bluuebunny/crossref_metadata_2025 huggingface dataset:
WNT‐3A and WNT‐5A counteract lipopolysaccharide‐induced pro‐inflammatory changes in mouse primary microglia
Authors: Halleskog Carina , Schulte Gunnar
Published: March 2013

Surveying microglia, the resident macrophage‐like cells in the central nervous system, continuously screen their surroundings to sense imbalance in tissue homeostasis. Their activity is tightly regulated in both a pro‐ and anti‐inflammatory manner. We have previously shown that the lipoglycoproteins WNT‐3A and WNT‐5A drive pro‐inflammatory transformation in primary mouse microglia cells, arguing that WNTs have a role in the modulation of the central nervous system immune response. In this study, we address the effects of recombinant WNT‐3A and WNT‐5A on lipopolysaccharide (LPS)‐activated mouse primary microglia to investigate the putative anti‐inflammatory modulation of microglia by WNTs. While both WNT‐3A and WNT‐5A alone induce an up‐regulation of cyclooxygenase 2 (COX2), a generic pro‐inflammatory microglia marker, LPS exceeds these effects dramatically. However, combination of LPS and WNTs results in a dose‐dependent decrease in LPS‐induced cyclooxygenase 2 protein and mRNA expression. In conclusion, our data suggest that WNTs have a dual and context‐dependent effect on microglia acting in a homeostatic pro‐ and anti‐inflammatory manner.
Heat‐mediated enrichment of α‐synuclein from cells and tissue for assessing post‐translational modifications
Authors: Miranda Hugo Vicente , Xiang Wei , de Oliveira Rita M. , Simões Tânia , Pimentel José , Klucken Jochen , Penque Deborah , Outeiro Tiago F.
Published: March 2013

α‐synuclein (α‐syn) is the major component of Lewy bodies, a pathological hallmark of Parkinson's disease and other synucleinopathies. The characterization of α‐syn post‐translational modifications (PTMs), thought to interfere with its aggregation propensity and cellular signaling, has been limited by the availability of extraction methods of endogenous protein from cells and tissues, and by the availability of antibodies toward α‐syn PTMs. Here, by taking advantage of α‐syn thermostability, we applied a method to achieve high enrichment of soluble α‐syn both from cultured cells and brain tissues followed by proteomics analysis. Using this approach, we obtained 98% α‐syn sequence coverage in a variety of model systems, including a transgenic mouse model of PD, and validated the strategy by identifying previously described PTMs such as phosphorylation and N‐terminal acetylation. Our findings demonstrate that this procedure overcomes existing technical limitations and can be used to facilitate the systematic study of α‐syn PTMs, thereby enabling the clarification of their role under physiological and pathological conditions. Ultimately, this approach may enable the development of novel biomarkers and strategies for therapeutic intervention in synucleinopathies.

image

In this study, we describe a method for enriching alpha‐synuclein (α‐syn) from a variety of biological samples, from cultured cells to brain tissues. Enrichment of α‐syn was achieved by heating samples, further facilitating the identification of specific post‐translational modifications by immunoblot, or mass spectrometry‐based techniques. This approach will contribute to the clarification of the role of α‐syn PTMs in Parkinson's disease.
Looking at the world through a frosted window: experiences of loneliness among persons with mental ill‐health
Authors: Lindgren B.‐M. , Sundbaum J. , Eriksson M. , Graneheim U. H.
Published: March 2013

Accessible summary

Experiences of loneliness among people with mental ill‐health can be metaphorically described as looking at the world through a frosted window.

The experiences are multifaceted and developing as well as emotionally and socially excluding.

People suffering from mental ill‐health and loneliness carry a twofolded stigma. They feel socially undesirable, and the social perceptions of lonely people are generally unfavourable.

Mental ill‐health is reported to be of major concern in public health. Persons suffering from mental ill‐health are a vulnerable group, and loneliness influences the perception of physical, social, and emotional well‐being. However, there are few studies exploring lived experiences of loneliness among people with mental ill‐health. This qualitative study aimed to illuminate experiences of loneliness among people with mental ill‐health. Five individual, informal conversational interviews were performed and subjected to qualitative content analysis. The main findings showed that experiences of loneliness could be metaphorically described as looking at the world through a frosted window. The experiences of loneliness were multifaceted and altering as well as emotionally and socially excluding. The findings are discussed in relation to Tillich dimensions of loneliness: loneliness as a painful dimension of being alone, and solitude as the enriching dimension of being alone. People suffering from mental ill‐health carry a twofolded stigma. They feel socially undesirable because of their mental ill‐health, and the social perceptions of lonely people are generally unfavourable. We believe that mental health nurses can support the developing and creative dimension of loneliness through a confirming approach, where people with mental ill‐health feel seen, heard, and respected as human beings.
Long-Term Evaluation of Donor-Site Morbidity After Radial Forearm Flap Phalloplasty for Transsexual Men
Authors: Van Caenegem Eva , Verhaeghe Evelien , Taes Youri , Wierckx Katrien , Toye Kaatje , Goemaere Stefan , Zmierczak Hans-Georg , Hoebeke Piet , Monstrey Stan , T'Sjoen Guy
Published: March 2013

Introduction

Phalloplasty using the radial forearm flap is currently the most frequently used technique to create the neophallus in transsexual men (formerly described as female-to-male transsexual persons). Although it is considered the gold standard, its main disadvantage is the eventual donor-site morbidity in a young, healthy patient population.

Aim

The study aims to examine the long-term effects of radial forearm flap phalloplasty in transsexual men and to evaluate aesthetic outcome, scar acceptance, bone health, and daily functioning.

Main Outcome Measures

Scars were evaluated with the patient and observer scar assessment scale, the Vancouver Scar Scale, and self-reported satisfaction. Bone health was assessed using dual X-ray absorptiometry and peripheral quantitative computed tomography, and daily functioning using a physical activity questionnaire (Baecke). These measurements were compared with 44 age-matched control women.

Methods

This is a cross-sectional study of 44 transsexual, a median of 7 years after radial forearm flap phalloplasty, recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital, Belgium.

Results

We observed no functional limitations on daily life activities, a pain-free and rather aesthetic scar, and unaffected bone health a median of 7 years after radial foreram flap phalloplasty. Over 75% of transsexual men were either satisfied or neutral with the appearance of the scar.

Conclusions

Transsexual men, despite scarring the forearm, consider the radial forearm flap phalloplasty as worthwhile.
Sexual Functioning in Women with Mild and Severe Symptoms of Charcot-Marie-Tooth Disease
Authors: Gargiulo Paola , Vinci Paola , Navarro-Cremades Felipe , Rellini Alessandra H.
Published: March 2013

Introduction

Charcot-Marie-Tooth (CMT) disease is one of the most frequently inherited neurological disorders, and while it is known that individuals suffering from this condition have low quality of life, little is known about their sexual function and satisfaction.

Aim

To describe the functioning on different domains of sexuality in a relatively large sample of women with CMT, provide comparisons between mildly and severely affected patients and between women with the two different types of CMT (demyelinating vs. axonal), and assess the relationship between sexual function and age of onset.

Methods

Fifty-seven women (age: 18–60 years) were approached in a CMT rehabilitation clinic by a psychologist and administered the Italian version of the McCoy Female Sexuality Questionnaire (MFSQ). Data from 40 patients who had had sexual intercourse in the previous 4 weeks were analyzed.

Main Outcome Measure

The main outcome measures are the factors MFSQ-SEX and MFSQ-PARTNER, which describe sexual functioning and sexual satisfaction with a partner, respectively.

Results

Almost 30% of women did not engage in sexual intercourse with a partner. Overall sexual problems were more prominent in younger women and tended to be lower as age increased: this pattern was different from what was reported in previous studies in comparable samples of healthy Italian women. Severity of CMT was associated with better sexual functioning in the areas of desire, arousal, orgasm, and satisfaction, with women with more severe symptoms reporting greater functioning. Women with more severe CMT symptoms reported more pain during intercourse. Age of CMT onset and type of CMT (demyelinating vs. axonal) were not associated with differences in sexual functioning.

Conclusions

Findings point to the importance of including assessment of sexual dysfunction in young women with mild CMT symptoms and the importance of providing sex therapy or counseling to these patients.
Dysembryoplastic neuroepithelial tumor, a pure glial tumor? Immunohistochemical and morphometric studies
Authors: Komori Takashi , Arai Nobutaka
Published: March 2013

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal tumor, occurring in children and adolescents, typically associated with drug‐resistant partial seizures. Pathologically, DNT is characterized by a specific glioneuronal element that is comprised of oligodendroglia‐like cells (OLC) and floating neurons. The definition of DNT is currently controversial and the incidence of DNT varies among institutions. In this study we characterize the morphologic profiles of OLC and floating neurons by performing immunohistochemical and morphometric studies on seven cases of a simple form of DNT. While a majority of OLC was positive for oligodendrocyte transcription factor 2 (Olig2), only floating neurons and a few small cells were positive for neuronal nuclear antigens (NeuN). Double immunofluorescence studies revealed co‐localization of Olig2 and galectin 3 in OLC, but no co‐localization of Olig2 and NeuN. The distribution pattern of NeuN‐positive nuclei within the tumor tissue was not different from that in the adjacent neural tissue. A section cut perpendicular to the cortex stained with NeuN showed a continuous laminar arrangement with the adjacent cortex. Densities of NeuN‐positive nuclei from tumors embedded in the white matter were significantly lower than those from tumors in the gray matter. Our results suggest that the NeuN‐positive small and large cells observed within the specific glioneuronal element are in fact entrapped granular and pyramidal cells within the cortex and that OLCs are essentially glial and not neuronal in nature. DNT is thus a pure glial tumor rather than a glioneuronal tumor, that is, the equivalent of non‐infiltrating oligodendroglioma, grade I.
Modelling metabolic CO2 evolution – a fresh perspective on respiration
Authors: SWEETLOVE LEE J. , WILLIAMS THOMAS C. R. , CHEUNG C. Y. MAURICE , RATCLIFFE R. GEORGE
Published: March 2013

Respiration is a major contributor to net exchange of CO2 between plants and the atmosphere and thus an important aspect of the vegetation component of global climate change models. However, a mechanistic model of respiration is lacking, and so here we explore the potential for flux balance analysis (FBA) to predict cellular CO2 evolution rates. Metabolic flux analysis reveals that respiration is not always the dominant source of CO2, and that metabolic processes such as the oxidative pentose phosphate pathway (OPPP) and lipid synthesis can be quantitatively important. Moreover, there is considerable variation in the metabolic origin of evolved CO2 between tissues, species and conditions. Comparison of FBA‐predicted CO2 evolution profiles with those determined from flux measurements reveals that FBA is able to predict the metabolic origin of evolved CO2 in different tissues/species and under different conditions. However, FBA is poor at predicting flux through certain metabolic processes such as the OPPP and we identify the way in which maintenance costs are accounted for as a major area of improvement for future FBA studies. We conclude that FBA, in its standard form, can be used to predict CO2 evolution in a range of plant tissues and in response to environment.
POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer
Authors: Ishii Jun , Sato Hanako , Sakaeda Masashi , Shishido‐Hara Yukiko , Hiramatsu Chie , Kamma Hiroshi , Shimoyamada Hiroaki , Fujiwara Masachika , Endo Tetsuya , Aoki Ichiro , Yazawa Takuya
Published: March 2013

BRN2 is a developmental neural cell‐specific POU domain transcription factor and is crucial for cell lineage determination. We investigated the importance of BRN2 in the expression of the lineage‐specific transcription factors (achaete‐scute homolog‐like 1 (ASCL1) and NeuroD1 (ND1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP) and chromogranin A (CHGA)) in small cell lung cancer (SCLC) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN2, as well as ASCL1, ND1, NCAM1, SYP and CHGA. The expression levels of ASCL1, ND1, NCAM1, SYP and CHGA considerably decreased when BRN2 was knocked down in SCLC cells, and the addition of a BRN2 transgene into non‐SCLC (NSCLC) cells induced the expression of ASCL1, ND1, NCAM1, SYP and CHGA. However, the BRN2 gene was not activated by the forced expression of ASCL1 or ND1 in NSCLC cells. The knockdown of BRN2 caused significant growth retardation with decrease of S to G2 phase population and mitotic cell rates and unaltered Ki‐67‐labeled or apoptotic cell rates in SCLC cells, indicating increase of G1 phase population. These findings suggest that BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of SCLC.
Ectopic expression of wheat TaCIPK14, encoding a calcineurin B‐like protein‐interacting protein kinase, confers salinity and cold tolerance in tobacco
Authors: Deng Xiaomin , Zhou Shiyi , Hu Wei , Feng Jialu , Zhang Fan , Chen Lihong , Huang Chao , Luo Qingchen , He Yanzhen , Yang Guangxiao , He Guangyuan
Published: March 2013

Calcineurin B‐like protein‐interacting protein kinases (CIPKs) are components of Ca2+ signaling in responses to abiotic stresses. In this work, the full‐length cDNA of a novel CIPK gene (TaCIPK14) was isolated from wheat and was found to have significant sequence similarity to OsCIPK14/15. Subcellular localization assay revealed the presence of TaCIPK14 throughout the cell. qRT‐PCR analysis showed that TaCIPK14 was upregulated under cold conditions or when treated with salt, PEG or exogenous stresses related signaling molecules including ABA, ethylene and H2O2. Transgenic tobaccos overexpressing TaCIPK14 exhibited higher contents of chlorophyll and sugar, higher catalase activity, while decreased amounts of H2O2 and malondialdehyde, and lesser ion leakage under cold and salt stresses. In addition, overexpression also increased seed germination rate, root elongation and decreased Na+ content in the transgenic lines under salt stress. Higher expression of stress‐related genes was observed in lines overexpressing TaCIPK14 compared to controls under stress conditions. In summary, these results suggested that TaCIPK14 is an abiotic stress‐responsive gene in plants.
Geological and Geochemical Characteristics of the Huangshilao Stratabound Gold Deposit in the Tongguanshan Orefield, Tongling, East‐Central China
Authors: Li Gongjian , Wang Qingfei , Wang Jiaqi , Fang Qilin
Published: March 2013

The Huangshilao gold deposit (>13.5 t Au) is comprised of stratabound pyrite‐dominant massive sulfide ores, and is distinguished from the skarn Cu, Au, and Cu–Au deposits that are dominant in the Tongguanshan orefield, Tongling, east‐central China. The stratabound orebodies are situated along flexural slip faults along the unconformity between the Upper Devonian Wutong and the Upper Carboniferous Huanglong Formations. The ores, dominated by crystallized pyrite, colloform pyrite, and pyrrhotite, are systematically sampled from the underground stopes along strike drifts. The δ34S values of ore sulfides yield a wide variation from −11.3 to 11.4‰, but mostly within 4–8‰, corresponding to the δ34S range (3.4–8.7‰) of the Yanshanian Tongguanshan and Tianshan quartz diorite intrusions in the Tongguanshan orefield, suggesting a magmatic dominated sulfur source. Few obvious negative δ34S values are induced by an involvement of sedimentation‐related biogenic sulfur. The wide δ34S variation denotes an incongruent physical and chemical interaction of the two sources. Combined analysis of gold contents and sulfur isotopes of the sulfides show that the magmatic hydrothermal solution provides primary metals despite a small quantity that may have been contributed by the sedimentary pyrites. The hydrothermal alteration, thermal metamorphism, trace element concentration in pyrites, and existing aeromagnetic data jointly suggest that the hydrothermal fluid migrated vertically from an intrusion below, along the flexural slip faults, but not laterally from the nearby outcrop of Tianshan stock.
Characteristics of Mineralizing Fluids of the Darreh‐Zerreshk and Ali‐Abad Porphyry Copper Deposits, Central Iran, Determined by Fluid Inclusion Microthermometry
Authors: Zarasvandi Alireza , Liaghat Sassan , Lentz David , Hossaini Mahboobeh
Published: March 2013

The Darreh‐Zereshk (DZ) and Ali‐Abad (AB) porphyry copper deposits are located in southwest of the Yazd city, central Iran. These deposits occur in granitoid intrusions, ranging in composition from quartz monzodiorite through granodiorite to granite. The ore‐hosting intrusions exhibit intense hydrofracturing that lead to the formation of quartz‐sulfide veinlets. Fluid inclusions in hydrothermal quartz in these deposits are classified as a mono‐phase vapor type (Type I), liquid‐rich two phase (liquid + vapor) type (Type IIA), vapor‐rich two phase (vapor + liquid) type (Type IIB), and multi‐phase (liquid + vapor + halite + sylvite + hematite + chalcopyrite and pyrite) type (Types III). Homogenization temperatures (Th) and salinity data are presented for fluid inclusions from hydrothermal quartz veinlets associated with potassic alteration and other varieties of hypogene mineralization. Ore precipitation occurred between 150° to >600°C from low to very high salinity (1.1–73.9 wt% NaCl equivalent) aqueous fluids. Two stages of hydrothermal activity characterized are recognized; one which shows relatively high Th and lower salinity fluid (Type IIIa; Th(L‐V) > Tm(NaCl)); and one which shows lower Th and higher salinity (Type IIIb; Th(L‐V) < Tm(NaCl)). The high Th(L‐V) and salinities of Type IIIa inclusions are interpreted to represent the initial existence of a dense fluid of magmatic origin. The coexistence of Type IIIb, Type I and Type IIB fluid inclusions suggest that these inclusions resulted either from trapping of boiling fluids and/or represent two immiscible fluids. These processes probably occurred as the result of pressure fluctuations from lithostatic to hydrostatic conditions under a pressure of 200 to 300 bar. Dilution of these early fluids by meteoritic water resulted in lower temperatures and low to moderate salinity (<20 wt% NaCl equiv.) fluids (Type IIA). Fluid inclusion analysis reveals that the hydrothermal fluid, which formed mineralized quartz veinlets in the rocks with potassic alteration, had temperatures of ∼500°C and salinity ∼50 wt% NaCl equiv. Cryogenic SEM‐EDS analyses of frozen and decrepitated ore‐bearing fluids trapped in the inclusions indicate the fluids were dominated with NaCl, and KCl with minor CaCl2.
Mean central corneal thickness and corneal power measurements in pigmented and white rabbits using Visante optical coherence tomography and ATLAS corneal topography
Authors: Wang Xiaogang , Dong Jing , Wu Qiang
Published: March 2013

Objective

To document central corneal thickness (CCT) and power measurements in pigmented and white rabbits using Visante anterior segment optical coherence tomography (AS‐OCT) and the Humphrey ATLAS Corneal Topography System (HACTS).

Animal studied

Fourteen female rabbits (seven pigmented and seven white rabbits) were involved in this study.

Procedure

Twenty‐eight eyes underwent AS‐OCT and HACTS examination. Central corneal thickness, corneal power in the steepest and flattest meridians, astigmatism, pupil diameter (PD), and white‐to‐white (WTW) were calculated.

Results

The CCT was 390 ± 14.2 and 373 ± 7.2 μm for pigmented and white rabbits, respectively. The CCT values showed statistical difference between the two breeds (P = 0.017). The corneal power in the steepest meridian was 44.6 ± 1.9 Diopter (D) in pigmented rabbits and 47.8 ± 1.5 D in white rabbits. The corneal power in the flattest meridian was 44.0 ± 2.1 D in pigmented rabbits and 47.4 ± 1.5 D in white rabbits. The astigmatism, PD, and WTW values were 0.6 ± 0.22 D, 7.9 ± 0.9, and 14.5 ± 0.1 mm in pigmented rabbits, respectively. The corresponding values in white rabbits were 0.4 ± 0.23 D, 7.5 ± 0.5, and 13.5 ± 0.2 mm. There was a statistically significant difference in corneal power in the steepest and flattest meridians and for WTW. No such difference was observed for astigmatism or PD between them.

Conclusions

Differences exist in the CCT, corneal power, and WTW between 5‐month‐old pigmented and white rabbits. Such difference should be considered when designing cornea‐related experiments in rabbits.
Decision support systems in water resources in the demarcated region of Douro – case study in Pinhão river basin, Portugal
Authors: Fernandes Luís Filipe Sanches , Marques Maria João , Oliveira Paula Cristina , Moura João Paulo
Published: March 2013

This paper puts forward the importance of decision support systems (DSS) for the planning and management of water resources. A case study of the Pinhão river basin, in Portugal, is presented. Given the importance of vineyards in the Douro region, it is important to determine if water availability will be enough to meet present and future water demands. In order to answer this question, DSS tools were used to assess different scenarios. The MIKE BASIN software was used in the hydrographical basin of Pinhão river, assisted by a geographic information system, GIS, which allowed the modelling of the basin, both temporally and spatially, facilitating the visualisation and interpretation of results. According to the attained results, it was verified that, at present, the hydrographical basin meets the considered water needs. The DSS proved to be an important tool to assist the decision‐making process in the studied river basin.
Cable Modeling and Internal Damping Developments
Authors: Spak Kaitlin , Agnes Gregory , Inman Daniel
Published: March 2013

This paper reviews models of helical cable behavior with an emphasis on recent models that study internal cable damping. Cable models are categorized into three major classes consisting of thin rod models, semicontinuous models, and beam models. Research on cable vibration damping resulting from internal factors is investigated and related, with conclusions supported by multiple bodies of work highlighted and inconsistencies that may require further study noted. Internal damping mechanisms due to interwire friction, variable bending stiffness, and internal and viscoelastic dissipation are explored with specific damping terms presented for the various models. Damping through inclusion of friction forces, viscoelastic shear effects, or bending stiffness as a function of cable curvature and wire properties must be included to produce a realistic cable model.
Nonlinear Dynamic Probabilistic Analysis for Turbine Casing Radial Deformation Using Extremum Response Surface Method Based on Support Vector Machine
Authors: Fei Chengwei , Bai Guangchen
Published: March 2013

To improve the computational efficiency of nonlinear dynamic probabilistic analysis for aeroengine typical components, an extremum response surface method based on the support vector machine (SVM ERSM) was proposed in this paper. The basic principle was introduced and the mathematical model was established for the SVM ERSM. The probabilistic analysis of turbine casing radial deformation was taken as an example to validate the SVM ERSM considering the influences of nonlinear material property and dynamic heat loads. The results of probabilistic analysis imply that the distribution features of random parameters and the major factors are gained for more accurate the design of casing radial deformation. The SVM ERSM offers a feasible and valid method, which possesses high efficiency and high precision in the nonlinear dynamic probabilistic analysis. Moreover, the SVM ERSM is promising to provide an useful insight for casing dynamic optimal design and the blade-tip clearance control of aeroengine high pressure turbine.
Three-Dimensional Normal Shock-Wave/Boundary-Layer Interaction in a Diffuser
Authors: Ono Daisuke , Handa Taro , Masuda Mitsuharu
Published: March 2013

The 3D flow structure induced by a normal shock-wave/boundary-layer interaction in a transonic diffuser is experimentally and computationally investigated. In the diffuser, the shock wave is located in the diverging section. The experiments are done with wall pressure measurements, oil-flow surface visualization, and Mach number measurements with a laser-induced fluorescence (LIF) method. In the computational work, the Reynolds-averaged Navier–Stokes equations are numerically solved with the k-ω two-equation turbulence model. The numerical solution agrees reasonably well with the experiment and clarifies the vortex structure in the interaction zone along with the 3D behavior of the boundary layer downstream of the shock wave. A careful investigation of the calculated flow reveals that the vortices are generated at the foot of the shock wave. It is also found that a complicated wave configuration is formed near the diffuser corner. A flow model is constructed by considering this wave configuration. This model explains the 3D flow characteristics in the transonic diffuser very well.
Robust Stability and Stabilization of Fractional Order Systems Based on Uncertain Takagi-Sugeno Fuzzy Model With the Fractional Order 1≤v < 2
Authors: Junmin Li , Yuting Li
Published: March 2013

This paper addresses the problems of the robust stability and stabilization for fractional order systems based on the uncertain Takagi-Sugeno fuzzy model. A sufficient and necessary condition of asymptotical stability for fractional order uncertain T-S fuzzy model is given, and a parallel distributed compensate fuzzy controller is designed to asymptotically stabilize the model. The results are obtained in terms of linear matrix inequalities. Finally, a numerical example and fractional order Van der Pol system are given to show the effectiveness of our results.
Continuum Models for the Plastic Deformation of Octet-Truss Lattice Materials Under Multiaxial Loading
Authors: Wan Hu Jong , Park Taehyo
Published: March 2013

The continuum models that take plastic material behavior into consideration are derived to analyze periodic octet-truss lattice materials under multiaxial loading. The main focus of this study is to investigate the basic topology of unit cell structures having the cubic symmetry and to formulate the analytical models for predicting pressure load-dependent stress surfaces accurately. The discrete lattice materials are converted into equivalent model continua that are obtained by physically homogenizing the property of the unit cell structures. The effective continuum models contain information on the mechanical characteristics of internal truss members with respect to axial stiffness, internal stress variable, structural packing, and material density at the microscale level. With the hardening material model introduced in the homogenization process, the plastic flow acting on the microscopic truss members gives rise to extend the elastic domain of the analytical stress function derived from homogenize constitutive equations at the macroscale level. Analytical stress predictions show excellent agreements with the results obtained from finite element (FE) analyses.
Multiscale Modeling of Damage Evolution in Viscoelastic Bituminous Mixtures Subjected to Cyclic Loading
Authors: Kim Yong-Rak , Souza Flavio V. , Park Taehyo
Published: March 2013

This study presents a multiscale computational model and its application to predict damage dependent mechanical behavior of bituminous mixtures subjected to cyclic loading. Two length scales (global and local) are two-way coupled in the model framework by linking a homogenized global scale to a heterogeneous local scale representative volume element. Based on the unique two-way coupled multiscaling and the use of the finite element technique incorporated with the material viscoelasticity and cohesive zone fracture, the model approach can successfully account for the effect of mixture heterogeneity, material viscoelasticity, and damage accumulation due to cracks in the small scale on the overall performance of larger scale mixtures or structures. This step requires only the properties of individual constituents. To demonstrate the model and its features, bending beam fatigue testing of a bituminous mixture, which is composed of elastic aggregates and viscoelastic bitumen, is simulated by altering the mixture's constituent properties. The model clearly presents progressive damage characteristics with repetitive loading cycles and the analysis clearly demonstrates the sensitivity of the approach to constituent material properties. The multiscale model presented herein is expected to drastically reduce time-consuming and expensive fatigue tests, which, when performed in the traditional manner, require many replicates and do not define the cause of microstructural fatigue, damage, and failure.
Multiscale Simulations for Impact Load–Induced Vibration: Assessing a Structure's Vulnerability
Authors: Park Jeongwon , Koo Man Hoi , Kim Hak-Sung , Park Junhong
Published: March 2013

Vibration resulting from high-velocity projectiles impacting a structure was simulated at multiple scales. Local impact simulations were performed to predict the material deformation and penetration phenomena at the location of impact. The resulting penetration behavior of a steel panel was analyzed for various projectile velocities, sizes, and panel thicknesses. Three-layer panels with Kevlar as the core material were simulated to understand the effects of structural layering on the reduction of the impact force. The forces acting on the panel in the longitudinal and transverse directions were calculated from the obtained stress distribution in the local deformation model. Using the estimated force input, transient longitudinal and flexural wave propagations were calculated to analyze the radiation of the impact energy along the structural span. Vulnerable positions with high possibilities of damage to crucial components due to impact loading were identified from the resulting vibration responses.
Dynamic Localizations in HSLA-65 and DH-36 Structural Steel at Elevated Temperatures
Authors: Abed Farid H. , Makarem Fadi , Voyiadjis George Z.
Published: March 2013

This study addresses the problem of dynamic strain localization in two steel alloys; HSLA-65 and DH-36 at elevated temperatures. It aims at understanding the adiabatic deformation of high strength structural steel by performing a nonlinear finite element (FE) analysis. A microstructural-based viscoplasticity model is integrated and implemented into the commercial FE code ABAQUS/Explicit via the user material subroutine coded as VUMAT. Numerical implementation for a simple compression problem meshed with one element is used for testing the efficiency of the proposed model implementation. The numerical results of the isothermal and adiabatic true stress-true strain curves compare very well with the experimental data for the two steel alloys over a wide range of temperatures and strain rates. The effectiveness of the present approach enables the study of strain localizations in a cylindrical hat-shaped specimen with certain dimensions, where the location of shear localization preceding shear band formation is forced to be between the hat and the brim. The FE simulations of the material instability problems converge to meaningful results upon further refinement of the FE mesh. Material length scales are implicitly introduced into the governing equations through material rate-dependency (viscosity). A sensitivity analysis is also performed on the physically-based viscoplasticity model parameters in order to study their effect on dynamic localizations. Several conclusions related to the width and intensity of the shear localization, considering various velocities and temperatures, are discussed.
An Innovative Layout Design Methodology for Stiffened Plate/Shell Structures by Material Increasing Criterion
Authors: Li Baotong , Hong Jun , Wang Zhelin , Liu Zhifeng
Published: March 2013

The motivation of this paper is to develop a new and straightforward approach to provide a topology optimization solution for the layout design of stiffened plate/shell structures. Inspired by the similarities between the branching patterns in nature and stiffener layout patterns in engineering, a so-called material increasing design concept is first introduced to represent the topology configuration of the stiffened plate/shell structures. In addition, a well-founded mathematical explanation for the principles, properties, and mechanisms of adaptive growth behaviors of branching patterns in nature is derived from the Kuhn–Tucker conditions, leading to a novel optimality criterion which can serve engineering purposes for stiffener layout design. In this criterion, the common growth mechanism is described as an ideal ‘balanced point’ among individual branches in terms of their weight distribution. After characterizing the relationship between the growth behavior and mechanics self-adaptability, the reproduction of branching patterns in nature is implemented by a global coordinative model, which consists of several bottom programming models to find the optimal height distributions of individual branches and a top programming model to play a global coordinative role among them. The benefit and the advantages of the suggested method are illustrated with several 2D examples that are widely used in the recent research of topology optimization.
Shape Matters Too
Authors: Chow Edward Kai-Hua
Published: March 2013

Nanoparticle shape can affect the specificity and efficacy of therapeutic antibodies targeting cancer.
Genomics of T-ALL Reveals a Weapon of an Evasive Foe
Authors: Margolin Adam A.
Published: March 2013

Genomic profiling of T-ALL samples at diagnosis, remission, and relapse identifies NT5C2 as a chemoresistance gene.
The Evolving Field of Human Papillomavirus Receptor Research: a Review of Binding and Entry
Authors: Raff Adam B. , Woodham Andrew W. , Raff Laura M. , Skeate Joseph G. , Yan Lisa , Da Silva Diane M. , Schelhaas Mario , Kast W. Martin
Published: March 2013

Human papillomaviruses (HPVs) infect epithelia and can lead to the development of lesions, some of which have malignant potential. HPV type 16 (HPV16) is the most oncogenic genotype and causes various types of cancer, including cervical, anal, and head and neck cancers. However, despite significant research, our understanding of the mechanism by which HPV16 binds to and enters host cells remains fragmented. Over several decades, many HPV receptors and entry pathways have been described. This review puts those studies into context and offers a model of HPV16 binding and entry as a framework for future research. Our model suggests that HPV16 binds to heparin sulfate proteoglycans (HSPGs) on either the epithelial cell surface or basement membrane through interactions with the L1 major capsid protein. Growth factor receptors may also become activated through HSPG/growth factor/HPV16 complexes that initiate signaling cascades during early virion-host cell interactions. After binding to HSPGs, the virion undergoes conformational changes, leading to isomerization by cyclophilin B and proprotein convertase-mediated L2 minor capsid protein cleavage that increases L2 N terminus exposure. Along with binding to HSPGs, HPV16 binds to α6 integrins, which initiate further intracellular signaling events. Following these primary binding events, HPV16 binds to a newly identified L2-specific receptor, the annexin A2 heterotetramer. Subsequently, clathrin-, caveolin-, lipid raft-, flotillin-, cholesterol-, and dynamin-independent endocytosis of HPV16 occurs.
Comparative Analysis of Chlamydia psittaci Genomes Reveals the Recent Emergence of a Pathogenic Lineage with a Broad Host Range
Authors: Read Timothy D. , Joseph Sandeep J. , Didelot Xavier , Liang Brooke , Patel Lisa , Dean Deborah
Published: March 2013

Chlamydia psittaci
is an obligate intracellular bacterium. Interest in
Chlamydia
stems from its high degree of virulence as an intestinal and pulmonary pathogen across a broad range of animals, including humans.
C. psittaci
human pulmonary infections, referred to as psittacosis, can be life-threatening, which is why the organism was developed as a bioweapon in the 20th century and is listed as a CDC biothreat agent. One remarkable recent result from comparative genomics is the finding of frequent homologous recombination across the genome of the sexually transmitted and trachoma pathogen
Chlamydia trachomatis
. We sought to determine if similar evolutionary dynamics occurred in
C. psittaci
. We analyzed 20
C. psittaci
genomes from diverse strains representing the nine known serotypes of the organism as well as infections in a range of birds and mammals, including humans. Genome annotation revealed a core genome in all strains of 911 genes. Our analyses showed that
C. psittaci
has a history of frequently switching hosts and undergoing recombination more often than
C. trachomatis
. Evolutionary history reconstructions showed genome-wide homologous recombination and evidence of whole-plasmid exchange. Tracking the origins of recombinant segments revealed that some strains have imported DNA from as-yet-unsampled or -unsequenced
C. psittaci
lineages or other
Chlamydiaceae
species. Three ancestral populations of
C. psittaci
were predicted, explaining the current population structure. Molecular clock analysis found that certain strains are part of a clonal epidemic expansion likely introduced into North America by South American bird traders, suggesting that psittacosis is a recently emerged disease originating in New World parrots.

IMPORTANCE
Chlamydia psittaci
is classified as a CDC biothreat agent based on its association with life-threatening lung disease, termed psittacosis, in humans. Because of the recent remarkable findings of frequent recombination across the genome of the human sexually transmitted and ocular trachoma pathogen
Chlamydia trachomatis
, we sought to determine if similar evolutionary dynamics occur in
C. psittaci
. Twenty
C. psittaci
genomes were analyzed from diverse strains that may play a pathogenic role in human disease. Evolution of the strains revealed genome-wide recombination occurring at a higher rate than for
C. trachomatis
. Certain strains were discovered to be part of a recent epidemic clonal expansion originating in South America. These strains may have been introduced into the United States from South American bird traders, suggesting that psittacosis is a recently emerged disease originating in New World parrots. Our analyses indicate that
C. psittaci
strains have a history of frequently switching hosts and undergoing recombination.
Inhibition of Viral Pathogenesis and Promotion of the Septic Shock Response to Bacterial Infection by IRF-3 Are Regulated by the Acetylation and Phosphorylation of Its Coactivators
Authors: Chattopadhyay Saurabh , Fensterl Volker , Zhang Ying , Veleeparambil Manoj , Wetzel Jaime L. , Sen Ganes C.
Published: March 2013

Interferon (IFN) is required for protecting mice from viral pathogenesis; reciprocally, it mediates the deleterious septic shock response to bacterial infection. The critical transcription factor for IFN induction, in both cases, is IRF-3, which is activated by TLR3 or RIG-I signaling in response to virus infection and TLR4 signaling in response to bacterial infection. Here, we report that IRF-3’s transcriptional activity required its coactivators, β-catenin and CBP, to be modified by HDAC6-mediated deacetylation and protein kinase C isozyme β (PKC-β)-mediated phosphorylation, respectively, so that activated nuclear IRF-3 could form a stable transcription initiation complex at the target gene promoters. β-Catenin bridges IRF-3 and CBP, and the modifications were required specifically for the interaction between β-catenin and CBP but not β-catenin and IRF-3. Consequently, like IRF-3
−/−
mice, HDAC6
−/−
mice were resistant to bacterial lipopolysaccharide-induced septic shock. Conversely, they were highly susceptible to pathogenesis caused by Sendai virus infection. Thus, HDAC6 is an essential component of the innate immune response to microbial infection.

IMPORTANCE
It is important to understand how we protect ourselves against microbial infection. Specific receptors present in mammalian cells, called Toll-like receptors, are assigned to sense different microbial chemicals, such as bacterial lipopolysaccharides or viral double-stranded RNA. Activation of these receptors leads to the activation of a critical transcription factor, IRF-3, which drives the induced synthesis of interferon, a secreted protein required for our protection. Here, we report that interferon synthesis is regulated not only by IRF-3 activation but also by activation of two proteins, β-catenin and CBP, which function together with IRF-3. β-Catenin is activated by its deacetylation by HDAC6, and CBP is activated by its phosphorylation by protein kinases C isozyme β (PKC-β). These regulations are operative not only in cell cultures but also in mice.
Salvage of distal non-target coil embolization with stent placement and intravenous eptifibatide in a ruptured, unsecured, atypical aneurysm
Authors: Janjua Nazli , Bulic Sebina , Tan Benedict C , Panichpisal Kessarin , Miller John
Published: March 2013

Introduction

Small aneurysms may be challenging to embolize. In cases of subarachnoid hemorrhage (SAH) where treatment is delayed, physicians may have to balance the risks of certain required therapies (antiplatelet agents) with the risk of rerupture. We describe a case of a technically challenging anterior cerebral artery aneurysm requiring eptifibatide infusion prior to definitive aneurysm treatment.

Case report

A 57-year-old woman with SAH, underwent coil embolization of a small fenestrated A1–A2 junction aneurysm. The procedure was complicated by downstream coil migration which was then treated with Enterprise stent placement in the pericallosal artery. This required subsequent infusion of a glycoprotein IIb/IIIa inhibitor until the aneurysm could be repaired surgically.

Conclusions

Revascularization with a stent in a distal cerebral vessel may salvage inadvertent coil migration. Although it is undesirable to administer antiplatelet agents to patients with SAH, in these circumstances short acting agents may be used.
Myocardial function in premature infants: a longitudinal observational study
Authors: Eriksen Beate Horsberg , Nestaas Eirik , Hole Torstein , Liestøl Knut , Støylen Asbjørn , Fugelseth Drude
Published: March 2013

Objectives

Gestational and chronological age may have an impact on myocardial function. We studied the longitudinal changes of the atrioventricular tissue Doppler velocities in premature infants through the neonatal transitional period and at expected term and explored the reproducibility of the measurements.

Design

Prospective, observational and longitudinal cohort study.

Setting

Two-centre study, from a secondary and a tertiary neonatal intensive care unit.

Participants

55 infants (29 males) with gestational age 31–35 weeks and birth weight 1127–2836 grams.

Primary and secondary outcome measures

Pulsed-wave atrioventricular left, septum and right ventricular annulus tissue Doppler systolic (S′), early diastolic (E′) and late diastolic (A′) velocities measured by repeated echocardiographic examinations days 1, 2 and 3 and at expected term.

Results

All velocities increased significantly from the neonatal period to expected term (p<0.001). We found a significant correlation between gestational age and right-sided S′, E′ and A′ on day 1 (Pearson correlation 0.32–0.46, p<0.05), for S′ in all three walls and septal E′ and A′ on day 2 (Pearson correlation 0.27–0.49, p<0.05). There was a moderate linear correlation between left ventricle end-diastolic length and septal and right S′ at term and for septal E′ and A′ at day 1 (Pearson correlation 0.30–0.56, p<0.05). We found no correlation between heart rate and tissue Doppler velocities when controlling for the effect of fusion. Continuous positive airway pressure showed moderate effect where as persistence of the ductus arteriosus showed no effect on the tissue Doppler velocities. The E′/A′ relationship was consistently reversed throughout the study with frequently fused diastolic tissue velocity signals.

Conclusions

Pulsed-wave atrioventricular annulus tissue Doppler velocities were related to gestational age, postnatal age and ventricular size. Right ventricle velocities showed more pronounced increase with postnatal maturation than left ventricle velocities. The degree of E′/A′ fusion influenced the diastolic tissue Doppler velocities and should be reported if present.
Would primary healthcare professionals prescribe a polypill to manage cardiovascular risk? A qualitative interview study
Authors: Virdee Satnam K , Greenfield Sheila M , Fletcher Kate , McManus Richard J , Hobbs F D Richard , Mant Jonathan
Published: March 2013

Objectives

A ‘polypill’ containing both blood pressure-lowering and cholesterol-lowering drugs could prevent up to 80% of cardiovascular disease events. Since little is known about the attitudes of primary healthcare professionals to use of such a pill for cardiovascular disease prevention, this study aimed to investigate opinions.

Design

Semistructured interviews were conducted with participants. A qualitative description approach was used to analyse and report the results.

Setting

Participants were recruited from nine primary care practices in Birmingham.

Participants

Sixteen healthcare professionals (11 primary care physicians and 5 practice nurses) were selected through purposive sampling to maximise variation of characteristics.

Outcome measures

Outcome measures for this study were: the attitude of healthcare professionals towards the use of a polypill for primary and secondary cardiovascular disease prevention; their views on monitoring the drug; and the factors influencing their willingness to prescribe the medication.

Results

Healthcare professionals expressed considerable concern over using a polypill for primary prevention for all people over a specific age, although there was greater acceptance of its use for secondary prevention. Regularly monitoring patients taking the polypill was deemed essential. Evidence of effectiveness, patient risk level and potential medicalisation were key determinants in willingness to prescribe such a pill.

Conclusions

Primary healthcare professionals have significant concerns about the use of a polypill, particularly in the prevention of cardiovascular disease in people who are not regarded as being at ‘high risk’. If a population-based polypill strategy is to be successfully implemented, healthcare professionals will need to be convinced of the potential benefits of a drug-based population approach to prevention.