bluuebunny/crossref_metadata_2025 huggingface dataset:
PNPLA 3I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection
Authors: Rembeck Karolina , Maglio Cristina , Lagging Martin , Christensen Peer Brehm , Färkkilä Martti , Langeland Nina , Buhl Mads Rauning , Pedersen Court , Mørch Kristine , Norkrans Gunnar , Hellstrand Kristoffer , Lindh Magnus , Pirazzi Carlo , Burza Maria Antonella , Romeo Stefano , Westin Johan ,   for the NORDynamIC group
Published: September 2012

Background

Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients.

Methods

Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients.

Results

In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients.

Conclusions

Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
A predictive tool for an effective use of 18F-FDG PET in assessing activity of sarcoidosis
Authors: Mostard Rémy LM , Kuijk Sander MJ Van , Verschakelen Johny A , Kroonenburgh Marinus JPG van , Nelemans Patty J , Wijnen Petal AHM , Drent Marjolein
Published: September 2012

Background

18F-FDG PET/CT (PET) is useful in assessing inflammatory activity in sarcoidosis. However, no appropriate indications are available. The aim of this study was to develop a prediction rule that can be used to identify symptomatic sarcoidosis patients who have a high probability of PET-positivity.

Methods

We retrospectively analyzed a cohort of sarcoidosis patients with non organ specific persistent disabling symptoms (n = 95). Results of soluble interleukin-2 receptor (sIL-2R) assessment and high-resolution computed tomography (HRCT) were included in the predefined model. HRCT scans were classified using a semi-quantitative scoring system and PET findings as positive or negative, respectively. A prediction model was derived based on logistic regression analysis. We quantified the model’s performance using measures of discrimination and calibration. Finally, we constructed a prediction rule that should be easily applicable in clinical practice.

Results

The prediction rule showed good calibration and good overall performance (goodness-of-fit test, p = 0.78, Brier score 20.1%) and discriminated between patients with positive and negative PET findings (area under the receiver-operating characteristic curve, 0.83). If a positive predictive value for the presence of inflammatory activity of ≥90% is considered acceptable for clinical decision-making without referral to PET, PET would be indicated in only 29.5% of the patients. Using a positive predictive value of 98%, about half of the patients (46.3%) would require referral to PET.

Conclusions

The derived and internally validated clinical prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be useful to identify sarcoidosis patients with a high probability of inflammatory activity. Using this rule may enable a more effective use of PET scan for assessment of inflammatory activity in sarcoidosis.
Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study
Authors: Shah Gaurang R , Chaudhari Manojkumar V , Patankar Suresh B , Pensalwar Shrikant V , Sabale Vilas P , Sonawane Navneet A
Published: September 2012

Background

Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) – a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study.

Methods

78 men aged 25–50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator’s Global assessment and Subjects’ opinion.

Results

In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator’s global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject’s rating for tolerability of treatment was similar in both groups.

Conclusions

VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men.

Trial Registration

Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009
Popcorn is more satiating than potato chips in normal-weight adults
Authors: Nguyen Von , Cooper Lisa , Lowndes Joshua , Melanson Kathleen , Angelopoulos Theodore J , Rippe James M , Reimers Kristin
Published: September 2012

Background

Strategies that may increase compliance to reduced energy intakes are needed to reduce the health burden of obesity. Conflicting evidence exists regarding the effects of snacking on satiety and energy intake.

Methods

This study compared short-term satiety from two common snack foods, low fat popcorn or potato chips. Using a counterbalanced within-subject design, 35 normal weight non-smoking participants (17 men, 18 women) ages 20–50 years (mean age 33 ± 11, BMI 23 ± 2 kg/m2) consumed four conditions each: 200 mL of water (control), one cup (4 g, 15 kcal) popcorn, 6 cups (27 g, 100 kcal) popcorn, and one cup (28 g, 150 kcal) potato chips, each with 200 mL water. Participants rated their hunger, satisfaction, prospective consumption, and thirst on 100 mm visual analogue scales 30 minutes after commencement of snack consumption. In addition, post-snack energy intake from an ad libitum meal (amount served less amount remaining) was measured, and the test food and meal combined energy intake and energy compensation were calculated.

Results

Participants expressed less hunger, more satisfaction, and lower estimates of prospective food consumption after six cups of popcorn compared to all other treatments (P < 0.05). Energy compensation was 220% ± 967%, 76% ± 143% and 42% ± 75% after one cup popcorn, six cups popcorn and one cup potato chips, respectively. Combined energy intake was significantly greater (P < 0.01) during the potato chips condition (803 ± 277 kcal) compared to control (716 ± 279 kcal) or popcorn conditions (698 ± 286 kcal for one cup and 739 ± 294 kcal for six cups). Combined energy intakes from both popcorn conditions were not significantly different than control (p > 0.05).

Conclusion

Popcorn exerted a stronger effect on short-term satiety than did potato chips as measured by subjective ratings and energy intake at a subsequent meal. This, combined with its relatively low calorie load, suggests that whole grain popcorn is a prudent choice for those wanting to reduce feelings of hunger while managing energy intake and ultimately, body weight.
Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -A study of the OVCAD consortium
Authors: Aust Stefanie , Bachmayr-Heyda Anna , Pateisky Petra , Tong Dan , Darb-Esfahani Silvia , Denkert Carsten , Chekerov Radoslav , Sehouli Jalid , Mahner Sven , Van Gorp Toon , Vergote Ignace , Speiser Paul , Horvat Reinhard , Zeillinger Robert , Pils Dietmar
Published: September 2012

Background

The role of the tumor necrosis factor receptor associated protein 1 (TRAP1) – supposed to be involved in protection of cells from apoptosis and oxidative stress – has just started to be investigated in ovarian cancer. TRAP1 has been shown to be estrogen up-regulated in estrogen receptor α (ERα) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ERα expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ERα in regard to clinicopathological parameters, chemotherapy response, and survival.

Methods and results

Expressions of TRAP1 and ERα were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERα was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ERα (p < 0.001) but high TRAP1 expression was also found in 42% of ERα negative cases. High TRAP1 expression correlated significantly with favorable chemotherapy-response (HR = 0.48; 95%CI 0.24-0.96, p=0.037) and showed a significant impact on overall survival (OS) (HR = 0.65; 95%CI 0.43-0.99, p = 0.044). ERα expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ERα positive and/or TRAP1-high) revealed the strongest independent and significant positive influence on OS (HR = 0.41; 95%CI 0.27-0.64).

Conclusion

Immunohistochemical evaluation of TRAP1 together with ERα provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.
Low accuracy of endoscopic ultrasonography for detailed T staging in gastric cancer
Authors: Lee Han Hong , Lim Chul Hyun , Park Jae Myung , Cho Yu Kyung , Song Kyo Young , Jeon Hae Myung , Park Cho Hyun
Published: September 2012

Background

The accuracy of endoscopic ultrasonography (EUS) for preoperative staging of gastric cancer varies. The aim of this study was to investigate the accuracy of EUS tumor (T) and node (N) staging, and to identify the histopathological factors influencing accuracy based on the detailed tumor depth of gastric cancer.

Methods

In total, 309 patients with gastric cancer with confirmed pathological staging underwent EUS examination for preoperative staging at Seoul St. Mary’s Hospital, Korea, between January and December 2009. The T and N staging of EUS and the pathologic report were compared.

Results

The overall accuracies of EUS for T stage and the detailed T stages were 70.2% and 43.0%, respectively. In detailed stage, tumors greater than 50 mm in diameter were significantly associated with T overstaging (odds ratio (OR) = 2.094). The overall accuracy of EUS for N staging was 71.2%. Tumor size (20 mm ≤ size < 50 mm, OR = 4.389; and 50 mm ≤ size, OR = 8.170), cross-sectional tumor location (circumferential, OR = 4.381) and tumor depth (submucosa, OR = 3.324; muscular propria, OR = 6.923; sub-serosa, OR = 4.517; and serosa-exposed, OR = 6.495) were significant factors affecting incorrect nodal detection.

Conclusions

Careful attention is required during EUS examination of large-sized gastric cancers to increase accuracy, especially for T staging.
Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity
Authors: Nejatbakhsh Reza , Kabir-Salmani Maryam , Dimitriadis Eva , Hosseini Ahmad , Taheripanah Robabeh , Sadeghi Yousef , Akimoto Yoshihiro , Iwashita Mitsutoshi
Published: September 2012

Background

Apical surfaces of human endometrial epithelium and endothelium are key elements for the initiation of molecular interactions to capture the blastocyst or leukocyte, respectively. The L-selectin adhesion system has been strongly proposed to play an important role in the initial steps of trophoblast adhesion and promotion of integrin-dependent processes, ultimately culminating in the establishment of the embryo-maternal interface. On the basis of these facts, we hypothesized a novel role for pinopodes as the first embryo-fetal contact sites to contain the highest subcellular expression of L-selectin ligand suggesting its role in early adhesion as predicted. Thus, the objective of this study was therefore to determine the subcellular pattern of distribution of the L-selectin ligand (MECA-79) in human endometrial apical membrane region during the window of implantation.

Methods

Endometrial biopsies of secretory phases from fertile females ranging in age between 25 and 42years were studied using several approaches, including scanning electron microscopy (SEM), immunostaining for light microscopy and transmission electron microscopy (TEM), and immunoblotting as well as statistical analysis of the area-related numerical densities of immunoreactive MECA-79-bound nanogolds to detect the expression pattern and the subcellular distribution pattern of L-selectin ligand (MECA-79) in human endometrium during the window of implantation.

Results

The endometrial biopsies were scored according the dating criteria of Noyes et al. by an experienced histologist. The SEM images of the midluteal phase specimens revealed that fully developed pinopodes were abundant in our samples. HRP-immunostaining and immunofluorescent staining as well as immunoblotting revealed that MECA-79 was expressed in the midluteal phase specimens. The results of immunogold TEM illustrated the expression of MECA-79 in human pinopodes in the midluteal phase and a higher area-relate numerical density in pinopodes compared to that of the uterodome-free areas.

Conclusions

This is the first demonstration of the subcellular localization of MECA-79 in the human pinopodes which may indicate a novel role for pinopodes to be capable of shear-stress-dependent tethering-type adhesion in the initial phases of human embryo implantation.
Short-wavelength light beam in situ monitoring growth of InGaN/GaN green LEDs by MOCVD
Authors: Sun Xiaojuan , Li Dabing , Song Hang , Chen Yiren , Jiang Hong , Miao Guoqing , Li Zhiming
Published: September 2012

In this paper, five-period InGaN/GaN multiple quantum well green light-emitting diodes (LEDs) were grown by metal organic chemical vapor deposition with 405-nm light beam in situ monitoring system. Based on the signal of 405-nm in situ monitoring system, the related information of growth rate, indium composition and interfacial quality of each InGaN/GaN QW were obtained, and thus, the growth conditions and structural parameters were optimized to grow high-quality InGaN/GaN green LED structure. Finally, a green LED with a wavelength of 509 nm was fabricated under the optimal parameters, which was also proved by ex situ characterization such as high-resolution X-ray diffraction, photoluminescence, and electroluminescence. The results demonstrated that short-wavelength in situ monitoring system was a quick and non-destroyed tool to provide the growth information on InGaN/GaN, which would accelerate the research and development of GaN-based green LEDs.
Identification of B cell epitopes reactive to human papillomavirus type-16L1- derived peptides
Authors: Fukui Akimasa , Matsueda Satoko , Kawano Kouichiro , Tsuda Naotake , Komatsu Nobukazu , Shichijo Shigeki , Sasada Tetsuro , Hattori Satoshi , Ushijima Kimio , Itoh Kyogo , Kamura Toshiharu
Published: September 2012

Background

Persistent infection of human papillomavirus (HPV) types 16 and 18 causes cervical cancer. To better understand immune responses to the prophylactic vaccine, HPV 16/18 L1 virus-like particles (HPV-VLPs), we investigated B cell epitopes of HPV16 L1-derived peptides.

Methods

Sera from mice immunized with HPV-16/18 L1 VLPs were analyzed for their IgG titers against 10 different HPV16 L1-derived peptides (20-mer) that contain human leukocyte antigen (HLA)-class I A-2, A-24 and class II DR.

Results

One 20-mer peptide at positions 300 to 319 was identified as a common B cell epitope in both Balb/c (H-2d) and C57BL/6 (H-2b) mice. Mapping analysis showed that the 10-amino-acid sequence at positions 304to 313 was an immunogenic portion. It is of note that the binding capability of this 10-mer peptide to the HLA-A2 and HLA-A24 molecules was confirmed by the HLA class I stabilization assay. In addition, one unique 20-mer was determined as a B cell epitope in each strain.

Conclusions

These results might provide new information for better understanding of immune responses to HPV 16 L1.
Immune genes are associated with human glioblastoma pathology and patient survival
Authors: Vauléon Elodie , Tony Avril , Hamlat Abderrahmane , Etcheverry Amandine , Chiforeanu Dan Cristian , Menei Philippe , Mosser Jean , Quillien Véronique , Aubry Marc
Published: September 2012

Background

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. Several recent transcriptomic studies in GBM have identified different signatures involving immune genes associated with GBM pathology, overall survival (OS) or response to treatment.

Methods

In order to clarify the immune signatures found in GBM, we performed a co-expression network analysis that grouped 791 immune-associated genes (IA genes) in large clusters using a combined dataset of 161 GBM specimens from published databases. We next studied IA genes associated with patient survival using 3 different statistical methods. We then developed a 6-IA gene risk predictor which stratified patients into two groups with statistically significantly different survivals. We validated this risk predictor on two other Affymetrix data series, on a local Agilent data series, and using RT-Q-PCR on a local series of GBM patients treated by standard chemo-radiation therapy.

Results

The co-expression network analysis of the immune genes disclosed 6 powerful modules identifying innate immune system and natural killer cells, myeloid cells and cytokine signatures. Two of these modules were significantly enriched in genes associated with OS. We also found 108 IA genes linked to the immune system significantly associated with OS in GBM patients. The 6-IA gene risk predictor successfully distinguished two groups of GBM patients with significantly different survival (OS low risk: 22.3 months versus high risk: 7.3 months; p < 0.001). Patients with significantly different OS could even be identified among those with known good prognosis (methylated MGMT promoter-bearing tumor) using Agilent (OS 25 versus 8.1 months; p < 0.01) and RT-PCR (OS 21.8 versus 13.9 months; p < 0.05) technologies. Interestingly, the 6-IA gene risk could also distinguish proneural GBM subtypes.

Conclusions

This study demonstrates the immune signatures found in previous GBM genomic analyses and suggests the involvement of immune cells in GBM biology. The robust 6-IA gene risk predictor should be helpful in establishing prognosis in GBM patients, in particular in those with a proneural GBM subtype, and even in the well-known good prognosis group of patients with methylated MGMT promoter-bearing tumors.
The immunosuppressive factors IL-10, TGF-β, and VEGF do not affect the antigen-presenting function of CD40-activated B cells
Authors: Shimabukuro-Vornhagen Alexander , Draube Andreas , Liebig Tanja M , Rothe Achim , Kochanek Matthias , von Bergwelt-Baildon Michael S
Published: September 2012

Background

Progress in recent years strengthened the concept of cellular tumor vaccinations. However, a crucial barrier to successful cancer immunotherapy is tumor-mediated immunosuppression. Tumor-derived soluble factors such as IL-10, TGF-β, and VEGF suppress effector cells either directly or indirectly by disruption of dendritic cell (DC) differentiation, migration and antigen presentation. Human B cells acquire potent immunostimulatory properties when activated via CD40 and have been shown to be an alternative source of antigen-presenting cells (APCs) for cellular cancer vaccines. Nevertheless, in contrast to DCs little knowledge exists about their susceptibility to tumor derived immunosuppressive factors. Thus, we assessed whether IL-10, TGF-β, or VEGF do affect key aspects of the immunostimulatory function of human CD40-activated B cells.

Methods

Cell surface expression of adhesion and costimulatory molecules and the proliferation capacity of CD40-activated B cells were compared to untreated controls by flow cytometry. Migration towards important chemokines of secondary lymph organs was measured with or without exposure to the immunosuppressive cytokines. Finally, an influence on T cell stimulation was investigated by allogeneic mixed lymphocyte reactions. For statistical analysis Student’s ttest or two-way analysis of variance followed by Bonferroni's post-hoc test was used to compare groups.Pvalues of <0.05 were considered statistically significant.

Results

Neither cell adhesion nor the expression of MHC class II and costimulatory molecules CD80 and CD86 was inhibited by addition of IL-10, TGF-β, or VEGF. Likewise, the proliferation of CD40-activated B cells was not impaired. Despite being exposed to IL-10, TGF-β, or VEGF the B cells migrated equally well as untreated controls to the chemokines SLC and SDF-1α. Most importantly, the capacity of CD40-activated B cells to stimulate CD4+and CD8+T cells remained unaffected.

Conclusion

Our findings suggest that key immunostimulatory functions of CD40-activated B cells are resistant to inhibition by the immunosuppressive factors IL-10, TGF-β, and VEGF. This supports considerations to use ex vivo generated CD40-activated B cells as a promising alternative or additional APC for cellular immunotherapy, especially in settings where these immunosuppressive cytokines are present in tumor environment.
Alpha-1-antitrypsin inhibits nitric oxide production
Authors: Chan Edward D , Pott Gregory B , Silkoff Philip E , Ralston Annemarie H , Bryan Courtney L , Shapiro Leland
Published: September 2012

Alpha-1-antitrypsin inhibits NO production, iNOS expression, and NFκB activation in murine macrophagic cells; exhaled NO is increased in AAT-deficient patients compared to controls.

NO is an endogenously produced gas that regulates inflammation, vascular tone, neurotransmission, and immunity. NO production can be increased by exposing cells to several endogenous and exogenous proinflammatory mediators, including IFN-γ, TNF-α, IL-1β, and LPS. As AAT has been shown to inhibit cell activation and suppress cytokine production associated with proinflammatory stimulation, we examined AAT for NO-suppressive function. In RAW 264.7 murine macrophagic cells, physiological AAT concentrations significantly inhibited combined LPS- and IFN-γ-induced NO synthesis, and NO synthesis inhibition was associated with decreased expression of iNOS, suppressed NF-κB activation, and reduced translocation of extracellular AAT into the interior of RAW 264.7 cells. CE-2072, a synthetic inhibitor of serine proteases, also suppressed NO production, iNOS expression, and NF-κB activation. However, AAT did not alter activation of intracellular MAPKs. In subjects with genetic AAT deficiency, exhaled NO was increased significantly compared with exhaled NO in healthy controls. These in vitro and in vivo studies suggest that AAT is an endogenous inhibitor of NO production. Administering AAT or AAT-like molecules may have use as a treatment for diseases associated with excessive NO production.
Sir Marc Armand Ruffer and Giulio Bizzozero: the first reports on efferocytosis
Authors: Cavaillon Jean-Marc
Published: September 2012

Review of the discovery of efferocytosis.

Sir Marc Armand Ruffer, a physician and a bacteriologist, well-known for his discoveries in paleopathology, and Giulio Bizzozero, an Italian pathologist, famous for his work on platelets, have made significant contributions in the field of phagocytosis. They both reported among the very first descriptions of efferocytosis.
Evaluation of Building Damage and Tsunami Inundation Based on Satellite Images and GIS Data following the 2010 Chile Earthquake
Authors: Maruyama Yoshihisa , Yamazaki Fumio , Matsuzaki Shizuko , Miura Hiroyuki , Estrada Miguel
Published: September 2012

This paper presents the results of a field survey conducted by the authors after the 2010 Chile earthquake. The authors visited the affected area about a month after the earthquake. The usefulness of satellite images captured after the earthquake to detect damaged buildings in Concepción is discussed, compared with the field photos taken by the authors. GIS datasets for the damage levels of buildings in Talca and the tsunami-inundated areas in Talcahuano, Dichato, and Constitución are constructed in this study. The GIS dataset for the damage levels of buildings in Talca is compared with the satellite images, and the possibility of detecting damage to adobe houses is investigated. Further, a series of fundamental analyses are performed using a digital elevation model (DEM) that is constructed from ASTER images (ERSDAC 2009), and the usefulness of the DEM is evaluated comparing with the field survey results.
Effects of Ground Failure on Bridges, Roads, and Railroads
Authors: Ledezma Christian , Hutchinson Tara , Ashford Scott A. , Moss Robb , Arduino Pedro , Bray Jonathan D. , Olson Scott , Hashash Youssef M.A. , Verdugo Ramón , Frost David , Kayen Robert , Rollins Kyle
Published: September 2012

The long duration and strong velocity content of the motions produced by the 27 February 2010 Maule earthquake resulted in widespread liquefaction and lateral spreading in several urban and other regions of Chile. In particular, critical lifeline structures such as bridges, roadway embankments, and railroads were damaged by ground shaking and ground failure. This paper describes the effects that ground failure had on a number of bridges, roadway embankments, and railroads during this major earthquake.
Rebuild Fast but Rebuild Better: Chile's Initial Recovery following the 27 February 2010 Earthquake and Tsunami
Authors: Siembieda William , Johnson Laurie , Franco Guillermo
Published: September 2012

The Chilean earthquake and tsunami disaster of 27 February 2010 impacted 12 million people in 900 cities and towns, causing more than US$30 billion in losses. This paper considers how the national government responded to the challenges of coastal and urban reconstruction, and examines the actions taken in the housing, land use mitigation planning, insurance, and risk reduction management sectors. The Chilean government utilized a mixed decentralized model for recovery management with strong direction from the national-level ministries and subnational planning and housing efforts at the regional and municipal levels. The national recovery plan guiding principles are used in this paper as a framework for progress. In 12 months, a series of temporary shelter villages and a system of recovery housing subsidies were established; risk-based land use plans were conducted in various coastal areas; a finance plan was adopted; changes to the national emergency management agency were made; and rapid payment of insurance claims were completed. Conflicts did arise related to the speed of housing recovery support, expropriation of land sites as future tsunami protection barriers, and extent of public participation in recovery plan making.
Site Effects and Damage Patterns
Authors: Assimaki Dominic , Ledezma Christian , Montalva Gonzalo A. , Tassara Andres , Mylonakis George , Boroschek Ruben
Published: September 2012

A set of observations on site effects and damage patterns from the Mw 8.8 Maule, Chile, earthquake is presented, focusing on identification of structural damage variability associated with nonuniform soil conditions and subsurface geology. Observations are reported from: (1) the City of Santiago de Chile (Américo Vespucio Norte Ring Highway, Ciudad Empresarial business park), (2) the Municipality of Viña del Mar, and (3) the City of Concepción, extending over 600 km along the Chilean coast. Reconnaissance information and ground motion recordings from the megathrust event are combined with site investigation data in the regions of interest. Comparisons against macroseismic observations related to uneven damage distribution from the Mw 8.0 1985 Valparaíso earthquake are discussed. Complexities associated with identifying the mechanics and underlying physical processes responsible for the manifestation of these effects are elucidated.
Performance of Nonstructural Components during the 27 February 2010 Chile Earthquake
Authors: Miranda Eduardo , Mosqueda Gilberto , Retamales Rodrigo , Pekcan Gokhan
Published: September 2012

The 27 February 2010 Chile earthquake caused widespread nonstructural damage in practically all types of buildings. While few commercial, residential, office, and industrial buildings suffered structural damage, the functionality of many more facilities was disrupted, and significant economic losses were reported due mainly to nonstructural damage. Design requirements for nonstructural components in Chilean design codes are rarely enforced, unless explicitly requested by owners. In addition, construction predating modern codes has not been upgraded to current standards, even for such critical facilities as hospitals. This earthquake highlights that more attention should be devoted to enforcing regulations and improving the seismic performance of nonstructural components whose failure can lead to injuries, substantial economic losses, and partial or total loss of functionality. This is especially important for facilities critical to the response and recovery, such as hospitals and airports that should remain operational even after strong earthquakes.
Seismic Performance of Engineered Masonry Buildings in the 2010 Maule Earthquake
Authors: Astroza Maximiliano , Moroni Ofelia , Brzev Svetlana , Tanner Jennifer
Published: September 2012

Engineered masonry, namely reinforced and confined masonry, has been widely used for housing construction in Chile over the last few decades. Most one- and two-story single-family masonry dwellings did not experience any damage due to the 27 February 2010 Maule earthquake, with the exception of a few dwellings of pre-1970 vintage, which suffered moderate damage. A similar statement can be made for three- and four-story confined masonry buildings: a large majority of buildings remained undamaged. However, several reinforced and partially confined three- and four-story masonry buildings suffered extensive damage, and two three-story partially confined buildings collapsed. The key damage patterns and the causes of damage are discussed in the paper. The extent of damage observed in the field was correlated with calculated vulnerability indices, and relevant recommendations were made related to the design and construction practices.
Behavior of Instrumented Base-Isolated Structures during the 27 February 2010 Chile Earthquake
Authors: Moroni Maria Ofelia , Sarrazin Mauricio , Soto Pedro
Published: September 2012

Several buildings and bridges with base isolation were in the area struck by the 27 February 2010, Mw 8.8 Maule earthquake. A building and two bridges that were instrumented with networks of accelerometers registered the quake; these records are analyzed here. Results of this kind are very valuable because a strong motion earthquake of large magnitude occurs only from time to time, and these rather new types of structures had not been exposed to such severe action. The isolated building is a four-story reinforced concrete and confined masonry structure located in the city of Santiago. The bridges are: (a) a 368m long continuous bridge located in Viña del Mar and (b) one section of a Santiago metropolitan train viaduct. Results show important reductions in horizontal accelerations, especially at the roof level of the building (to nearly 20% of the twin fixed-base case), and in the longitudinal direction of the bridges.
Coseismic Tectonic Surface Deformation during the 2010 Maule, Chile, Mw 8.8 Earthquake
Authors: Kelson Keith , Witter Robert C. , Tassara Andrés , Ryder Isabelle , Ledezma Christian , Montalva Gonzalo , Frost David , Sitar Nicholas , Moss Robb , Johnson Laurie
Published: September 2012

Tectonic deformation from the 2010 Maule (Chile) Mw 8.8 earthquake included both uplift and subsidence along about 470 km of the central Chilean coast. In the south, deformation included as much as 3 m of uplift of the Arauco Peninsula, which produced emergent marine platforms and affected harbor infrastructure. In the central part of the deformation zone, north of Constitución, coastal subsidence drowned supratidal floodplains and caused extensive shoreline modification. In the north, coastal areas experienced either slight uplift or no detected change in land level. Also, river-channel deposition and decreased gradients suggest tectonic subsidence may have occurred in inland areas. The overall north-south pattern of 2010 coastal uplift and subsidence is similar to the average crestal elevation of the Coast Range between latitudes 33°S and 40°S. This similarity implies that the topography of the Coast Range may reflect long-term permanent strain accrued incrementally over many earthquake cycles.
Influences of lamin A levels on induction of pluripotent stem cells
Authors: Zuo Bingfeng , Yang Jiao , Wang Fang , Wang Lei , Yin Yu , Dan Jiameng , Liu Na , Liu Lin
Published: September 2012

Lamin A is an inner nuclear membrane protein that maintains nuclear structure integrity, is involved in transcription, DNA damage response and genomic stability, and also links to cell differentiation, senescence, premature aging and associated diseases. Induced pluripotent stem (iPS) cells have been successfully generated from various types of cells and used to model human diseases. It remains unclear whether levels of lamin A influence reprogramming of somatic cells to pluripotent states during iPS induction. Consistently, lamin A is expressed more in differentiated than in relatively undifferentiated somatic cells, and increases in expression levels with age. Somatic cells with various expression levels of lamin A differ in their dynamics and efficiency during iPS cell induction. Cells with higher levels of lamin A show slower reprogramming and decreased efficiency to iPS cells. Furthermore, depletion of lamin A by transient shRNA accelerates iPS cell induction from fibroblasts. Reduced levels of lamin A are associated with increased expression of pluripotent genes Oct4 and Nanog, and telomerase genes Tert and Terc. On the contrary, overexpression of lamin A retards somatic cell reprogramming to iPS-like colony formation. Our data suggest that levels of lamin A influence reprogramming of somatic cells to pluripotent stem cells and that artificial silencing of lamin A facilitates iPS cell induction. These findings may have implications in enhancing rejuvenation of senescent or older cells by iPS technology and manipulating lamin A levels.
SDF and GABA interact to regulate axophilic migration of GnRH neurons
Authors: Casoni Filippo , Hutchins B. Ian , Donohue Duncan , Fornaro Michele , Condie Brian G. , Wray Susan
Published: September 2012

Stromal derived growth factor (SDF-1) and Gamma-aminobutyric acid (GABA) are two extracellular cues that regulate the rate of neuronal migration during development and may, in fact, act synergistically. The molecular mechanisms of this interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons are essential for vertebrate reproduction. During development, these neurons emerge from the nasal placode and migrate through the cribriform plate into the brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal migration by accelerating and slowing migration, respectively. As, such, this system was used to explore the mechanism by which these molecules act to produce coordinated cell movement during development. In the present study, GABA and SDF-1 are shown to exert opposite effects on the speed of cell movement by activating depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act synergistically to promote linear rather than random movement. The simultaneous activation of these signaling pathways therefore results in tight control of cellular speed and improved directionality along the migratory pathway of GnRH neurons.
CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFβ type II receptor with implications for nephropathic cell phenotypes
Authors: Faherty Noel , Curran Simon P. , O’Donovan Helen , Martin Finian , Godson Catherine , Brazil Derek P. , Crean John K.
Published: September 2012

Signalling interplay between transforming growth factor-β (TGFβ) and CCN2 [also called connective tissue growth factor (CTGF)] plays a crucial role in the progression of diabetic nephropathy and has been implicated in cellular differentiation. To investigate the potential role of microRNAs (miRNAs) in the mediation of this signalling network, we performed miRNA screening in mesangial cells treated with recombinant human CCN2. Analysis revealed a cohort of 22 miRNAs differentially expressed by twofold or more, including members of the miR-302 family. Target analysis of miRNA to 3′-untranslated regions (3′-UTRs) identified TGFβ receptor II (TβRII) as a potential miR-302 target. In mesangial cells, decreased TβRII expression was confirmed in response to CCN2 together with increased expression of miR-302d. TβRII was confirmed as an miR-302 target, and inhibition of miR-302d was sufficient to attenuate the effect of CCN2 on TβRII. Data from the European Renal cDNA Biopsy Bank revealed decreased TβRII in diabetic patients, suggesting pathophysiological significance. In a mouse model of fibrosis (UUO), miR-302d was increased, with decreased TβRII expression and aberrant signalling, suggesting relevance in chronic fibrosis. miR-302d decreased TGFβ-induced epithelial mesenchymal transition (EMT) in renal HKC8 epithelial cells and attenuated TGFβ-induced mesangial production of fibronectin and thrombospondin. In summary, we demonstrate a new mode of regulation of TGFβ by CCN2, and conclude that the miR-302 family has a role in regulating growth factor signalling pathways, with implications for nephropathic cell fate transitions.
Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function
Authors: Xiao Xiang , Cheng C. Yan , Mruk Dolores D.
Published: September 2012

The mechanism underlying the movement of preleptotene/leptotene spermatocytes across the blood–testis barrier (BTB) during spermatogenesis is not well understood largely owing to the fact that the BTB, unlike most other blood–tissue barriers, is composed of several co-existing and co-functioning junction types. In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like domains, in addition to transmembrane and cytoplasmic domains] is a regulator of BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co-localize with tight junction and basal ectoplasmic specialization proteins such as occludin and N-cadherin, which contribute to BTB function. More importantly, overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when monitored by transepithelial electrical resistance measurements, illustrating that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand, overexpression of a truncated form of ICAM-1 that consisted only of the five Ig-like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an opposite effect when Sertoli cell barrier function was found to be perturbed in vitro; in this case, sICAM-1 overexpression resulted in the downregulation of several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402 and c-Src/p-Src-Y530. These findings were expanded to the in vivo level when BTB function was found to be disrupted following sICAM-1 overexpression. These data illustrate the existence of a unique mechanism in the mammalian testis where ICAM-1 can either positively or negatively regulate BTB function.
The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart
Authors: Simpson Shannon J. , Fong Angelina Y. , Cummings Kevin J. , Frappell Peter B.
Published: September 2012

At birth, the newborn fat-tailed dunnart relies on cutaneous gas exchange to meet metabolic demands, with continuous lung ventilation emerging several days later. We hypothesized that the delayed expression of lung ventilation (VE) in these animals is in part owing to a low responsiveness of the respiratory control system to blood gas perturbations. To address this hypothesis we assessed the ventilatory and metabolic response to hypoxia (10% O2) and hypercapnia (5% CO2) using closed-system respirometry from birth to 23 days postpartum (P). Neonatal fat-tailed dunnarts displayed no significant hypoxic or hypercapnic ventilatory responses at any age. Regardless, significant hyperventilation through a suppression of metabolic rate (Vo2) was observed at birth in response to hypercapnia and in response to hypoxia at all ages, except P12. Therefore, reliance on cutaneous gas exchange during early life may be partially attributed to reduced chemosensitivity or a lack of central integration of chemosensitive afferent information. This may be in part due to the relative immaturity of this species at birth, compared to other mammals.
Recruitment of faster motor units is associated with greater rates of fascicle strain and rapid changes in muscle force during locomotion
Authors: Lee Sabrina S.M. , de Boef Miara Maria , Arnold Allison S. , Biewener Andrew A. , Wakeling James M.
Published: September 2012

Animals modulate the power output needed for different locomotor tasks by changing muscle forces and fascicle strain rates. To generate the necessary forces, appropriate motor units must be recruited. Faster motor units have faster activation-deactivation rates than slower motor units, and they contract at higher strain rates; therefore, recruitment of faster motor units may be advantageous for tasks that involve rapid movements or high rates of work. This study identified motor unit recruitment patterns in the gastrocnemii muscles of goats and examined whether faster motor units are recruited when locomotor speed is increased. The study also examined whether locomotor tasks that elicit faster (or slower) motor units are associated with increased (or decreased) in vivo tendon forces, force rise-relaxation rates, fascicle strains, and/or strain rates. Electromyography (EMG), sonomicrometric, and muscle-tendon force data were collected from the lateral and medial gastrocnemius muscles of goats during level walking, trotting, and galloping and during inclined walking and trotting. EMG signals were analyzed using wavelet and principal component analyses to quantify changes in the EMG frequency spectra across the different locomotor conditions. Fascicle strain and strain rate were calculated from the sonomicrometric data, and force rise and relaxation rates were determined from the tendon force data. The results of this study showed that faster motor units were recruited as goats increased their locomotor speeds from level walking to galloping. Slow inclined walking elicited similar EMG intensities as fast level galloping but different EMG frequency spectra — indicating that recruitment of the different motor unit types depended, in part, on characteristics of the task. For the locomotor tasks and muscles analyzed here, recruitment patterns were generally associated with in vivo fascicle strain rates, EMG intensity, and tendon force. Together, these data provide new evidence that changes in motor unit recruitment have an underlying mechanical basis, at least for certain locomotor tasks.
Ovarian developmental variation in the primitively eusocial waspRopalidia marginatasuggests a gateway to worker ontogeny and the evolution of sociality
Authors: Shukla Shantanu , Chandran Swarnalatha , Gadagkar Raghavendra
Published: September 2012

Social insects are characterized by reproductive caste differentiation of colony members into one or a small number of fertile queens and a large number of sterile workers. The evolutionary origin and maintenance of such sterile workers remains an enduring puzzle in insect sociobiology. Here we studied ovarian development in over 600 freshly eclosed, isolated, virgin female Ropalidia marginata wasps, maintained in the laboratory. The wasps differed greatly both in the time taken to develop their ovaries and in the magnitude of ovarian development despite having similar access to resources. All females started with no ovarian development at day zero, and the percentage of individuals with at least one oocyte at any stage of development increased gradually across age, reached 100% at 100 days and decreased slightly thereafter. Approximately 40% of the females failed to develop ovaries within the average ecological lifespan of the species. Age, body size and adult feeding rate, when considered together were the most important factors governing ovarian development. We suggest that such flexibility and variation in the potential and timing of reproductive development may physiologically predispose females to accept worker roles and thus provide a gateway to worker ontogeny and the evolution of sociality.