bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
Authors: Magnusson Karin , Appelqvist Hanna , Cieślar‐Pobuda Artur , Wigenius Jens , Karlsson Thommie , Łos Marek J. , Kågedal Bertil , Jonasson Jon , Nilsson K. Peter R.
Published: January 2015

Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one‐sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer‐related biological and pathological processes. © 2015 International Society for Advancement of Cytometry
Statistical analysis of molecule colocalization in bioimaging
Authors: Lagache Thibault , Sauvonnet Nathalie , Danglot Lydia , Olivo‐Marin Jean‐Christophe
Published: January 2015

The quantitative analysis of molecule interactions in bioimaging is key for understanding the molecular orchestration of cellular processes and is generally achieved through the study of the spatial colocalization between the different populations of molecules. Colocalization methods are traditionally divided into pixel‐based methods that measure global correlation coefficients from the overlap between pixel intensities in different color channels, and object‐based methods that first segment molecule spots and then analyze their spatial distributions with second‐order statistics. Here, we present a review of such colocalization methods and give a quantitative comparison of their relative merits in different types of biological applications and contexts. We show on synthetic and biological images that object‐based methods are more robust statistically than pixel‐based methods, and allow moreover to quantify accurately the number of colocalized molecules. © 2015 International Society for Advancement of Cytometry
Rare event counting of CD59− red cells in human blood: A 47‐month experience using PNH consensus guidelines for WBC and RBC testing in a reference lab
Authors: Liew Michael , Farley Marjorie , Andreasen John , Parker Charles J. , Wittwer Carl T.
Published: January 2015

Introduction

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by increased complement‐mediated lysis of erythrocytes (RBCs) because of low/absent glycophosphatidylinositol (GPI) anchors of numerous cell surface proteins.

Methods

Rare event analysis was applied to 120 million RBCs (12 normal individuals) and 102 million RBCs (102 normal individuals) to establish a reference range and verify a methodology for rare event analysis. Patient PNH testing (n = 10,984) was performed over 47 months using the 2010 consensus guidelines with CD59‐PE and glycophorin A‐FITC for RBCs and FLAER‐Alexa 488, CD33‐PerCP‐Cy5.5, CD15‐APC, CD14‐APC‐Cy7, and CD24‐PE for WBCs.

Results

The distribution of CD59−RBCs in the normal population was asymmetric with a mean of 5.9, median between 3 and 4, and mode of 2 per million RBCs. The normal range of CD59−RBCs was 0‐17/million RBCs. A natural cutoff of 2.5% of the peak expression of CD59 delineates CD59+ from CD59−populations. The incidence of GPI‐ samples received by the laboratory was 6–7% without correlation to age (P = 0.35) or sex (P = 0.45). The percentage of GPI‐ neutrophils and monocytes were strongly correlated (R2 = 0.96) and usually greater than the percentage of GPI‐ RBCs.

Conclusion

PNH RBC testing is a good example of rare event analysis applied to clinical cytometry—only 2.5 min are required to collect 1 million RBCs. With an established normal range of CD59−RBCs, the correlation between total cell count and sensitivity for detecting an abnormal population can be calculated using Poisson statistics. © 2015 International Clinical Cytometry Society
Toward mobile Internet‐based layered vehicular networks with efficient access management
Authors: Li Xi , Zhang Heli , Wang Ke
Published: January 2015

Vehicular networks have been considered as an important part of realizing the ubiquitous mobile Internet services in the near future. This puts forward the challenge of providing more access opportunities and wireless resources to meet the increasing QoS requirements from various applications. Traditional vehicular ad hoc networks afford the access to Internet by dedicated roadside units. In order to resolve the problems resulting from limited RSUs, insufficient resources and unsatisfied user experience, we propose a layered structure for vehicular networks. The vehicles are virtualized as special vehicular small cells (VSCs) within the first layer and then integrated with the layered heterogeneous networks as the second layer. Furthermore, the access management problem is discussed, and then an optimal access strategy has been designed for VSC to choose the proper roadside infrastructure from several candidates. Evaluation model has been derived with consideration on QoS, handover frequency, moving speed, security, and cost. Simulation results have proved the effectiveness of our proposed scheme from the performance evaluation. Copyright © 2015 John Wiley & Sons, Ltd.
Anti‐inflammatory compounds to reduce infarct size in large‐animal models of myocardial infarction: A meta‐analysis
Authors: van Hout G.P.J. , Jansen of Lorkeers S.J. , Wever K.E. , Sena E.S. , van Solinge W.W. , Doevendans P.A. , Pasterkamp G. , Chamuleau S.A.J. , Hoefer I.E.
Published: January 2015

Targeting the inflammatory response after myocardial infarction (MI) could potentially prevent infarct expansion, resulting in a preservation of cardiac function. Despite extensive testing in large‐animal models of MI, anti‐inflammatory therapeutics are not incorporated in daily clinical practice. Methodological review of the literature describing the effects of anti‐inflammatory compounds in large‐animal models of MI may provide useful insights into the reasons for the translational failure from preclinical to clinical studies. Moreover, systematic review of these preclinical studies may allow us to determine which anti‐inflammatory agents have the greatest potential to successfully treat MI in the clinic and guide which preclinical setting appears most appropriate to test these future treatment strategies in. The current systematic review protocol provides a detailed description of the design of this systematic review of studies investigating the effects of anti‐inflammatory compounds in large‐animal models of MI.
Evolution of leaf warbler songs (Aves: Phylloscopidae)
Authors: Tietze Dieter Thomas , Martens Jochen , Fischer Balduin S. , Sun Yue‐Hua , Klussmann‐Kolb Annette , Päckert Martin
Published: January 2015

Songs in passerine birds are important for territory defense and mating. Speciation rates in oscine passerines are so high, due to cultural evolution, that this bird lineage makes up half of the extant bird species. Leaf warblers are a speciose Old‐World passerine family of limited morphological differentiation, so that songs are even more important for species delimitation. We took 16 sonographic traits from song recordings of 80 leaf warbler taxa and correlated them with 15 potentially explanatory variables, pairwise, and in linear models. Based on a well‐resolved molecular phylogeny of the same taxa, all pairwise correlations were corrected for relatedness with phylogenetically independent contrasts and phylogenetic generalized linear models were used. We found a phylogenetic signal for most song traits, but a strong one only for the duration of the longest and of the shortest element, which are presumably inherited instead of learned. Body size of a leaf warbler species is a constraint on song frequencies independent of phylogeny. At least in this study, habitat density had only marginal impact on song features, which even disappeared through phylogenetic correction. Maybe most leaf warblers avoid the deterioration through sound propagation in dense vegetation by singing from exposed perches. Latitudinal (and longitudinal) extension of the breeding ranges was correlated with most song features, especially verse duration (longer polewards and westwards) and complexity (lower polewards). Climate niche or expansion history might explain these correlations. The number of different element types per verse decreases with elevation, possibly due to fewer resources and congeneric species at higher elevations.
Steps forward in regulatory pathways for acute and chronic heart failure
Authors: Pani Luca , Pecorelli Sergio , Rosano Giuseppe , Anker Stefan D. , Peracino Andrea , Fregonese Laura , Prasad Krishna , Rasi Guido
Published: January 2015

A workshop was organized by the Agenzia Italiana del Farmaco (AIFA) to discuss unmet needs and ways forward in the development of medicines in heart failure, their rationale, and cost‐effective use. An integrated, multidisciplinary approach, including patients' needs and perspectives, was advocated by all the participants as the way to the most effective treatment regimens. More work is needed for reaching consensus on clinical and functional endpoints, for validating patient reported outcomes and measurements of well‐being. Similarly, the integration into the clinical programmes of the health technology assessment/payers perspective, in particular, the evaluation of ‘real‐life’ treatment effectiveness and of health as a value, would help in shifting the development and authorization of medicines from the molecule paradigm to their evaluation in the context of the whole health care regimen. Through this kind of workshop, AIFA is trying to build a template for meetings devoted to debate unmet needs with all stakeholders towards tentative road maps for the future.
A Mn6 Cluster inside a Mn10 Wheel: Characterization of a Mn16‐Oximate Complex Resulting from a Tetrazole‐2‐pyridylketoneoximate Ligand
Authors: Alcazar Laura , Font‐Bardia Mercè , Escuer Albert
Published: January 2015

A new Mn16 topology consisting of one hexanuclear {MnII2MnIII4} unit coordinated inside a decametallic {MnII6MnIII2MnIV2} wheel was synthesized from 2‐pyridylcyanoxime and azido ligands. A new tetrazole‐2‐pyridylketoneoximate ligand was obtained in situ by cyclization of the cyano group and azide mediated by manganese cations.
Synthesis of Acyloxy‐Semicyclic Dienes Using an Enyne Metathesis/Ring Closing Metathesis Approach
Authors: Kueh Jui Thiang Brian , Moodie Lindon W. K. , Lucas Nigel T. , Larsen David S.
Published: January 2015

An enyne metathesis/ring closing metathesis (EM/RCM) sequence was used to synthesise acyloxy‐semicyclic dienes from an enyne substrate and various vinyl esters. This allowed convenient access to acyloxy‐semicyclic dienes not accessible by cross metathesis alone due to the low reactivity of Fischer carbenes with the termini of 1,3‐dienes. This new approach also provides an alternative method for the synthesis of 1‐acyloxy‐1,3‐dienes which are useful reactants for Diels–Alder cycloadditions.
One‐Pot Preparation of Alkyl Iodides from Esters by Indium‐Catalyzed Reductive Cleavage of a Carbon–Oxygen Bond
Authors: Sakai Norio , Matsushita Yohei , Konakahara Takeo , Ogiwara Yohei , Hirano Keisuke
Published: January 2015

We describe the indium‐catalyzed reductive iodination of aliphatic and aromatic esters with iodine and 1,1,3,3‐tetramethyldisiloxane (TMDS). This reducing procedure accommodates a variety of esters, including esters containing alkyl groups, halogens, a hydroxy group, a thioether, and an alkene moiety. Also, this procedure was applied to the cleavage of carbon–oxygen bonds in acrylate polymers.
Optimal energy‐based seismic design of non‐conventional Tuned Mass Damper (TMD) implemented via inter‐story isolation
Authors: Reggio Anna , Angelis Maurizio De
Published: January 2015

Inter‐story isolation, an effective strategy for mitigating the seismic risk of both new and existing buildings, has gained more and more interest in recent years as alternative to base isolation, whenever the latter results to be impractical, technically difficult or uneconomic. As suggested by the name, the technique consists in inserting flexible isolators at floor levels other than the base along the height of a multi‐story building, thus realizing a non‐conventional Tuned Mass Damper (TMD). Consistent with this, an optimal design methodology is developed in the present paper with the objective of achieving the global protection of both the structural portions separated by the inter‐story isolation system, that is, the lower portion (below the isolation system) and the isolated upper portion (above the isolation system). The optimization procedure is formulated on the basis of an energy performance criterion that consists in maximizing the ratio between the energy dissipated in the isolation system and the input energy globally transferred to the entire structure. Numerical simulations, performed under natural accelerograms with different frequency content and considering increasing isolation levels along the height of a reference frame structure, are used to investigate the seismic performance of the optimized inter‐story isolation systems. Copyright © 2015 John Wiley & Sons, Ltd.
Informed Genome‐Wide Association Analysis With Family History As a Secondary Phenotype Identifies Novel Loci of Lung Cancer
Authors: Poirier Julia G. , Brennan Paul , McKay James D. , Spitz Margaret R. , Bickeböller Heike , Risch Angela , Liu Geoffrey , Le Marchand Loic , Tworoger Shelley , McLaughlin John , Rosenberger Albert , Heinrich Joachim , Brüske Irene , Muley Thomas , Henderson Brian E. , Wilkens Lynne R. , Zong Xuchen , Li Yafang , Hao Ke , Timens Wim , Bossé Yohan , Sin Don D. , Obeidat Ma'en , Amos Christopher I. , Hung Rayjean J.
Published: January 2015

Lung cancer is the leading cause of cancer death worldwide. Although several genetic variants associated with lung cancer have been identified in the past, stringent selection criteria of genome‐wide association studies (GWAS) can lead to missed variants. The objective of this study was to uncover missed variants by using the known association between lung cancer and first‐degree family history of lung cancer to enrich the variant prioritization for lung cancer susceptibility regions. In this two‐stage GWAS study, we first selected a list of variants associated with both lung cancer and family history of lung cancer in four GWAS (3,953 cases, 4,730 controls), then replicated our findings for 30 variants in a meta‐analysis of four additional studies (7,510 cases, 7,476 controls). The top ranked genetic variant rs12415204 in chr10q23.33 encoding FFAR4 in the Discovery set was validated in the Replication set with an overall OR of 1.09 (95% CI = 1.04, 1.14, P = 1.63 × 10−4). When combining the two stages of the study, the strongest association was found in rs1158970 at Ch4p15.2 encoding KCNIP4 with an OR of 0.89 (95% CI = 0.85, 0.94, P = 9.64 × 10−6). We performed a stratified analysis of rs12415204 and rs1158970 across all eight studies by age, gender, smoking status, and histology, and found consistent results across strata. Four of the 30 replicated variants act as expression quantitative trait loci (eQTL) sites in 1,111 nontumor lung tissues and meet the genome‐wide 10% FDR threshold.
Fatty acid‐binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin‐1
Authors: Kagawa Yoshiteru , Yasumoto Yuki , Sharifi Kazem , Ebrahimi Majid , Islam Ariful , Miyazaki Hirofumi , Yamamoto Yui , Sawada Tomoo , Kishi Hiroko , Kobayashi Sei , Maekawa Motoko , Yoshikawa Takeo , Takaki Eiichi , Nakai Akira , Kogo Hiroshi , Fujimoto Toyoshi , Owada Yuji
Published: January 2015

Fatty acid‐binding proteins (FABPs) bind and solubilize long‐chain fatty acids, controlling intracellular lipid dynamics. FABP7 is expressed by astrocytes in the developing brain, and suggested to be involved in the control of astrocyte lipid homeostasis. In this study, we sought to examine the role of FABP7 in astrocytes, focusing on plasma membrane lipid raft function, which is important for receptor‐mediated signal transduction in response to extracellular stimuli. In FABP7‐knockout (KO) astrocytes, the ligand‐dependent accumulation of Toll‐like receptor 4 (TLR4) and glial cell‐line‐derived neurotrophic factor receptor alpha 1 into lipid raft was decreased, and the activation of mitogen‐activated protein kinases and nuclear factor‐κB was impaired after lipopolysaccharide (LPS) stimulation when compared with wild‐type astrocytes. In addition, the expression of caveolin‐1, not cavin‐1, 2, 3, caveolin‐2, and flotillin‐1, was found to be decreased at the protein and transcriptional levels. FABP7 re‐expression in FABP7‐KO astrocytes rescued the decreased level of caveolin‐1. Furthermore, caveolin‐1‐transfection into FABP7‐KO astrocytes significantly increased TLR4 recruitment into lipid raft and tumor necrosis factor‐α production after LPS stimulation. Taken together, these data suggest that FABP7 controls lipid raft function through the regulation of caveolin‐1 expression and is involved in the response of astrocytes to the external stimuli. GLIA 2015;63:780–794
In the Right Place at the Right Time!: The Influence of Knowledge Governance Tools on Knowledge Transfer and Utilization in MNEs
Authors: Andersson Ulf , Buckley Peter J. , Dellestrand Henrik
Published: January 2015

This article examines the utilization of knowledge transferred between sending and receiving subsidiaries within multinational enterprises. A model was developed and tested on 169 specific knowledge transfer projects. The model explains the utilization of knowledge subject to transfer in terms of hierarchical governance tool efficacy and lateral relationships within the multinational enterprise. The results show that headquarters' involvement during knowledge development does not have any significant impact on subsequent knowledge utilization in the receiving units and, in fact, hierarchical governance forms have a negative impact on knowledge utilization. However, lateral relationships are positive stimuli to building subsidiary capabilities in the knowledge transfer process that enhance receiving unit knowledge utilization.
Attacked from Both Sides: A Dynamic Model of Multinational Corporations' Strategies for Protection of Their Property Rights
Authors: Bucheli Marcelo , Kim Minyoung
Published: January 2015

Multinationals operating in site‐specific industries face two types of opportunistic behavior. If they vertically integrate, host governments have incentives to change existing legislation challenging the firms' property rights. If they do not, they can be held up by business partners or lose control over the production process. These conflicting problems are reflected in the contradictory assessment made by the obsolescing bargaining power and transaction costs economics theories. Drawing on property rights theory, we introduce political integration as a strategy to address the two conflicting problems. It involves the integration of the host country's polities within the multinational's structure to avoid government opportunism, while still benefiting from the advantages of vertical integration. However, this strategy can backfire after institutional changes in the host country.
The Authors Reply
Authors: Appelbaum Paul S. , Chung Wendy , Fyer Abby J. , Klitzman Robert L. , Martinez Josue , Parens Erik , Price W. Nicholson , Waldman Cameron
Published: January 2015

Reply to a commentary by Felicitas Holzer and Ignacio Mastroleoon “Models of Consent to Return of Incidental Findings in Genomic Research.”
Faith and Futility in the ICU
Authors: Mendola Annette , Bock Gregory L.
Published: January 2015

James is a seventy‐two‐year‐old man with end‐stage dementia who was transferred from another hospital. At the time of transfer James had sepsis from two multidrug‐resistant organisms, respiratory failure requiring ventilatory support, renal insufficiency, pancytopenia, and hypotension requiring vasopressors. He has severe contractures and foot drop, has a feeding tube, and has been nonverbal for several months. His son, Paul, is requesting full code and treatment focused on recovery despite James's extremely poor prognosis.

Paul is James's only child, and James's wife is deceased. Paul says he has the “gift of prophecy” and knows for certain when God is speaking to him. “God,” he says, “doesn't lie.” He says that he and his father spent years preaching together and have witnessed many healings. He believes that they are being “rebuked” because at a time when his father was too tired to travel much, they held fewer revivals and did not save enough souls.

James's condition has worsened slowly. He has almost no urine output and does not breathe over the ventilator. He is extremely volume overloaded; his toenails have bloodied and popped off. By hospital‐day twenty‐one, he had only corneal reflexes. The medical team is troubled; if James is to stay on the ventilator, he will need a tracheostomy, but this would only further prolong what has already been an agonizingly prolonged dying process.

Paul continues to pray for his father to get up.
Ebola, Quarantine, and the Law
Authors: Rothstein Mark A.
Published: January 2015

Judged by the key measures of morbidity and mortality, the United States has been very fortunate in the Ebola outbreak so far. We have had a limited number of cases and only a few fatalities. As of this writing, all of the health care workers who became infected in the United States have recovered, and none of the other nonhealth care contacts of Ebola patients has become infected. Yet by almost any other measure, the response to Ebola in the United States has been a disaster. Among other things, there has been a wealth of misinformation, politicization of public health, public panic, and unnecessary quarantine. There is plenty of blame to go around. But one often overlooked factor that complicated the response to Ebola is American public health law.
The Regulatory Gap for Preimplantation Genetic Diagnosis
Authors: Bayefsky Michelle
Published: January 2015

The use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory‐developed tests, including many genetic tests, the clinical validity of the tests may also need to be demonstrated. But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice, and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed. The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes.
SUPPORT and Comparative Effectiveness Trials: What's at Stake?
Authors: Shepherd Lois
Published: January 2015

Lantos and Feudtner argue that SUPPORT was an instance of CER and that CER differs from research involving unproven, experimental therapies because it exposes research subjects to the same risks patients regularly face in clinical practice. Like many defenders of SUPPORT, they formally acknowledge the study as research but want it to be thought of as clinical care. They develop an appealing argument, but it is misleading. Whatever doctors might have done in clinical practice, their choice of target range within the study and for study participants was influenced by research aims. Just as in research involving unproven, experimental therapies, the care of patients in SUPPORT was altered for the goal of obtaining knowledge to help future patients.
Low Frequency of Peripheral Lymphocyte in Chronic Hepatitis B Patients Predicts Poor Progression to Hepatocellular Carcinoma
Authors: Li Jian , Li Juan , Bao Yunwen , Pan Kunyi , Lin Xianghua , Liu Xiaoqiang , Wang Han , Xu Ying , Luo Xiaohong , Li Hongyu , Duan Chaohui
Published: January 2015

Background

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer‐related deaths worldwide. The poor prognosis of HCC is mainly because of its discovery at advanced stages. Because chronic hepatitis B (CHB) accounts for 50–80% HCC occurrence worldwide, and immunity is regarded as an emerging hallmark of cancer, we investigated the predictive role of peripheral immune cells in HCC incidence in CHB patients.

Methods

This investigation collected and analyzed data from 89 CHB patients, 94 primary HCC patients with hepatitis B virus (HBV), 81 primary HCC patients without HBV, 69 normal healthy patients, and 257 CHB patients with at least 3‐year regular followup.

Results

The results demonstrated that CHB and primary HCC patients had different concentrations of lymphocytes, neutrophils, and monocytes in their peripheral circulation. Further study showed that the peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients during the 3 years of followup. Finally, a predictive HCC incidence model with an AUROC (area under the receiver operating characteristic) of 0.832 was constructed based on the peripheral lymphocyte concentration, serum alpha‐fetoprotein (AFP) concentration, and cirrhosis status of CHB patients.

Conclusions

The peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients, and a more accurate predictive model based on peripheral lymphocytes, serum AFP, and cirrhosis status was constructed.
Dynamics of CYP51: implications for function and inhibitor design
Authors: Yu Xiaofeng , Cojocaru Vlad , Mustafa Ghulam , Salo‐Ahen Outi M. H. , Lepesheva Galina I. , Wade Rebecca C.
Published: January 2015

Sterol 14α‐demethylase (cytochrome P450 family 51 (CYP51)) is an essential enzyme occurring in all biological kingdoms. In eukaryotes, it is located in the membrane of the endoplasmic reticulum. Selective inhibitors of trypanosomal CYP51s that do not affect the human CYP51 have been discovered in vitro and found to cure acute and chronic mouse Chagas disease without severe side effects in vivo. Crystal structures indicate that CYP51 may be more rigid than most CYPs, and it has been proposed that this property may facilitate antiparasitic drug design. Therefore, to investigate the dynamics of trypanosomal CYP51, we built a model of membrane‐bound Trypanosoma brucei CYP51 and then performed molecular dynamics simulations of T. brucei CYP51 in membrane‐bound and soluble forms. We compared the dynamics of T. brucei CYP51 with those of human CYP51, CYP2C9, and CYP2E1. In the simulations, the CYP51s display low mobility in the buried active site although overall mobility is similar in all the CYPs studied. The simulations suggest that in CYP51, pathway 2f serves as the major ligand access tunnel, and both pathways 2f (leading to membrane) and S (leading to solvent) can serve as ligand egress tunnels. Compared with the other CYPs, the residues at the entrance of the ligand access tunnels in CYP51 have higher mobility that may be necessary to facilitate the passage of its large sterol ligands. The water (W) tunnel is accessible to solvent during most of the simulations of CYP51, but its width is affected by the conformations of the heme's two propionate groups. These differ from those observed in the other CYPs studied because of differences in their hydrogen‐bonding network. Our simulations give insights into the dynamics of CYP51 that complement the available experimental data and have implications for drug design against CYP51 enzymes. Copyright © 2015 John Wiley & Sons, Ltd.
A simple and efficient honey bee mating optimization approach to performance characterization of a microwave transistor for the maximum power delivery and required noise
Authors: Güneş Filiz , Demirel Salih , Mahouti Peyman
Published: January 2015

In this work, a simple, efficient and multi objective Honey Bee Mating Optimization (HBMO) is presented for the performance characterization of a microwave transistor to deliver maximum power to the load with the required noise Freq. Thus all the possible compatible {Freq ≥ Fmin, Vout = 1, GTmax} triplets and the corresponding source ZS and load ZL = Z*out (ZS) terminations can be obtained in the device operation domain of (VDS, IDS and f) without working analytically for the nonlinear performance and stability equations. HBMO is a recently emerging meta‐heuristic algorithm that combines the powers of the simulated annealing and genetic algorithms. Here, a microwave transistor is chosen as a case study, effectiveness and efficiency of the HBMO are shown by comparing its performance to those of the standard meta‐heuristics Genetic and Particle Swarm algorithms and the mean cost results for 10 runs are found to be 0.22, 1.65 and 1.85, respectively, for the comparable execution times. Furthermore, all the numerical results are found to agree with their analytical counterparts obtained using the microwave, linear circuit and noise theories. The Feasible Design Target Space FDTS can be built by the cross relations among all the possible compatible {Freq ≥ Fmin, Vout = 1, GTmax} triplets together their terminations {ZS, ZL = Z*out (ZS)} covering all the possible amplifier designs where both noise figure and output power are at a premium. Copyright © 2015 John Wiley & Sons, Ltd.
Large‐scale identification of hot spots for soil carbon demand under climate change and bioenergy production
Authors: Franko Uwe , Witing Felix , Jäckel Greta , Volk Martin
Published: January 2015

Global change scenarios predict an increased risk for declining amounts of soil organic matter (SOM) for Central Germany. Within this region the production of bioenergy is one important strategy to counteract the rising anthropogenic CO2‐emissions. Both issues have a close connection: SOM is an important basis for soil productivity and requires a steady reproduction flux. Bioenergy production requires productive soils and partly consumes plant biomass C. Therefore, the available amount for SOM reproduction is reduced. This study provides a methodology for the large‐scale identification of areas with possible conflicts between bioenergy production and SOM reproduction based on (1) the prediction of climate change impact on SOM reproduction and (2) an analysis of the regional distribution of biogas plants. With the C demand index (CDI) and the capacity index (CAP), two indicators were developed which enable the identification of hot spots of high carbon demand for SOM reproduction due to climate change and the usage of bioenergy. As a result of low data requirements, the indicators are widely applicable and transferable to other large‐scale studies. The proposed methodology was applied to Central Germany as a pilot region. Results indicate a growing demand (10–40%) of fresh organic C from biomass for SOM production in comparison to the current level. The analysis reveals that the bioenergy C demand is not evenly distributed within the study region. It also shows some regional clustering. Furthermore, the analysis identifies certain hot spots of a high C demand, where a high capacity of biogas production may conflict with rising demands for biomass to mitigate climate change effects on SOM storage. The hot spot areas—identified and selected on a large scale—can subsequently be analyzed in more detail on a local to farm scale by using high‐resolution data and models which enable the quantification of soil C dynamics.
Last interglacial vegetation and climate history from the Portuguese coast
Authors: MINCKLEY T. A. , HAWS J. A. , BENEDETTI M. M. , BREWER S. C. , FORMAN S. L.
Published: January 2015

We examine the Atlantic maritime vegetation history from Praia Rei Cortiço, Portugal, to understand natural vegetation patterns and infer climatic conditions during the transition from the last interglacial to early glacial periods. Optically stimulated luminescence dating of quartz grains from sediments surrounding the 1.3‐m‐thick organic deposit date the section to within 120–89 ka. Pollen data were used to reconstruct the vegetation history and determine a range of possible past climates using an ensemble of seven modern analogue approaches. A five‐part environmental sequence transitioned from heath‐pine‐dominated communities, deciduous hardwood forests and pine forests to heathlands surrounded by steppe‐like environments. Mixed temperate and Mediterranean forest elements existed during the last interglacial period at Praia Rei Cortiço, suggesting a proximal limit to these floras. Abundant Fagus pollen (>6%) suggests local beech populations existed within maritime forests of the Iberian Atlantic margin, representing a greater distribution of this genus during interglacial periods than has previously been recognized. Climate reconstructions indicate that variations in moisture availability may have been a major driver of the observed environmental changes.
Determination of the triterpene glycosides in sea cucumbers by liquid chromatography with evaporative light scattering and mass spectrometry detection
Authors: Yang Jie , Wang Yuanhong , Zhang Ran , Jiang Tifngfu , Lv Zhihua
Published: January 2015

Holothurian triterpene glycosides possess various kinds of biological activities, including antifungal, cytotoxic, hemolytic, cytostatic, and immunomodulatory effects. In this study, a rapid extraction method of triterpene glycosides from sea cucumbers using a small column of C18 solid phase was first developed. Furthermore, a novel high‐performance liquid chromatography method coupled with evaporative light scattering detection and electrospray ionization mass spectrometry was established for the determination of each triterpene glycosides from different sea cucumbers. Simultaneous separation of all kind of triterpene glycoside were achieved on a C18 column. A gradient of aqueous acetonitrile was applied, and the method was validated. The liquid chromatography method was applied to the online mass detection to identify the triterpene glycosides in the purified extraction of eight kinds of pulverized sea cucumber from the market of Qingdao, China. The negative mode of [M–H]−/[M–Na]− exclusively shown signals corresponding to the triterpene glycosides previously reported and the MS2 product ions of those ions indicate the specific structure of each triterpene glycoside.
Automatic Mechanism and Kinetic Model Generation for Gas‐ and Solution‐Phase Processes: A Perspective on Best Practices, Recent Advances, and Future Challenges
Authors: Van de Vijver Ruben , Vandewiele Nick M. , Bhoorasingh Pierre L. , Slakman Belinda L. , Seyedzadeh Khanshan Fariba , Carstensen Hans‐Heinrich , Reyniers Marie‐Françoise , Marin Guy B. , West Richard H. , Van Geem Kevin M.
Published: January 2015

Completely automated mechanism generation of detailed kinetic models is within reach in the coming decade. The recent developments in this field of chemical reaction engineering are anticipated to lead to some groundbreaking discoveries in the future, extending our fundamental understanding and resolving many of today's society problems such as energy production and conversion, emission reduction, greener chemical production processes, etc. In the present review, the focus is on the core of these automated mechanism generation for gas‐phase and solution‐phase processes that is on how the reaction kinetics and thermodynamic and transport properties of species are estimated and calculated starting from the fundamental elements of the software. With tasks such as the definition of reaction rules and reaction families, the unambiguous representation of species, and the choice of different termination criteria, generating a good reaction mechanism is still not as simple as pressing a “run” button. One of the main challenges that still needs to be overcome is how to deal with data scarcity and the combination with affordable computational chemistry calculations seems the logical step forward. The best practices are illustrated in a butane pyrolysis case study, which also exposes the challenges in the field of automatic kinetic model generation.
Evaluation of an otoscopy simulator to teach otoscopy and normative anatomy to first year medical students
Authors: Lee Daniel J. , Fu Terence S. , Carrillo Brian , Campisi Paolo , Forte Vito , Chiodo Albino
Published: January 2015

Objective/Hypothesis

Our study evaluates the effectiveness of the OtoSim as an educational tool for teaching otoscopy and normal middle ear anatomy to first‐year medical students.

Study Design

Cross‐sectional survey design.

Methods

A large group otoscopy simulator teaching session was held in January 2014 for 29 first‐year medical students at the University of Toronto. Following the training session, survey questions were administered to assess the student experience.

Results

A total of 29 students completed the survey. All respondents rated the overall quality of the event as very good or excellent. Ninety‐three percent of respondents indicated that the simulator increased their confidence in otoscopy. Students also commented that they were able to learn normal middle ear anatomy without causing discomfort to patients.

Conclusions

The use of otoscopy simulation is a novel addition to traditional learning methods for undergraduate medical students. Students can effectively learn normal external and middle ear anatomy and improve their confidence in performing otoscopy examination.

Level of Evidence

NA Laryngoscope, 125:2159–2162, 2015
The Tool Laser Beam with New Degrees of Freedom
Authors: Kimme Thomas , Quellmalz Benjamin
Published: January 2015

Highly dynamic drives, e. g., piezo or voice coil drives, enable a high‐frequency deflection of the laser beam on the workpiece surface. Modern solid‐state lasers allow modulation of the specified laser power in frequencies of several kilohertz. If these possibilities are combined strictly synchronously, the result is previously unavailable technological advantage on the component to be processed: the programmable beam quality. Using the example of specific optical and machine solutions, the following describes how these possibilities have been realised for industrial use and proves the technological advantages on application examples in the processes of laser welding and laser powder cladding.
Fire Alters Vegetation and Soil Microbial Community in Alpine Meadow
Authors: Wang Changting , Wang Genxu , Wang Yong , Rafique Rashid , Ma Li , Hu Lei , Luo Yiqi
Published: January 2015

Grassland fire, as an important ecological factor, is quite influential in determining the structural and functional stability of ecosystem. In this work, the fire‐induced changes on the vegetation and soil microbial community were studied in alpine meadow. Microbial community composition was assessed by phospholipid fatty acid (PLFA) analysis, and functional diversity was determined by Biolog EcoPlate method. Our results showed that burning caused a significant increase in plant functional group coverage, biomass of grasses, soil bulk density and the ratio of roots to soils. Fire also caused an increase in soil pH and a decrease in total soil nutrient contents and soil moisture. The average well colour development of soil microorganism, the microbial functional diversity and the number of carbon source utilisation were also significantly affected by fire. Total bacteria PLFA, Gram‐positive bacteria (G+) PLFA, Gram‐negative bacteria (G−) PLFA and total PLFA of the burnt sites all increased significantly in burnt soil. The BACT/FUNG, SAT/MONO and G+/G− ratio also appeared to be higher in burnt sites. The total PLFA, G+ PLFA and G− PLFA are closely related to the plant community quantitative characteristics and soil nutrients. The total PLFA, bacteria and G+ PLFA are significantly correlated with the soil total nutrients and available nutrients. These results suggest that the ability of soil microorganisms to use a single‐carbon substrate was increased after a fire event. Grassland fire not only has direct impacts on plant community structure and function but also indirectly alters the soil microbial properties because of fire‐induced changes in plant community. Copyright © 2015 John Wiley & Sons, Ltd.
Treatment of hepatitis C in liver transplant patients: Interferon out, direct antiviral combos in
Authors: Price Jennifer C. , Terrault Norah A.
Published: January 2015

Although chronic infection with hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States, graft and patient survival rates are reduced because of HCV recurrence after transplant. Interferon‐based antiviral treatment administered either before or after transplant to prevent or treat HCV recurrence, respectively, is limited because of poor tolerability and low efficacy. However, the treatment of HCV in the transplant setting is changing considerably with the availability of newer direct‐acting antivirals and interferon‐free regimens. This article will review the experience to date with treating HCV in the setting of cirrhosis and liver transplantation and will discuss the unique challenges encountered when this population is being treated. Liver Transpl 21:423‐434, 2015. © 2015 AASLD.
Safety and efficacy of splenic artery embolization for portal hyperperfusion in liver transplant recipients: A 5‐year experience
Authors: Presser Naftali , Quintini Cristiano , Tom Cynthia , Wang Weiping , Liu Qiang , Diago‐Uso Teresa , Fujiki Masato , Winans Charles , Kelly Dympna , Aucejo Federico , Hashimoto Koji , Eghtesad Bijan , Miller Charles
Published: January 2015

Severe portal hyperperfusion (PHP) after liver transplantation has been shown to cause intrahepatic arterial vasoconstriction secondary to increased adenosine washout (hepatic artery buffer response). Clinically, posttransplant PHP can cause severe cases of refractory ascites and hydrothorax. In the past, we reported our preliminary experience with the use of splenic artery embolization (SAE) as a way to reduce PHP. Here we present our 5‐year experience with SAE in orthotopic liver transplantation (OLT). Between January 2007 and December 2011, 681 patients underwent OLT at our institution, and 54 of these patients underwent SAE for increased hepatic arterial resistance and PHP (n = 42) or refractory ascites/hepatic hydrothorax (n = 12). Patients undergoing SAE were compared to a control group matched by year of embolization, calculated Model for End‐Stage Liver Disease score, and liver weight. SAE resulted in improvements in hepatic artery resistive indices (0.92 ± 0.14 and 0.76 ± 0.10 before and after SAE, respectively; P < 0.001) and improved hepatic arterial blood flow (HAF; 15.6 ± 9.69 and 28.7 ± 14.83, respectively; P < 0.001). Calculated splenic volumes and spleen/liver volume ratios were correlated with patients requiring SAE versus matched controls (P = 0.002 and P = 0.001, respectively). Among the 54 patients undergoing SAE, there was 1 case of postsplenectomy syndrome. No abscesses, significant infections, or bleeding was noted. We thus conclude that SAE is a safe and effective technique able to improve HAF parameters in patients with elevated portal venous flow and its sequelae. Liver Transpl 21:435‐441, 2015. © 2015 AASLD.
Synthesis of Polyphosphazene Derivatives via Thiol‐ene Click Reactions in an Aqueous Medium
Authors: Qian Yuecheng , Huang Xiaojun , Xu Zhikang
Published: January 2015

A green route is reported for functionalizing polyphosphazene via the thiol‐ene click reaction in an aqueous medium. Poly[bis(allylamino)phosphazene] is used as the precursor polymer, which is easily dissolved in water containing 5% (v/v) phosphoric acid, but barely dissolved in other acidic aqueous solutions with the same pH value. Three thiol reagents, namely, 3‐mercapto‐1,2‐propanediol, 2‐mercaptoethoxy ethanol, and l‐cysteine, are then reacted with the precursor in the phosphoric acid aqueous solutions. 1H and 31P NMR analyses confirm that the allyl polyphosphazene can be quantitatively modified by the mercaptans without hydrolysis degradation during the synthesis and purification processes. Moreover, these polyphosphazenes exhibit higher regioselectivity than those functionalized in organic solvents. This method provides a facile route for the green synthesis of functional polyphosphazenes without organic solvents.

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Antisaccades and executive dysfunction in early drug‐naive Parkinson's disease: The discovery study
Authors: Antoniades Chrystalina A. , Demeyere Nele , Kennard Christopher , Humphreys Glyn W. , Hu Michele T.
Published: January 2015

Background

Cognitive impairment is well recognized in Parkinson's disease (PD), but when it begins to develop is unclear. The aim of this study was to identify early signs of cognitive impairment along with abnormalities in saccadic behavior in newly diagnosed unmedicated PD patients.

Methods

Nineteen drug‐naive PD patients and 20 controls were examined using a battery of tests, including an antisaccade task, phonemic and semantic verbal fluencies, and a switching and rule finding task.

Results

With simple tasks, no differences were found between the two groups. However, cognitive performance of the two groups diverged with more complex tasks, occurring independently of PD‐related motor impairment. Patients exhibited higher antisaccadic error rates and switch costs in the task switching test, and performed significantly worse in the rule finding task.

Conclusions

Certain cognitive domains and saccadic parameters are already significantly impoverished in newly diagnosed Parkinson's patients, even before the initiation of medication. © 2015 International Parkinson and Movement Disorder Society
On a logistic growth model with predation and a power‐type diffusion coefficient: I. Existence of solutions and extinction criteria
Authors: Pinheiro Susana
Published: January 2015

We consider a logistic growth model with a predation term and a stochastic perturbation yielding constant elasticity of variance. The resulting stochastic differential equation does not satisfy the standard assumptions for existence and uniqueness of solutions, namely, linear growth and the Lipschitz condition. Nevertheless, for any positive initial condition, we prove that a solution exists and is unique up to the first time it hits zero. Additionally, we provide alternative criteria for population extinction depending on the choice of parameters. More precisely, we provide criteria that guarantee the following: (i) population extinction with positive probability for a set of initial conditions with positive Lebesgue measure; (ii) exponentially fast population extinction with full probability for any positive initial condition; and (iii) population extinction in finite time with full probability for any positive initial condition. Copyright © 2015 John Wiley & Sons, Ltd.