bluuebunny/crossref_metadata_2025 huggingface dataset:
Liberal Pessimism: International Relations Theory and the Emerging Powers
Authors: Haggard Stephan
Published: October 2013

The triumphalism of the immediate post‐ColdWar period in theUnitedStates has faded, and concern about decline has returned. In the field of international relations, the return of power transition models is exemplary of the new mood. This article argues that realist models misjudge the source of foreign policy risks for theUnitedStates and its allies. Rather, the standard canon of liberal international relations theory also suggests sources of pessimism. These include the enduring nature of authoritarian rule, the difficulty of coordinating emerging actors through existing international institutions, and the ambiguous effects of increased interdependence on the foreign policy behaviour and leverage of emerging powers.
Health Policy inAsia and thePacific: Navigating Local Needs and Global Challenges
Authors: Lee Kelley
Published: October 2013

Asia and thePacific is undergoing a remarkable economic transformation, which is occurring at an exceptional pace. There is clear evidence of an equally rapid epidemiological transition in the region. This article sets out the policy challenges of building healthy societies in the context of rapid economic change. The region's location at the crossroads of contemporary globalisation, resulting in intensified population mobility, large‐scale trade and investment, and pressures to take collective action on shared problems, adds to the complexity of this task. The article argues that health is integral to building stable and sustainable societies, and that there are opportunities to develop more holistic approaches that bring together hitherto separate policy spheres.
Post‐release mortality estimates of loggerhead sea turtles (Caretta caretta) caught in pelagic longline fisheries based on satellite data and hooking location
Authors: Swimmer Y. , Empey Campora C. , Mcnaughton L. , Musyl M. , Parga M.
Published: October 2013

There are few reliable estimates of post‐release mortality for sea turtle species because of the many challenges and costs associated with tracking animals released at sea. In this study, the likelihood of sea turtle mortality as a result of interactions with longline fishing gear was estimated based on satellite telemetry data, such as the number of days an animal was successfully tracked, or days at liberty (DAL) and dive depth data, as well as anatomical hooking locations.

Pop‐up satellite archival tags were deployed on 29 loggerhead sea turtles (Caretta caretta) caught by the North Pacific US‐based pelagic longline fishery operating from California and Hawaii between 2002 and 2006. Loggerhead turtles were catagorized by observers as shallow‐hooked (55%) if the animal was entangled in the line or the hook was in the flipper, jaw or mouth and could be removed, or deep‐hooked (45%) if the hook was ingested and could not be removed. The vertical movements of turtles were used to infer potential mortalities.

Of the 25 tags that reported data, the DAL ranged from 3 to 243 days (mean = 68 days). The DAL was shorter (by nearly 50%) for shallow‐hooked (mean = 48 days, range: 3 to 127) compared to deep‐hooked turtles (mean = 94 days, range: 5 to 243), but these changes were not statistically significant (P = 0.0658).

Although aspects of these analyses may be considered speculative, these data provide empirical evidence to indicate that deep‐hooking is not linked to shorter DAL.

DAL, anatomical hooking location, and gear removal were evaluated with inferences about the extent of injuries and rates of infection to estimate an overall post‐release mortality rate of 28% (95% bootstrap CI: 16–52%).

This range of estimates is consistent with those used to shape some US fisheries management plans, suggesting that conservation goals are being achieved at the expected level and ideally striking a balance between the interests of industry and those of protected species.

Copyright © 2013 John Wiley & Sons, Ltd.
Which factors strongly influence the sinking speed of a demersal longline?
Authors: Lee Jihoon , Lee Chun‐Woo , Karlsen Ludvig , Kim Taeho , Song Jeehun
Published: October 2013

Sinking speed is one of the main factors affecting the performance of longlines. Demersal and pelagic longlines need to sink quickly, to prevent bycatch of marine animals and bait loss to seabirds. The incidental catch or bycatch of seabirds by longlining is a problem from the environmental conservation point of view. Thus, it is necessary to develop techniques to reduce the incidental catch or bycatch by longlining.

This study focuses on the sinking speed of longlines. To determine the significant factors that may influence the sinking speed, the study considers the various parameters for longlining such as bait properties, rope materials, rope thickness, anchor weights, shooting speeds, shooting methods, and the ratio between the depth and mainline length.

The results of the numerical analysis were verified by comparing them with observations from field experiments. The results suggest that the sinking speed can be increased and the bycatch during the sinking process can be reduced when baits have elliptical shapes with a small projected area relative to the sinking orientation, as well as when high‐density and thicker materials are used. Heavier anchors also help to increase the sinking speed of the anchor part, excluding other parts such as the middle part of a mainline. If the water is shallow compared with the line's length, the anchor's weight has a smaller influence on the speed of sinking in the middle of the line. In this case, the factors that influence the sinking speed of a longline 10, 30, and 50 m from the stern are rope material, rope thickness, and shooting speed.

These results may be used to design techniques for bycatch prevention. Based on these results, accounting for these important factors when designing a longline is expected to increase the fishing efficiency. Copyright © 2013 John Wiley & Sons, Ltd.
CLONING, EXPRESSION PATTERNS, AND PRELIMINARY CHARACTERIZATION OF AccCPR24, A NOVEL RR‐1 TYPE CUTICLE PROTEIN GENE FROM Apis cerana cerana
Authors: Chu Xiaoqian , Lu Wenjing , Zhang Yuanying , Guo Xingqi , Sun Rujiang , Xu Baohua
Published: October 2013

Cuticular proteins (CPs) are key components of insect cuticle, a structure that plays a pivotal role in insect development and defense. In this study, we cloned the full‐length cDNA of a CP gene from Apis cerana cerana (AccCPR24). An amino acid sequence alignment indicated that AccCPR24 contains the conserved Rebers and Riddiford consensus sequence and shares high similarity with the genes from other hymenopteran insects. We then isolated the genomic DNA and found that the first intron, which is present in other CP genes, is absent in AccCPR24. Real‐time quantitative polymerase chain reaction (qPCR) analysis revealed that AccCPR24 is highly expressed in the late pupal stage and midgut. Expression was inhibited by an exogenous ecdysteroid in vitro but was enhanced by this hormone in vivo; environmental stressors, such as heavy metals and pesticides, also influenced gene expression. In addition, a disc diffusion assay showed that AccCPR24 enhanced the ability of bacterial cells to resist multiple stresses. We infer from our results that AccCPR24 acts in honeybee development and in protecting these insects from abiotic stresses.
Discovery of 2‐Phenyl‐N‐(5‐(trifluoromethyl)‐1,3,4‐thiadiazol‐2‐yl)acetamide Derivatives as Apoptosis Inducers via the Caspase Pathway with Potential Anticancer Activity
Authors: Hosseinzadeh Leila , Khorand Amanc , Aliabadi Alireza
Published: October 2013

In the current research of medicinal chemistry, apoptosis induction is one of the novel strategies for the development and discovery of novel anticancer therapeutics. In the present study, a new series of 1,3,4‐thiadiazole derivatives (4a–4p) were synthesized and their in vitro anticancer activities were evaluated against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and SKNMC (neuroblastoma). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin. Apoptosis induction was also investigated through exploration of the activation of caspases 3, 8, and 9. According to the obtained results, compounds 4b (3‐Cl) and 4c (4‐Cl) demonstrated the best caspase activation. In fact, compounds 4b and 4c enhanced the activity of caspases 3 and 9 in the MCF7 cell line.
Synthesis and Biological Evaluation of Novel 4‐(2‐Fluorophenoxy)‐2‐(1H‐tetrazol‐1‐yl)pyridines Bearing Semicarbazone Moieties as Potent Antitumor Agents
Authors: Qin Mingze , Liao Weike , Xu Chen , Fu Baolin , Ren Jianguo , Gu Yucheng , Gong Ping
Published: October 2013

A series of 4‐(2‐fluorophenoxy)‐2‐(1H‐tetrazol‐1‐yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their in vitro antitumor potency. Some of the compounds (10b, 10c, 10e–10h, 10m–10p, 10r, and 11b) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC‐1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI‐38. The most promising compound 10p (IC50 = 0.08, 0.36, 0.97 µM) was 45.1‐, 6.1‐, and 2.4‐fold more active than sorafenib (IC50 = 3.61, 2.19, 2.32 µM), and 17, 3.2, and 2.9 times better than PAC‐1 (IC50 = 1.36, 1.17, 2.83 µM) against three cancer cell lines (HT‐29, H460, and MKN‐45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase.
Ultradense Topographic Correction by 3D‐Laser Scanning in Pseudo‐3D Ground‐penetrating Radar Data: Application to the Constructive Pattern of the Monumental Platform at the Segeda I Site (Spain)
Authors: Teixidó Teresa , Peña José Antonio , Fernández Gloria , Burillo Francisco , Mostaza Teresa , Zancajo Julio
Published: October 2013

Three‐dimensional ground‐penetrating radar (3D‐GPR) is one of the highest resolution geophysical methods for exploring the shallow subsurface and it is widely utilized in the diverse fields requiring this kind of information: for example archaeology, civil engineering and environmental studies. Currently, there are several ways to present 3D‐GPR results: 2D vertical pictures (radargrams), time‐ and depth‐slices, a mixture of radargram‐slice images, GPR reflectivity maps and GPR isosurface images. All of these techniques, however, require the maximum number of details possible. When the recognition surface is not horizontal, the GPR image is distorted due the topographic irregularities. To eliminate these distortions, a classic topographic correction is applied to the GPR data set, particularly in 2D GPR profiles. Generally, this topographic information is obtained by laser levelling, total station, differential Global Positioning System (GPS) or similar equipment. This study uses a new method of topographic correction based on three‐dimensional laser scanner (3D‐laser scanner) technology that provides ultradense coordinates of the terrain. A strategy for applying this topographic correction to 3D‐GPR vertical traces is discussed and evaluated by comparing corrected images with other uncorrected images obtained using the same standard processing flow. The GPR dataset used to test this method is from a monumental structure located in the Celtiberian site of Segeda I (Mara, Spain). The data were acquired using a 400 MHz antenna on 0.25 m spaced profiles. Although the relief of this structure is not overly complex, we demonstrate how the results obtained by applying this topographic correction technique allow a better archaeological interpretation of the internal architecture. The technique is therefore presented as a new archaeological tool to obtain clearer images of buried structures and/or their internal elements. Copyright © 2013 John Wiley & Sons, Ltd.
A Global Increase in 5‐Hydroxymethylcytosine Levels Marks Osteoarthritic Chondrocytes
Authors: Taylor Sarah E. B. , Smeriglio Piera , Dhulipala Lakshmi , Rath Madhusikta , Bhutani Nidhi
Published: October 2013

Objective

To investigate the role of the newly discovered epigenetic mark 5‐hydroxymethylcytosine (5hmC) and its regulators in altered gene expression in osteoarthritis (OA).

Methods

Cartilage was obtained from OA patients undergoing total knee arthroplasty and from control patients undergoing anterior cruciate ligament reconstruction. Global levels of 5hmC and 5‐methylcytosine (5mC) were investigated using immunoblotting, enzyme‐linked immunosorbent assays, and cellular staining. Gene expression changes were monitored by quantitative polymerase chain reaction (PCR) analysis. Levels of locus‐specific 5hmC and 5mC at CpG sites in the matrix metalloproteinase 1 (MMP‐1), MMP‐3, ADAMTS‐5, and hypoxanthine guanine phosphoribosyltransferase 1 (HPRT‐1) promoters were quantified using a glucosylation and enzyme digestion–based method followed by quantitative PCR analysis. Global and locus‐specific 5hmC levels and gene expression changes were monitored in normal chondrocytes stimulated with inflammatory cytokines to identify the effect of joint inflammation.

Results

A global 5–6‐fold increase in 5hmC concomitant with a loss of TET1 was observed in human OA chondrocytes compared to normal chondrocytes. Enrichment of 5hmC was observed in promoters of enzymes critical to OA pathology, MMP‐1 and MMP‐3. Short‐term treatment of normal chondrocytes with inflammatory cytokines induced a rapid decrease in TET1 expression but no global or locus‐specific 5hmC enrichment.

Conclusion

This study provides the first evidence of an epigenetic imbalance of the 5hmC homeostasis in OA leading to TET1 down‐regulation and 5hmC accumulation. Our experiments identify 5hmC and its regulators as potential diagnostic and therapeutic targets in OA.
Therapeutic Effect of Human Amniotic Membrane–Derived Cells on Experimental Arthritis and Other Inflammatory Disorders
Authors: Parolini Ornella , Souza‐Moreira Luciana , O'Valle Francisco , Magatti Marta , Hernandez‐Cortes Pedro , Gonzalez‐Rey Elena , Delgado Mario
Published: October 2013

Objective

Rheumatoid arthritis (RA) is an autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Cells isolated from human amniotic membrane (HAMCs) were recently found to display immunosuppressive properties. The aim of this study was to characterize the effect of HAMCs on antigen‐specific T cell responses in RA patients and to evaluate their therapeutic potential in a preclinical experimental model of RA.

Methods

We investigated the effects of HAMCs on collagen‐reactive T cell proliferation and cytokine production, on the production of mediators of inflammation by synoviocytes, and on the generation of Treg cells in peripheral blood mononuclear cells and synovial membrane cells isolated from RA patients. Mice with collagen‐induced arthritis (CIA) were treated with HAMCs after disease onset, and clinical scores and joint levels of mediators of inflammation were evaluated. We determined Th1/Th17‐mediated autoreactive responses in the mice by measuring the proliferation and the cytokine profile of lymph node cells restimulated with collagen.

Results

Treatment with HAMCs suppressed synovial inflammatory responses and antigen‐specific Th1/Th17 activation in cells isolated from RA patients. Moreover, HAMCs stimulated the generation of human CD4+CD25+FoxP3+ Treg cells with a capacity to suppress collagen‐specific T cell responses. Systemic infusion of HAMCs significantly reduced the incidence and severity of CIA by down‐regulating the 2 deleterious components of disease: Th1‐driven autoimmunity and inflammation. In mice with CIA, HAMC treatment decreased the production of various inflammatory cytokines and chemokines in the joints, impaired antigen‐specific Th1/Th17 cell expansion in the lymph nodes, and generated peripheral antigen‐specific Treg cells. HAMCs also protected the mice from experimental sepsis, inflammatory bowel disease, and autoimmune encephalomyelitis.

Conclusion

HAMCs have emerged as attractive candidates for a cell‐based therapy for RA.
B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice
Authors: Hamel Keith M. , Cao Yanxia , Olalekan Susan A. , Finnegan Alison
Published: October 2013

Objective

Inducible costimulator (ICOS)–ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)–induced arthritis (PGIA).

Methods

PGIA was initiated by immunizing wild‐type and ICOSL‐deficient (ICOSL−/−) or B cell–specific ICOSL−/− chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies.

Results

Arthritis progression was completely inhibited in both ICOSL−/− mice and B cell–specific ICOSL−/− chimeric mice. Production of the Teff cell–produced cytokines interferon‐γ and interleukin‐17 (IL‐17) and the antiinflammatory cytokine IL‐4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL‐21 correlated with a decrease in the anti‐mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses.

Conclusion

These data indicate that the signals provided by ICOSL‐expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL−ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.
Glucocorticoid Dose Thresholds Associated With All‐Cause and Cardiovascular Mortality in Rheumatoid Arthritis
Authors: del Rincón Inmaculada , Battafarano Daniel F. , Restrepo Jose F. , Erikson John M. , Escalante Agustín
Published: October 2013

Objective

To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA).

Methods

We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death.

Results

We studied 779 RA patients with a total of 7,203 person‐years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person‐years (95% confidence interval [95% CI] 2.8–3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5–2.1). Exposure to glucocorticoids was associated with a dose‐dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05–1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all‐cause mortality was 8–15 mg, with an adjusted HR of 1.78 (95% CI 1.22–2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all‐cause mortality was 40 gm (HR 1.74 [95% CI 1.25–2.44]).

Conclusion

Glucocorticoid use in RA is associated with a dose‐dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose‐dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents.
Interactive overlays of journals and the measurement of interdisciplinarity on the basis of aggregated journal–journal citations
Authors: Leydesdorff Loet , Rafols Ismael , Chen Chaomei
Published: October 2013

Using the option Analyze Results with the Web of Science, one can directly generate overlays onto global journal maps of science. The maps are based on the 10,000+ journals contained in the Journal Citation Reports (JCR) of the Science and Social Sciences Citation Indices (2011). The disciplinary diversity of the retrieval is measured in terms of Rao‐Stirling's “quadratic entropy” (Izsák & Papp, 1995). Since this indicator of interdisciplinarity is normalized between 0 and 1, interdisciplinarity can be compared among document sets and across years, cited or citing. The colors used for the overlays are based on Blondel, Guillaume, Lambiotte, and Lefebvre's (2008) community‐finding algorithms operating on the relations among journals included in the JCR. The results can be exported from VOSViewer with different options such as proportional labels, heat maps, or cluster density maps. The maps can also be web‐started or animated (e.g., using PowerPoint). The “citing” dimension of the aggregated journal–journal citation matrix was found to provide a more comprehensive description than the matrix based on the cited archive. The relations between local and global maps and their different functions in studying the sciences in terms of journal literatures are further discussed: Local and global maps are based on different assumptions and can be expected to serve different purposes for the explanation.
F1000 Recommendations as a Potential New Data Source for Research Evaluation: A Comparison With Citations
Authors: Waltman Ludo , Costas Rodrigo
Published: October 2013

F1000 is a postpublication peer review service for biological and medical research. F1000 recommends important publications in the biomedical literature, and from this perspective F1000 could be an interesting tool for research evaluation. By linking the complete database of F1000 recommendations to the Web of Science bibliographic database, we are able to make a comprehensive comparison between F1000 recommendations and citations. We find that about 2% of the publications in the biomedical literature receive at least one F1000 recommendation. Recommended publications on average receive 1.30 recommendations, and more than 90% of the recommendations are given within half a year after a publication has appeared. There turns out to be a clear correlation between F1000 recommendations and citations. However, the correlation is relatively weak, at least weaker than the correlation between journal impact and citations. More research is needed to identify the main reasons for differences between recommendations and citations in assessing the impact of publications.
Triazole‐Substituted Nitroarene Derivatives: Synthesis, Characterization, and Energetic Studies
Authors: Kommu Nagarjuna , Ghule Vikas D. , Kumar A. Sudheer , Sahoo Akhila K.
Published: October 2013

A series of dense and energetic polynitroaryl‐1,2,4‐triazoles were synthesized through the nitration of aryl‐1,2,4‐triazoles. The Cu‐catalyzed/base‐mediated coupling reactions of haloarenes with 1,2,4‐triazoles delivered N‐aryl‐1,2,4‐triazoles. These new nitro‐rich‐aryltriazoles were characterized by analytical and spectroscopic methods. The solid‐state structures of most of these compounds were established by X‐ray diffraction analysis. Their thermal properties were determined by differential scanning calorimetry–thermogravimetric analysis. Their heats of formation (HOFs) and crystal densities were also calculated. The densities of the synthesized compounds ranged from 1.40 to 1.85 g cm−3. Some of these newly synthesized compounds exhibited high positive HOFs, good thermal stabilities, high densities, and reasonable detonation velocities and pressures.
Sensorless Inverter‐Fed Compressor Drive System Using Back‐EMF Estimator with PIDNN Torque Observer
Authors: Lin Faa‐Jeng , Hung Ying‐Chih , Chen Jia‐Ming , Kao Zi‐Yin
Published: October 2013

A saliency back‐EMF estimator with a proportional–integral–derivative neural network (PIDNN) torque observer is proposed in this study to improve the speed estimating performance of a sensorless interior permanent magnet synchronous motor (IPMSM) drive system for an inverter‐fed compressor. The PIDNN torque observer is proposed to replace the conventional proportional–integral–derivative (PID) torque observer in a saliency back‐EMF estimator to improve the estimating performance of the rotor flux angle and speed. The proposed sensorless control scheme use square‐wave type voltage injection method as the start‐up strategy to achieve sinusoidal starting. When the motor speed gradually increases to a preset speed, the sensorless drive will switch to the conventional saliency back‐EMF estimator using the PID observer or the proposed saliency back‐EMF estimator using the PIDNN observer for medium and high speed control. The theories of the proposed saliency back‐EMF rotor flux angle and speed estimation method are introduced in detail. Moreover, the network structure, the online learning algorithms and the convergence analyses of the PIDNN are discussed. Furthermore, a DSP‐based control system is developed to implement the sensorless inverter‐fed compressor drive system. Finally, some experimental results are given to verify the feasibility of the proposed estimator.
Admissible Consensus of Multi‐Agent Singular Systems
Authors: Li Min , Li Qiqiang
Published: October 2013

Consensus problems are studied for both continuous‐time and discrete‐time multi‐agent singular systems with time‐invariant and directed communication topologies. Under restricted system equivalence of singular agents, sufficient and necessary conditions are obtained for admissible consensus ability with static protocols, which are based on both the relative information of the dynamic states and the absolute information of the static states. For a network of continuous‐time singular systems, the existence of admissible consensualization can be cast into strong stabilizability of the agent dynamics. Once discrete‐time multi‐agent singular systems satisfy the condition of reaching nontrivial final consensus states, strong stabilizability is a sufficient condition to achieve admissible consensualization. Two algorithms are proposed to construct two protocols, which are based on a linear matrix inequality and a modified Riccati equation, respectively. Finally, the algorithms are illustrated by two simulation examples.
Optimal Control of Finite‐Valued Networks
Authors: Cheng Daizhan , Zhao Yin , Liu Jiang‐Bo
Published: October 2013

Control of finite‐valued networks, including Boolean networks, is currently a hot topic. In this paper the optimization of the networks with time‐discounted performance criterion is discussed. The problem is formulated as a finite strategy game between human and machine. It is first proved that the optimal strategy can be found in the set of essentially periodic strategies, which makes the problem finitely computable, though the computational complexity of exhaustion might be a severe problem. Then an efficient numerical method is develossped to solve the problem. Some interesting examples are presented to demonstrate the efficiency of our results.
Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
Authors: Lucchina Luciana , Depino Amaicha Mara
Published: October 2013

Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600 mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism‐related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. Autism Res 2013, 7: 273–289. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Do Individuals with and without Autism Spectrum Disorder Scan Faces Differently? A New Multi‐Method Look at an Existing Controversy
Authors: Yi Li , Feng Cong , Quinn Paul C. , Ding Haiyan , Li Jiao , Liu Yubing , Lee Kang
Published: October 2013

Individuals with autism spectrum disorder (ASD) are known to process faces atypically. However, there has been considerable controversy regarding whether ASD individuals also scan faces differently from typical adults. Here we compared ASD individuals' face‐scanning patterns with those of typically developing (TD) controls and intellectually disabled (ID) but non‐ASD individuals with the use of an eye tracker and multiple approaches to analyze eye‐tracking data. First, we analyzed the eye movement data with a traditional approach, measuring fixation duration on each area of interest within the face. We found that compared with TD and ID individuals, ASD individuals looked significantly shorter at the right eye. Second, we used a data‐driven method that analyzes fixations on each pixel of the face stimulus and found that individuals with ASD looked more at the central nasal area than TD and ID individuals. Third, we used a novel saccade path analysis that measures frequencies of saccades between major face areas. We found that ASD individuals scanned less often between core facial features than TD individuals but did not differ from ID individuals. Findings from the multi‐method approaches show that individuals with ASD appear not to have a pervasive ASD‐specific atypicality in visual attention toward the face. The ASD‐specific atypical face‐scanning patterns were shown to be limited to fixations on the eyes and nose. Autism Res 2014, 7: 72–83. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Cloning and in vitro function analysis of codon‐optimized FatI gene
Authors: Sun Xiao‐Feng , Sun Xing‐Hong , Teng Mei‐Li , Liu Huan‐Qi , Min Ling‐Jiang , Pan Qing‐Jie , Qin Guo‐Qing , Shen Wei , Li Lan
Published: October 2013

Currently, n‐3 polyunsaturated fatty acids (n‐3 PUFAs) have attracted great attention because of their biological significance to organisms. In addition, PUFAs show an obvious impact on prevention and treatment of various diseases. Because n‐3 PUFAs cannot be endogenously synthesized by mammals, mammals have to rely on a dietary supplement for sufficient supply. The finding and application of the fatty acid dehydrogenase I (FatI) gene are expected to change the current situation because it can convert n‐6 polyunsaturated fatty acids (n‐6 PUFAs) to n‐3 PUFAs. Meanwhile, the gradual maturation of transgenic technology makes it possible to produce transgenic animals that can synthesize n‐3 PUFAs by themselves. In this study, the DNA coding sequence of FatI was synthesized by a chemical method after codon optimization according to the mammal's codon bias. The synthesized DNA sequence was introduced into Boer goat fetal fibroblasts by the constructed recombinant eukaryotic expression vector pcDNA3.1(+)‐FatI. Boer goat fetal fibroblasts were transfected by electroporation, and the stable transfected cell lines were obtained by G418 selection. Genomic DNA PCR and Southern blot were applied to verify that the foreign gene FatI was integrated into the genome of the Boer goat fibroblasts. RT‐PCR results showed the expression of FatI gene at the mRNA level. The fatty acid profile of cells carrying the FatI gene revealed an increase in total n‐3 PUFAs (from 0.61 to 0.95), but a decrease in n‐6 PUFAs (from 10.34 to 9.85), resulting in a remarkable increase in the n‐3:n‐6 ratio (from 0.059 to 0.096). The n‐3:n‐6 ratio had a 63.49 percent increase, which is a precursor of the response of n‐3 desaturase activity of the FatI gene. The study may provide a practical tool for producing transgenic animals that can produce n‐3 PUFAs by themselves, and we hope that the application will lay the foundation for animals producing n‐3 PUFAs, which will benefit human nutrition and wellness.
Techno‐economic analysis and life‐cycle assessment of cellulosic isobutanol and comparison with cellulosic ethanol and n‐butanol
Authors: Tao Ling , Tan Eric C. D. , McCormick Robert , Zhang Min , Aden Andy , He Xin , Zigler Bradley T.
Published: October 2013

This work presents a detailed analysis of the production design and economics of the cellulosic isobutanol conversion processes and compares cellulosic isobutanol with cellulosic ethanol and n‐butanol in the areas of fuel properties and engine compatibility, fermentation technology, product purification process design and energy consumption, overall process economics, and life cycle assessment. Techno‐economic analysis is used to understand the current stage of isobutanol process development and the impact of key parameters on the overall process economics in a consistent way (i.e. using the same financial assumptions, plant scale, and cost basis). The calculated minimum isobutanol selling price is $3.62/gasoline gallon equivalent ($/GGE) – similar to $3.66/GGE from the n‐butanol process and higher than $3.26/GGE from the cellulosic ethanol conversion process. At the conversion stage, the n‐butanol process emits the most direct CO2, at 26.42 kg CO2/GGE. Isobutanol and ethanol plants have relatively similar CO2 emissions, at 21.91 kg CO2/GGE and 21.01 kg CO2/GGE, respectively. The consumptive water use of the biorefineries increases in the following order: ethanol (8.19 gal/GGE) < isobutanol (8.98 gal/GGE) < n‐butanol (10.84 gal/GGE). Field‐to‐wheel life cycle greenhouse gas (GHG) emissions for the ethanol and n‐butanol conversion processes are similar at 4.3 and 4.5 kg CO2‐eq/GGE, respectively. The life cycle GHG emissions result for the isobutanol conversion process is 5.0 kg CO2‐eq/GGE, approximately 17% higher than that of ethanol. The life cycle fossil fuel consumption is 39 MJ/GGE for n‐butanol, 43 MJ/GGE for ethanol and 51 MJ/GGE for isobutanol. The energy return on investment for each biofuel is also determined and compared: isobutanol (2.2:1) < ethanol (2.7:1) < n‐butanol (2.8:1). © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
Development of an integrated tactical and operational planning model for supply of feedstock to a commercial‐scale bioethanol plant
Authors: Ebadian Mahmood , Sowlati Taraneh , Sokhansanj Shahab , Smith Lawrence T , Stumborg Mark
Published: October 2013

In this paper, a new modeling approach is proposed to integrate the tactical and operational planning levels in the biomass supply chain. The proposed approach includes an optimization model and a simulation model. The integration is made between these models (i) to assure the fulfillment of the daily biomass demand year‐round for a commercial‐scale cellulosic ethanol plant and (ii) to reduce biomass delivery costs. The optimization model prescribes the design of the supply area in a way that the annual biomass demand is met at a minimum delivery cost for a five‐year planning horizon. Given the design of the supply area, the simulation model schedules the flow of multi‐biomass in the supply chain to meet the daily biomass demand of the ethanol plant subject to the dynamics and uncertainties in the supply chain. If the daily demand cannot be met, the outputs of the simulation model are used to adjust the design in the optimization model to assure the fulfillment of the daily demand. The application of the integrated model to a proposed commercial‐sized bioethanol plant shows the efficiency of the integrated approach to design the supply area in a way that the daily biomass demand is met at the minimum delivery cost possible. The results of the sensitivity analysis reveal that the most influential parameter on the design is biomass yield. In addition, bale bulk density, in‐farm and road transportation operations, and farmer participation rates have the highest impact on delivery cost compared to other input parameters. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
Skin uptake and clearance of ciclopirox following topical application
Authors: Nair Anroop B. , Singh Kishan , Al‐Dhubiab Bandar E. , Attimarad Mahesh , Harsha Sree , Alhaider Ibrahim A.
Published: October 2013

The assessment of skin uptake and clearance are important to determine the efficiency and systemic safety of dermatological formulations. The objective of this study was to assess the skin uptake, clearance and possible systemic delivery of ciclopirox following topical application in Wistar rats. In vitro studies (3 h) were carried out in excised pig skin to assess the permeation and retention capacity of ciclopirox in skin layers using gel formulations (1% and 2% w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by measuring the drug levels in the skin as a function of time post application (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in Wistar rats. The plasma drug concentrations were also determined in the same animals. In vitro data indicate the low permeability and high retention of ciclopirox in the stratum corneum. The DPK data observed indicate a higher Cmax value (175.43 ± 25.62 µg/cm2) and AUC (632.14 ± 102.26 µg.h/cm2) with the 2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows first order kinetics with a short half‐life (t1/2 ~2 h). The fraction of drug reaching the systemic circulation was found to be significantly low (~0.15% of the applied dose). A relation between the drug concentration in the skin layers and the plasma was observed with a short lag period. The topical availability of ciclopirox was found to be relatively low and endured rapid clearance with minimal systemic uptake. Copyright © 2013 John Wiley & Sons, Ltd.
Biodistribution of diclofenac following repeated topical applications of two diclofenac sodium formulations to minipigs
Authors: Wible James H. , Barrett Thomas , Devarakonda Krishna , Giuliani Michael
Published: October 2013

This study evaluated diclofenac concentrations in plasma, selected hind limb tissues and synovial fluid after repeated topical applications of two diclofenac formulations. Group 1 Gottingen minipigs (n = 18) were administered diclofenac sodium 2.0% topical solution twice daily on days 1–6 and once on day 7. Group 2 minipigs (n = 18) were administered diclofenac sodium 1.5% topical solution four times daily on days 1–6 and twice on day 7. Approximately 20 mg of diclofenac was applied daily to a 10 × 15 cm dosing site centered over the patella of the right knee. Plasma and tissue samples were collected throughout and analysed for diclofenac concentrations using liquid chromatography with tandem mass spectrometry. On day 1, diclofenac sodium 2.0% topical solution produced higher plasma concentrations compared with the 1.5% formulation; however, after 24 h and throughout the remainder of the dosing period, plasma concentrations appeared similar, except at the 72 h time point. Twenty‐four hours after the final application, skin treated with diclofenac sodium 2.0% topical solution retained a significantly (p < 0.02) greater amount of diclofenac than the 1.5% formulation. Generally, both formulations produced similar diclofenac concentrations in synovial fluid, underlying muscle, tendon and bone 24 h after the last application. The 2.0% diclofenac formulation applied twice daily delivered similar amounts of diclofenac as the 1.5% formulation administered four times daily. The skin retained a significant portion of the applied dose to serve as a depot for continuous diffusion of diclofenac into underlying tissues and systemic circulation. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of exposure to extremely low frequency magnetic fields on spermatogenesis in adult rats
Authors: Duan Weixia , Liu Chuan , Wu Hongjuan , Chen Chunhai , Zhang Tao , Gao Peng , Luo Xue , Yu Zhengping , Zhou Zhou
Published: October 2013

The constant exposure of modern society to extremely low frequency magnetic fields (ELF‐MF) has raised considerable concerns about the potential risks to male reproduction. However, the epidemiological and experimental data remain contradictory and inconclusive. In the present study, we investigated the effects of 50 Hz ELF‐MF of 500 µT applied 4 h/day, 7 days/week for 4 and 8 weeks on male reproduction, focusing on changes in spermatogenesis. Several biological endpoints related to testicular function and spermatogenesis were measured, including the following: body mass, masses of testes and epididymis, sperm count and abnormal sperm ratio in the caudal epididymis, serum testosterone level, testicular histology, frequency of 14 stages of the cycle of the seminiferous epithelium and of four stages of meiosis I, germ cell apoptosis and testicular oxidative status. No significant differences were found in the biological endpoints between the sham control and the exposed rats in either the 4‐ or 8‐week exposure period. These negative results may result from the lack of change in serum testosterone. In conclusion, our study indicates that exposure to low intensity ELF‐MF may have no adverse effects on spermatogenesis. Bioelectromagnetics. 35:58–69, 2014. © 2013 Wiley Periodicals, Inc.
ELF magnetic fields do not affect cell survival and DNA damage induced by ultraviolet B
Authors: Mizuno Kohei , Narita Eijiro , Yamada Masaru , Shinohara Naoki , Miyakoshi Junji
Published: October 2013

We investigated whether extremely low frequency (ELF) magnetic field exposure has modification effects on cell survival after ultraviolet B (UV‐B) irradiation and on repair process of DNA damage induced by UV‐B irradiation in WI38VA13 subcloned 2RA and XP2OS(SV) cells. The ELF magnetic field exposure was conducted using a Helmholtz coil‐based system that was designed to generate a sinusoidal magnetic field at 5 mT and 60 Hz. Cell survival was assessed by WST assay after UV‐B irradiation at 20–80 J/m2, ELF magnetic field exposure for 24 h, followed by incubation for 48 h. DNA damage was assessed by quantification of cyclobutane pyrimidine dimer formation and 6‐4 photoproduct formation using ELISA after UV‐B irradiation at 20–80 J/m2 followed by ELF magnetic field exposure for 24 h. No significant changes were observed in cell survival between ELF magnetic field and sham exposures. Similarly, DNA damage induced by UV‐B irradiation did not change significantly following ELF magnetic field exposure. Our results suggest that ELF magnetic field exposure at 5 mT does not have modification effect on cell survival after UV‐B irradiation and on repair process of DNA damage induced by UV‐B irradiation. Bioelectromagnetics. 35:108–115, 2014. © 2013 Wiley Periodicals, Inc.
Theorising student engagement in higher education
Authors: Kahn Peter E.
Published: October 2013

Student engagement has become problematic following the rise of mass and universal forms of higher education. Significant attention has been devoted to identifying factors that are associated with higher levels of engagement, but it remains the case that the underlying reasons for student engagement and, indeed, the notion itself of ‘student engagement’ remain weakly theorised. In this article, we seek to develop the theoretical basis for student engagement in a way that highlights the student's own contribution. We explore how learning involves students taking responsibility for action in the face of uncertainty, whether in pursuit of personal or communal concerns. Drawing on perspectives primarily from realist social theory, we suggest that student engagement may be shaped by extended, restricted and fractured modes of reflexivity and co‐reflexivity. In this way student engagement in higher education is theorised as a form of distributed agency, with the impact of a learning environment on this agency mediated by reflexivity. Reflexivity itself is further influenced by the tasks and social relations encountered by students in a given learning environment. The role that social relations play in students' responses to learning specifically offers a means to strengthen the moral basis for education. Our account provides an explanation as to why specific educational practices, such as those termed ‘high impact’, might lead to higher levels of student engagement within the wider context of a knowledge society. We thus offer insights towards new forms of educational practice and relations that have the potential to engage students more fully.
The non‐coding skin: Exploring the roles of long non‐coding RNAs in epidermal homeostasis and disease
Authors: Hombach Sonja , Kretz Markus
Published: October 2013

Long non‐coding RNAs (lncRNAs) have recently gained increasing attention because of their crucial roles in gene regulatory processes. Functional studies using mammalian skin as a model system have revealed their role in controlling normal tissue homeostasis as well as the transition to a diseased state. Here, we describe how lncRNAs regulate differentiation to preserve an undifferentiated epidermal progenitor compartment, and to maintain a functional skin permeability barrier. Furthermore, we will reflect on recent work analyzing the impact of lncRNAs on the progression from normal epithelium to the development of skin disorders and cancer.
Electrophoresis–chemiluminescence detection of phenols catalyzed by hemin
Authors: Shu Lu , Zhu Jinkun , Wang Qingjiang , He Pingang , Fang Yuzhi
Published: October 2013

Based on the catalytic activity of hemin, an efficient biocatalyst, an indirect capillary electrophoresis–chemiluminescence (CE‐CL) detection method for phenols using a hemin–luminol–hydrogen peroxide system was developed. Through a series of static injection experiments, hemin was found to perform best in a neutral solution rather than an acidic or alkaline medium. Although halide ions such as Br− and F− could further enhance the CL signal catalyzed by hemin, it is difficult to apply these conditions to this CE‐CL detection system because of the self‐polymerization of hemin, as it hinders the CE process. The addition of concentrated ammonium hydroxide to an aqueous/dimethyl sulfoxide solution of hemin–luminol afforded a stable CE‐CL baseline. The indirect CE‐CL detection of five phenols using this method gave the following limits of detections: 4.8 × 10−8 mol/L (o‐sec‐butylphenol), 4.9 × 10−8 mol/L (o‐cresol), 5.4 × 10−8 mol/L (m‐cresol), 5.3 × 10−8 mol/L (2,4‐dichlorophenol) and 7.1 × 10−8 mol/L (phenol). Copyright © 2013 John Wiley & Sons, Ltd.
Photoluminescence in K3Ca2(SO4)3Cl‐doped Eu3+ phosphor
Authors: Baig Nahida , Dhoble N. S. , Pawade V. B. , Kokode N. S. , Dhoble S. J.
Published: October 2013

In this article we report Eu3+ luminescence in novel K3Ca2(SO4)3Cl phosphors prepared by wet chemical methods. The Eu3+ emission was observed at 594 nm and 615 nm, keeping the excitation wavelength constant at 396 nm nearer to light‐emitting diode excitation, Furthermore, phosphors were characterized by X‐ray diffraction for the confirmation of crystallinity. The variation of the photoluminescence intensity with impurity concentration has also been discussed. Thus, prominent emission in the red region makes prepared phosphors more applicable for white light‐emitting diodes. Copyright © 2013 John Wiley & Sons, Ltd.