followed by the duration of the run and the day of the week. This research ultimately shows the extent to which the unique combination of spatial and temporal information available in online sports tracking networks can enable criminals to predict where a potential target lives and when he or she will be out running.
Brief Communication: Patient Satisfaction with the Use of Tablet Computers: A Pilot Study in Two Outpatient Home Dialysis Clinics
Authors: Schick-Makaroff Kara , Molzahn Anita
Published: August 2014

Background:

Electronic capture of patients' reports of their health is significant in clinical nephrology research because health-related quality of life (HRQOL) for patients with end-stage renal disease is compromised and assessment by patients of their HRQOL in practice is relatively uncommon.

Objective:

The purpose of this study was to evaluate patient satisfaction with and time involved in administering HRQOL and symptom assessment measures using tablet computers in two outpatient home dialysis clinics.

Design:

A cross-sectional observational study design was employed.

Setting:

The study was conducted in two home dialysis clinics.

Patients:

Fifty-six patients participated in the study; 35 males (63%) and 21 females (37%) with a mean age of 66 ± 12 (36–90 years old) were included. Forty-nine participants were on peritoneal dialysis (87%), 6 on home hemodialysis (11%), and 1 on nocturnal home hemodialysis (2%).

Measurements:

Measures included the Kidney Disease Quality of Life-36 (KDQOL-36), the Edmonton Symptom Assessment Scale (ESAS) and Participant's Level of Satisfaction in Using a Tablet Computer.

Methods:

Using a tablet computer, participants completed the three measures. Descriptive statistics and bivariate correlations were calculated.

Results:

Participants' satisfaction with use of the tablet computer was high; 66% were “very satisfied”, 7% “satisfied”, 2% “slightly satisfied”, and 18% “neutral”. On the 7-point Likert-type scale, the mean satisfaction score was 5.11 (SD = 1.6). Mean time to complete the measures was: Level of Satisfaction 1.15 minutes (SD = 0.41), ESAS 2.55 minutes (SD = 1.04), and KDQOL 9.56 minutes (SD = 2.03); the mean time to complete all three instruments was 13.19 minutes (SD = 2.42). There were no significant correlations between level of satisfaction and age, gender, HRQOL, time taken to complete surveys, computer experience, or comfort with technology. Comfort with technology and computer experience were highly correlated, r = .7, p (one-tailed) < 0.01.

Limitations:

Limitations include lack of generalizability because of a small self-selected sample of relatively healthy patients and a lack of psychometric testing on the measure of satisfaction.

Conclusions:

Participants were satisfied with the platform and the time involved for completion of instruments was modest. Routine use of HRQOL measures for clinical purposes may be facilitated through use of tablet computers.
Is it Ethical to Prescribe Generic Immunosuppressive Drugs to Renal Transplant Patients?
Authors: Allard Julie , Fortin Marie-Chantal
Published: August 2014

Purpose of the review:

This review was conducted to determine the ethical acceptability of prescribing generic immunosuppressive drugs to renal transplant patients.

Sources of information:

The literature search was conducted using Pubmed and Google Scholar.

Findings:

The use of generic immunosuppressive drugs (ISDs) in transplantation is a controversial topic. There is a consensus among transplant societies that clinical data is lacking and that caution should be exercised. The reluctance to use generic ISDs in organ transplantation is partly related to the fact that most are “critical dose drugs”, and that either low dosing or overdosing could have serious adverse consequences for both patients and society (i.e., the loss of scarce organs). In this paper, we examine the various ethical issues involved such as distributive justice, physician duties, risks versus benefits, conflict of interest, informed consent, and logistical and economic issues.

Limitations:

Our analysis was limited by the paucity of clinical data on generic ISDs and the absence of health economics studies to quantify the benefits of prescribing generic ISDs.

Implications:

Our study led us to conclude that it would be ethical to prescribe generic ISDs provided certain conditions were met. These include regulatory safeguards to minimize the risks of substitution; education of patients; and further clinical and health economics studies to better inform clinicians, patients and society of the risks and costs related to drug substitution.
Improvement of cardiac function by placenta-derived mesenchymal stem cells does not require permanent engraftment and is independent of the insulin signaling pathway
Authors: Passipieri Juliana A , Kasai-Brunswick Tais H , Suhett Grazielle , Martins Andreza B , Brasil Guilherme V , Campos Dilza B , Rocha Nazareth N , Ramos Isalira P , Mello Debora B , Rodrigues Deivid C , Christie Beatriz B , Silva-Mendes Bernardo J , Balduíno Alex , Sá Renato M , Lopes Laudelino M , Goldenberg Regina C , Campos de Carvalho Antonio C , Carvalho Adriana B
Published: August 2014

Introduction

The objective of this work was to evaluate the efficacy of placenta-derived mesenchymal stem cell (MSC) therapy in a mouse model of myocardial infarction (MI). Since MSCs can be obtained from two different regions of the human term placenta (chorionic plate or villi), cells obtained from both these regions were compared so that the best candidate for cell therapy could be selected.

Methods

For the in vitro studies, chorionic plate MSCs (cp-MSCs) and chorionic villi MSCs (cv-MSCs) were extensively characterized for their genetic stability, clonogenic and differentiation potential, gene expression, and immunophenotype. For the in vivo studies, C57Bl/6 mice were submitted to MI and, after 21 days, received weekly intramyocardial injections of cp-MSCs for 3 weeks. Cells were also stably transduced with a viral construct expressing luciferase, under the control of the murine stem cell virus (MSCV) promoter, and were used in a bioluminescence assay. The expression of genes associated with the insulin signaling pathway was analyzed in the cardiac tissue from cp-MSCs and placebo groups.

Results

Morphology, differentiation, immunophenotype, and proliferation were quite similar between these cells. However, cp-MSCs had a greater clonogenic potential and higher expression of genes related to cell cycle progression and genome stability. Therefore, we considered that the chorionic plate was preferable to the chorionic villi for the isolation of MSCs. Sixty days after MI, cell-treated mice had a significant increase in ejection fraction and a reduction in end-systolic volume. This improvement was not caused by a reduction in infarct size. In addition, tracking of cp-MSCs transduced with luciferase revealed that cells remained in the heart for 4 days after the first injection but that the survival period was reduced after the second and third injections. Quantitative reverse transcription-polymerase chain reaction revealed similar expression of genes involved in the insulin signaling pathway when comparing cell-treated and placebo groups.

Conclusions

Improvement of cardiac function by cp-MSCs did not require permanent engraftment and was not mediated by the insulin signaling pathway.
Curvatures and inhomogeneities: An improved common-reflection-surface approach
Authors: Schwarz Benjamin , Vanelle Claudia , Gajewski Dirk , Kashtan Boris
Published: August 2014

Multiparameter stacking is an important tool to obtain a first reliable time image of the subsurface. In addition, it provides wavefield attributes, which form the basis for many important applications. The quality of the image and the attribute estimates relies heavily on the accuracy of the traveltime moveout description. The commonly used hyperbolic common-reflection-surface (CRS) operator reduces to the NMO hyperbola in the common-midpoint gather. Its accuracy, however, depends on the curvature of the reflector under consideration. The conventional multifocusing (MF) operator, a time-shifted double-square-root expression, leads to good results for high reflector curvatures and moderate inhomogeneities of the overburden. We used a new implicit CRS formulation that combines the robustness of CRS regarding heterogeneities with the high sensitivity to curvature of the MF approach. It assumes reflectors to be locally circular and can be applied in an iterative fashion. For simple but common acquisition and subsurface configurations, the new traveltime expression reduces to familiar formulas. Quantitative studies revealed that the new operator performs equally well over the full range of curvatures even in the presence of strong heterogeneities, while providing higher accuracy than the conventional CRS and MF methods. In addition, its application resulted in more reliable attribute estimates and an improved time-migrated section. Comparison of stacking and migration results for the complex synthetic Sigsbee 2a data set confirmed the potential of the suggested approach.
Characterization of GAB1 Expression Over the Menstrual Cycle in Women With and Without Polycystic Ovarian Syndrome Provides a New Insight Into Its Pathophysiology
Authors: Roemer K. L. , Young S. L. , Savaris R. F.
Published: August 2014

Context:

In a previous microarray analysis, GRB2-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, was down-regulated in endometrium of women with polycystic ovary syndrome (PCOS).

Objective:

The objective of the study was to characterize the cyclic expression of endometrial GAB1 in vivo in normal women and those with PCOS as well as investigate the possible mechanisms of endometrial regulation of GAB1 expression and action in vitro.

Design:

This was an experimental and case-control study.

Setting:

The study was conducted at a tertiary university hospital.

Patients:

Normal proven fertile women (controls; n = 31) and women with PCOS (cases; n = 26) participated in the study.

Interventions:

Interventions included timed endometrial biopsies at different phases of the menstrual cycle. Ishikawa cells were cultured with β-estradiol (E2), medroxyprogesterone acetate, and E2 + medroxyprogesterone acetate. Transfection of small interfering RNA for GAB1 in Ishikawa cells incubated with or without insulin.

Main Outcome Measures:

GAB1 mRNA expression in Ishikawa cells and in endometrium of cases and controls was measured. Protein expression of phosphorylated MAPK by Western blot was also measured. Immunohistochemical localization and expression of phosphorylated GAB1 in endometrium was also measured, using a digital histological score.

Results:

In endometrial tissue, GAB1 mRNA was reduced in the proliferative phase of PCOS women, compared with controls (P = .003; ANOVA). When all the phases of the menstrual cycle were grouped, GAB1 protein expression was reduced in endometrium of PCOS women (P < .0001; Student t test). E2 increases GAB1 mRNA expression in Ishikawa cells (P = .001; ANOVA). Phosphorylated MAPK is reduced in cells transfected with small interfering RNA for GAB1 (P = .008; ANOVA) and incubated with insulin.

Conclusions:

GAB1 mRNA expression is positively modulated by E2. Endometrial GAB1 protein and mRNA expression are reduced in women with PCOS, suggesting that the endometrium of PCOS women have a defect in insulin signaling due to GAB1 down-regulation.
The Dutch Black Legend
Authors: Nocentelli Carmen
Published: August 2014

English “Hollandophobia” is usually understood as a function or reflection of the rivalries that characterized Anglo-Dutch relations during the seventeenth century. Working against such a circumscribed understanding, this essay contends that Hollandophobia is best thought of as a “Dutch Black Legend”—that is, as a deliberate repetition of the Hispanophobic topoi known as the Spanish Black Legend. Only by acknowledging the intimate relationship between these two phenomena can we make sense of Hollandophobia’s peculiar features while discerning how this seventeenth-century discourse helped construct what the English took to be proper Europeanness.
Metal-free Reductive Cyclization and Isomerization of Sulfanyl-1,6-diynes Using Sodium Borohydride
Authors: Ito Yukiteru , Yoshimatsu Mitsuhiro
Published: August 2014

In this study, we demonstrated the metal-free reductive cyclization of sulfanyl-1,6-diynes with sodium borohydride in ethanol in the presence of diazabicyclo[5.4.0]undec-7-ene. 1,6-Diynes 1 and 5a–5h bearing hydrogen or phenyl as the R2 group afforded pyrroles 2 and 6a–6e in high yields without any side reaction products such as enynyl sulfides. 1,6-Diyne (R2 = Et) produced both pyrrole and enynyl sulfides; however, the use of cesium fluoride succeeded in the selective formation of pyrrole 6f.
Preparation of Highly Dispersed Pt Nanoparticles Supported on Zeolite-templated Carbon and Catalytic Application in Hydrogenation Reaction
Authors: Jiang Chuanxia , Hara Kenji , Namba Kotaro , Kobayashi Hirokazu , Ittisanronnachai Somlak , Nishihara Hirotomo , Kyotani Takashi , Fukuoka Atsushi
Published: August 2014

Zeolite-templated carbon (ZTC) was utilized to prepare Pt nanoparticles as a support by using a simple impregnation method. The choice of a cationic Pt precursor led to the formation of highly and uniformly dispersed Pt nanoparticles on ZTC, which afforded high conversion in the catalytic hydrogenation of phenylacetylene.
Electrodeposition Study on a Single-crystal Titanium Dioxide Electrode: Platinum on a Niobium-doped Titanium Dioxide(110) Electrode
Authors: Takakusagi Satoru , Ogawa Takafumi , Uehara Hiromitsu , Ariga Hiroko , Shimizu Ken-ichi , Asakura Kiyotaka
Published: August 2014

Pt was successfully electrodeposited on a Nb-doped TiO2(110) electrode from a solution of 1 mM K2[PtCl4] and 50 mM H2SO4 using single-pulse chronoamperometry. The morphology of the deposited Pt nanoparticles was sensitive to the deposition potential and holding time. A novel method for the preparation of metal particles on a single-crystal TiO2 surface in a controlled manner has been proposed.
De novo translation initiation on membrane-bound ribosomes as a mechanism for localization of cytosolic protein mRNAs to the endoplasmic reticulum
Authors: Jagannathan Sujatha , Reid David W. , Cox Amanda H. , Nicchitta Christopher V.
Published: August 2014

The specialized protein synthesis functions of the cytosol and endoplasmic reticulum compartments are conferred by the signal recognition particle (SRP) pathway, which directs the cotranslational trafficking of signal sequence-encoding mRNAs from the cytosol to the endoplasmic reticulum (ER). Although subcellular mRNA distributions largely mirror the binary pattern predicted by the SRP pathway model, studies in mammalian cells, yeast, and Drosophila have also demonstrated that cytosolic protein-encoding mRNAs are broadly represented on ER-bound ribosomes. A mechanism for such noncanonical mRNA localization remains, however, to be identified. Here, we examine the hypothesis that de novo translation initiation on ER-bound ribosomes serves as a mechanism for localizing cytosolic protein-encoding mRNAs to the ER. As a test of this hypothesis, we performed single molecule RNA fluorescence in situ hybridization studies of subcellular mRNA distributions and report that a substantial fraction of mRNAs encoding the cytosolic protein GAPDH resides in close proximity to the ER. Consistent with these data, analyses of subcellular mRNA and ribosome distributions in multiple cell lines demonstrated that cytosolic protein mRNA-ribosome distributions were strongly correlated, whereas signal sequence-encoding mRNA-ribosome distributions were divergent. Ribosome footprinting studies of ER-bound polysomes revealed a substantial initiation codon read density enrichment for cytosolic protein-encoding mRNAs. We also demonstrate that eukaryotic initiation factor 2α is bound to the ER via a salt-sensitive, ribosome-independent mechanism. Combined, these data support ER-localized translation initiation as a mechanism for mRNA recruitment to the ER.
Ethical research standards in a world of big data
Authors: Rivers Caitlin M. , Lewis Bryan L.
Published: August 2014

In 2009 Ginsberg et al. reported using Google search query volume to estimate influenza activity in advance of traditional methodologies. It was a groundbreaking example of digital disease detection, and it still remains illustrative of the power of gathering data from the internet for important research. In recent years, the methodologies have been extended to include new topics and data sources; Twitter in particular has been used for surveillance of influenza-like-illnesses, political sentiments, and even behavioral risk factors like sentiments about childhood vaccination programs. As the research landscape continuously changes, the protection of human subjects in online research needs to keep pace. Here we propose a number of guidelines for ensuring that the work done by digital researchers is supported by ethical-use principles. Our proposed guidelines include: 1) Study designs using Twitter-derived data should be transparent and readily available to the public. 2) The context in which a tweet is sent should be respected by researchers. 3) All data that could be used to identify tweet authors, including geolocations, should be secured. 4) No information collected from Twitter should be used to procure more data about tweet authors from other sources. 5) Study designs that require data collection from a few individuals rather than aggregate analysis require Institutional Review Board (IRB) approval. 6) Researchers should adhere to a user’s attempt to control his or her data by respecting privacy settings. As researchers, we believe that a discourse within the research community is needed to ensure protection of research subjects. These guidelines are offered to help start this discourse and to lay the foundations for the ethical use of Twitter data.
Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model
Authors: Vaquer Sergi , Cuyàs Elisabet , Rabadán Arnau , González Albert , Fenollosa Felip , de la Torre Rafael
Published: August 2014

Microgravity has been shown to influence the expression of ABC (ATP-Binding Cassette) transporters in bacteria, fungi and mammals, but also to modify the activity of certain cellular components with structural and functional similarities to ABC transporters. Changes in activity of ABC transporters could lead to important metabolic disorders and undesired pharmacological effects during spaceflights. However, no current means exist to study the functionality of these transporters in microgravity. To this end, a Vesicular Transport Assay® (Solvo Biotechnology, Hungary) was adapted to evaluate multi-drug resistance-associated protein 2 (MRP2) trans-membrane estradiol-17-β-glucuronide (E17βG) transport activity, when activated by adenosine-tri-phosphate (ATP) during parabolic flights. Simple diffusion, ATP-independent transport and benzbromarone inhibition were also evaluated. A high accuracy engineering system was designed to perform, monitor and synchronize all procedures. Samples were analysed using a validated high sensitivity drug detection protocol. Experiments were performed in microgravity during parabolic flights, and compared to 1g on ground results using identical equipment and procedures in all cases. Our results revealed that sufficient equipment accuracy and analytical sensitivity were reached to detect transport activity in both gravitational conditions. Additionally, transport activity levels of on ground samples were within commercial transport standards, proving the validity of the methods and equipment used. MRP2 net transport activity was significantly reduced in microgravity, so was signal detected in simple diffusion samples. Ultra-structural changes induced by gravitational stress upon vesicle membranes or transporters could explain the current results, although alternative explanations are possible. Further research is needed to provide a conclusive answer in this regard. Nevertheless, the present validated technology opens new and interesting research lines in biology and human physiology with the potential for significant benefits for both space and terrestrial medicine.
The Utah Beacon Experience: Integrating Quality Improvement, Health Information
Technology, and Practice Facilitation to Improve Diabetes Outcomes in Small Healthcare
Facilities
Authors: Tennison Janet , Rajeev Deepthi , Woolsey Sarah , Black Jeff , Oostema Steven J. , North Christie
Published: August 2014

Purpose: The Utah Improving Care through Connectivity and Collaboration (IC3)
Beacon community (2010–2013) was spearheaded by HealthInsight, a nonprofit,
community-based organization. One of the main objectives of IC3 was to improve health
care provided to patients with diabetes in three Utah counties, collaborating with 21
independent smaller clinics and two large health care enterprises. This paper will focus
on the use of health information technology (HIT) and practice facilitation to develop
and implement new care processes to improve clinic workflow and ultimately improve
patients’ diabetes outcomes at 21 participating smaller, independent clinics.Innovation:
Early in the project, we learned that most of the 21 clinics did not have the resources
needed to successfully implement quality improvement (QI) initiatives. IC3helped clinics
effectively use data generated from their electronic health records (EHRs) to design and
implement interventions to improve patients’ diabetes outcomes. This close coupling of
HIT, expert practice facilitation, and Learning Collaboratives was found to be
especially valuable in clinics with limited resources.Findings: Through this process we
learned that (1) an extensive readiness assessment improved clinic retention, (2) clinic
champions were important for a successful collaboration, and (3) current EHR systems
have limited functionality to assist in QI initiatives. In general, smaller, independent
clinics lack knowledge and experience with QI and have limited HIT experience to improve
patient care using electronic clinical data. Additionally, future projects like
IC3 Beacon will be instrumental in changing clinic culture so that QI is integrated into
routine workflow.Conclusion and Discussion: Our efforts led to significant changes in
how practice staff optimized their EHRs to manage and improve diabetes care, while
establishing the framework for sustainability. Some of the IC3 Beacon practices are
currently smoothly transitioning to new models of care such as Patient-Centered Medical
Homes. Thus, IC3 Beacon has been instrumental in creating a strong community partnership
among various organizations to meet the shared vision of better health and lower costs,
and the experience over the last few years has helped the community prepare for the
changing health care landscape.
Brightfield Proximity Ligation Assay Reveals Both Canonical and Mixed Transforming Growth Factor-β/Bone Morphogenetic Protein Smad Signaling Complexes in Tissue Sections
Authors: Flanders Kathleen C. , Heger Christopher D. , Conway Catherine , Tang Binwu , Sato Misako , Dengler Samuel L. , Goldsmith Paul K. , Hewitt Stephen M. , Wakefield Lalage M.
Published: August 2014

Transforming growth factor-β (TGF-β) is an important regulator of cellular homeostasis and disease pathogenesis. Canonical TGF-β signaling occurs through Smad2/3–Smad4 complexes; however, recent in vitro studies suggest that elevated levels of TGF-β may activate a novel mixed Smad complex (Smad2/3-Smad1/5/9), which is required for some of the pro-oncogenic activities of TGF-β. To determine if mixed Smad complexes are evident in vivo, we developed antibodies that can be used with a proximity ligation assay to detect either canonical or mixed Smad complexes in formalin-fixed paraffin-embedded sections. We demonstrate high expression of mixed Smad complexes in the tissues from mice genetically engineered to express high levels of TGF-β1. Mixed Smad complexes were also prominent in 15–16 day gestation mouse embryos and in breast cancer xenografts, suggesting important roles in embryonic development and tumorigenesis. In contrast, mixed Smad complexes were expressed at extremely low levels in normal adult mouse tissue, where canonical complexes were correspondingly higher. We show that this methodology can be used in archival patient samples and tissue microarrays, and we have developed an algorithm to quantitate the brightfield read-out. These methods will allow quantitative analysis of cell type-specific Smad signaling pathways in physiological and pathological processes.
Tacrolimus Pharmacodynamics and Pharmacogenetics along the Calcineurin Pathway in Human Lymphocytes
Authors: Noceti Ofelia M , Woillard Jean-Baptiste , Boumediene Ahmed , Esperón Patricia , Taupin Jean-Luc , Gerona Solange , Valverde Marcelo , Touriño Cristina , Marquet Pierre
Published: August 2014

BACKGROUND

Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway.

METHODS

Peripheral blood mononuclear cells from 35 healthy volunteers were incubated with tacrolimus (0.1–50 ng/mL) and stimulated ex vivo. Inhibition of NFAT1 (nuclear factor of activated T cells 1) translocation to the nucleus and intracellular expression of interleukin-2 in CD4+ and CD8+ T cells and the surface activation marker CD25 in CD3+ cells were measured by flow cytometry. We sequenced the promoter regions of immunophilins and calcineurin subunits and characterized selected single nucleotide polymorphisms in the genes of the calcineurin pathway with allelic discrimination assays.

RESULTS

All responses closely fitted an I/Imax sigmoid model. Large interindividual variability (n = 30) in I0 and IC50 was found for all biomarkers. Moreover, strong and statistically significant associations were found between tacrolimus pharmacodynamic parameters and polymorphisms in the genes coding cyclophilin A, the calcineurin catalytic subunit α isoenzyme, and CD25.

CONCLUSIONS

This study demonstrates the consistency and large interindividual variability of signal transduction along the calcineurin pathway, as well as the strong influence of pharmacogenetic polymorphisms in the calcineurin cascade on both the physiological activity of this route and tacrolimus pharmacodynamics.
Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion
Authors: Kim Jongdoo , Bae Seunghee , An Sungkwan , Park Jong Kuk , Kim Eun Mi , Hwang Sang‐Gu , Kim Wun‐Jae , Um Hong‐Duck
Published: August 2014

How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21WAF1, a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2‐dependent Slug degradation and that this p53 function is mimicked by p53R273H, a mutant lacking trans‐activating activity. These actions of p21 and p53 are induced by γ‐irradiation of cells and also operate in vivo. This is the first study to elucidate a mechanism involving p53 and p21 cooperation.
Investigating property damage along Dublin Port Tunnel alignment
Authors: Gillarduzzi Andrea
Published: August 2014

During the winter of 2002/2003, Dublin City Council received various complaints regarding aesthetic and serviceability damage of several residential buildings located within the highly populated residential area of Marino (1ṡ8 km north-east of Dublin centre, in the Republic of Ireland) allegedly caused by rock-tunnelling operations of the southwards tunnel-boring machine in the northbound tunnel carried out in execution of the Dublin Port Tunnel scheme. A holistic engineering–geological ground model for the area north of Dublin centre shows that structural elements crossing the bedrock have markedly affected the geological evolution and post-glacial drainage of the site, including the formation of buried valleys. A review of groundwater monitoring and tunnel construction records has allowed the causes of settlement at ground level to be identified. These include volume loss of the ground due to deformation and local failure of the tunnel excavation, dewatering of the bedrock and of coarse strata embedded in the Boulder Clay, resulting in the removal of fine soil particles, vibro-densification due to tunnel-boring machine ground-borne vibrations, and slow production and possibly consolidation of clayey strata. A comparison between the position of the properties where damages are being claimed and that of post-glacial rivulets and lakes, backfilled in the 1920s following a rapid expansion of Dublin suburbs, clearly indicates a direct linkage between the two.
Performance of two geosynthetic reinforced walls with recycled construction waste backfill and constructed on collapsible ground
Authors: Santos E.C.G. , Palmeira E.M. , Bathurst R.J.
Published: August 2014

ABSTRACT: Geosynthetic reinforced soil walls are now an accepted technology for the solution of earth-retaining problems due to cost savings, easy and quick construction, and associated environmental benefits. Additional savings and reduction in environmental impact can be realised by using recycled construction and demolition waste (RCDW) as the backfill material. This paper describes two such structures that were built to full scale and instrumented. One of the walls was reinforced with a woven polyester geogrid (wall 1) and the other (wall 2) with a relatively more extensible nonwoven polypropylene geotextile. Both walls were constructed using RCDW as backfill material and were built on a foundation soil prone to fabric collapse due to increased stress and/or increase in moisture content. During the monitoring period the walls were subjected to a rainy season followed by induced inundation of the foundation to trigger soil fabric collapse. The results showed that foundation soil collapse influenced wall behaviour more than geosynthetic type. The exception to similar performance was local face bulging which was greater for wall 2 (geotextile) with the more extensible reinforcement under unconfined conditions than for wall 1 (geogrid) which was expected in the moving formwork construction method. However, directly behind the wall face where both reinforcement material types were confined the horizontal displacements were similar. In addition, at locations beyond half of the wall base length the strain distributions were low (1% or less) for both walls. A practical conclusion from this study is that if the wrap-face appearance at end of construction is not a concern (i.e. large bulging) then wall performance is unaffected by the choice of reinforcement types used in this investigation.