bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of on‐line CE assay with MS detection for the study of drug metabolism by cytochromes P450
Authors: Langmajerová Monika , Řemínek Roman , Pelcová Marta , Foret František , Glatz Zdeněk
Published: March 2015

A new CE‐MS method with enzymatic reaction inside the capillary was developed for the study of drug metabolism by cytochromes P450. This automated method, based on the transverse diffusion of laminar flow profiles methodology, is comprised of the injection of substrates and enzyme, their mixing, incubation, and separation of the reaction products, all performed by CE, and their detection, identification, and quantification by MS. The developed and validated method was finally used to conduct a kinetic study of cytochrome P450 isoform 2C9 or human liver microsomes with diclofenac in order to demonstrate its practical functionality. All the estimated kinetic values—apparent Michaelis constants and apparent maximum reaction velocities were in agreement with literature data obtained using other techniques. In addition, the consumption of reactants was in the tens of nL per analysis. The method's usability was further demonstrated on tolbutamide, the other probe substrate of cytochrome P450 isoform 2C9. As a result, the method is conceptually applicable for the screening of any other cytochrome P450 isoform and its substrates and inhibitors after adapting the incubation and separation conditions.
Integration of metabolic activation with a predictive toxicogenomics signature to classify genotoxic versus nongenotoxic chemicals in human TK6 cells
Authors: Buick Julie K. , Moffat Ivy , Williams Andrew , Swartz Carol D. , Recio Leslie , Hyduke Daniel R. , Li Heng‐Hong , Fornace Albert J. , Aubrecht Jiri , Yauk Carole L.
Published: March 2015

The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the molecular pathways involved in the response, is becoming more common. In a companion article, a genomic biomarker was developed in human TK6 cells to classify chemicals as genotoxic or nongenotoxic. Because TK6 cells are not metabolically competent, we set out to broaden the utility of the biomarker for use with chemicals requiring metabolic activation. Specifically, chemical exposures were conducted in the presence of rat liver S9. The ability of the biomarker to classify genotoxic (benzo[a]pyrene, BaP; aflatoxin B1, AFB1) and nongenotoxic (dexamethasone, DEX; phenobarbital, PB) agents correctly was evaluated. Cells were exposed to increasing chemical concentrations for 4 hr and collected 0 hr, 4 hr, and 20 hr postexposure. Relative survival, apoptosis, and micronucleus frequency were measured at 24 hr. Transcriptome profiles were measured with Agilent microarrays. Statistical modeling and bioinformatics tools were applied to classify each chemical using the genomic biomarker. BaP and AFB1 were correctly classified as genotoxic at the mid‐ and high concentrations at all three time points, whereas DEX was correctly classified as nongenotoxic at all concentrations and time points. The high concentration of PB was misclassified at 24 hr, suggesting that cytotoxicity at later time points may cause misclassification. The data suggest that the use of S9 does not impair the ability of the biomarker to classify genotoxicity in TK6 cells. Finally, we demonstrate that the biomarker is also able to accurately classify genotoxicity using a publicly available dataset derived from human HepaRG cells. Environ. Mol. Mutagen. 56:520–534, 2015. © 2015 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.
NFAT transcription factors regulate survival, proliferation, migration, and differentiation of neural precursor cells
Authors: Serrano‐Pérez María C. , Fernández Miriam , Neria Fernando , Berjón‐Otero Mónica , Doncel‐Pérez Ernesto , Cano Eva , Tranque Pedro
Published: March 2015

The study of factors that regulate the survival, proliferation, and differentiation of neural precursor cells (NPCs) is essential to understand neural development as well as brain regeneration. The Nuclear Factor of Activated T Cells (NFAT) is a family of transcription factors that can affect these processes besides playing key roles during development, such as stimulating axonal growth in neurons, maturation of immune system cells, heart valve formation, and differentiation of skeletal muscle and bone. Interestingly, NFAT signaling can also promote cell differentiation in adults, participating in tissue regeneration. The goal of the present study is to evaluate the expression of NFAT isoforms in NPCs, and to investigate its possible role in NPC survival, proliferation, migration, and differentiation. Our findings indicate that NFAT proteins are active not only in neurogenic brain regions such as hippocampus and subventricular zone (SVZ), but also in cultured NPCs. The inhibition of NFAT activation with the peptide VIVIT reduced neurosphere size and cell density in NPC cultures by decreasing proliferation and increasing cell death. VIVIT also decreased NPC migration and differentiation of astrocytes and neurons from NPCs. In addition, we identified NFATc3 as a predominant NFAT isoform in NPC cultures, finding that a constitutively‐active form of NFATc3 expressed by adenoviral infection reduces NPC proliferation, stimulates migration, and is a potent inducer of NPC differentiation into astrocytes and neurons. In summary, our work uncovers active roles for NFAT signaling in NPC survival, proliferation and differentiation, and highlights its therapeutic potential for tissue regeneration. GLIA 2015;63:987–1004
Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review
Authors: Strojan Primož , Vermorken Jan B. , Beitler Jonathan J. , Saba Nabil F. , Haigentz Missak , Bossi Paolo , Worden Francis P. , Langendijk Johannes A. , Eisbruch Avraham , Mendenhall William M. , Lee Anne W. M. , Harrison Louis B. , Bradford Carol R. , Smee Robert , Silver Carl E. , Rinaldo Alessandra , Ferlito Alfio
Published: March 2015

Background

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined.

Methods

The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses.

Results

Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses.

Conclusion

Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151–E2158, 2016
Managerial Social Networks and Ambidexterity of SMEs: The Moderating Role of a Proactive Commitment to Innovation
Authors: Heavey Ciaran , Simsek Zeki , Fox Brian Curtis
Published: March 2015

Organizational research suggests that ambidexterity is attainable if top managers cultivate collective behavioral routines that enable them to synthesize large amounts of information and decision alternatives, and manage conflict and ambiguity. However, the type of information and knowledge sources that enable top managers to meet the knowledge demands of ambidexterity remains poorly understood. Toward that end, we argue that the extensiveness of top managers’ social networks inside and outside the firm, on an integrative basis, can offer the dual knowledge benefits conducive to ambidexterity. Because ambidexterity entails the firm's departure from existing products, technologies, and practices, we further argue that the contribution of extensive networks to ambidexterity is conditional upon the collective volition of top managers to parlay extensive network opportunities into innovative pursuits. From a study of CEOs and top management teams in SMEs operating in technology‐based industries, we find support for both a network extensiveness effect and the moderating role of a proactive commitment to innovation in shaping this effect. © 2015 Wiley Periodicals, Inc.
Overexpression of a Novel Tumor Metastasis Suppressor Gene TMSG1/LASS2 Induces Apoptosis via a Caspase‐dependent Mitochondrial Pathway
Authors: Su Jing , Yu Wenjuan , Gong Miaozi , You Jiangfeng , Liu Jianying , Zheng Jie
Published: March 2015

The tumor metastasis suppressor gene 1 (TMSG1), also designated homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2), is a novel tumor metastatic suppressor gene. Although its effects on metastasis have been reported, its biological functions remain unclear. The purpose of this study was to investigate the effects of TMSG1/LASS2 protein on apoptosis and proliferation in human embryonic kidney cell lines HEK293 and 293 T and explore the potential mechanisms. Cell growth, morphology, expressions of apoptotic‐related proteins and cell cycle distribution were evaluated in HEK293 and 293 T cells transfected with TMSG1/LASS2 expression plasmids or vector controls. MTT assays showed that overexpression of TMSG1/LASS2 inhibited cell proliferation; and morphological observations and flow cytometric assays with Annexin V/propidium iodide showed TMSG1/LASS2 overexpression increased apoptosis in these cells. Western blot analysis demonstrated that overexpression of TMSG1/LASS2 resulted in the downregulation of Bcl‐2, release of cytochrome c from mitochondria, activation of procaspase‐9 and procaspase‐3, and the cleavage of PARP. Subsequent cell cycle analysis showed that TMSG1/LASS2 overexpression inhibited cell proliferation by mediating the induction of G0/G1 cell cycle arrest. Together, these results confirmed that TMSG1/LASS2 is a potential metastasis suppressor gene, and suggested that the mechanism involved the induction of apoptosis and inhibition of cell proliferation via a caspase‐dependent mitochondrial pathway. J. Cell. Biochem. 116: 1310–1317, 2015. © 2015 Wiley Periodicals, Inc.
Gene Signatures of 1,25‐Dihydroxyvitamin D3 Exposure in Normal and Transformed Mammary Cells
Authors: Simmons Katrina M. , Beaudin Sarah G. , Narvaez Carmen J. , Welsh JoEllen
Published: March 2015

To elucidate potential mediators of vitamin D receptor (VDR) action in breast cancer, we profiled the genomic effects of its ligand 1,25‐dihydroxyvitamin D3 (1,25D) in cells derived from normal mammary tissue and breast cancer. In non‐transformed hTERT‐HME cells, 483 1,25D responsive entities in 42 pathways were identified, whereas in MCF7 breast cancer cells, 249 1,25D responsive entities in 31 pathways were identified. Only 21 annotated genes were commonly altered by 1,25D in both MCF7 and hTERT‐HME cells. Gene set enrichment analysis highlighted eight pathways (including senescence/autophagy, TGFβ signaling, endochondral ossification, and adipogenesis) commonly altered by 1,25D in hTERT‐HME and MCF7 cells. Regulation of a subset of immune (CD14, IL1RL1, MALL, CAMP, SEMA6D, TREM1, CSF1, IL33, TLR4) and metabolic (ITGB3, SLC1A1, G6PD, GLUL, HIF1A, KDR, BIRC3) genes by 1,25D was confirmed in hTERT‐HME cells and similar changes were observed in another comparable non‐transformed mammary cell line (HME cells). The effects of 1,25D on these genes were retained in HME cells expressing SV40 large T antigen but were selectively abrogated in HME cells expressing SV40 + RAS and in MCF7 cells. Integration of the datasets from hTERT‐HME and MCF7 cells with publically available RNA‐SEQ data from 1,25D treated SKBR3 breast cancer cells enabled identification of an 11‐gene signature representative of 1,25D exposure in all three breast‐derived cell lines. Four of these 11 genes (CYP24A1, CLMN, EFTUD1, and SERPINB1) were also identified as 1,25D responsive in human breast tumor explants, suggesting that this gene signature may prove useful as a biomarker of vitamin D exposure in breast tissue. J. Cell. Biochem. 116: 1693–1711, 2015. © 2015 Wiley Periodicals, Inc.
EGF Protects Cells Against Dox‐Induced Growth Arrest Through Activating Cyclin D1 Expression
Authors: Yao Chun‐Xia , Shi Jia‐Chen , Ma Cai‐Xia , Xiong Cheng‐Juan , Song Yang‐Liu , Zhang Shu‐Feng , Zhang Shan‐Feng , Zang Ming‐Xi , Xue Li‐Xiang
Published: March 2015

It has been reported that the antitumor drug doxorubicin (Dox) exerts its toxic effects via GATA‐4 depletion and that over‐expression of GATA‐4 reverses Dox‐induced toxicity and apoptosis; however, the precise mechanisms remain unclear. In this study, we observed, for the first time, that EGF protects cells against Dox‐mediated growth arrest, G2/M‐phase arrest, and apoptosis. Additionally, EGF expression was down‐regulated in Dox‐treated cells and up‐regulated in GATA‐4 over‐expressing cells. Utilizing real‐time PCR and western blotting analysis, we found that the expression of the cell cycle‐associated protein cyclin D1 was inhibited in GATA‐4‐silenced cells and Dox‐treated cells and was enhanced in GATA‐4 over‐expressing cells and EGF‐treated cells. Furthermore, EGF treatment reversed the inhibited expression of cyclin D1 that was mediated by GATA‐4 RNAi or Dox. Our results indicate that EGF, as a downstream target of Dox, may be involved in Dox‐induced toxicity as well as in the protective role of GATA‐4 against toxicity induced by Dox via regulating cyclin D1 expression, which elucidates a new molecular mechanism of Dox toxicity with important clinical implications. J. Cell. Biochem. 116: 1755–1765, 2015. © 2015 Wiley Periodicals, Inc.
A fast algorithm for denoising magnitude diffusion‐weighted images with rank and edge constraints
Authors: Lam Fan , Liu Ding , Song Zhuang , Schuff Norbert , Liang Zhi‐Pei
Published: March 2015

Purpose

To accelerate denoising of magnitude diffusion‐weighted images subject to joint rank and edge constraints.

Methods

We extend a previously proposed majorize‐minimize method for statistical estimation that involves noncentral χ distributions to incorporate joint rank and edge constraints. A new algorithm is derived which decomposes the constrained noncentral χ denoising problem into a series of constrained Gaussian denoising problems each of which is then solved using an efficient alternating minimization scheme.

Results

The performance of the proposed algorithm has been evaluated using both simulated and experimental data. Results from simulations based on ex vivo data show that the new algorithm achieves about a factor of 10 speed up over the original Quasi‐Newton‐based algorithm. This improvement in computational efficiency enabled denoising of large datasets containing many diffusion‐encoding directions. The denoising performance of the new efficient algorithm is found to be comparable to or even better than that of the original slow algorithm. For an in vivo high‐resolution Q‐ball acquisition, comparison of fiber tracking results around hippocampus region before and after denoising will also be shown to demonstrate the denoising effects of the new algorithm.

Conclusion

The optimization problem associated with denoising noncentral χ distributed diffusion‐weighted images subject to joint rank and edge constraints can be solved efficiently using a majorize‐minimize‐based algorithm. Magn Reson Med 75:433–440, 2016. © 2015 Wiley Periodicals, Inc.
The composition of cellular infiltrates in anti‐HMG‐CoA reductase‐associated myopathy
Authors: Chung Tae , Christopher‐Stine Lisa , Paik Julie J. , Corse Andrea , Mammen Andrew L.
Published: March 2015

Introduction: To characterize cellular infiltrates in muscle biopsies from patients with anti‐3‐hydroxy‐3‐methyl‐gulatryl‐CoA reductase (HMGCR)‐associated myopathy. Methods: Biopsies from 18 anti‐HMGCR myopathy and 7 control dermatomyositis patients were analyzed. Results: CD4+ and CD8+ T‐cells were scattered within the endomysium in 50% of anti‐HMGCR biopsies. All anti‐HMGCR biopsies included increased endomysial and/or perivascular CD163+ M2 macrophages; CD11c+ M1 macrophages were present in 18.8%. CD123+ plasmacytoid dendritic (PD) cells were observed within the endomysium and perivascular spaces in 62.5% of anti‐HMGCR biopsies. Membrane attack complex was deposited on endothelial cells in 50% and on the sarcolemma of nonnecrotic muscle fibers in 85.7% of anti‐HMGCR cases. Major histocompatibility complex class I antigen was up‐regulated in 87.5% of the anti‐HMGCR cases. Conclusions: In addition to necrosis, scattered CD4+, CD8+, and PD cells are characteristic of anti‐HMGCR myopathy. Predominant M2 polarization suggests infiltrating macrophages are more likely to be involved with tissue repair than destruction. Muscle Nerve, 2015. Muscle Nerve 52: 189–195, 2015
Fetal laser therapy: applications in the management of fetal pathologies
Authors: Mathis Jérôme , Raio Luigi , Baud David
Published: March 2015

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin‐to‐twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long‐term follow‐up of these rare cases are now needed to prove the value of endoscopic or ultrasound‐guided laser therapy. © 2015 John Wiley & Sons, Ltd.
The Antiinflammatory Properties of Humic Substances: A Mini Review
Authors: van Rensburg Constance E. J.
Published: March 2015

Humic substances are effective in the suppression of delayed type hypersensitivity, rat paw oedema, a graft‐versus‐host reaction and contact hypersensitivity in rats. They reduce the C‐reactive protein levels of patients suffering from osteoarthritis of the knee and the wheel and flare reaction of patients suffering from hay fever. They have also been described as cardioprotective and pro‐angiogenic. Toxicity studies have indicated that potassium humate is safe in humans up to a daily dosage of 1 g/kg, whereas fulvic acid is safe in humans up to a daily dosage of 1.8 g per adult. The antiinflammatory action of potassium humate can be contributed to the inhibition of the release of inflammatory‐related cytokines, an adhesion molecule, oxidants and components of the complement system. Copyright © 2015 John Wiley & Sons, Ltd.
Raising the achievement of white working class pupils: good practice in schools
Authors: Lewis Kirstin , Demie Feyisa
Published: March 2015

This research identifies strategies that schools have used to raise achievement among white working class pupils in multiracial schools. The methodological approach comprises case studies of schools and focus group interviews to ascertain the views of teachers, parents and children about strategies that worked to raise achievement. The study identifies a number of successful strategies for promoting the achievement of white working class pupils including strong leadership; an inclusive curriculum that meets the needs of white working class pupils; engaging parents and breaking the cycle of low aspiration; supporting pupils through extensive use of teaching assistants and learning mentors and specific support for language development. The transition between primary and secondary school was also managed carefully so that support for white working class pupils continued in a similar vein. This study also highlights that where achievement for white working class pupils was best, headteachers either had white working class roots themselves or a deep commitment to the issues of white working class communities. There were also many people from the local community working at the case study schools who were role models to children. Implications for policy and practice are given in the final section.
Migrating legacy software to the cloud: approach and verification by means of two medical software use cases
Authors: Maenhaut Pieter‐Jan , Moens Hendrik , Ongenae Veerle , De Turck Filip
Published: March 2015

Cloud computing is a technology that enables elastic, on‐demand resource provisioning, allowing application developers to build highly scalable systems. Multi‐tenancy, the hosting of multiple customers by a single application instance, leads to improved efficiency, improved scalability, and less costs. While these technologies make it possible to create many new applications, legacy applications can also benefit from the added flexibility and cost savings of cloud computing and multi‐tenancy. In this article, we describe the steps required to migrate existing applications to a public cloud environment, and the steps required to add multi‐tenancy to these applications. We present a generic approach and verify this approach by means of two case studies, a commercial medical communications software package mainly used within hospitals for nurse call systems and a schedule planner for managing medical appointments. Both case studies are subject to stringent security and performance constraints, which need to be taken into account during the migration. In our evaluation, we estimate the required investment costs and compare them to the long‐term benefits of the migration. Copyright © 2015 John Wiley & Sons Ltd.
Understanding the roles of modernity, science, and risk in shaping flood management
Authors: Nobert Sébastien , Krieger Kristian , Pappenberger Florian
Published: March 2015

In the face of an unprecedented climate crisis, uncertainties over both the frequency and the magnitude of extreme weather events are positioning the development of scientific and political responses to flood hazards as pivotal to adaptation strategies. While floods are generally understood as the results of hydro‐meteorological processes, their physical nature is also hiding some wider theoretical and practical dimensions that are intrinsically social. In turn, those dimensions unveil floods as social ‘revealers’, capable to exhibit the central role played by the fusion between science and politics in defining regimes of risk‐based flood governance. From the emergence of numerical weather predictions to the increasing sophistication of meteorological and hydrological predictions, the age‐old threat of flooding is increasingly viewed through a distinctively modern lens, which ultimately aims at organizing, producing, and securing futures by the consolidation of resilient societies. In spite of the considerable research efforts and resources invested into science and risk assessment instruments to underpin a more anticipatory and adaptive strategy to flooding, it is important to recognize that both science and risk politics are framing our capacity to engage with new forms of hazards that cannot be measured or quantified. WIREs Water 2015, 2:245–258. doi: 10.1002/wat2.1075

This article is categorized under:

Engineering Water > Planning Water

Science of Water > Water Extremes

Human Water > Water Governance
Evaluation of translocation of black bears involved in human–bear conflicts in South‐central Colorado
Authors: Alldredge Mat W. , Walsh Daniel P. , Sweanor Linda L. , Davies Robert B. , Trujillo Al
Published: March 2015

From 1995 to 1997, black bears (Ursus americanus) involved in conflicts with humans in southeastern Colorado, USA, were radiocollared, translocated, and monitored by the Colorado Division of Wildlife to evaluate translocation as a management tool for problem black bears. Specific objectives were to 1) determine postrelease movement patterns of relocated black bears, and 2) estimate cumulative incidence and survival functions. Subadults did not move as far after translocation as adults and less frequently oriented toward the capture site (29% of subad vs. 51% of ad). No subadults returned to the vicinity of capture, whereas 33% of adults did. We used a cause‐specific hazards model with a constant age effect across the cause‐specific hazards to estimate annual survival rate for translocated adult bears (0.50, 95% credible interval CI = 0.36–0.65) and for subadult bears (0.28, 95% CI = 0.12–0.48). The annual probability of dying due to repeat conflict behavior was slightly lower (0.22 [95% CI = 0.13–0.33] and 0.32 [95% CI = 0.19–0.47]) for adults and subadults, respectively, compared with nonconflict mortalities (0.28 [95% CI = 0.17–0.40] and 0.40 [95% CI = 0.25–0.56]). Based on bears that were not involved in known repeat human–bear conflicts, translocation success was 0.64 (95% CI = 0.49–0.78) and 0.58 (95% CI = 0.42–0.73) for adults and subadults, respectively. Translocation of problem bears had mixed success relative to repeat nuisance activity in Colorado, but should remain a viable management option. Managers should make decisions on the appropriateness of translocation based on the characteristics of the bear, identification of an adequate release site, potential effect of the translocation on the release‐site bear population, and other available options. © 2015 The Wildlife Society.
Early Intervention in Children (0–6 Years) with a Rare Developmental Disability: The Occupational Therapy Role
Authors: Dall'Alba Lucy , Gray Marion , Williams Gary , Lowe Sharon
Published: March 2015

Objective/Background

This study aims to explore the occupational therapists’ role in early intervention for children diagnosed with a rare developmental disability.

Methods

A survey was distributed by mail or online, to eligible occupational therapists currently used by the Disability and Community Care Services throughout Queensland, Australia. Eligible occupational therapists were those working with children aged 0–6 years. Two in-depth phone interviews were also undertaken.

Results

Eleven participants who had previously worked with at least one child with a rare developmental disability returned the survey. One participant nominated for a follow-up interview and a second interview with a speech and language pathologist was conducted to gain a multidisciplinary perspective. The most common areas requiring intervention were play support (85.3%), activities of daily living, communication, gross motor, and fine motor skills (79.4%).

Conclusion

Family-centred practice, play therapy, and individually tailored programmes are identified as key practice areas for this population. The important role occupational therapists play in early intervention teams is highlighted; however, further research is needed to develop the evidence base for best practice with particular rare developmental conditions.
They look while they leap: Generative co-occurrence of enactment and effectuation in entrepreneurial action
Authors: Bhowmick Sanjay
Published: March 2015

It has been said that entrepreneurs plan in order to deal with market uncertainty. It has also been argued that entrepreneurs act spontaneously and with insufficient planning, as time is of the essence and as market uncertainty seldom yields to planning. Theoretically, in uncertain market conditions, the concept of effectuation posits that entrepreneurs control their resources enhancing them through likeminded stakeholder buy-ins towards creating an opportunity. Alternatively, the first prospective action steps under uncertainty are argued to be taken regardless of resources position, reflecting enactment before sensemaking. Thus, enactment embodies resource-independent action-embracing ambiguity, whereas effectuation, i.e., controlling resources and enhancing stakeholder buy-ins, represents resource-dependent action that mitigates ambiguity and risk. This paper proposes that prospective enactment action and effectuation control action are analytically distinct, complementary and simultaneous aspects of entrepreneurial action. It further proposes that successful outcomes of entrepreneurial action may be anticipated by a high and matching combination of enactment and effectual action in a generative co-occurrence. The paper illustrates the propositions using cases that exhibit diverse action outcomes. It also potentially reconciles the ambiguity-embracing or risk-taking approach and the ambiguity-reducing or risk-mitigating control approach in understanding entrepreneurial action seeking opportunity in an uncertain and dynamic market.
Sinonasal outcomes following endoscopic anterior skull base surgery with nasoseptal flap reconstruction: a prospective study
Authors: Hanson M , Patel P M , Betz C , Olson S , Panizza B , Wallwork B
Published: March 2015

Objective:

To assess nasal morbidity resulting from nasoseptal flap use in the repair of skull base defects in endoscopic anterior skull base surgery.

Methods:

Thirty-six patients awaiting endoscopic anterior skull base surgery were prospectively recruited. A nasoseptal flap was used for reconstruction in all cases. Patients were assessed pre-operatively and 90 days post-operatively via the Sino-Nasal Outcome Test 20 questionnaire and visual analogue scales for nasal obstruction, pain, secretions and smell; endoscopic examination findings and mucociliary clearance times were also recorded.

Results:

Sino-Nasal Outcome Test 20 questionnaire data and visual analogue scale scores for pain, smell and secretions showed no significant differences between pre- and post-operative outcomes, with visual analogue scale scores for nasal obstruction actually showing a significant improvement (p = 0.0007). A significant deterioration for both flap and non-flap sides was demonstrated post-operatively on endoscopic examination (p = 0.002 and p = 0.02 respectively).

Conclusion:

Whilst elevation of a nasoseptal flap in endoscopic surgery of the anterior skull base engendered significant clinical deterioration on examination post-operatively, quality of life outcomes showed that no such deterioration was subjectively experienced by the patient. In fact, there was significant nasal airway improvement following nasoseptal flap reconstruction.
Differences between chimpanzee and baboon gastrointestinal parasite communities
Authors: EBBERT M. A. , McGREW W. C. , MARCHANT L. F.
Published: March 2015

Cross-species infection among humans, chimpanzees (Pan troglodytes) and baboons (Papiospp.) is potentially a significant public health issue in Africa, and of concern in the conservation ofP. troglodytes. However, to date, no statistical comparisons have been made between the prevalence, richness and composition of parasite communities in sympatric populations of baboons andP. troglodytes. We compared parasite communities in sympatricP. troglodytesandPapio papioliving in a wilderness site, in the Republic of Senegal, West Africa. We asked whether, in the absence of humans, there are significant differences between these hosts in their interactions with gastrointestinal parasites. We tested whether host, location, or time of collection accounted for variation in prevalence, richness and community composition, and compared prevalence across six studies. We concluded that, despite being closely related, there are significant differences between these two hosts with respect to their parasite communities. At our study site, prevalence ofBalantidium, TrichurisandWatsoniuswas higher inP. papio. Papio papioharboured more parasites per host, and we found evidence of a positive association betweenTrichurisandBalantidiuminP. troglodytesbut notP. papio.
Analysis of an inter-centre, web-based radiation oncology peer-review case conference
Authors: Crispen Chamunyonga , Kellini Osama M. , Kumar Milind
Published: March 2015

Purpose

Peer-review programmes in radiation oncology are used to facilitate the process and evaluation of clinical decision-making. However, web-based peer-review methods are still uncommon. This study analysed an inter-centre, web-based peer-review case conference as a method of facilitating the decision-making process in radiation oncology.

Methodology

A benchmark form was designed based on the American Society for Radiation Oncology targets for radiation oncology peer review. This was used for evaluating the contents of the peer-review case presentations on 40 cases, selected from three participating radiation oncology centres. A scoring system was used for comparison of data, and a survey was conducted to analyse the experiences of radiation oncology professionals who attended the web-based peer-review meetings in order to identify priorities for improvement.

Results

The mean scores for the evaluations were 82·7, 84·5, 86·3 and 87·3% for cervical, prostate, breast and head and neck presentations, respectively. The survey showed that radiation oncology professionals were confident about the role of web-based peer-reviews in facilitating sharing of good practice, stimulating professionalism and promoting professional growth. The participants were satisfied with the quality of the audio and visual aspects of the web-based meeting.

Conclusion

The results of this study suggest that simple inter-centre web-based peer-review case conferences are a feasible technique for peer review in radiation oncology. Limitations such as data security and confidentiality can be overcome by the use of appropriate structure and technology. To drive the issues of quality and safety a step further, small radiotherapy departments may need to consider web-based peer-review case conference as part of their routine quality assurance practices.
Exploring Radioisotopic Geochronology and Astrochronology
Authors: Meyers Stephen R. , Singer Bradley S. , Schmitz Mark D.
Published: March 2015

IsoAstro Geochronology Workshop: The Integration and Intercalibration of Radioisotopic and Astrochronologic Time Scales; Madison, Wisconsin, 18–23 August 2014
W. James “Jim” Shuttleworth Receives 2014 Robert E. Horton Medal
Authors:   AGU
Published: March 2015

W. James “Jim” Shuttleworth was awarded the 2014 Robert E. Horton Medal at the AGU Fall Meeting Honors Ceremony, held on 17 December 2014 in San Francisco, Calif. The medal is for “outstanding contributions to hydrology.”
Ohio Earthquake Directly Tied to Fracking
Authors: Wendel JoAnna
Published: March 2015

A small earthquake that occurred in Ohio in 2014 is among the largest earthquakes thought to be induced directly by hydraulic fracturing.
Trace Element Holds the Key to Deformation of Continents
Authors: Betz Eric
Published: March 2015

Studies of titanium in quartz grains could help scientists gain a better understanding of our planet's shifting surface.
Warming Hiatus Periods to Become Increasingly Unlikely
Authors: Schultz Colin
Published: March 2015

Anthropogenic climate change is reducing the likelihood of the Earth seeing another slowdown in the rate of surface warming.
Obama Highlights Climate Change and Infrastructure Needs
Authors: Showstack Randy
Published: March 2015

“No challenge poses a greater threat to future generations than climate change,” the president said.
Study Stresses Ocean Science Priorities and Budget Rebalance
Authors: Showstack Randy
Published: March 2015

With infrastructure costs eating into research programs at the National Science Foundation's Division of Ocean Sciences, a new report urges a rebalance of funding and a focus on science priorities.
AGU Board and Council Assess 2014 and Set the Stage for 2015
Authors: Rehm Dana D. , Enderlein Cheryl
Published: March 2015

The Council and Board of Directors honored outgoing leaders and introduced newly elected leaders.
Can Scientists Boost Solar Modeling Despite a Lack of Data?
Authors: Schultz Colin
Published: March 2015

Researchers show that a data processing technique could salvage useful information from raw solar observations, opening the door to improved understanding of the solar dynamo.
Scouts, Students, and Faculty Benefit from Education Programs
Authors: Adamec Bethany , Asher Pranoti M.
Published: March 2015

The American Geophysical Union hosted more than 30 events at the 2014 Fall Meeting for K–12 teachers, higher education faculty, early-career scientists, and the public.
Thriving Earth Exchange Hosts Community Science in Action Events
Authors: Udu-gama Natasha , Pandya Raj
Published: March 2015

Three events at the American Geophysical Union’s 2014 Fall Meeting showcased how partnerships between scientists and the public can solve local problems.
Donors Engage and Connect at Fall Meeting Events
Authors: Thompson Victoria
Published: March 2015

From participating in a fun run to enjoying lunch with recipients of student travel grants, donors to the American Geophysical Union helped make the 2014 Fall Meeting a success.
Gαq controls rheumatoid arthritis via regulation of Th17 differentiation
Authors: Liu Yuan , Wang Dashan , Li Fang , Shi Guixiu
Published: March 2015

Gαq, the α‐subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq−/− mice. We observed that the expression of Gαq was negatively associated with interleukin‐17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq−/− mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal‐regulated kinase‐1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR‐related orphan receptor‐α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.
Diagnostic and Prognostic Significances of MUC5B and TTF-1 Expressions in Resected Non-Small Cell Lung Cancer
Authors: Nagashio Ryo , Ueda Junpei , Ryuge Shinichiro , Nakashima Hiroyasu , Jiang Shi-Xu , Kobayashi Makoto , Yanagita Kengo , Katono Ken , Satoh Yukitoshi , Masuda Noriyuki , Murakumo Yoshiki , Hachimura Kazuo , Sato Yuichi
Published: March 2015

To investigate the relationships between the expression of MUC5B and clinicopathological parameters, the expression of MUC5B was immunohistochemically studied. MUC5B expression was observed in 129 of 198 (65.2%) adenocarcinomas and in 4 of 49 (8.2%) squamous cell carcinomas (P < 0.00001). MUC5B expression was significantly associated with poorer differentiation (P = 0.0303), higher pathological TNM stage (p = 0.0153) and poorer prognosis of adenocarcinoma patients (P = 0.0017). Multivariable analysis with Cox proportional hazards models confirmed that MUC5B expression increased the hazard of death after adjusting for other clinicopathological factors (HR = 2.66; 95%CI, 1.26–5.61). We also immunohistochemically evaluated TTF-1 expression and found that the combination of MUC5B with TTF-1 is a useful marker for adenocarcinomas. The diagnostic accuracies of TTF-1 and MUC5B for adenocarcinoma were 83.8% and 70.4%, respectively. The accuracy increased to 94.3% when the two factors were combined. In survival analysis, the MUC5B(High)/TTF-1(−) group was significantly associated with a poorer outcome compared with the MUC5B(Low)/TTF-1(+) group (p < 0.0001). The present study suggested that the combination of MUC5B and TTF-1 expression is useful for discriminating adenocarcinomas from squamous cell carcinomas, yielding prognostic significance in patients with lung adenocarcinoma.
MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro
Authors: Feng Ruizhi , Sang Qing , Zhu Yan , Fu Wei , Liu Miao , Xu Yan , Shi Huijuan , Xu Yao , Qu Ronggui , Chai Renjie , Shao Ruijin , Jin Li , He Lin , Sun Xiaoxi , Wang Lei
Published: March 2015

Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality.
Microbial communities on flower surfaces act as signatures of pollinator visitation
Authors: Ushio Masayuki , Yamasaki Eri , Takasu Hiroyuki , Nagano Atsushi J. , Fujinaga Shohei , Honjo Mie N. , Ikemoto Mito , Sakai Shoko , Kudoh Hiroshi
Published: March 2015

Microbes are easily dispersed from one place to another and immigrant microbes might contain information about the environments from which they came. We hypothesized that part of the microbial community on a flower's surface is transferred there from insect body surfaces and that this community can provide information to identify potential pollinator insects of that plant. We collected insect samples from the field and found that an insect individual harbored an average of 12.2 × 105 microbial cells on its surface. A laboratory experiment showed that the microbial community composition on a flower surface changed after contact with an insect, suggesting that microbes are transferred from the insect to the flower. Comparison of the microbial fingerprint approach and direct visual observation under field condition suggested that the microbial community on a flower surface could to some extent indicate the structure of plant–pollinator interactions. In conclusion, species-specific insect microbial communities specific to insect species can be transferred from an insect body to a flower surface and these microbes can serve as a “fingerprint” of the insect species, especially for large-bodied insects. Dispersal of microbes is a ubiquitous phenomenon that has unexpected and novel applications in many fields and disciplines.
Detecting local heterogeneity and ionization ability in the head group region of different lipidic phases using modified fluorescent probes
Authors: Abou-Zied Osama K. , Zahid N. Idayu , Khyasudeen M. Faisal , Giera David S. , Thimm Julian C. , Hashim Rauzah
Published: March 2015

Local heterogeneity in lipid self-assembly is important for executing the cellular membrane functions. In this work, we chemically modified 2-(2′-hydroxyphenyl)benzoxazole (HBO) and attached a C8 alkyl chain in two different locations to probe the microscopic environment of four lipidic phases of dodecyl β-maltoside. The fluorescence change in HBO and the new probes (HBO-1 and HBO-2) shows that in all phases (micellar, hexagonal, cubic and lamellar) three HBO tautomeric species (solvated syn-enol, anionic and closed syn-keto) are stable. The formation of multi tautomers reflects the heterogeneity of the lipidic phases. The results indicate that HBO and HBO-1 reside in a similar location within the head group region, whereas HBO-2 is slightly pushed away from the sugar-dominated area. The stability of the solvated syn-enol tautomer is due to the formation of a hydrogen bond between the OH group of the HBO moiety and an adjacent oxygen atom of a sugar unit. The detected HBO anions was proposed to be a consequence of this solvation effect where a hydrogen ion abstraction by the sugar units is enhanced. Our results point to a degree of local heterogeneity and ionization ability in the head group region as a consequence of the sugar amphoterism.
Endocytic pathway mediates refractoriness of insect Bactrocera dorsalis to RNA interference
Authors: Li Xiaoxue , Dong Xiaolong , Zou Cong , Zhang Hongyu
Published: March 2015

RNA interference (RNAi) is a powerful and convenient tool for sequence-specific gene silencing and it is triggered by double-stranded RNA (dsRNA). RNAi can be easily achieved in many eukaryotes by either injecting or feeding dsRNAs. This mechanism has demonstrated its potential in fundamental research on genetics, medicine and agriculture. However, the possibility that insects might develop refractoriness to RNAi remains unexplored. In this study, we report that the oriental fruit fly, Bactrocera dorsalis, became refractory to RNAi using orally administered dsRNA targeting endogenous genes. Furthermore, refractoriness to RNAi is not gene-specific and its duration depends on the dsRNA concentration. RNAi blockage requires the endocytic pathway. Fluorescence microscopy indicated that in RNAi refractory flies, dsRNA uptake is blocked. Genes involved in the entry of dsRNAs into cells, including chc, cog3, light and others, are down-regulated in RNAi refractory flies. Increasing the endocytic capacity by improving F-actin polymerization disrupts RNAi refractoriness after both primary and secondary dsRNA exposures. Our results demonstrate that an insect can become refractory to RNAi by preventing the entry of dsRNA into its cells.
A short review of applications of liquid chromatography mass spectrometry based metabolomics techniques to the analysis of human urine
Authors: Zhang Tong , Watson David G.
Published: March 2015

Mass spectrometry based metabolomics profiling.
Self-triggered conformations of disulfide ensembles in coordination polymers with multiple metal clusters
Authors: Tseng Tien-Wen , Luo Tzuoo-Tsair , Shih Ying-Ru , Shen Jing-Wen , Lee Li-Wei , Chiang Ming-Hsi , Lu Kuang-Lieh
Published: March 2015

Five coordination polymers containing manganese(ii) ions, 6,6′-dithiodinicotinate, and/or N-donor coligands display mononuclear, trinuclear cluster and polymeric metal oxide wire and exhibit intrinsic biomimetic characteristics.
Modification of the supramolecular structure of [(thione)IY] (Y = Cl, Br) systems by cooperation of strong halogen bonds and hydrogen bonds
Authors: Koskinen L. , Hirva P. , Hasu A. , Jääskeläinen S. , Koivistoinen J. , Pettersson M. , Haukka M.
Published: March 2015

Strong halogen bonds and hydrogen bonds cooperated to control the supramolecular structures of [(thione)IY] (Y = Cl, Br) compounds.