bluuebunny/crossref_metadata_2025 huggingface dataset:
“Designed” grafts for HLA-haploidentical stem cell transplantation
Authors: Martelli Massimo F. , Di Ianni Mauro , Ruggeri Loredana , Pierini Antonio , Falzetti Franca , Carotti Alessandra , Terenzi Adelmo , Reisner Yair , Aversa Franco , Falini Brunangelo , Velardi Andrea
Published: December 2013

Today human leukocyte antigen-haploidentical transplantation is a feasible option for patients with high-risk acute leukemia who do not have matched donors. Whether it is T-cell replete or T-cell depleted, it is still, however, associated with issues of transplant-related mortality and posttransplant leukemia relapse. After reports that adoptive immunotherapy with T-regulatory cells controls the alloreactivity of conventional T lymphocytes in animal models, tomorrow’s world of haploidentical transplantation will focus on new “designed” grafts. They will contain an appropriate ratio of conventional T lymphocytes and T-regulatory cells, natural killer cells, γ δ T cells, and other accessory cells. Preliminary results of ongoing clinical trials show the approach is feasible. It is associated with better immune reconstitution and a quite powerful graft-versus-leukemia effect with a low incidence of graft-versus-host disease and no need for posttransplant pharmacological prophylaxis. Future strategies will focus on enhancing the clinical benefit of T-regulatory cells by increasing their number and strengthening their function.
Fluorescent tagging of VP22 in N-terminus reveals that VP22 favors Marek’s disease virus (MDV) virulence in chickens and allows morphogenesis study in MD tumor cells
Authors: Rémy Sylvie , Blondeau Caroline , Vern Yves Le , Lemesle Monique , Vautherot Jean-François , Denesvre Caroline
Published: December 2013

Marek’s disease virus (MDV) is an alpha-herpesvirus causing Marek’s disease in chickens, mostly associated with T-cell lymphoma. VP22 is a tegument protein abundantly expressed in cells during the lytic cycle, which is essential for MDV spread in culture. Our aim was to generate a pathogenic MDV expressing a green fluorescent protein (EGFP) fused to the N-terminus of VP22 to better decipher the role of VP22 in vivo and monitor MDV morphogenesis in tumors cells. In culture, rRB-1B EGFP22 led to 1.6-fold smaller plaques than the parental virus. In chickens, the rRB-1B EGFP22 virus was impaired in its ability to induce lymphoma and to spread in contact birds. The MDV genome copy number in blood and feathers during the time course of infection indicated that rRB-1B EGFP22 reached its two major target cells, but had a growth defect in these two tissues. Therefore, the integrity of VP22 is critical for an efficient replication in vivo, for tumor formation and horizontal transmission. An examination of EGFP fluorescence in rRB-1B EGFP22-induced tumors showed that about 0.1% of the cells were in lytic phase. EGFP-positive tumor cells were selected by cytometry and analyzed for MDV morphogenesis by transmission electron microscopy. Only few particles were present per cell, and all types of virions (except mature enveloped virions) were detected unequivocally inside tumor lymphoid cells. These results indicate that MDV morphogenesis in tumor cells is more similar to the morphorgenesis in fibroblastic cells in culture, albeit poorly efficient, than in feather follicle epithelial cells.
Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury
Authors: Fletcher Lauren , Isgor Elif , Sprague Shane , Williams Lindsey H , Alajajian Betty B , Jimenez David F , Digicaylioglu Murat
Published: December 2013

Background

Insulin-like growth factor binding protein-2 (IGFBP-2) regulates the bioavailability, transportation, and localization of insulin-like growth factor-I (IGF-I), an effective neuroprotectant in animal stroke models especially when administered intranasally. Therefore, determining IGFBP-2′s endogenous distribution in the normal and ischemic brain is essential in maximizing the neuroprotective potential of the intranasal IGF-I treatment approach. However, current data on IGFBP-2 is limited to mRNA and in situ hybridization studies. The purpose of this study was to determine if there are any changes in IGFBP-2 protein levels and distribution in ischemic brain and also to determine if IGFBPs play a role in the transportation of intranasally administered IGF-I into the brain.

Results

Using an in vitro approach, we show that ischemia causes changes in the distribution of IGFBP-2 in primary cortical neurons and astrocytes. In addition, we show using the transient middle cerebral artery occlusion (MCAO) model in mice that there is a significant increase in IGFBP-2 levels in the stroke penumbra and core after 72 h. This correlated with an overall increase in IGF-I after stroke, with the highest levels of IGF-I in the stroke core after 72 h. Brain sections from stroke mice indicate that neurons and astrocytes located in the penumbra both have increased expression of IGFBP-2, however, IGFBP-2 was not detected in microglia. We used binding competition studies to show that intranasally administered exogenous IGF-I uptake into the brain is not receptor mediated and is likely facilitated by IGFBPs.

Conclusions

The change in protein levels indicates that IGFBP-2 plays an IGF-I-dependent and -independent role in the brain’s acute (neuroprotection) and chronic (tissue remodeling) response to hypoxic-ischemic injury. Competition studies indicate that IGFBPs may have a role in rapid transportation of exogenous IGF-I from the nasal tissue to the site of injury.
The mediating role of dietary factors and leisure time physical activity on socioeconomic inequalities in body mass index among Australian adults
Authors: Gearon Emma , Backholer Kathryn , Hodge Allison , Peeters Anna
Published: December 2013

Background

The relationship between socioeconomic position and obesity has been clearly established, however, the extent to which specific behavioural factors mediate this relationship is less clear. This study aimed to ascertain the contribution of specific dietary elements and leisure-time physical activity (LTPA) to variations in obesity with education in the baseline (1990–1994) Melbourne Collaborative Cohort Study (MCCS).

Methods

18, 489 women and 12, 141 men were included in this cross-sectional analysis. A series of linear regression models were used in accordance with the products of coefficients method to examine the mediating role of alcohol, soft drink (regular and diet), snacks (healthy and sweet), savoury items (healthy and unhealthy), meeting fruit and vegetable guidelines and LTPA on the relationship between education and body mass index (BMI).

Results

Compared to those with lowest educational attainment, those with the highest educational attainment had a 1 kg/m2lower BMI. Among men and women, 27% and 48%, respectively, of this disparity was attributable to differences in LTPA and diet. Unhealthy savoury item consumption and LTPA contributed most to the mediated effects for men and women. Alcohol and diet soft drink were additionally important mediators for women.

Conclusions

Diet and LTPA are potentially modifiable behavioural risk factors for the development of obesity that contribute substantially to inequalities in BMI. Our findings highlight the importance of specific behaviours which may be useful to the implementation of effective, targeted public policy to reduce socioeconomic inequalities in obesity.
Getting vaccinated or not getting vaccinated? Different reasons for getting vaccinated against seasonal or pandemic influenza
Authors: Bonfiglioli Roberta , Vignoli Michela , Guglielmi Dina , Depolo Marco , Violante Francesco Saverio
Published: December 2013

Background

A large number of studies have investigated the motivation behind health care workers (HCWs) taking the influenza vaccine. But with the appearance of pandemic influenza, it became important to better analyse the reasons why workers get vaccinated against seasonal and/or pandemic influenza.

Methods

Three main categories of reasons were identified with an Exploratory Factor Analysis. An analysis of variance (ANOVA) was used to verify the existence of differences between three categories of choices (taking of seasonal and pandemic vaccine, only the seasonal vaccine or none). In addition, a multinomial logistic regression analysis was performed to analyse the association between stated intentions and update of seasonal and pandemic vaccine. Questionnaires were returned from 168 HCWs (67.3% women).

Results

The results showed that age and being well-informed about vaccination topics are the most important variables in determining the choice to take the vaccine.

Conclusions

The results highlight the importance of enhancing education programs to improve awareness among HCWs concerning the benefits of taking the influenza vaccination, with particular attention paid to younger workers.
Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis
Authors: Lee Song-Tay , Lu Min-Hua , Chien Lan-Hsiang , Wu Ting-Feng , Huang Li-Chien , Liao Gwo-Ing
Published: December 2013

Background

Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action.

Methods

Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract.

Results

This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell.

Conclusions

The analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer.
Size-dependent mechanical behavior of nanoscale polymer particles through coarse-grained molecular dynamics simulation
Authors: Zhao Junhua , Nagao Shijo , Odegard Gregory M , Zhang Zhiliang , Kristiansen Helge , He Jianying
Published: December 2013

Anisotropic conductive adhesives (ACAs) are promising materials used for producing ultra-thin liquid-crystal displays. Because the mechanical response of polymer particles can have a significant impact in the performance of ACAs, understanding of this apparent size effect is of fundamental importance in the electronics industry. The objective of this research is to use a coarse-grained molecular dynamics model to verify and gain physical insight into the observed size dependence effect in polymer particles. In agreement with experimental studies, the results of this study clearly indicate that there is a strong size effect in spherical polymer particles with diameters approaching the nanometer length scale. The results of the simulations also clearly indicate that the source for the increases in modulus is the increase in relative surface energy for decreasing particle sizes. Finally, the actual contact conditions at the surface of the polymer nanoparticles are shown to be similar to those predicted using Hertz and perfectly plastic contact theory. As ACA thicknesses are reduced in response to reductions in polymer particle size, it is expected that the overall compressive stiffness of the ACA will increase, thus influencing the manufacturing process.
The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial
Authors: Feng Rui-zhi , Lv Jian-qin , Johnson Angela K , Montoya Juan D , Mao Bing
Published: December 2013

Background

Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets.

Methods/design

This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy.

Discussion

This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial.

Trial registration

This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197.
Does a placebo effect really occur in dogs afflicted by hip osteoarthritis as measured by force platform gait analysis?
Authors: Moreau Maxim , Lussier Bertrand , Pelletier Jean-Pierre , Troncy Eric
Published: December 2013

A recent study investigated the therapeutic response of dogs afflicted by hip osteoarthritis when evaluating therapeutic modalities compared to a negative (placebo) control group. Authors suggested a placebo effect based on peak vertical force measurement. In addition, small effect size for each of the tested therapeutics as well as the extremely large sample size needed (>450) to discern therapeutic efficacy using force platform gait analysis were reported. We wish to express our concerns regarding the eligibility criteria used to select the studied cohort, the small effect size, and the placebo effect reported in force platform gait analysis.
Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma
Authors: Kim Young-Il , Park Joong-Won , Kim Bo Hyun , Woo Sang Myung , Kim Tae Hyun , Koh Young Hwan , Lee Woo Jin , Kim Chang-Min
Published: December 2013

Background

A standard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma (IHCC) has not yet been established. Although neoadjuvant concurrent chemoradiotherapy (CCRT) and liver transplantation are associated with long-term survival in select patients, the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear. The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC.

Methods

We retrospectively reviewed the records of all patients with unresectable advanced stage (stage IVa or IVb) IHCC who were pathologically diagnosed and treated at National Cancer Center, Korea, from June 2001 to March 2012. Of the total of 92 patients, 25 (27.1%) received capecitabine plus cisplatin (XP) chemotherapy with external radiotherapy (RT) (XP-CCRT group) and 67 (72.8%) received XP chemotherapy alone (XP group). The clinical characteristics and outcomes of the 2 groups were compared.

Results

The 92 patients comprised 72 male and 20 female patients, with a median age of 58 years (range 26–78 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy, whereas patients in the XP group received a mean 4.0 cycles. The disease control rate was higher in the XP-CCRT group than in the XP group, but the difference was not statistically significant (56.0% vs. 41.5%, p = 0.217). Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group (48% vs. 9%, p < 0.001), the rates of other toxicities and > grade 3 toxicities did not differ. At a median follow-up of 5.3 months, PFS (4.3 vs. 1.9 months, p = 0.001) and OS (9.3 vs. 6.2 months, p = 0.048) were significantly longer in the XP-CCRT than in the XP group.

Conclusions

XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC. Controlled randomized trials are required to determine whether XP-CCRT is a primary treatment option for patients with unresectable advanced IHCC.
Safety and efficacy of thoracoscopic wedge resection for elderly high-risk patients with stage I peripheral non-small-cell lung cancer
Authors: Lin Ling , Hu Dingzhong , Zhong Chenxi , Zhao Heng
Published: December 2013

Background

Elderly patients with severe cardiopulmonary and other system dysfunctions are unable to tolerate pulmonary lobectomy. This study aimed to evaluate the risk and efficacy of wedge resection under video-assisted thoracoscopic surgery (VATS) on elderly high-risk patients with stage I peripheral non-small-cell lung cancer (PNSCLC).

Methods

Elderly patients (≥70 years) with suspected PNSCLC were divided into high-risk group and conventional risk group. The high-risk patients confirmed in stage I by the examination of positron emission tomography computed tomography (PET-CT) and the postoperative patients in stage I PNSCLC with negative incisal margin were treated with VATS wedge resection. The conventional risk patients were treated with VATS radical resection and systematic lymphadenectomy. The clinical and pathological data were recorded. The total survival, tumor-free survival, recurrence time and style of patients were followed up.

Results

The operative time and blood loss of the VATS wedge resection group (69.4 ± 15.5 min, 52.1 ± 11.2 ml) were significantly less than those of the VATS radical resection group (128 ± 35.5 min, 217.9 ± 87.1 ml). Neither groups had postoperative death. The overall and tumor-free survival rate of the VATS wedge resection group within three years were 66.7% and 60.0%, and those of the VATS radical resection group were 93.8% and 94.1%, without significant difference (P > 0.05). The recurrence rates of the VATS wedge resection group and VATS radical resection group were 14.3% and 3.0%, without significant difference (P > 0.05).

Conclusion

It is safe, minimally invasive and meaningful to perform VATS wedge resection on the elderly high-risk patients with stage I PNSCLC.
The placebo effect in allergen‐specific immunotherapy trials
Authors: Narkus Annemie , Lehnigk Ulrike , Haefner Dietrich , Klinger Regine , Pfaar Oliver , Worm Margitta
Published: December 2013

Background

Double‐blind, placebo‐controlled (DBPC) trials are the gold standard for demonstrating clinical efficacy and tolerability. The placebo effect, although an important feature in placebo‐controlled studies, has never been systematically investigated in allergen‐specific immunotherapy (SIT) studies. This study was performed to examine the placebo response in SIT trials that employed a baseline observational period and two treatment years using a symptom‐medication‐score (SMS) as the primary endpoint.

Methods

The placebo effect was evaluated in six DBPC SIT studies (five studies using subcutaneous SIT (SCIT) and one sublingual (SLIT)), two grass, two birch and two house dust mite (HDM) SIT, including a total of 472 adult patients treated with a placebo. The results were reported as changes from baseline of the SMS area under the curve after two years of perennial placebo therapy during the respective evaluation periods. Pollen counts and IgG4 levels were additionally analysed.

Results

Subcutaneously treated placebo patients displayed a marked decrease in the SMS. The mean placebo effect in the SCIT trials with comparable allergen exposure was up to 41% in the second treatment year and, in contrast, reached only 1% in the SLIT trial. Allergen exposure had an inverse influence on the placebo effect. No changes from baseline in allergen specific IgG4 antibodies were observed in the placebo‐treated patients.

Conclusions

SIT studies display a significant placebo effect, mainly observed in subcutaneous immunotherapy, with high variability depending on the route of application and allergen exposure. Our findings indicate the differential role of the placebo effect in SIT efficacy depending on the route of administration and pollen exposure.
The impact of extended release dopamine agonists on prescribing patterns for therapy of early Parkinson’s disease: an observational study
Authors: Pellicano Clelia , Benincasa Dario , Fanciulli Alessandra , Latino Pamela , Giovannelli Morena , Pontieri Francesco E
Published: December 2013

Background

Dopamine agonists (DA) are the first-choice drug for treatment of the early stage of Parkinson’s disease (PD) in subjects younger than 70 years. Recently, a number of third generation DA have been marketed, including transdermal patch of rotigotine and extended release oral formulation of ropinirole and pramipexole.

We investigated the impact of third generation DA on management of the early stage of PD in an outpatient service for Movement Disorders in Italy.

Methods

Two 12-month observation periods were selected (January - December, 2007, and January - December, 2011) as representative for prescription of immediate and extended release formulations of DA respectively. Within each period, PD patients were divided into subgroups according to age (<65 years; 65–75 years; >75 years) or functional requirement (high; moderate; low). For each period, the number of subjects receiving monotherapy with DA, monotherapy with levodopa (LD), or combined DA/LD therapy and the relative doses were calculated. The severity of parkinsonian motor symptoms was calculated by means of the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score. The frequency and severity of side-effects leading to discontinuation or reduction of DA drugs at each time point were also calculated.

Results

We found a significant reduction of daily LD dose (both as mono- and combined therapy) between the second and the first observation period. There was also a significant increase of monotherapy with DA and corresponding reduction of monotherapy with LD in patients aged 65–75 years, as well as in PD patients with moderate functional requirements. A significant reduction of frequency of side-effects was measured with extended release DA as compared to immediate release formulations. There were no significant differences of the UPDRS-III scores between the 2 observation periods in any subgroup.

Conclusions

Our results suggest that extended release DA might optimize therapeutic management of the early stages of PD even in patients older than 70 years of age.
Performance in Olympic triathlon: changes in performance of elite female and male triathletes in the ITU World Triathlon Series from 2009 to 2012
Authors: Rüst Christoph Alexander , Lepers Romuald , Stiefel Michael , Rosemann Thomas , Knechtle Beat
Published: December 2013

This study investigated the changes in performance and sex difference in performance of the world best triathletes at the ITU (International Triathlon Union) World Triathlon Series (i.e. 1.5 km swimming, 40 km cycling and 10 km running) during the 2009-2012 period including the 2012 London Olympic Games. Changes in overall race times, split times and sex difference in performance of the top ten women and men of each race were analyzed using single and multi-level regression analyses. Swimming and running split times remained unchanged whereas cycling split times (ß = 0.003, P < 0.001) and overall race times (ß = 0.003, P < 0.001) increased significantly for both women and men. The sex difference in performance remained unchanged for swimming and cycling but decreased for running (ß = -0.001, P = 0.001) from 14.9 ± 2.7% to 13.2 ± 2.6% and for overall race time (ß = -0.001, P = 0.006) from 11.9 ± 1.2% to 11.4 ± 1.4%. The sex difference in running (14.3 ± 2.4%) was greater (P < 0.001) compared to swimming (9.1 ± 5.1%) and cycling (9.5 ± 2.7%). These findings suggest that (i) the world’s best female short-distance triathletes reduced the gap with male athletes in running and total performance at short distance triathlon with drafting during the 2009-2012 period and (ii) the sex difference in running was greater compared to swimming and cycling. Further studies should investigate the reasons why the sex difference in performance was greater in running compared to swimming and cycling in elite short-distance triathletes.
A minimal number of MELT repeats supports all functions of KNL1 in chromosome segregation
Authors: Zhang Gang , Lischetti Tiziana , Nilsson Jakob
Published: December 2013

The Bub1-Bub3 and BubR1-Bub3 checkpoint complexes, or the Bubs, contribute to the accurate segregation of chromosomes during mitosis by promoting chromosome bi-orientation and halting exit from mitosis if this fails. The complexes associate with kinetochores during mitosis, which is required for proper chromosome segregation. The outer kinetochore protein KNL1 (also known as CASC5/Blinkin/AF15Q14) is the receptor for Bub proteins but the exact nature of the functional binding sites on KNL1 are yet to be determined. Here, we show that KNL1 contains multiple binding sites for the Bub proteins, with the Mps1-phosphorylated MELT repeats constituting individual functional docking sites for direct binding of Bub3. Surprisingly, chromosome congression and the Spindle Assembly Checkpoint (SAC) are still functional when KNL1 is deleted of all but four of its twelve MELT repeats. Systematically reducing the number of MELT repeats to less than four reduced KNL1 functionality. Furthermore, we show that Protein Phosphatase 1 (PP1) binding to KNL1 in prometaphase reduces the levels of Bub proteins at kinetochores to approximately the level recruited by four active MELT repeats.
Nup53 interaction with Ndc1 and Nup155 are required for nuclear pore complex assembly
Authors: Eisenhardt Nathalie , Redolfi Josef , Antonin Wolfram
Published: December 2013

Nuclear pore complexes (NPCs) are the gateways for nucleocytoplasmic exchange. The ordered assembly of these huge complexes from several hundred individual components into an intricate protein interaction network which deforms the two membranes of the nuclear envelope to a pore is only rudimentary understood. Here, we show that the interaction between the integral pore membrane protein Ndc1 and Nup53 is essential for vertebrate NPC assembly. The Ndc1 binding site on Nup53 overlaps with a region inducing membrane bending and is specifically required to modulate this activity suggesting that Nup53's membrane deforming capability is adjusted during the NPC assembly process. We further demonstrate that the interaction of Nup53 and Nup155 plays a crucial role in NPC formation as the main determinant of Nup155 recruitment to the assembling pore. Overall, our results pinpoint on the diversity of interaction modes accomplished by Nup53 highlighting this protein as essential link between the pore membrane and the NPC and a critical factor for pore membrane formation.
Glucose overload in yolk has little effects on the long term modulation of carbohydrate metabolic genes in zebrafish (Danio rerio)
Authors: Rocha Filipa , Dias Jorge , Engrola Sofia , Gavaia Paulo , Geurden Inge , Dinis Maria T. , Panserat Stephane
Published: December 2013

Some fish show a low metabolic ability to use dietary carbohydrates. The use of early nutritional stimuli to program metabolic pathways in fish is ill defined. Studies were undertaken with zebrafish to assess the effect of high glucose levels during embryonic stage as lifelong modulator of genes involved in carbohydrate metabolism. Genes related to carbohydrate metabolism showed low expression levels at 0.2 and 1 days post-fertilization (dpf). However, from 4 dpf onwards there was a significant increase on expression of all genes, suggesting that all analysed pathways were active. By microinjection, we successfully enriched zebrafish egg yolk with glucose (a 43-fold increase of basal levels). Acute effects of glucose injection on gene expression were assessed in larvae up to 10 dpf, while the programming concept was evaluated in juveniles (41 dpf) challenged with a hyperglucidic diet. At 4 dpf, larvae from glucose-enriched eggs showed a down-regulation of several genes related to glycolysis, glycogenolysis, lipogenesis and carbohydrate digestion in comparison with control (saline injected). This inhibitory regulation was suppressed after 10 dpf. At the juvenile stage and upon switching from a low to a high digestible carbohydrate diet, early glucose enrichment had no significant effect on most analysed genes. Still, these same fish showed altered expression of PEPCKc, SGLT1 and GS genes, suggesting changes on glucose storage capacity in muscle and glucose production and transport in viscera. On the overall, egg yolk supplementation with high glucose levels had little effects on the long term modulation of carbohydrate metabolic genes in zebrafish.
Impulsive ankle push-off powers leg swing in human walking
Authors: Lipfert Susanne , Günther Michael , Renjewski Daniel , Seyfarth Andre
Published: December 2013

Rapid unloading and a peak in power output of the ankle joint has been widely observed during push-off in human walking. Model based studies hypothesize this push-off to cause redirection of the body center of mass just before touch-down of the leading leg. Other research suggests, that work done by the ankle extensors provides kinetic energy for the initiation of swing. Also, muscle work is discussed to power a catapult-like action in late stance of human walking. However, there is a lack of knowledge about the biomechanical process leading to this widely observed high power output of the ankle extensors. In our study, we use kinematic and dynamic data of human walking collected at speeds between 0.5 and 2.5m/s for a comprehensive analysis of push-off mechanics. We identify two distinct phases, which divide the push-off: First, starting with positive ankle power output, an alleviation phase, where the trailing leg is alleviated from supporting the body mass, and second, a launching phase, where stored energy in the ankle joint is released. Our results show a release of just a small part of the energy stored in the ankle joint during the alleviation phase. A larger impulse for the trailing leg than for the remaining body is observed during the launching phase. Here, the buckling knee joint inhibits transfer of power from the ankle to the remaining body. It appears that swing initiation profits from an impulsive ankle push-off resulting from a catapult without escapement.
The honey bee tyramine receptor AmTYR1 and division of foraging labor
Authors: Scheiner Ricarda , Kulikovskaja Leonora , Thamm Markus
Published: December 2013

Honey bees display a fascinating division of labor among foragers. While some bees solely collect pollen, others only collect nectar. It is assumed that individual differences in sensory response thresholds are at the basis of division of labor. Biogenic amines and their receptors are important candidates for regulating division of labor, because they can modulate sensory response thresholds. We here investigate the role of the honey bee tyramine receptor AmTYR1 in regulating division of foraging labor. We report differential splicing of the Amtyr1 gene and show differential gene expression of one isoform in the suboesophageal ganglion of pollen and nectar foragers. This ganglion mediates gustatory inputs. These findings imply a role for the honey bee tyramine receptor in regulating division of foraging labor, possibly through the suboesophageal ganglion.
Weakly electric fish give behavioral responses to envelopes naturally occurring during movement: implications for neural processing
Authors: Metzen Michael G. , Chacron Maurice J.
Published: December 2013

How the brain processes natural sensory input remains an important and poorly understood problem in neuroscience. The efficient coding hypothesis asserts that the brain’s coding strategies are adapted to the statistics of natural stimuli in order to efficiently process them, thereby optimizing their perception by the organism. Here we examined whether Gymnotiform weakly electric fish displayed behavioral responses that are adapted to the statistics of the natural electrosensory envelopes. Previous studies have shown that the envelopes resulting from movement tend to consist of low (<1 Hz) temporal frequencies and are behaviorally relevant while those resulting from social interactions instead consist of higher (> 2 Hz) temporal frequencies that can thus mask more behaviorally relevant signals. We found that the self-generated electric organ discharge frequency follows the envelope’s detailed timecourse around a mean value that is positively offset with respect to its baseline value for temporal frequencies between 0.001 Hz and 1 Hz. The frequency following component of this behavioral response decreased in magnitude as a power law as a function of the envelope frequency and was negligible for envelope frequencies above 1 Hz. In contrast, the offset component was relatively constant and somewhat increased for envelope frequencies above 1 Hz. Thus, our results show that weakly electric fish give behavioral responses that track the detailed timecourse of low but not high frequency envelope stimuli. Further, we found that the magnitude of the frequency following behavioral response matches in a one-to-one fashion the spectral power of natural second order stimulus attributes observed during movement. Indeed, both decayed as a power law with the same exponent for temporal frequencies spanning three orders of magnitude. Thus, our findings suggest that the neural coding strategies used by weakly electric fish perceive the detailed timecourse of movement envelopes are adapted to their statistics as found in the natural environment. They also suggest that weakly electric fish might take advantage of the differential frequency content of movement and social envelopes in order to give appropriate behavioral responses during encounters between two or more conspecifics.
Phase Change Material on Augmentation of Fresh Water Production Using Pyramid Solar Still
Authors: Ravishankara S. , Nagarajan P.K. , Vijayakumar D. , Jawahar M.K.
Published: December 2013

The augmentation of fresh water and increase in the solar still efficiency of a triangular pyramid is added with phase change material (PCM) on the basin. Experimental studies were conducted and the effects of production of fresh water with and without PCM were investigated. Using paraffin as the PCM material, performance of the solar still were conducted on a hot, humid climate of Chennai (13°5′ 2" North, 80°16′ 12"East), India. The use of paraffin wax increases the latent heat storage so that the energy is stored in the PCM and in the absence of solar radiation it rejects its stored heat into the basin for further evaporation of water from the basin. Temperatures of water, Tw, Temperature of phase change material, TPCM, Temperature of cover, Tc were measured using thermocouple. Results show that there is an increase of maximum 20%, in productivity of fresh water with PCM. Keywords: fresh water production; PCM; thermal energy storage; phase change material
A Review of a Successful Unsubsidized Market-Based Rural Solar Development Initiative in Laikipia District, Central Kenya
Authors: Wambuguh O.
Published: December 2013

The development of renewable energy technologies (RETs) in many areas far from grid-based electricity have primarily involved solar photovoltaics (SPVs) which tap solar radiation to provide heat, light, hot water, electricity, and cooling for homes, businesses, and industry. A study on RETs took place in the Wiyumiririe Location of Laikipia District (north-central Kenya), a rich agricultural region. To explore this solar initiative in such a remote part of the country, a purposive randomized convenience sample of 246 households was selected and landowner interviews conducted, followed by field visits and observations. Although more than half of the households visited had SPV installations, solar energy was found to contribute only 18% of household estimated total energy needs; most residents still primarily relying on traditional energy sources. Several types of solar panels of different capacities and costs were utilized. Many landowners had at least one or two rooms using solar energy for household lighting, for appliance charging and to power radio and television. Almost all respondents appreciated that solar energy was clean renewable energy that greatly improved household living conditions; gave them some prestige; was easy to use and maintain; and was available year around. Although such significant benefits were associated with SPVs, only about 40% of residents interviewed were somehow satisfied with its development. Respondents expressed specific developmental initiatives that were closely associated with the availability of solar energy. Nevertheless, a number of challenges were raised associated with SPVs primarily investment capital and equipment costs and maintenance. As solutions to capital building will not solely rely on subsidies or individual farmer inputs, strategies must be found to mobilize the essential and tested tools for success including sustainable capital generation, building local institutions and capacities that integrate rural people, local participation in rural development activities and public education and training. Keywords: appliance charging,battery,development initiatives, household lighting, landowners,solar energy, SPVs, solar equipment and accessories
Biodiesel Production from Kapok (Ceiba pentandra) Seed Oil using Naturally Alkaline Catalyst as an Effort of Green Energy and Technology
Authors: Handayani N.A. , Santosa H. , Sofyan M. , Tanjung I. , Chyntia A. , Putri P.A.R.S. , Ramadhan Z.R.
Published: December 2013

Nowadays, energy that used to serve all the needs of community, mainly generated from fossil (conventional energy). Terrace in energy consumption is not balanced with adequate fossil fuel reserves and will be totally depleted in the near future. Indonesian Government through a Presidential Decree No. 5 year 2006 mandates an increased capacity in renewable energy production from 5 percent to 15 percent in 2025. C. pentandra seed oil has feasibility as a sustainable biodiesel feedstock in Indonesia. The aim of this paper was to investigate biodiesel production from ceiba petandra seed oil using naturally potassium hydroxide catalyst. Research designs are based on factorial design with 2 levels and 3 independent variables (temperature, reaction time and molar ratio of methanol to oil). According to data calculation, the most influential single variable is molar ratio of methanol to oil. Characterization of biodiesel products meet all the qualifications standardized by SNI 04-7182-2006.
Wind Power Generation in India: Evolution, Trends and Prospects
Authors: Khan M.F. , Khan M.R.
Published: December 2013

In the present context of shrinking conventional resources coupled with environmental perils, the wind power offers an attractive alternative. Wind power generation in India started way back in early 1980s with the installation of experimental wind turbines in western and southern states of Gujarat and Tamil Nadu. For first two decades of its existence until about 2000 the progress was slow but steady. In last one decade Indian wind electricity sector has grown at very rapid pace which has promoted the country to the fifth position as largest wind electric power generator and the third largest market in the world. The galvanization of wind sector has been achieved through some aggressive policy mechanisms and persistent support by government organizations such as MNRE and C-WET. This paper articulates the journey of Indian wind program right since its inception to the present trends and developments as well as the future prospects.
Macro Meets Micro: Stochastic (Calvo) Revisions in Games
Authors: Libich Jan , Nguyen Dat Thanh
Published: December 2013

The timing of moves in conventional games is deterministic. To better capture the uncertainty of many real world situations, we postulate a stochastic timing framework. The players get a revision opportunity at a pre-specified time (common to them) with some known probability (different across them). The probabilistic revisions resemble the Calvo (1983) timing widely used in macroeconomics, and by nesting the standard simultaneous move game and Stackelberg leadership they can serve as a “dynamic commitment” device. The analysis shows how the revision time and probabilities affect the outcomes in games with multiple and/or inefficient equilibria. Unsurprisingly, we show in the Battle of the sexes that commitment – low revision probability relative to the opponent – improves the player’s chances to uniquely achieve his preferred outcome (i.e. to dominate). What may, however, seem surprising is that the less committed (higher revision probability) player may dominate the game under some circumstances (for which we derive the necessary and sufficient conditions). This is in contrast to the intuition of Stackelberg leadership where the more committed player (leader) always does so. The paper then applies the framework to the strategic interaction between monetary and fiscal policies in the aftermath of the Global financial crisis. It is modelled as the Game of chicken in which a double-dip recession and deflation can occur when both policies postpone stimulatory measures – attempting to induce the other policy to carry them out. In order to link our theoretic results to the real world, we develop new indices of monetary and fiscal policy leadership (pre-commitment) and quantify them using institutional characteristics of high-income countries. This exercise shows that the danger of the undesirable deflationary scenario caused by a monetary–fiscal policy deadlock may be high in some major economies.
Improving the weathering on larch wood samples by electron beam irradiation (EBI)
Authors: Schnabel Thomas , Huber Hermann
Published: December 2013

High-energy irradiation of a biogenic polymer is of interest from different perspectives, as this type of modification process may beneficially influence various functional and structural properties of wood. This study deals with the influence of electron beam irradiation (EBI) on the artificial weathering behavior of larch wood. The results of color measurement and infrared spectra show different effects of the EBI at dosages of 1 and 30 kGy during weathering tests. The results may provide a helpful basis for further fundamental research to improve weathering of wood by EBI.
Lignin chemistry and topochemistry during kraft delignification of Eucalyptus globulus genotypes with contrasting pulpwood characteristics
Authors: Aguayo María Graciela , Ferraz André , Elissetche Juan Pedro , Masarin Fernando , Mendonça Regis Teixeira
Published: December 2013

Eucalyptus globulus Labill. is a short-fibre resource for pulp and paper production. Ten different E. globulus genotypes with varied pulpwood quality and chemical composition were evaluated under kraft pulping conditions. Characterisation of the wood and pulp samples by thioacidolysis indicated that the content of syringyl units in β-O-4 linkages (S-β-O-4) was distinct for the studied genotypes. The highest S-β-O-4 levels were detected in the samples with the lowest original lignin and highest glucan levels. This group of samples provided the pulps with the lowest final lignin content at higher yields. UV microspectrophotometric (UMSP) evaluation of the wood chips revealed that the samples with the lowest lignin levels have the lowest UV absorbances at 278 nm (A278 nm) in the secondary walls (S2). During kraft pulping, lignin from the S2 was dissolved, whereas lignins from the middle lamella and cell corner lignin was not removed not even for prolonged reaction periods, independently of the evaluated genotype. The A278 nm values of the S2 were significantly lower in the pulps from the genotypes with less original lignin content.
Targeted Data Adaptive Estimation of the Causal Dose–Response Curve
Authors: Díaz Iván , van der Laan Mark J.
Published: December 2013

Estimation of the causal dose–response curve is an old problem in statistics. In a non-parametric model, if the treatment is continuous, the dose–response curve is not a pathwise differentiable parameter, and no-consistent estimator is available. However, the risk of a candidate algorithm for estimation of the dose–response curve is a pathwise differentiable parameter, whose consistent and efficient estimation is possible. In this work, we review the cross-validated augmented inverse probability of treatment weighted estimator (CV A-IPTW) of the risk and present a cross-validated targeted minimum loss–based estimator (CV-TMLE) counterpart. These estimators are proven consistent and efficient under certain consistency and regularity conditions on the initial estimators of the outcome and treatment mechanism. We also present a methodology that uses these estimated risks to select among a library of candidate algorithms. These selectors are proven optimal in the sense that they are asymptotically equivalent to the oracle selector under certain consistency conditions on the estimators of the treatment and outcome mechanisms. Because the CV-TMLE is a substitution estimator, it is more robust than the CV-AIPTW against empirical violations of the positivity assumption. This and other small sample size differences between the CV-TMLE and the CV-A-IPTW are explored in a simulation study.