bluuebunny/crossref_metadata_2025 huggingface dataset:
Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells
Authors: Jang Jinsil , Jeong Soo-Jin , Kwon Hee-Young , Jung Ji Hoon , Sohn Eun Jung , Lee Hyo-Jung , Kim Ji-Hyun , Kim Sun-Hee , Kim Jin Hyoung , Kim Sung-Hoon
Published: May 2013

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin fromAngelica gigasand doxorubicin on the induction of apoptosis in three human multiple myeloma cells.Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells.Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.
New Iterative Method: An Application for Solving Fractional Physical Differential Equations
Authors: Hemeda A. A.
Published: May 2013

The new iterative method with a powerful algorithm is developed for the solution of linear and nonlinear ordinary and partial differential equations of fractional order as well. The analysis is accompanied by numerical examples where this method, in solving them, is used without linearization or small perturbation which confirm the power, accuracy, and simplicity of the given method compared with some of the other methods.
Bounds on the Distance Energy and the Distance Estrada Index of Strongly Quotient Graphs
Authors: Bozkurt Ş. Burcu , Adiga Chandrashekara , Bozkurt Durmuş
Published: May 2013

The notion of strongly quotient graph (SQG) was introduced by Adiga et al. (2007). In this paper, we obtain some better results for the distance energy and the distance Estrada index of any connected strongly quotient graph (CSQG) as well as some relations between the distance Estrada index and the distance energy. We also present some bounds for the distance energy and the distance Estrada index of CSQG whose diameter does not exceed two. Additionally, we show that our results improve most of the results obtained by Güngör and Bozkurt (2009) and Zaferani (2008).
Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders
Authors: Langley Adrian , Dameron Charles T.
Published: May 2013

Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.
Some Bivariate Smooth Compactly Supported Tight Framelets with Three Generators
Authors: San Antolín A. , Zalik R. A.
Published: May 2013

For any dilation matrix with integer entries and , we construct a family of smooth compactly supported tight wavelet frames with three generators in . Our construction involves some compactly supported refinable functions, the oblique extension principle, and a slight generalization of a theorem of Lai and Stöckler. Estimates for the degrees of smoothness are given. With the exception of a polynomial whose coefficients must in general be computed by spectral factorization, the framelets are expressed in closed form in the frequency domain, in terms of elementary transcendental functions. By means of two examples we also show that for low degrees of smoothness the use of spectral factorization may be avoided.
Comparative Proteomic Analysis of Peritoneal Dialysate from Chronic Glomerulonephritis Patients
Authors: Wu Hsin-Yi , Liao Alex Chien Hwa , Huang Chien-Cheng , Liao Pao-Chi , Chien Chih-Chiang , Kan Wei-Chih , Wang Hsien-Yi
Published: May 2013

Peritoneal dialysis (PD) frequently contributes to peritoneal damage which cannot be easily identified without invasive techniques, implying the urgent need for biomarkers and revealing mechanisms. Chronic glomerulonephritis (CGN) is one of the leading causes of receiving dialysis treatment. Here, we attempted to analyze the peritoneal dialysate collected from CGN patients when they receive continuous ambulatory peritoneal dialysis (CAPD) treatment for the first time and after a year to reveal the protein changes that resulted from PD. Proteins were displayed by two-dimensional gel electrophoresis (2DE). Altered gel spots were digested followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for protein identification. Eight proteins were found to have differential expression levels between two groups. Their differential expressions were validated by Western blots in other sets of peritoneal dialysates. Proteins identified with higher levels in the first-time dialysate suggested their dominant appearance in CGN patients, while those that showed higher levels in peritoneal dialysate collected after one year may result from initial peritoneal inflammation or changes in the permeability of the peritoneum to middle-sized proteins. All the identified proteins may provide a perceptiveness of peritoneal changes caused by PD and may function as potential biomarkers or drug targets.
Recovery of Extracellular Lipolytic Enzymes fromMacrophomina phaseolinaby Foam Fractionation with Air
Authors: Schinke Claudia , Germani José Carlos
Published: May 2013

Macrophomina phaseolinawas cultivated in complex and simple media for the production of extracellular lipolytic enzymes. Culture supernatants were batch foam fractionated for the recovery of these enzymes, and column design and operation included the use of P 2 frit (porosity 40 to 100 μm), air as sparging gas at variable flow rates, and Triton X-100 added at the beginning or gradually in aliquots. Samples taken at intervals showed the progress of the kinetic and the efficiency parameters. Best results were obtained with the simple medium supernatant by combining the stepwise addition of small amounts of the surfactant with the variation of the air flow rates along the separation. Inert proteins were foamed out first, and the subsequent foamate was enriched in the enzymes, showing estimated activity recovery(R), enrichment ratio(E), and purification factor(P)of 45%, 34.7, and 2.9, respectively. Lipases were present in the enriched foamate.
Developing and Testing a Middle‐Range Theory of the Well‐Being Supportive Physical Environment of Home‐Dwelling Elderly
Authors: Elo Satu , Kääriäinen Maria , Isola Arja , Kyngäs Helvi
Published: May 2013

The aim is to describe the development of a middle‐range theory by using an inductive‐deductive approach. A theory of well‐being supporting physical environment of home‐dwelling elderly is used as an example. The inductive‐deductive theory development process is described through four different phases: (1) the creations of concepts were described inductively through concept synthesis, (2) relationships between the concepts were examined to set up a hypothetical model, (3) hypotheses were set up to verify the concepts and to test hypothetical models, and (4) the verification and presentation of the theory.
Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors
Authors: Korn Ronald L. , Crowley John J.
Published: May 2013

Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors for both practical and clinical considerations. Although in its simplest form, PFS is the time from randomization to a predefined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. Clin Cancer Res; 19(10); 2607–12. ©2013 AACR.
Missing Data and Measurement Variability in Assessing Progression-Free Survival Endpoint in Randomized Clinical Trials
Authors: Sridhara Rajeshwari , Mandrekar Sumithra J. , Dodd Lori E.
Published: May 2013

Progression-free survival (PFS) is frequently used as the primary efficacy endpoint in the evaluation of cancer treatment that is considered for marketing approval. Missing or incomplete data problems become more acute with a PFS endpoint (compared with overall survival). In a given clinical trial, it is common to observe incomplete data due to premature treatment discontinuation, missed or flawed assessments, change of treatment, lack of follow-up, and unevaluable data. When incomplete data issues are substantial, interpretation of the data becomes tenuous. Plans to prevent, minimize, or properly analyze incomplete data are critical for generalizability of results from the clinical trial. Variability in progressive disease measurement between radiologists further contributes to data problems with a PFS endpoint. The repercussions of this on phase III clinical trials are complex and depend on several factors, including the magnitude of the variability and whether there is a systematic reader evaluation bias favoring one treatment arm particularly in open-label trials. Clin Cancer Res; 19(10); 2613–20. ©2013 AACR.
Modeling the Relationship between Progression-Free Survival and Overall Survival: The Phase II/III Trial
Authors: Redman Mary W. , Goldman Bryan H. , LeBlanc Michael , Schott Anne , Baker Laurence H.
Published: May 2013

The standard phase II trial design has changed dramatically over the past decade. Randomized phase II studies have essentially become the standard phase II design in oncology for a variety of reasons. The use of these designs is motivated by concerns about the use of historical data to determine if a new agent or regimen shows promise of activity. However, randomized phase II designs come with the cost of increased study duration and patient resources. Progression-free survival (PFS) is an important endpoint used in many phase II designs. In many clinical settings, changes in PFS with the introduction of a new treatment may represent true benefit in terms of the gold standard outcome, overall survival (OS). The phase II/III design has been proposed as an approach to shorten the time of discovery of an active regimen. In this article, design considerations for a phase II/III trial are discussed and presented in terms of a model defining the relationship between OS and PFS. The design is also evaluated using 15 phase III trials completed in the Southwest Oncology Group (SWOG) between 1990 and 2005. The model provides a framework to evaluate the validity and properties of using a phase II/III design. In the evaluation of SWOG trials, three of four positive studies would have also proceeded to the final analysis and 10 of 11 negative studies would have stopped at the phase II analysis if a phase II/III design had been used. Through careful consideration and thorough evaluation of design properties, substantial gains could occur using this approach. Clin Cancer Res; 19(10); 2646–56. ©2013 AACR.
Relapse of Scrotal Calcinosis 7 Years after Primary Excision
Authors: Sugihara Toru , Tsuru Nobuo , Kume Haruki , Homma Yukio , Ihara Hiroyuki
Published: May 2013

Idiopathic scrotal calcinosis is a rare, benign condition characterized by progressive calcification of the scrotal skin. A 29-year-old man who had undergone primary surgical excision of idiopathic scrotal calcinosis 7 years previously presented with recurrence that he had first noticed 3 years after surgery. Multiple yellowish nodules were observed in the scrotal skin and were confirmed by computed tomography. He underwent repeat resection without any postoperative complications. Histological examination of the surgical specimens revealed diffusely calcified areas within and beneath the squamous epithelium, some of which were associated with epithelial cysts. Immunopathological stains for antibodies against carcinoembryonic antigen, epithelial membrane antigen, and gross cystic disease fluid protein-15 were negative. This is the first reported case of recurrence of scrotal calcinosis. One possible reason for the relapse is that there were remnant seeds of calcification after the primary surgery. This case demonstrates the importance of careful identification and resection of all calcified areas, and of counseling patients about the possibility of relapse after surgical treatment.
Relapse (Number of Detoxifications) in Abstinent Male Alcohol-Dependent Patients as Related to Personality Traits and Types of Tolerance to Frustration
Authors: Baars Melanie Y. , Müller Matthias J. , Gallhofer Bernd , Netter Petra
Published: May 2013

Background: Personality traits like depression on the one hand and aggression and impulsivity on the other are assumed to be predisposing factors for different types of alcohol dependence. Both types are associated with sensitivity to frustration, but this may be different for the two types of personality according to whether they are confronted with frustrations caused by withdrawal from positive or infliction of negative events. It has not been shown so far if both types of personality factors and the two different sources of frustration are differently relevant for the propensity of relapse. This was investigated here in a study on 60 abstinent male alcohol-dependent patients. Methods: Correlations between the number of previous detoxifications reflecting liability to relapse and questionnaire scores on personality factors and on reactions to frustration were computed. Results: Bonferroni-corrected correlations yielded significant relationships between the number of detoxifications and the personality factor of aggression as well as pronounced depressive reactions to frustrating conditions of non-reward caused by humans. Controlling for impulsivity, aggression and depression revealed that depressive reactions to frustration are genuine predictors for probability of relapse independent of underlying personality factors. Persons particularly sensitive to frustrations from human denial of positive reinforcers are liable to relapse which fits the theory of sensitivity to reward in drug-addicted individuals. Conclusion: Results demonstrate that relapse is clearly more related to aggression than to impulsivity, depression and anxiety and may be facilitated if persons are sensitive to frustrating conditions of non-reward caused by social partners.
The rs9939609 Polymorphism in the FTO Gene Is Associated with Fat and Fiber Intakes in Patients with Type 2 Diabetes
Authors: Steemburgo Thais , Azevedo Mirela J. , Gross Jorge L. , Milagro Fermin I. , Campión Javier , Martínez Jose Alfredo
Published: May 2013

Background/Aims: The common polymorphism in the FTO gene (rs9939609) has been associated with obesity, type 2 diabetes, and appetite regulation. The aim of this study was to evaluate possible associations of FTO rs9939609 with dietary factors in patients with type 2 diabetes. Methods: This was a cross-sectional study of 236 patients with type 2 diabetes (age 60.0 ± 10.3 years; diabetes duration 12.7 ± 8.2 years; 53.4% females) who were genotyped for FTO rs9939609. Patients underwent clinical and laboratory evaluations and 3-day weighed diet records. Data on dietary intake were categorized as high or low, based on median values. Results: The AA genotype in the FTO gene was positively associated with high fat (>34% energy; OR = 2.17; 95% CI 1.02-4.63) and low fiber intakes (<16 g/day; OR = 2.42; 95% CI 1.05-5.57), adjusted for gender, BMI, total energy intake, systolic blood pressure, and HbA1c. When gender was taken into account, AA females had higher fat (37.4 ± 5.3 vs. 32.6 ± 7.5 and 32.2 ± 6.2% energy; p = 0.005) and lower fiber intakes (12.4 ± 4.4 vs. 15.1 ± 6.3 and 16.7 ± 5.6 g/day; p = 0.023) than patients with TT and AT genotypes. Multiple logistic regression models confirmed female associations for high fat (OR = 9.73; 95% CI 2.12-44.66) and low fiber intakes (OR = 4.28; 95% CI 1.14-16.06; p < 0.05 for all models). Conclusions: Patients with type 2 diabetes, who were carriers of the AA genotype of the FTO rs9939609, had increased fat and decreased fiber consumption, independently of BMI.
Risk Stratification in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy–Associated Desmosomal Mutation Carriers
Authors: Bhonsale Aditya , James Cynthia A. , Tichnell Crystal , Murray Brittney , Madhavan Srinivasa , Philips Binu , Russell Stuart D. , Abraham Theodore , Tandri Harikrishna , Judge Daniel P. , Calkins Hugh
Published: May 2013

Background—

We investigated the role of phenotypic characteristics in stratifying the risk of sustained ventricular arrhythmias in patients harboring arrhythmogenic right ventricular dysplasia/cardiomyopathy–associated mutations.

Methods and Results—

Clinical, electrocardiographic, and arrhythmic outcome (composite measure of first occurrence of sustained ventricular tachycardia/resuscitated sudden cardiac death/sudden cardiac death/appropriate implantable cardioverter-defibrillator therapy) data were obtained for 215 patients (104 families; 85% PKP-2). During a mean follow-up of 7 years, 86 (40%) patients experienced the arrhythmic outcome. Event-free survival was significantly lower among probands (
P
<0.001) and symptomatic (
P
<0.001) patients. Integration of ECG repolarization and depolarization abnormalities allowed for differential risk categorization. Event-free survival at 5 years for the low-risk ECG group (0–1 T inversions or minor depolarization changes) was 97% versus 81% for the intermediate-risk ECG group (2 T inversions+minor depolarization changes) versus 33% for the high-risk ECG group (≥3 T inversions±major or minor depolarization changes;
P
<0.001). Incremental arrhythmic risk was seen in patients with increasing premature ventricular complex count on a Holter (
P
<0.001). Proband status (hazard ratio, 7.7; 95% confidence interval, 2.8–22.5;
P
<0.001), ≥3 T-wave inversions (hazard ratio, 4.2; 95% confidence interval, 1.2–14.5;
P
=0.035), and male sex (hazard ratio, 1.8; 95% confidence interval, 1.2–2.8;
P
=0.004) were independent predictors of the first arrhythmic event on multivariable analysis.

Conclusions—

Pedigree evaluation, an ECG, and a Holter examination provide for comprehensive arrhythmic risk stratification in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy–associated mutations. We propose an approach to risk stratification based on these variables.
Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury
Authors: Javeshghani Danesh , Barhoumi Tlili , Idris-Khodja Nourredine , Paradis Pierre , Schiffrin Ernesto L.
Published: May 2013

Transgenic mice with endothelium-specific endothelin-1 (ET-1) overexpression exhibit endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. We previously observed that monocytes/macrophages play a role in angiotensin II, aldosterone, and deoxycorticosterone acetate/salt-induced vascular remodeling, oxidative stress, and inflammation using a model with reduced monocytes/macrophages, the osteopetrotic (Op) mouse, which has a mutation in the macrophage colony stimulating factor (
Csf1
) gene. However, it is unknown whether monocytes/macrophages are implicated in adverse vascular effects of ET-1. We hypothesized that reduction in monocytes/macrophages would blunt ET-1–induced vascular injury. We performed a study on 4- to 6-month-old male mice with endothelium-specific ET-1 overexpression (eET-1), reduction in CSF1 (
Csf1

Op/+

), or both (eET-1/
Csf1

Op/+

), and their wild-type littermate control mice. There was no difference in systolic blood pressure between groups. Endothelial function and vascular structure were determined on a pressurized myograph. Endothelium-dependent relaxation in response to acetylcholine was similar in eET-1 and eET-1/
Csf1

Op/+

mice. Media:lumen ratio and media cross-sectional area were ≈1.5-fold greater in eET-1 than in wild-type mice (
P
<0.05), which was not observed in mice deficient in CSF1. ET-1–induced oxidative stress measured by dihydroethidium staining (
P
<0.05) and NADPH oxidase activity assessed with lucigenin chemiluminescence (
P
<0.05) were blunted by CSF1 deficiency. ET-1 caused a 2.5-fold increase in monocyte/macrophage infiltration compared with wild-type mice (
P
<0.001), which was blunted in the mice deficient in CSF1. Reduction of monocyte/macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in reduced vascular remodeling and oxidative stress, providing evidence for a role of monocytes/macrophages and innate immunity in ET-1–induced vascular injury.
New species of lichenicolous fungi from the Canary Islands
Authors: PÉREZ-VARGAS ISRAEL , ETAYO JAVIER , HERNÁNDEZ-PADRÓN C.
Published: May 2013

Three new species of lichenicolous fungi from the Canary Islands (Leightoniomyces canariensis, Lichenodiplis anomalus and Perigrapha phaeophysciae), are described as new to science. A description of each species is given together with notes on their chemistry, distribution, ecology and taxonomy. Similar species are briefly discussed.
Phylogenetic relationships of Culex (Culex) species (Diptera, Culicidae) from Argentina based on morphological characters
Authors: LAURITO MAGDALENA , ALMIRÓN WALTER R.
Published: May 2013

The purpose of this study was for the first time to establish phylogenetic hypotheses among Culex (Culex) species from Argentina, and to evaluate the relationships of this subgenus with subgenera Phenacomyia and Phytotelmatomyia. We em-ployed maximum parsimony to analyse morphological characters derived from the morphology of the adult, pupal and larval stages. More than 30 figures, including photographs, illustrating 87 characters are provided. The cladistic analysis of 61 terminal taxa and 95 characters was undertaken, under implied weighting method, with a range of K values from 6 to 9. Three unstable taxa were detected therefore a reduced strict consensus tree was created. The subgenus Culex appears polyphyletic relative to subgenus Oculeomyia. The internal classification of subgenus Culex is shown to be chaotic; the Pipiens Group is polyphyletic relative to the Sitiens and Coronator Groups, the latter being polyphyletic with respect to the Pipiens Group. Phylogenetic analysis combining characters provided by morphology and molecular sources are need-ed to interpret more fully the relationships in the group.
Environment and the Lifetime of Tropical Deep Convection in a Cloud-Permitting Regional Model Simulation
Authors: Hagos Samson , Feng Zhe , McFarlane Sally , Leung L. Ruby
Published: May 2013

By applying a cloud-tracking algorithm to tropical convective systems in a regional high-resolution model simulation, this study documents the environmental conditions before and after convective systems are initiated over ocean and land by following them during their lifetime. The comparative roles of various mechanisms of convection–environment interaction on the longevity of convective systems are quantified. The statistics of lifetime, maximum area, and propagation speed of the simulated deep convection agree well with geostationary satellite observations.

Among the environmental variables considered, lifetime of convective systems is found to be most related to midtropospheric moisture before as well as after the initiation of convection. Over ocean, convective systems enhance surface fluxes through the associated cooling and drying of the boundary layer as well as increased wind gusts. This process appears to play a minor positive role in the longevity of systems. For systems of equal lifetime, those over land tend to be more intense than those over ocean especially during the early stages of their life cycle. Both over ocean and land, convection is found to transport momentum vertically to increase low-level shear and decrease upper-level shear, but no discernible effect of shear on the lifetime of the convective systems is found.
Informing Hydrometric Network Design for Statistical Seasonal Streamflow Forecasts
Authors: Rosenberg Eric A. , Wood Andrew W. , Steinemann Anne C.
Published: May 2013

A hydrometric network design approach is developed for enhancing statistical seasonal streamflow forecasts. The approach employs gridded, model-simulated water balance variables as predictors in equations generated via principal components regression in order to identify locations for additional observations that most improve forecast skill. The approach is applied toward the expansion of the Natural Resources Conservation Service (NRCS) Snowpack Telemetry (SNOTEL) network in 24 western U.S. basins using two forecasting scenarios: one that assumes the currently standard predictors of snow water equivalent and water year-to-date precipitation and one that considers soil moisture as an additional predictor variable. Resulting improvements are spatially and temporally analyzed, attributed to dominant predictor contributions, and evaluated in the context of operational NRCS forecasts, ensemble-based National Weather Service (NWS) forecasts, and historical as-issued NRCS/NWS coordinated forecasts. Findings indicate that, except for basins with sparse existing networks, substantial improvements in forecast skill are only possible through the addition of soil moisture variables. Furthermore, locations identified as optimal for soil moisture sensor installation are primarily found in regions of low to mid elevation, in contrast to the higher elevations where SNOTEL stations are traditionally situated. The study corroborates prior research while demonstrating that soil moisture data can explicitly improve operational water supply forecasts (particularly during the accumulation season), that statistical forecasts are comparable in skill to ensemble-based forecasts, and that simulated hydrologic data can be combined with observations to improve statistical forecasts. The approach can be generalized to other settings and applications involving the use of point observations for statistical prediction models.
A Free-Floating PIV System: Measurements of Small-Scale Turbulence under the Wind Wave Surface
Authors: Wang Binbin , Liao Qian , Xiao Jianen , Bootsma Harvey A.
Published: May 2013

An in situ free-floating underwater miniature particle image velocimetry (UWMPIV) system is developed and applied to measure the structure of turbulence in the aqueous side of the wind wave surface boundary layer. The UWMPIV system provides a direct way to measure the aqueous side turbulence dissipation rate and vortex structures immediately below the air–water interface, which are important parameters that determine the gas exchange rate across the air–water interface subjected to a low-to-moderate wind shear. The impact of platform motion on the measurement of small-scale turbulence is discussed and found to be insignificant. A series of field experiments under a near “zero-fetch” wind wave condition and one open water experiment under a low wind condition were conducted on Lake Michigan to demonstrate the capabilities of the free-floating particle image velocimetry (PIV) system. The dissipation rate estimated with a “direct method” and with a “spectra fitting” method are compared. Vertical profiles of the turbulence dissipation rate suggest a power-law dependency with depth below the water surface. Surface shear velocities estimated through the aqueous side Reynolds stress distribution agreed well with wind stresses estimated by the classic drag law for zero-fetch wind wave conditions, where the primary source of turbulence was wind shear. For the open water experiment under a very low wind condition, a high dissipation rate was observed near the water surface, suggesting a high turbulence production rate by surface waves, and the profile of dissipation rate showed a slower decay rate with depth in the presence of waves.
Women’s income and childbearing in context
Authors: Berninger Ina
Published: May 2013

The objective of this article is to examine the association between women’s income and first birth risks in two fairly similar countries: Denmark and Finland. The benefit of comparing these two countries is that observed variation in fertility behaviour might be attributed to the few differences in context factors, with a special focus on detailed differences in family policies. The economic theory of fertility, as well as models about bargaining processes within the family, serve as a theoretical framework for explaining individual childbearing decisions within the specific context of each country. Discrete time multiple regressions are estimated to test the hypotheses on the data from the European Community Household Panel (1994–2001). In Denmark, women’s income has a positive effect on first birth risks, but the effect in Finland is insignificant. A second result is that Finnish women who earn more than their partner have lower first birth risks than those earning approximately the same.
The importance of work
Authors: Evertsson Marie
Published: May 2013

We use the longitudinal Young Adult Panel Study to examine changes in subjective work commitment among new mothers in Sweden. With a sample of childless women in 1999, we study changes in work commitment occurring between 1999 and 2003, comparing those who had a child during this period with those who did not. In the 1999 sample, there is no difference between the two groups in terms of work commitment. However, in 2003, women who gave birth during this period are less work committed than other women. Although the changes in women’s work commitment on average are small, our findings indicate that the transition to motherhood – with all of the changes it brings – may lead to a redistribution of priorities and slightly lower work commitment among new mothers compared with non-mothers. Additional analyses indicate that the negative relationship between becoming a mother and work commitment is restricted to the first few years of a child’s life. When women have children older than four years of age, they are not less work committed than non-mothers. We interpret this lower work commitment as a way of temporarily adjusting to the difficulties of combining work and family during the early pre-school years.
The benefit of using CT-perfusion imaging for reliable response monitoring in patients with gastrointestinal stromal tumor (GIST) undergoing treatment with novel targeted agents
Authors: Betz Martina , Kopp Hans Georg , Spira Daniel , Claussen Claus D , Horger Marius
Published: May 2013

Solely size-based response criteria may be unreliable in patients with gastrointestinal stromal tumors (GIST) treated with tyrosine kinase inhibitors, because they typically underestimate responses to treatment. As GISTs are generally hypervascularized and novel targeted drugs knowingly affect angiogenic signaling pathways, perfusion measurements are expected to deliver important information about their efficacy. This pictorial essay illustrates the benefit of using complementary CT-perfusion-based measurements for more accurate evaluation of response to therapy in GIST.
Pearls and pitfalls in experimental in vivo models of migraine: Dural trigeminovascular nociception
Authors: Akerman Simon , Holland Philip R , Hoffmann Jan
Published: May 2013

Background

Migraine is a disorder of the brain and is thought to involve activation of the trigeminovascular system, which includes the peripheral afferent projection to the nociceptive specific dura mater, as well as the central afferent projection to the trigeminal nucleus caudalis. Stimulation of the blood vessels of the dura mater produces pain in patients that is referred to the head similar to headache.

Headache mechanisms

The likely reason for the pain is because the vascular structures of the dura mater, including the superior sagittal sinus and middle meningeal artery, are richly innervated by a plexus of largely unmyelinated sensory nerve fibers from the ophthalmic division of the trigeminal ganglion.

Methodology

Stimulation of these nociceptive specific nerve fibers is painful and produces neuronal activation in the trigeminal nucleus caudalis. Preclinical models of headache have taken advantage of this primarily nociceptive pathway, and various animal models use dural trigeminovascular nociception to assay aspects of head pain. These assays measure responses at the level of the dural vasculature and the central trigeminal nucleus caudalis as a correlate of trigeminovascular activation thought to be involved in headache.

This review will summarize the history of the development of models of dural trigeminovascular nociception, including intravital microscopy and laser Doppler flowmetry at the level of the vasculature, and electrophysiology and Fos techniques used to observe neuronal activation at the trigeminal nucleus caudalis. It will also describe some of pitfalls of these assays and developments for the future.
Pearls and pitfalls: Neurostimulation in headache
Authors: Jürgens Tim P , Leone Massimo
Published: May 2013

Context

A variety of neuromodulatory approaches available today has broadened our therapeutic options significantly especially in drug refractory patients with chronic cluster headache and chronic migraine.

Overview

It is a dynamic field with a current trend to non-invasive transcutaneous stimulation approaches. However, sound studies providing evidence for the widespread use of these novel approaches are sparse. For invasive approaches, occipital nerve stimulation is now widely considered the treatment of first choice in chronic trigeminal autonomic cephalgias and – with limitations – chronic migraine. Although equally effective, deep brain stimulation is considered second-line treatment in cluster headache because of its potentially life-threatening side effects. Most recently, stimulation of the sphenopalatine ganglion has also been shown to effectively abort acute cluster headache attacks. Interesting other upcoming approaches include transcutaneous supraorbital nerve stimulation and transcutaneous vagal nerve stimulation.

Conclusion

Pearls and pitfalls of common invasive and non-invasive neuromodulatory approaches and open questions are summarised in this review along with recommendations for future studies.
Embedded dialogue and dreams: the worlds and accessibility relations of Inception
Authors: Lugea Jane
Published: May 2013

In this article, Text World Theory (Gavins, 2007; Werth, 1999) and Ryan’s model of fictional worlds (1991a, 1991b) are both applied to Nolan’s blockbuster film, Inception (2010) to explore the multi-layered architecture of the narrative. The opening two scenes of Nolan’s screenplay are analysed using Text World Theory, with particular attention to the embedded nature of character dialogue, or, more generally, ‘represented discourse’ (Herman, 1993), otherwise known as Direct Speech (Leech and Short, 2007). Based on this analysis, I suggest a modification to the way in which Text World Theory deals with represented discourse, which improves the framework’s applicability to all text types. Moving from the micro-analysis of the screenplay text, to a macro-analysis of the film narrative as a whole, I outline the various different worlds that make up the reality, dream and ‘limbo’ layers in the film, explaining how most of the action takes place at a remove from the world at the centre of the textual system. I use Deictic Shift Theory’s terms PUSH and POP (Galbraith, 1995) to describe the movements between the ontological layers of the narrative and suggest that these terms are better suited to describe hierarchies of ontology rather than horizontal deictic shifts. Ryan’s taxonomy of accessibility relations is used to describe the ways in which the film differs from reality, as well as the ways in which the dreams differ from the internal reality of the film. The complex ontological structure and asymmetric accessibility relations between the worlds are ascribed as the reason for many viewers’ difficulty in processing the film’s narrative. With its attention to discourse-world factors, Text World Theory is then used to account for the myriad of reactions to Inception – as expressed on online discussion forums – which range from engagement and enjoyment to frustration and resistance.
Selecting an Asset Management System for Intelligent Transportation Systems
Authors: Fries Ryan , Anjuman Tahera , Chowdhury Mashrur
Published: May 2013

Intelligent Transportation System (ITS) often includes technologically sophisticated devices, computer hardware and software, and communications infrastructure; for which traditional asset management tools are not always appropriate. In challenging economic times, it is essential that public agencies manage their ITS systemsmore efficiently, yet ITS asset management is new to many. There is a need to review different asset management systems for their ability to support the ITS needs of public transportation agencies. The primary contribution of this paperis establishing a method for making this comparison andidentifying measures of effectiveness to use for evaluating such systems. Thesemeasuresof effectiveness were identified through a nationwide survey of public transportation agencies and the method was demonstrated through a case study in South Carolina.
Intermolecular interactions of the malate synthase of Paracoccidioides spp
Authors: de Oliveira Karine Martins , da Silva Neto Benedito Rodrigues , Parente Juliana Alves , da Silva Roosevelt Alves , Quintino Guilherme Oliveira , Voltan Aline Raquel , Mendes-Giannini Maria José Soares , de Almeida Soares Célia Maria , Pereira Maristela
Published: May 2013

Background

The fungus Paracoccidioides spp is the agent of paracoccidioidomycosis (PCM), a pulmonary mycosis acquired by the inhalation of fungal propagules. Paracoccidioides malate synthase (PbMLS) is important in the infectious process of Paracoccidioides spp because the transcript is up-regulated during the transition from mycelium to yeast and in yeast cells during phagocytosis by murine macrophages. In addition, PbMLS acts as an adhesin in Paracoccidioides spp. The evidence for the multifunctionality of PbMLS indicates that it could interact with other proteins from the fungus and host. The objective of this study was to identify and analyze proteins that possibly bind to PbMLS (PbMLS-interacting proteins) because protein interactions are intrinsic to cell processes, and it might be possible to infer the function of a protein through the identification of its ligands.

Results

The search for interactions was performed using an in vivo assay with a two-hybrid library constructed in S. cerevisiae; the transcripts were sequenced and identified. In addition, an in vitro assay using pull-down GST methodology with different protein extracts (yeast, mycelium, yeast-secreted proteins and macrophage) was performed, and the resulting interactions were identified by mass spectrometry (MS). Some of the protein interactions were confirmed by Far-Western blotting using specific antibodies, and the interaction of PbMLS with macrophages was validated by indirect immunofluorescence and confocal microscopy. In silico analysis using molecular modeling, dynamics and docking identified the amino acids that were involved in the interactions between PbMLS and PbMLS-interacting proteins. Finally, the interactions were visualized graphically using Osprey software.

Conclusion

These observations indicate that PbMLS interacts with proteins that are in different functional categories, such as cellular transport, protein biosynthesis, modification and degradation of proteins and signal transduction. These data suggest that PbMLS could play different roles in the fungal cell.
Polymorphisms of PTPN11 gene could influence serum lipid levels in a sex-specific pattern
Authors: Jia Zhi-Fang , Cao Xue-Yuan , Cao Dong-Hui , Kong Fei , Kharbuja Punyaram , Jiang Jing
Published: May 2013

Background

Previous studies have reported that different genotypes of PTPN11 gene (protein tyrosine phosphatase, non-receptor 11) were associated with different levels of serum lipids. The aim of this study was to explore the relationship between single nucleotide polymorphisms (SNPs) of PTPN11 and serum lipids in Northeast Chinese.

Methods

A total of 1003 subjects, 584 males and 419 females, were included in the study and their serum lipids were determined. Five htSNPs (rs2301756, rs12423190, rs12229892, rs7958372 and rs4767860) of PTPN11 gene were genotyped using TaqMan assay method.

Results

All of the five SNPs were in Hardy-Weinberg equilibrium. The male subjects had higher triglyceride (TG), higher low-density lipoprotein cholesterol (LDL-C) and lower high-density lipoprotein cholesterol (HDL-C) level than females. In males, rs4767860 was found to be associated with serum TG and total cholesterol (TC) levels and rs12229892 was associated with TC level. However, these significant associations could not be observed in females. In females, rs2301756 was found to be associated with TG and rs7958372 was associated with LDL-C level. Haplotype analysis showed that the GCGTG haplotype was associated with slightly higher TG level and ATGCG with higher TC level.

Conclusions

SNPs of PTPN11 may play a role in serum lipids in a sex-specific pattern. However, more studies are needed to confirm the conclusion and explore the underlying mechanism.
SF2/ASF binding region within JC virus NCCR limits early gene transcription in glial cells
Authors: Uleri Elena , Regan Patrick , Dolei Antonina , Sariyer Ilker Kudret
Published: May 2013

Background

Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the white matter caused by human neurotropic polyomavirus, JC virus. It is now widely accepted that pathologic strains of JCV shows unique rearrangements consist of deletions and insertions within viral NCCR. While these kinds of rearrangements are related to viral tropism and pathology of the disease, their roles in molecular regulation of JCV gene expression and replication are unclear. We have previously identified SF2/ASF as a negative regulator of JCV gene expression in glial cells. This negative impact of SF2/ASF was dependent on its ability to bind a specific region mapped to the tandem repeat within viral promoter. In this report, functional role of SF2/ASF binding region in viral gene expression and replication was investigated by using deletion mutants of viral regulatory sequences.

Results

The second 98-base-pair tandem repeat on Mad1 strain was first mutated by deletion and named Mad1-(1X98). In addition to this mutant, the CR3 region which served the binding side for SF2/ASF was also mutated and named Mad1-ΔCR3 (1X73). Both mutations were tested for SF2/ASF binding by ChIP assay. While SF2/ASF was associated with Mad1-WT and Mad1-(1X98), its interaction was completely abolished on Mad1-ΔCR3 (1X73) construct as expected. Surprisingly, reporter gene analysis of Mad1-(1X98) and Mad1-ΔCR3 (1X73) early promoter sequences showed two and three fold increase in promoter activities, respectively. The impact of “CR3” region on JCV propagation was also tested on the viral background. While replication of Mad1-(1X98) strain in glial cells was similar to Mad1-WT strain, propagation of Mad1-ΔCR3 (1X73) was less productive. Further analysis of the transcription mediated by Mad1-ΔCR3 (1X73) NCCR revealed that late gene expression was significantly affected.

Conclusions

The results of this study reveal a differential role of CR3 region within JCV NCCR in expression of JCV early and late genes.
Human monoclonal ScFv that bind to different functional domains of M2 and inhibit H5N1 influenza virus replication
Authors: Pissawong Tippawan , Maneewatch Santi , Thueng-in Kanyarat , Srimanote Potjanee , Dong-din-on Fonthip , Thanongsaksrikul Jeeraphong , Songserm Thaweesak , Tongtawe Pongsri , Bangphoomi Kunan , Chaicumpa Wanpen
Published: May 2013

Background

Novel effective anti-influenza agent that tolerates influenza virus antigenic variation is needed. Highly conserved influenza virus M2 protein has multiple pivotal functions including ion channel activity for vRNP uncoating, anti-autophagy and virus assembly, morphogenesis and release. Thus, M2 is an attractive target of anti-influenza agents including small molecular drugs and specific antibodies.

Methods

Fully human monoclonal single chain antibodies (HuScFv) specific to recombinant and native M2 proteins of A/H5N1 virus were produced fromhuscfv-phagemid transformedE. coliclones selected from a HuScFv phage display library using recombinant M2 of clade 1 A/H5N1 as panning antigen. The HuScFv were tested for their ability to inhibit replication of A/H5N1 of both homologous and heterologous clades. M2 domains bound by HuScFv of individualE. coliclones were identified by phage mimotope searching and computerized molecular docking.

Results

HuScFv derived from fourhuscfv-phagemid transformedE. coliclones (no. 2, 19, 23 and 27) showed different amino acid sequences particularly at the CDRs. Cells infected with A/H5N1 influenza viruses (both adamantane sensitive and resistant) that had been exposed to the HuScFv had reduced virus release and intracellular virus. Phage peptide mimotope search and multiple alignments revealed that conformational epitopes of HuScFv2 located at the residues important for ion channel activity, anti-autophagy and M1 binding; epitopic residues of HuScFv19 located at the M2 amphipathic helix and cytoplasmic tail important for anti-autophagy, virus assembly, morphogenesis and release; epitope of HuScFv23 involved residues important for the M2 activities similar to HuScFv2 and also amphipathic helix residues for viral budding and release while HuScFv27 epitope spanned ectodomain, ion channel and anti-autophagy residues. Results of computerized homology modelling and molecular docking conformed to the epitope identification by phages.

Conclusions

HuScFv that bound to highly conserved epitopes across influenza A subtypes and human pathogenic H5N1clades located on different functional domains of M2 were produced. The HuScFv reduced viral release and intracellular virus of infected cells. While the molecular mechanisms of the HuScFv await experimental validation, the small human antibody fragments have high potential for developing further as a safe, novel and mutation tolerable anti-influenza agent especially against drug resistant variants.