bluuebunny/crossref_metadata_2025 huggingface dataset:
Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations
Authors: Antonenko Daria , Diekelmann Susanne , Olsen Cathrin , Born Jan , Mölle Matthias
Published: January 2013

As well as consolidating memory, sleep has been proposed to serve a second important function for memory, i.e. to free capacities for the learning of new information during succeeding wakefulness. The slow wave activity (SWA) that is a hallmark of slow wave sleep could be involved in both functions. Here, we aimed to demonstrate a causative role for SWA in enhancing the capacity for encoding of information during subsequent wakefulness, using transcranial slow oscillation stimulation (tSOS) oscillating at 0.75 Hz to induce SWA in healthy humans during an afternoon nap. Encoding following the nap was tested for hippocampus‐dependent declarative materials (pictures, word pairs, and word lists) and procedural skills (finger sequence tapping). As compared with a sham stimulation control condition, tSOS during the nap enhanced SWA and significantly improved subsequent encoding on all three declarative tasks (picture recognition, cued recall of word pairs, and free recall of word lists), whereas procedural finger sequence tapping skill was not affected. Our results indicate that sleep SWA enhances the capacity for encoding of declarative materials, possibly by down‐scaling hippocampal synaptic networks that were potentiated towards saturation during the preceding period of wakefulness.
Quantifying multivariate plasticity: genetic variation in resource acquisition drives plasticity in resource allocation to components of life history
Authors: Robinson Matthew R. , Beckerman Andrew P.
Published: January 2013

Acquisition and allocation of resources are central to life‐history theory. However, empirical work typically focuses only on allocation despite the fact that relationships between fitness components may be governed by differences in the ability of individuals to acquire resources across environments. Here, we outline a statistical framework to partition the genetic basis of multivariate plasticity into independent axes of genetic variation, and quantify for the first time, the extent to which specific traits drive multitrait genotype–environment interactions. Our framework generalises to analyses of plasticity, growth and ageing. We apply this approach to a unique, large‐scale, multivariate study of acquisition, allocation and plasticity in the life history of the cricket, Gryllus firmus. We demonstrate that resource acquisition and allocation are genetically correlated, and that plasticity in trade‐offs between allocation to components of fitness is 90% dependent on genetic variance for total resource acquisition. These results suggest that genotype–environment effects for resource acquisition can maintain variation in life‐history components that are typically observed in the wild.
Sex differences in host defence interfere with parasite‐mediated selection for outcrossing during host–parasite coevolution
Authors: Masri Leila , Schulte Rebecca D. , Timmermeyer Nadine , Thanisch Stefanie , Crummenerl Lena Luise , Jansen Gunther , Michiels Nico K. , Schulenburg Hinrich
Published: January 2013

The Red Queen hypothesis proposes that coevolving parasites select for outcrossing in the host. Outcrossing relies on males, which often show lower immune investment due to, for example, sexual selection. Here, we demonstrate that such sex differences in immunity interfere with parasite‐mediated selection for outcrossing. Two independent coevolution experiments with Caenorhabditis elegans and its microparasite Bacillus thuringiensis produced decreased yet stable frequencies of outcrossing male hosts. A subsequent systematic analysis verified that male C. elegans suffered from a direct selective disadvantage under parasite pressure (i.e. lower resistance, decreased sexual activity, increased escape behaviour), which can reduce outcrossing and thus male frequencies. At the same time, males offered an indirect selective benefit, because male‐mediated outcrossing increased offspring resistance, thus favouring male persistence in the evolving populations. As sex differences in immunity are widespread, such interference of opposing selective constraints is likely of central importance during host adaptation to a coevolving parasite.
Primary productivity demands of global fishing fleets
Authors: Watson Reg , Zeller Dirk , Pauly Daniel
Published: January 2013

To be sustainable, the extractive process of fishing requires biomass renewal via primary production driven by solar energy. Primary production required (PPR) estimates how much primary production is needed to replace the biomass of fisheries landings removed from marine ecosystems. Here, we examine the historical fishing behaviour of global fishing fleets, which parts of the food web they rely on, which ecosystems they fish and how intensively. Highly mobile European and Asian fleets have moved to ever more distant productive waters since the 1970s, especially once they are faced with the costs of access agreements for exclusive economic zones (EEZs) declared by host countries. We examine fleet PPR demands in the context of large marine ecosystems (LMEs), which are frequently fished with PPR demands well above their average primary productivity (PP). In some cases, this was mitigated by subsequent emigration of fleets or by management intervention. Fleet movements, however, have stressed additional marine areas, including the EEZs of developing countries. This suggests the potential for spatial serial depletion, if fishing capacity is not reduced to more sustainable PP removal levels. Fundamentally, fishing is limited by solar‐powered PP limits. Fishing beyond solar production has occurred, but in the future, marine systems may not be as forgiving, especially if overfishing and climate change compromise their resilience.
Global biomass potentials under sustainability restrictions defined by the European Renewable Energy Directive 2009/28/EC
Authors: Schueler Vivian , Weddige Ulf , Beringer Tim , Gamba Liliana , Lamers Patrick
Published: January 2013

The political will to reduce global GHG emissions has largely contributed to increased global biofuel production and trade. The expanding cultivation of energy crops may drive changes in the terrestrial ecosystems such as land cover and biodiversity loss. When biomass replaces fossil energy carriers, sustainability criteria are therefore crucial to avoid adverse impacts and ensure a net positive GHG balance. The European Union has set mandatory sustainability criteria for liquid biofuels in its Renewable Energy Directive (RED) 2009/28/EC to ensure net positive impacts of its biofuel policy. The adoption of sustainability criteria in other world regions and their extension to solid and gaseous biomass in the EU is ongoing. This paper examines the effect of the EU RED sustainability criteria on the availability of biomass resources at global and regional scale. It quantifies the relevance of sustainability criteria in biomass resource assessments taking into account the criteria's spatial distribution. This assessment does not include agricultural and forestry residues and aquatic biomass. Previously unknown interrelations between sustainability criteria are examined and described for ten world regions. The analysis concludes that roughly 10% (98.5 EJ) of the total theoretical potential of 977.2 EJ occurs in areas free of sustainability concerns.
Influence of biofuel crops on mosquito production and oviposition site selection
Authors: Muturi Ephantus J. , Spencer Joseph L. , Allan Brian F.
Published: January 2013

The proposed expansion of biofuels production may cause unintended land‐use changes and potentially alter ecosystem services. This study evaluated the impact of first‐generation (corn) and second‐generation (switchgrass and Miscanthus) biofuel crops on production and oviposition site selection by two vector mosquitoes, the yellow fever mosquito Aedes aegypti and the Asian tiger mosquito Aedes albopictus. Larvae of the two species were reared at varying conspecific and heterospecific densities in senescent leaf infusions prepared from one of the three biofuel crops and their survival and development time to adulthood determined. The effects of the three leaf infusions on water chemistry and oviposition site selection by the two mosquito species were also determined. Ae. albopictus females deposited significantly fewer eggs in Miscanthus than in corn infusion while Ae. aegypti females deposited significantly fewer eggs in Miscanthus than in both corn and switchgrass infusion. Survival to adulthood for both mosquito species was significantly lower in corn than in switchgrass and Miscanthus infusions; was consistently lower at high‐ (0:40 and 20:20) than at low density treatments in both switchgrass and Miscanthus infusions; and significantly lower at high intraspecific density (40:0 and 0: 40) than at high interspecific density (20:20) in Miscanthus infusion. Development time to adulthood was positively related to larval density, but was not influenced by biofuel leaf treatment. Corn infusion had lower pH values and higher salinity, conductivity, total dissolved solids (TDS), and temperature values than switchgrass and Miscanthus infusions. These findings demonstrate the potential for biofuel crops to modify the chemistry of aquatic habitats in ways that may influence mosquito production and thereby the risk of exposure to mosquito‐borne diseases.
Structures of D14 and D14L in the strigolactone and karrikin signaling pathways
Authors: Kagiyama Megumi , Hirano Yoshinori , Mori Tomoyuki , Kim Sun‐Yong , Kyozuka Junko , Seto Yoshiya , Yamaguchi Shinjiro , Hakoshima Toshio
Published: January 2013

Strigolactones (SLs) are plant hormones that inhibit shoot branching. DWARF14 (D14) inhibits rice tillering and is an SL receptor candidate in the branching inhibition pathway, whereas the close homologue DWARF14‐LIKE (D14L) participates in the signaling pathway of karrikins (KARs), which are derived from burnt vegetation as smoke stimulants of seed germination. We provide the first evidence for direct binding of the bioactive SL analogue GR24 to D14. Isothermal titration calorimetry measurements show a D14–GR24 binding affinity in the sub‐micromolar range. Similarly, bioactive KAR1 directly binds D14L in the micromolar range. The crystal structure of rice D14 shows a compact α‐/β‐fold hydrolase domain forming a deep ligand‐binding pocket capable of accommodating GR24. Insertion of four α‐helices between β6 strand and αD helix forms the helical cap of the pocket, although the pocket is open to the solvent. The pocket contains the conserved catalytic triad Ser‐His‐Asp aligned with the oxyanion hole, suggesting hydrolase activity. Although these structural characteristics are conserved in D14L, the D14L pocket is smaller than that of D14. The KAR‐insensitive mutation kai2‐1 is located at the prominent long β6‐αD1 loop, which is characteristic in D14 and D14L, but not in related α‐/β‐fold hydrolases.
miR‐214 and hypoxia down‐regulate Necl‐2/CADM1 and enhance ErbB2/ErbB3 signaling
Authors: Momose Kenji , Minami Akihiro , Shimono Yohei , Mizutani Kiyohito , Nobutani Kentaro , Azuma Takeshi , Takai Yoshimi
Published: January 2013

Necl‐2/CADM1 is down‐regulated by the promoter hypermethylation and/or the loss of heterozygosity at chromosome 11q23.2 in many types of cancers and serves as a tumor suppressor by interacting in cis with ErbB3 and suppressing the ligand‐induced ErbB2/ErbB3 signaling for cell movement and death. However, the incidence of these epigenetic and genetic abnormalities of Necl‐2 is 30–60% in these cancers. We investigated here other mechanisms that down‐regulate Necl‐2. miR‐214, that is frequently up‐regulated in a variety of cancers, targeted the 3′UTR of the Necl‐2 mRNA directly, suppressed the translation of Necl‐2 and enhanced the ligand‐induced ErbB2/ErbB3 signaling in human colon cancer Caco‐2 cells. Hypoxia reduced the Necl‐2 protein level in a manner independent of miR‐214 or hypoxia‐inducible factor‐1α in Caco‐2 cells. These results indicate that miR‐214 and hypoxia are novel regulators that down‐regulate Necl‐2 and enhance ErbB2/ErbB3 signaling.
Interferon‐alpha plus adefovir combination therapy versus interferon‐alpha monotherapy for chronic hepatitis B treatment: A meta‐analysis
Authors: Huang Rui , Hao Yingying , Zhang Jun , Wu Chao
Published: January 2013

Aim

The therapeutic effect of interferon (IFN)‐α plus adefovir (ADV) combination therapy versus IFN‐α monotherapy in chronic hepatitis B (CHB) treatment remains under debate. The objective of the present study was to compare the efficacy between these two regimens in CHB treatment.

Methods

MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, National Knowledge Infrastructure, WANFANG and VIP databases were searched until 15 April 2012. All randomized controlled trials (RCT) comparing IFN‐α plus ADV combination therapy versus IFN‐α monotherapy for treating CHB patients were included. Review Manager ver. 5.1.0 was used for meta‐analysis.

Results

Our results showed that the rate of undetectable serum hepatitis B virus (HBV) DNA was significantly higher in the IFN‐α plus ADV combination group than in the IFN‐α monotherapy group, both at 24 weeks (relative risk [RR] = 1.74, 95% confidence interval [CI] = 1.47–2.05, P < 0.00001) and 48 weeks (RR = 1.56, 95% CI = 1.35–1.80, P < 0.00001) of treatment and after treatment (RR = 1.35, 95% CI = 1.10–1.66, P = 0.004). The serum hepatitis B e‐antigen (HBeAg) negativation and HBeAg seroconversion rates were also higher in the combination group. However, a greater hepatitis B surface antigen loss rate was not found in the combination group. Forty‐eight weeks of combination therapy improved the alanine aminotransferase normalization rate, but did not improve the rate of undetectable HBV DNA or that of HBeAg seroconversion as compared with 24 weeks of combination therapy.

Conclusion

Based on the current studies, the efficacy of IFN‐α plus ADV combination therapy is superior to IFN‐α monotherapy.
Does Poverty Wear a Woman's Face? Some Moral Dimensions of a Transnational Feminist Research Project
Authors: Jaggar Alison M.
Published: January 2013

This article explains some moral dimensions of a transnational feminist research project designed to provide a better standard or metric for measuring poverty across the world. The author is an investigator on this project. Poverty metrics incorporate moral judgments about what is necessary for a decent life, so justifying metrics requires moral argumentation. The article clarifies the moral aspects of poverty valuation, indicates some moral flaws in existing global poverty metrics, and outlines some conditions for a better global metric. It then explains the methodology used in our project, providing its moral rationale and discussing some remaining moral concerns.
Metals in female scalp hair globally and its impact on perceived hair health
Authors: Godfrey Simon , Staite William , Bowtell Philip , Marsh Jennifer
Published: January 2013

Synopsis

Globally, billions of individuals wash their hair in water, which acts as an exogenous metal source. Many studies which measure the metal levels found on human hair specifically aim to remove exogenous materials prior to analysis. Although this is needed when using hair analysis to probe the impact of the local environment on endogenous metal levels, it is not relevant for understanding exactly what is on hair as a result of contact with its daily environment. Understanding these levels are important, as the presence of redox active metals, such as copper and iron, can impact fibre health, either as a result of UV irradiation, or during the hair colouring process. A global hair sampling study of over 300 individuals from nine countries has been performed, and the combined endogenous and exogenous metals analysed. The levels measured vary widely, even within the narrow geography of each hair sampling location. The levels of calcium, magnesium, copper and iron were not correlated, and within each location, there are expected to be individuals with high metal levels. Levels increased from hair root to tip for calcium, magnesium and copper, attributed to hair contact with the environment showing the impact of exogenous metals in the overall levels on hair. Levels of redox metals were comparable between individuals who coloured or did not colour their hair, although water hardness ions were statistically significantly higher for hair colouring individuals. Individuals who perceived their hair health as poor had higher metal levels on their hair. Controlling metals on hair, either by preventing their binding during environmental contact, or through controlling their ability to cause hair damage, should lead to improved consumer perceived hair health.
Complex Permittivity and Microwave‐Absorbing Properties of Fe/Al2O3 Coatings by Air Plasma Spraying Technique
Authors: Zhao Dong , Luo Fa , Zhou Wancheng , Zhu Dongmei
Published: January 2013

The Fe/Al2O3 coatings for application as microwave absorbers were deposited by air plasma spraying (APS). The morphologies of powders and cross‐section of coatings were characterized by scanning electron microscope (SEM). The investigations of electrical conductivity and complex permittivity properties of coatings were performed. The real part (ε′) of permittivity increases with increasing Fe volume fraction, which is attributed to the space charge polarization, and the imaginary part (ε″) also increases which is ascribed to the increasing electrical conductivity result from the formation of Fe conductive network. The effect of Fe content on dielectric properties and the corresponding mechanisms are analyzed. By measuring the microwave absorption properties of the Fe/Al2O3 coatings as a single‐layer absorbers, it was find that the reflection loss varies with the changes of thickness and Fe content, due to the deviation of impedance‐matching condition.
Nova Scotia pharmacists' knowledge of, experiences with and perception of factors interfering with their ability to provide emergency contraceptive pill consultations
Authors: Whelan Anne Marie , Langille Donald B , Hurst Eileen
Published: January 2013

Objective

The objective of this research was to explore pharmacists' knowledge of, experiences with and perception of factors interfering with their ability to provide non-prescription emergency contraceptive pill consultations in the Canadian province of Nova Scotia.

Methods

A self-administered paper questionnaire was mailed, using Dillman's tailored design method, to all pharmacists (n = 1123) registered with the Nova Scotia College of Pharmacists.

Key findings

The response rate was 53.0% (595/1123), with 451 respondents working in community practice. Most respondents reported that they had provided consultations for the emergency contraceptive product Plan B since it became available without a prescription (93.6%), and that Plan B is kept behind the pharmacy counter (83.6%). Pharmacists most frequently (47.8%) reported spending 6–10 min providing Plan B consultations. Respondents were generally knowledgeable about Plan B; however, only 39.2% knew that it can be effective for up to 5 days and 69.3% knew that the incidence of vomiting is less than 50%. The factors interfering the most with providing Plan B consultations were lack of privacy (46.1%) and lack of staff to cover during the consultation (50.9%).

Conclusions

In general, Nova Scotia pharmacists are knowledgeable about emergency contraceptive pills; however, education regarding effective timing for use of such pills would be helpful. Private areas for counselling and consideration of pharmacy staffing schedules in community pharmacies may help address pharmacist concerns regarding their ability to provide Plan B consultations.
Segmental dosimetry, toxicity and long‐term outcome in patients with prostate cancer treated with permanent seed implants
Authors: Meyer Andreas , Wassermann Julia , Warszawski‐Baumann Antje , Baumann Rolf , Machtens Stefan , Karstens Johann H. , Christiansen Hans , Merseburger Axel , Kuczyk Markus A. , von Klot Christoph
Published: January 2013

What's known on the subject? and What does the study add?

The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting.

We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome.

Objective

To report on the side effects of patients with low to low–intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry.

Patients and Methods

A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I‐125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects.

Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF‐5) in a mean follow‐up interval of 30 months.

The scores were correlated with segmental dosimetry performed 6 weeks after the implantation.

Results

The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF‐5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months.

After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00).

Conclusions

We could not demonstrate a correlation of segmental dosimetry with induction of side effects.

There is no relationship between dose exposure of partial volumes and the development of radiation‐induced toxicities.

The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.
Acquired resistance to sunitinib in human renal cell carcinoma cells is mediated by constitutive activation of signal transduction pathways associated with tumour cell proliferation
Authors: Sakai Iori , Miyake Hideaki , Fujisawa Masato
Published: January 2013

What's known on the subject? and What does the study add?

Although there have been a few studies investigating the molecular mechanism mediating the acquisition of resistance to molecular‐targeted agents, including sunitinib, by renal cell carcinoma (RCC) cells, this mechanism remains largely unclear.

The maintenance of protein kinase activation during sunitinib treatment may be involved in the acquisition of a phenotype resistant to sunitinib in RCC, and additional treatment with agents targeting activated protein kinases could be a promising approach for overcoming resistance to sunitinib in RCC.

Objective

To characterise the mechanism involved in the acquired resistance to sunitinib, a potential inhibitor of multiple receptor tyrosine kinases (RTKs), in renal cell carcinoma (RCC).

Materials and Methods

A parental human RCC cell line, ACHN (ACHN/P), was continuously exposed to increasing doses of sunitinib, and a cell line resistant to sunitinib (ACHN/R), showing an ≈5‐fold higher IC50 (concentration that reduces the effect by 50%) than that of ACHN/P, was developed.

Results

ACHN/R appeared to acquire significant cross resistance to sorafenib; however, there were no significant differences in sensitivities to the Mammalian target of rapamycin inhibitors, temsirolimus and everolimus, between ACHN/P and ACHN/R.

After sunitinib treatment, the expression levels of phosphorylated Akt and p44/42 mitogen‐activated protein kinase in ACHN/P, but not those in ACHN/R, were significantly inhibited.

RTK assay showed that treatment of ACHN/P with sunitinib resulted in the marked downregulation of several phosphorylated RTKs compared with that of ACHN/R.

Additional treatment with a specific inhibitor of Akt significantly increased the sensitivity of ACHN/R to sunitinib, but not that of ACHN/P.

There were no significant differences between in vivo growth patterns of ACHN/P and ACHN/R in mice before and after the administration of sunitinib; however, the proportion of cells positive for TUNEL (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling) staining in ACHN/P tumour was significantly greater than that in ACHN/R tumour in mice treated with sunitinib.

Conclusion

The maintenance of protein kinase activation during sunitinib treatment may be involved in the acquisition of resistant phenotype to sunitinib in RCC cells.
Yuchengia, a new polypore genus segregated from Perenniporia (Polyporales) based on morphological and molecular evidence
Authors: Zhao Chang‐Lin , Cui Bao‐Kai , Steffen Kari Timo
Published: January 2013

Yuchengia gen. nov. is proposed to accommodate Perenniporia narymica. It represents a monophyletic lineage within the core polyporoid clade based on sequences of the rDNA ITS and nLSU regions, and it is distinct from Perenniporia s.s. Yuchengia shares some characters with Perenniporia, both having thick‐walled and cyanophilous basidiospores, but differs by having acyanophilous and amyloid skeletal hyphae dissolving in KOH, and non‐dextrinoid basidiospores.
The Process ofChinese Manufacturing Upgrading: Transitioning fromUnilateraltoRecursive Mutual LearningRelations
Authors: Herrigel Gary , Wittke Volker , Voskamp Ulrich
Published: January 2013

This article argues that upgrading inChina has been a historical success, that upgrading must be seen as a learning process, and that currentChinese upgrading involves a transformation in industrial learning dynamics. DuringChina's initial export‐oriented industrialization strategy, indigenous producers successfully upgraded by apprenticing themselves to their foreign customers, and they learned through integration in transnational communities of practice. The success of those initial unilateral learning relations enhanced the sophistication of theChinese market, both as a community of producers and as a market for manufactured goods. This has generated a new phase of learning‐driven upgrading in whichChinese producers andMNCmanufacturers both seek to make theirChinese operations more sophisticated. In this new context, apprenticeship disappears andChinese and foreign players learn from one another. A core claim about the new mutual learning is that it is facilitated by the globalization of formal learning systems, such as corporate production systems (CPSs).
Modularity‐as‐Property, Modularization‐as‐Process, and ‘Modularity'‐as‐Frame: Lessons from Product Architecture Initiatives in the Global Automotive Industry
Authors: MacDuffie John Paul
Published: January 2013

Modularity is a design property of the architecture of products, organizations, and interfirm networks; modularization is a process that affects those designs while also shaping firm boundaries and industry landscapes; and ‘modularity’ is a cognitive frame that guides categorization and interpretation of a wide array of economic phenomena. Modularity‐as‐property and modularization‐as‐process are deeply intertwined; while modularization processes are ubiquitous and perpetual as engineers and managers seek to understand interdependencies across the boundaries of product and organizational architecture, the extent to which modularity‐as‐property is achieved must be assessed empirically. The framing of ‘modularity’ affects strategy by prompting a particular dynamic—and directionality—in the interplay between modularity‐as‐property and modularization‐as‐process. I analyze product architecture initiatives in the global automotive industry, examining first the industry‐level antecedents of the emergent production‐based definition of modules and then two firm‐level modularity initiatives that both were based on this common definition, but framed their strategies differently. In the first case, a ‘modularity’ frame based on a computer industry analogy resulted in overemphasis on achieving modularity‐as‐property that created barriers to learning about cross‐module interdependencies. In the second case, early emphasis on modularization‐as‐process yielded quasi‐integrated organizational arrangements that facilitated long‐term design improvements. Overall, this single‐industry case study demonstrates the importance of examining the context‐specific antecedents of module definition; the multiplicity of potential barriers to modularity that can lead to persistent integrality; the need for longitudinal inquiry into the ‘mirroring’ hypothesis that pays as much attention to process as to property; and the power of modularity as a cognitive frame, which helps explain divergent findings in modularity research.
Dielectric and Magnetic Properties of Sr(Fe1/2Ta1/2)O3 Complex Perovskite Ceramics
Authors: Lv Xin , Liu Xiao Qiang , Zhao Hong Jian , Yang Wen Zhi , Chen Xiang Ming
Published: January 2013

The dielectric and magnetic properties of Sr(Fe1/2Ta1/2)O3 complex perovskite ceramics were systematically investigated together with the structure. The X‐ray powder diffraction analysis confirmed a B‐site disordered orthorhombic structure in space group Pbnm. Only one broadened dielectric peak with strong frequency dispersion was observed in the present ceramics, which was significantly different from that for the analogue Ba(Fe1/2Nb1/2)O3 and Ba(Fe1/2Ta1/2)O3. The strong dependence of sample thickness and electrode material indicated that the dielectric relaxation behavior at lower frequency was due to the interface effects. The present ceramics were spin glass state with slight ferromagnetic behavior below the Néel temperature (20 K). The co‐presence of Fe3+ and Fe2+ was confirmed by the μeff value.
Patients With Hypertensive Crises Who Are Admitted to a Coronary Care Unit: Clinical Characteristics and Outcomes
Authors: Pacheco Héctor González , Victorino Neisser Morales , Urquiza Juan Pablo Núñez , Castillo Alfredo Altamirano , Herrera Ursulo Juárez , Mendoza Alexandra Arias , Manzur Francisco Azar , de la Cruz Jose Luis Briseño , Sánchez Carlos Martínez
Published: January 2013

Patients with hypertensive crises, especially hypertensive emergencies, require immediate admittance to an intensive care unit for rapid blood pressure (BP) control. The authors analyzed the prevalence of hypertensive crisis, the clinical characteristics, and the evolution of patients with hypertensive emergencies and urgencies. Patients were divided into 3 groups according to their BP values: group I, predominant systolic hypertension (≥180/≤119 mm Hg); group II, severe systolic and diastolic hypertension (≥180/≥120 mm Hg); and group III, predominant diastolic hypertension (≤179/≥120 mm Hg). Of all of the patients admitted to a coronary care unit, 538 experienced a hypertensive crisis, which represented 5.08% of all admissions. Hypertensive emergency was predominant in 76.6% of the cases, which corresponded to acute coronary syndrome and acute decompensated heart failure in 59.5% and 25.2% of the cases, respectively. A pattern of predominant systolic hypertension (≥180/≤119 mm Hg) was most commonly observed in the hypertensive crisis group (71.4%) and the hypertensive emergency group (72.1%). The medications that were most commonly used at onset included intravenous vasodilators (nitroglycerin in 63.4% and sodium nitroprusside in 16.4% of the patients). The overall mortality rate was 3.7%. The mortality rate was 4.6% for hypertensive emergency cases and 0.8% for hypertensive urgencies cases.
Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development
Authors: Jain Mayur V. , Paczulla Anna M. , Klonisch Thomas , Dimgba Florence N. , Rao Sahana B. , Roberg Karin , Schweizer Frank , Lengerke Claudia , Davoodpour Padideh , Palicharla Vivek R. , Maddika Subbareddy , Łos Marek
Published: January 2013

The rapid accumulation of knowledge on apoptosis regulation in the 1990s was followed by the development of several experimental anticancer‐ and anti‐ischaemia (stroke or myocardial infarction) drugs. Activation of apoptotic pathways or the removal of cellular apoptotic inhibitors has been suggested to aid cancer therapy and the inhibition of apoptosis was thought to limit ischaemia‐induced damage. However, initial clinical studies on apoptosis‐modulating drugs led to unexpected results in different clinical conditions and this may have been due to co‐effects on non‐apoptotic interconnected cell death mechanisms and the ‘yin‐yang’ role of autophagy in survival versus cell death. In this review, we extend the analysis of cell death beyond apoptosis. Upon introduction of molecular pathways governing autophagy and necrosis (also called necroptosis or programmed necrosis), we focus on the interconnected character of cell death signals and on the shared cell death processes involving mitochondria (e.g. mitophagy and mitoptosis) and molecular signals playing prominent roles in multiple pathways (e.g. Bcl2‐family members and p53). We also briefly highlight stress‐induced cell senescence that plays a role not only in organismal ageing but also offers the development of novel anticancer strategies. Finally, we briefly illustrate the interconnected character of cell death forms in clinical settings while discussing irradiation‐induced mitotic catastrophe. The signalling pathways are discussed in their relation to cancer biology and treatment approaches.
Hypoxia‐inducing factors as master regulators of stemness properties and altered metabolism of cancer‐ and metastasis‐initiating cells
Authors: Mimeault Murielle , Batra Surinder K.
Published: January 2013

Accumulating lines of experimental evidence have revealed that hypoxia‐inducible factors, HIF‐1α and HIF‐2α, are key regulators of the adaptation of cancer‐ and metastasis‐initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin‐like growth factor‐1 receptor (IGF‐1R), stem cell factor (SCF) receptor KIT, transforming growth factor‐β receptors (TGF‐βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′‐kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up‐regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency‐associated transcription factors (Oct‐3/4, Nanog and Sox‐2), glycolysis‐ and epithelial‐mesenchymal transition (EMT) programme‐associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self‐renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.
Bone marrow mesenchymal stem cells increase motility of prostate cancer cells via production of stromal cell‐derived factor‐1α
Authors: Mognetti Barbara , Montagna Giuseppe La , Perrelli Maria Giulia , Pagliaro Pasquale , Penna Claudia
Published: January 2013

Prostate cancer frequently metastasizes to the bone, and the interaction between cancer cells and bone microenvironment has proven to be crucial in the establishment of new metastases. Bone marrow mesenchymal stem cells (BM‐MSCs) secrete various cytokines that can regulate the behaviour of neighbouring cell. However, little is known about the role of BM‐MSCs in influencing the migration and the invasion of prostate cancer cells. We hypothesize that the stromal cell‐derived factor‐1α released by BM‐MSCs may play a pivotal role in these processes. To study the interaction between factors secreted by BM‐MSCs and prostate cancer cells we established an in vitro model of transwell co‐culture of BM‐MSCs and prostate cancer cells DU145. Using this model, we have shown that BM‐MSCs produce soluble factors which increase the motility of prostate cancer cells DU145. Neutralization of stromal cell‐derived factor‐1α (SDF1α) via a blocking antibody significantly limits the chemoattractive effect of bone marrow MSCs. Moreover, soluble factors produced by BM‐MSCs greatly activate prosurvival kinases, namely AKT and ERK 1/2. We provide further evidence that SDF1α is involved in the interaction between prostate cancer cells and BM‐MSCs. Such interaction may play an important role in the migration and the invasion of prostate cancer cells within bone.
Molecular microarray analysis reveals allergen‐ and exotoxin‐specific IgE repertoires in children with atopic dermatitis
Authors: Ott H. , Weißmantel S. , Kennes L.N. , Merk H.F. , Baron J.M. , Fölster‐Holst R.
Published: January 2013

Background

Children suffering from atopic dermatitis frequently show allergen‐specific sensitization. However, the corresponding IgE‐recognition patterns have not yet been extensively characterized using multiallergen microarrays.

Objective

To provide comprehensive, molecular IgE repertoires in paediatric patients with atopic dermatitis using microarray technology.

Methods

Sera of 140 affected children were screened with a protein microarray containing a panel of 95 inhalant, food and staphylococcal antigen components. In addition, total serum IgE levels and further clinical parameters were recorded.

Results

At a mean total IgE level of 1528 kU/L, the number of sensitizations varied from 0 to 32 per patient, and regression analysis revealed a significant association between total IgE and the quantity of recognized antigens. A total of 78 single allergen and microbial components elicited at least one IgE response, while 11 plant and 13 non‐plant molecules were recognized by more than 10% of patients. Specific IgE against Staphylococcus aureus could be detected in 14% of children. Sensitization rates against the studied allergen molecules differed significantly when stratified by age. Whereas reactivity against inhalant allergens and SEC was lowest in the youngest group (<24 months) reaching highest values in children ≥72 months, IgE responses against food allergen components peaked in younger age groups (0–48 months) and clearly declined in patients of higher age. The large amount of microarray data could be aggregated by centroid cluster analysis revealing valid allergen clusters possibly linked with higher disease severity as determined by multivariate analysis of covariance.

Conclusion

Allergenic molecule microarray analysis can be regarded as a suitable research tool for large‐scale IgE screening in infants and children with atopic dermatitis (AD). Still, further studies in well‐defined populations are needed to exactly identify its tangible benefits in the diagnostic and therapeutic management of affected patients in daily clinical practice.
Tacrolimus abrogates TGF‐β1‐induced type I collagen production in normal human fibroblasts through suppressing p38MAPK signalling pathway: implications on treatment of chronic atopic dermatitis lesions
Authors: Lan C.‐C.E. , Fang A.‐H. , Wu P.‐H. , Wu C.‐S.
Published: January 2013

Background

Atopic dermatitis (AD) is a commonly encountered inflammatory skin disease. Although acute lesions of acute AD are characterized by intense inflammation, the hallmarks of chronic AD lesions include lichenified fibrosis and thickening of the upper dermis. The increased expression of transforming growth factor beta 1 (TGF‐β1), a well‐known fibrogenic cytokine, is observed in chronic AD lesions. Tacrolimus (FK506) ointment has been reported to be effective for treating AD as well as some TGF‐β1‐induced fibrotic diseases.

Objectives

To evaluate the effect of tacrolimus on TGF‐β1‐stimulated cultured normal human dermal fibroblasts and explore the potential signalling pathways involved.

Methods

Fibroblasts cultured from healthy adult human foreskins were treated with TGF‐β1 with or without tacrolimus. The impact on cell viability and proliferation were assessed by [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] (MTT) assay and BrdU incorporation assay respectively. Reverse transcription‐polymerase chain reaction (RT‐PCR), quantitative real‐time PCR, enzyme‐linked immunosorbent assay (ELISA) and western blotting were performed to evaluate the relevant expressions of mRNA or proteins in fibroblasts.

Results

Our results revealed that the increased expressions of transforming growth factor‐β receptor I (TGF‐βRI) and TGF‐βRII in TGF‐β1‐treated fibroblasts were suppressed by tacrolimus treatment. In addition, tacrolimus significantly inhibited fibroblast proliferation enhanced by TGF‐β1. TGF‐β1 increased type I collagen production, and this enhancing effect was suppressed by tacrolimus. The down‐regulation of MMP‐1 and up‐regulation of TIMP‐1 induced by TGF‐β1 were reversed by tacrolimus. The increase in phosphorylated p38 mitogen‐activated protein kinase (p38MAPK) expression stimulated by TGF‐β1 was down‐regulated by tacrolimus. Moreover, the fibroblasts treated with p38MAPK inhibitor significantly reduced type I collagen expression induced by TGF‐β1.

Conclusions

The present results demonstrated that tacrolimus significantly inhibited physiological functions of fibroblasts enhanced by TGF‐β1 in vitro. Clinically, we propose that topical tacrolimus may not only reduce AD recurrence but also ameliorate dermal fibrosis often seen in chronic AD lesions.
Measurement of health‐related quality of life in dermatological research and practice: outcome of theEADVTaskforce on Quality of Life
Authors: Prinsen C.A.C. , de Korte J. , Augustin M. , Sampogna F. , Salek S.S. , Basra M.K.A. , Holm E.A. , Nijsten T.E.C. ,   The EADV Taskforce on Quality of Life
Published: January 2013

In the last decade, the importance of the measurement of health‐related quality of life (HRQoL) has grown significantly. Today,HRQoL measurement is generally considered to be important in clinical trials, in the assessment of disease severity, in patient management and in the field of health economics. Therefore, a good understanding of the concept ofHRQoL and its measurement instruments is a prerequisite for both researchers and clinicians. The European Academy for Dermatology and Venereology (EADV) Taskforce on Quality of Life encourages the application ofHRQoL instruments in research and clinical practice, and with this manuscript, the Taskforce aims to contribute to the quality of this application. In dermatology, a large number ofHRQoL instruments exist and herewith, we summarize the most commonly used generic and dermatology‐specificHRQoL instruments. Information is given on the most important psychometric characteristics of these instruments, including: scale structure, reliability, validity and responsiveness. Furthermore, a flow chart is provided to support researchers and clinicians in selecting an existing instrument or, in case an appropriate instrument does not exist, in finding alternative solutions. The present manuscript is the first of a series of manuscripts to be written on behalf of theEADVTaskforce on Quality of Life, aiming to contribute to the scientific knowledge and measurement of patient reported outcomes in dermatological research and practice.
Increases in crop pests caused by Wasmannia auropunctata in Solomon Islands subsistence gardens
Authors: Fasi J. , Brodie G. , Vanderwoude C.
Published: January 2013

The impacts of Wasmannia auropunctata (the little fire ant) on the native biota and subsistence agriculture in the Solomon Islands are poorly understood. This species was originally introduced as a biological control against nut‐fall bugs (Amblypelta sp.) around 30 years ago and in the intervening time has spread throughout the Solomon Islands, aided movement of produce and planting material. It is now itself a major pest of coconut, cocoa and subsistence agriculture. In this study, we show the negative effects of this invasive ant on subsistence agriculture in the Solomon Islands. We do this by (i) assessing the presence of insect pests that develop a mutual relationship with W. auropunctata on four common subsistence crops; and (ii) measuring the impact of a significant pest (Tarophagus sp.) and its natural predator the bug Cyrtohinus fulvus, in the presence and absence of W. auropunctata on taro crops. The existence of insect pests that form a mutual relationship with W. auropunctata was measured in a total of 36 gardens of the four subsistence crops. This was conducted through standardized visual searches, plus identification and collecting from randomly selected plants within the gardens. A number of additional insect pests causing major problems to subsistence crops have also developed mutual relationships with W. auropunctata. Infested taro gardens have more Tarophagus sp. compared with taro plants that are free of the little fire ant. The presence and abundance of Wasmannia therefore has the potential to inflict considerable crop loss in rural subsistence gardens in the Solomon Islands.
Non‐alcoholic fatty liver disease contributes to hepatocarcinogenesis in non‐cirrhotic liver: A clinical and pathological study
Authors: Alexander Jacob , Torbenson Michael , Wu Tsung‐Teh , Yeh Matthew M.
Published: January 2013

Background and Aim

Hepatocellular carcinoma (HCC) is a major complication of cirrhosis and has been increasing in incidence in recent years. Fatty liver disease is an increasingly common cause of chronic liver disease, and there have been several case reports of HCC in patients with non‐cirrhotic fatty liver disease. However, there is limited data from systematic studies with histological confirmation of the presence of both the HCC and the non‐cirrhotic fatty liver disease.

Methods

We studied the occurrence of fatty liver disease and the associated demographic, clinical, and pathological characteristics of a large cohort of patients with HCC in non‐cirrhotic livers. Patients with intrahepatic cholangiocarcinoma (CC) occurring in non‐cirrhotic livers and diagnosed during the same time period were used as the comparison group.

Results

Significant steatosis in the nontumor liver had a statistically significant association with HCC, being present in 54% (85/157) of HCC compared with 27% (32/120) of CC (P < 0.0001). Steatohepatitis was present in 15% (24/157) of HCC and 1% (2/120) of CC (P = 0.0014). Furthermore, HCC was more prevalent in cases with higher grades of steatosis. In addition, the recently described intratumoral steatohepatitic morphology of HCC (SH‐HCC) was also associated with significant steatosis in nontumor liver, with significant steatosis being present in 89% with SH‐HCC compared with 50% without SH‐HCC (P = 0.0162). Finally, SH‐HCC was increasingly more prevalent in patients with higher grades of nontumor steatosis.

Conclusions

Taken together, these findings suggest a strong association between fatty liver disease and HCC in non‐cirrhotic livers.