bluuebunny/crossref_metadata_2025 huggingface dataset:
Innerstädtischer Tunnelbau – Herausforderungen des Spezialtiefbaus am Beispiel der S‐Bahnlinie S21 in Berlin
Authors: Quick Hubert , Meißner Simon , Hippe Simon , Fahlbusch Dietrich , Jaeger Arno
Published: June 2015

Das Projekt S21 stellt eines der wichtigsten infrastrukturellen Bauprojekte in Berlin da. Aufgrund der bereits vorhanden unter‐ und oberirdischen Bebauung nördlich des Bahnhofs und der geplanten städtebaulichen Entwicklung ergeben sich für die Teilbaugruben des Projekts S21 unterschiedlichste Randbedingungen. Insbesondere die Nähe zu den unterirdischen baulichen Anlagen der Fern‐ und U‐Bahn sowie die Nutzung der B96 und der Invalidenstraße während der Bauausführung stellen besondere ingenieurtechnische Herausforderungen dar. In diesem Bericht werden die daraus resultierenden Baugruben‐ und Abdichtungssysteme aufgezeigt und insbesondere die Herausforderungen des Tunnelbereichs mit Überbauung unter anderem durch das Hochhaus MK8 beleuchtet. Die vielfältigen technischen und formellen Anforderungen eines komplexen innerstädtischen Tunnelbauvorhabens werden aus Sicht der Prüfer für das Eisenbahn‐Bundesamt dargestellt.

Tunnelling in urban area – Challenging demands on the geotechnical construction using the example of the S21 railway project in Berlin. The S21 railway project is one of the most important infrastructural projects in Berlin. With existing structures above and below ground plus further urban developments in the pipeline, the result is highly diverse boundary conditions for the numerous excavations needed for this project. In particular, the proximity to underground structures for long‐distance and metro lines as well as the B96 trunk road and Invalidenstrasse, which have to remain open during construction, place high demands on the engineering. This report describes the ensuing shoring and waterproofing systems for the excavations and, in particular, the challenges posed by tunnels beneath buildings, including the high‐rise building MK8. The various technical and procedural requirements of a complex urban tunnelling project are presented from the perspective of the checking engineers appointed by Germany's Federal Railway Authority.
HDAC6 mediates HIV‐1 tat‐induced proinflammatory responses by regulating MAPK‐NF‐kappaB/AP‐1 pathways in astrocytes
Authors: Youn Gi Soo , Ju Sung Mi , Choi Soo Young , Park Jinseu
Published: June 2015

Human immunodeficiency virus (HIV)‐1 transactivator of transcription (Tat) is a viral protein that induces extensive neuroinflammation by up‐regulating proinflammatory mediators, including cytokines, chemokines, and adhesion molecules. Histone deacetylase 6 (HDAC6) has been implicated in the transcriptional regulation of inflammatory genes. In this study, we investigated the possible role of HDAC6 in HIV‐1 Tat‐induced up‐regulation of proinflammatory mediators in astrocytes. HIV‐1 Tat augmented HDAC6 expression, which was correlated with a reduction in acetylated α‐tubulin in CRT‐MG human astroglioma cells and primary mouse astrocytes. Knockdown and pharmacological inhibition of HDAC6 significantly inhibited HIV‐1 Tat‐induced expression of CCL2, CXCL8, and CXCL10 chemokines; adhesion molecules; and subsequent adhesion of monocytes to astrocytes. HDAC6 knockdown attenuated HIV‐1 Tat‐induced activation of mitogen‐activated protein kinase species, including ERK, JNK, and p38. Furthermore, HDAC6 knockdown suppressed HIV‐1 Tat‐induced activation of NF‐κB and AP‐1. Thus, HDAC6 is involved in HIV‐1 Tat‐induced expression of proinflammatory genes by regulating mitogen‐activated protein kinase‐NF‐κB/AP‐1 pathways and serves as a molecular target for HIV‐1 Tat‐mediated neuroinflammation GLIA 2015;63:1953–1965
Older people experiencing homelessness show marked impairment on tests of frontal lobe function
Authors: Rogoz Astrid , Burke David
Published: June 2015

Objective

Reported rates of mild and moderate cognitive impairment in older people experiencing homelessness range from 5–80%. The objective of this study was to determine the prevalence and characteristics of cognitive impairment in older people experiencing homelessness in the inner city of Sydney, Australia.

Method

Men and women experiencing homelessness aged 45 years and over in the inner city were screened for cognitive impairment. Participants who scored 26 or below on the mini‐mental state examination and/or were impaired on any one of the clock‐drawing test, the verbal fluency test and the trail‐making test, part B were then assessed with a semi‐structured interview, including the 21‐item Depression Anxiety Stress Scale and the 12‐item General Health Questionnaire.

Results

Screening of 144 men and 27 women aged between 45 years and 93 years identified cognitive impairment in 78%. Subsequently, high rates of mental and physical illness were identified, and 75% of subjects who were cognitively impaired performed poorly on frontal lobe tests. The trail‐making test, part B was the most sensitive measure of frontal function.

Conclusions

This study demonstrated that a large majority of older people experiencing homelessness, in the inner city of a high‐income country, showed impairment on tests of frontal lobe function, a finding that could have significant implications for any medical or psychosocial intervention. Copyright © 2015 John Wiley & Sons, Ltd.
Automated iterative reclustering framework for determining hierarchical functional networks in resting state fMRI
Authors: Shams Seyed‐Mohammad , Afshin‐Pour Babak , Soltanian‐Zadeh Hamid , Hossein‐Zadeh Gholam‐Ali , Strother Stephen C.
Published: June 2015

To spatially cluster resting state‐functional magnetic resonance imaging (rs‐fMRI) data into potential networks, there are only a few general approaches that determine the number of networks/clusters, despite a wide variety of techniques proposed for clustering. For individual subjects, extraction of a large number of spatially disjoint clusters results in multiple small networks that are spatio‐temporally homogeneous but irreproducible across subjects. Alternatively, extraction of a small number of clusters creates spatially large networks that are temporally heterogeneous but spatially reproducible across subjects. We propose a fully automatic, iterative reclustering framework in which a small number of spatially large, heterogeneous networks are initially extracted to maximize spatial reproducibility. Subsequently, the large networks are iteratively subdivided to create spatially reproducible subnetworks until the overall within‐network homogeneity does not increase substantially. The proposed approach discovers a rich network hierarchy in the brain while simultaneously optimizing spatial reproducibility of networks across subjects and individual network homogeneity. We also propose a novel metric to measure the connectivity of brain regions, and in a simulation study show that our connectivity metric and framework perform well in the face of low signal to noise and initial segmentation errors. Experimental results generated using real fMRI data show that the proposed metric improves stability of network clusters across subjects, and generates a meaningful pattern for spatially hierarchical structure of the brain. Hum Brain Mapp 36:3303–3322, 2015. © 2015 Wiley Periodicals, Inc.
Upregulation of CD200 is associated with regulatory T cell expansion and disease progression in multiple myeloma
Authors: Aref Salah , Azmy Emaad , El‐Gilany Abdel Hady
Published: June 2015

Immune dysfunction is an important feature of multiple myeloma (MM) leading to infections, enhancement of tumour growth and resistance to chemotherapy. The overexpression of CD200, expansion of T regulatory (Treg) cell and increased levels of immune modulatory cytokines like IL10, IL6 and transforming growth factor beta (TGFβ) were suggested to have a role in this context. The aim of this study was to assess CD200 expression, Treg percentage by flow cytometry and immune modulatory cytokines (IL10, IL6, TGFβ) by enzyme‐linked immunosorbent assay in MM patients at diagnosis. This study included 50 MM patients at diagnosis and 20 healthy controls. The positive CD200 expression was detected in 72% of MM patients. Among the CD200 positive group, 4/13 patients (30.8%) were classified as stage I, 18/23 (78.3%) were in stage II and 14/14 (100%) were in stage III; according to International scoring system. Treg percentage was significantly higher in stage III, followed by stage II then stage I (p < 0.01). Serum IL6, IL10 and TGFβ were significantly higher in MM patients as compared with controls (p < 0.01, p < 0.01, p < 0.05, respectively). The increased expression of CD200 and Treg percentages was associated with increased severity biomarkers (serum LDH and β2 microglobulin). The degree of CD200 expression was significantly positively correlated to Treg percentage (r = 0.565, p < 0.01). Analysis of the CD200 negative patients had a better progression free survival (p = 0.032) and overall survival (p = 0.04) as compared with those positive for CD200 expression. These findings illustrate a clear correlation between myeloma cell CD200 expression level and the frequency of immunosuppressive Treg cells. In conclusion, increased expression of CD200, expansion of suppressive Treg cells and elevation of cytokines might have a role in MM progression in this cohort of patients. Copyright © 2015 John Wiley & Sons, Ltd.
Resource availability hypothesis: Perceived financial and caloric status affect individuals' height preferences for potential partners
Authors: Sun Qingzhou , Lou Liandi , Lu Jingyi , Wang Xiaoming , Zhong Jun , Tan Xuyun , Li Yanxia , Liu Yongfang
Published: June 2015

Height is an important concern in human mate choices. Prior research indicates that people who live in areas with abundant resources differ from those who live in areas with scarce resources regarding height preferences. Based on a health‐maximizing principle, we propose a resource availability account for such differences. Compared with women's height preferences, men's height preferences are hypothesized to be more dependent on either financial or caloric resource availability. Specifically, taller females would be more preferred by males who are poor in resources than those who are rich in resources. Results from three studies supported these hypotheses. In Study 1, men from remote areas of China who had lower family income preferred taller women more than those from eastern China who had higher family income. In Study 2, men who were financially dissatisfied preferred taller women more than those who were financially satisfied. In Study 3, men with low caloric status preferred taller women more than men with high caloric status. In addition, women's height preferences in Studies 1, 2 and 3 were less determined by resource availability. These findings suggest that height preferences are changeable, depending on financial or caloric status.
A functional approach for research on cognitive control: Analysing cognitive control tasks and their effects in terms of operant conditioning
Authors: Liefooghe Baptist , De Houwer Jan
Published: June 2015

Cognitive control is an important mental ability that is examined using a multitude of cognitive control tasks and effects. The present paper presents the first steps in the elaboration of a functional approach, which aims to uncover the communalities and differences between different cognitive control tasks and their effects. Based on the idea that responses in cognitive control tasks qualify as operant behaviour, we propose to reinterpret cognitive control tasks in terms of operant contingencies and cognitive control effects as instances of moderated stimulus control. We illustrate how our approach can be used to uncover communalities between topographically different cognitive control tasks and can lead to novel questions about the processes underlying cognitive control.
The Role of Donors in Addressing Water Problems in Central Asia
Authors: Dukhovny Victor A. , Sokolov Vadim I. , Ziganshina Dinara R.
Published: June 2015

This paper examines the role of donors in addressing a complex set of water‐related challenges in Central Asia and draws some lessons with a view to improving the efficiency and effectiveness of development assistance in the region.

In the first years following independence, collaboration between the republics was strongly supported by development agencies under the leadership of the World Bank. This effort was marked by the establishment of the Interstate Fund of saving the Aral Sea (IFAS) and the Interstate Commission for Water Coordination (SIC ICWC) in Central Asia, preparation and signing of interstate agreements in 1993 and 1994, as well as development of a regional water strategy.

Despite significant donor contribution, the last several years have also demonstrated weaknesses in donors' activities in the region, which is especially discouraging, given the increased tensions over competing uses of water for hydropower upstream and irrigation and ecosystem demands downstream. Among the main weaknesses are:

lack of sound coordination;

avoidable involvement of international experts and ignorance of local capacity;

cut in support of regional water‐related projects.

Given the above, donors should rethink their development assistance policies in the region in order to encourage more active interaction between the countries for the benefit of people and the environment. Copyright © 2015 John Wiley & Sons, Ltd.
Role of Women in the Irrigated Agriculture Sector in the Fergana Valley: Findings of Field Surveys
Authors: Stulina Galina V.
Published: June 2015

Since 2008 the Scientific‐Information Centre of the Interstate Coordination Water Commission of Central Asia (SIC ICWC) has been actively attempting to draw greater attention to the role of women in water management and irrigated farming, taking into consideration the specificity of current demographic and ecological conditions in the rural areas. In the past and at present, women's labour is widely used in the irrigated agriculture sector, especially for cultivating crops on household plots where they perform heavy manual work, particularly during harvesting. At the same time the current stratification of the rural population and the significant migration of men outside Central Asian countries as temporary wage workers have additionally increased the burden on women's shoulders of having full responsibility for maintaining their families and for childcare.

In the process of its researches related to gender mainstreaming, the SIC ICWC uses direct working with women associated with enhancing their awareness and aimed at their involvement in the Women's Movement Network and special training for women engaged in the water management sector or irrigated farming.

This paper presents the findings of such researches conducted in the Fergana Valley in the framework of different pilot projects. Copyright © 2015 John Wiley & Sons, Ltd.
Differentiating Digital Writing Instruction
Authors: Martin Nicole M. , Lambert Claire
Published: June 2015

U.S. adolescents’ prior technology experiences and exposure to digital genres vary, but they will often write digital texts as they enter college and adulthood. We explored middle school students’ digital writing instructional experience in the context of a university‐based summer digital writing camp. The sixth‐ through eighth‐grade adolescents fell into three profile groups: digital passengers, digital navigators, and digital drivers. Each group displayed distinct patterns of prior technology experiences and exposure to digital genres, digital writing processes, and instructional needs. Their digital writing instructional experience suggests that prior technology experiences and exposure to digital genres influence the ways adolescents envision and enact digital writing. In the middle school classroom, teachers may need to address a range of instructional needs during digital writing instruction.
Investigating Criteria That Seventh Graders Use to Evaluate the Quality of Online Information
Authors: Coiro Julie , Coscarelli Carla , Maykel Cheryl , Forzani Elena
Published: June 2015

This article presents qualitative findings from a study that examined the types of criteria that middle school students use to evaluate the quality of online information and sources for a Web‐based research assignment. Open‐constructed responses from four critical evaluation items were compiled from diverse seventh graders in a representative, two‐state, stratified random sample (n = 773). Content analysis revealed that many students used a range of unacceptable or superficial criteria to determine the author of a website and whether that author is an expert, to state the author's point of view, and to provide reasoned evidence about the overall reliability of a website. Criteria and evidence patterns that students used for each of the critical evaluation tasks are shared, as well as implications for instruction.
Reducing Staphylococcus aureus growth on Ti alloy nanostructured surfaces through the addition of Sn
Authors: Verissimo Nathália C. , Geilich Benjamin M. , Oliveira Haroldo G. , Caram Rubens , Webster Thomas J.
Published: June 2015

β‐type Ti alloys containing Nb are exciting materials for numerous orthopedic and dental applications due to their exceptional mechanical properties. To improve their cytocompatibility properties (such as increasing bone growth and decreasing infection), the surfaces of such materials can be optimized by adding elements and/or nanotexturing through anodization. Because of the increasing prevalence of orthopedic implant infections, the objective of this in vitro study was to add Sn and create unique nanoscale surface features on β‐type Ti alloys. Nanotubes and nanofeatures on Ti‐35Nb and Ti‐35Nb‐4Sn alloys were created by anodization in a HF‐based electrolyte and then heat treated in a furnace to promote amorphous structures and phases such as anatase, a mixture of anatase‐rutile, and rutile. Samples were characterized by SEM, which indicated different morphologies dependent on the oxide content and method of modification. XPS experiments identified the oxide content which resulted in a phase transformation in the oxide layer formed onto Ti‐35Nb and Ti‐35Nb‐4Sn alloys. Most importantly, regardless of the resulting nanostructures (nanotubes or nanofeatures) and crystalline phase, this study showed for the first time that adding Sn to β‐type Ti alloys strongly decreased the adhesion of Staphylococcus aureus (S. aureus; a bacteria which commonly infects orthopedic implants leading to their failure). Thus, this study demonstrated that β‐type Ti alloys with Nb and Sn have great promise to improve numerous orthopedic applications where infection may be a concern. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3757–3763, 2015.
Dried blood spot analysis for therapeutic drug monitoring of pazopanib
Authors: de Wit Djoeke , den Hartigh Jan , Gelderblom Hans , Qian Yanwen , den Hollander Margret , Verheul Henk , Guchelaar Henk‐Jan , van Erp Nielka P.
Published: June 2015

Dried blood spot (DBS) sampling is potentially a more patient‐friendly and flexible alternative to venous sampling of pazopanib. This study determined the agreement between pazopanib DBS and plasma concentrations to facilitate implementation of pazopanib DBS sampling into clinical practice. Paired DBS and plasma samples were collected in 12 patients. Pazopanib plasma concentrations were calculated from DBS concentrations using the formula: plasma concentration = DBSconcentration/(1 ‐ hematocrit). Passing‐Bablok and Bland‐Altman analyses were used to determine the agreement between calculated and measured plasma concentrations. We predefined a clinical acceptance limit of 25% for the Bland‐Altman analysis. Passing‐Bablok analysis showed a small constant (intercept estimate, −8.53 [95%CI, −12.22 to −4.41]) and slightly proportional (slope estimate, 1.15 [95%CI, 1.04–1.24]) bias between calculated and measured concentrations. This bias was clinically nonrelevant, as shown by Bland‐Altman analysis; the mean ratio of calculated to measured concentrations was 0.94 (95%CI, 0.65–1.23). The clinical acceptance limits were well within these 95% limits of agreement. More specifically, 92.6% of the data points were within the predefined acceptance limits. Pazopanib plasma concentrations can be accurately calculated from DBS concentrations. Although validation of DBS cards prepared by patients themselves is required, these results show that DBS sampling can be used to monitor pazopanib therapy in clinical practice.
A novel method of analytically extracting model parameters for stacked transformers
Authors: Wang Jie , Liu Jun , Sun Lingling , Zhou Mingzhu
Published: June 2015

An accurate compact model for stacked transformers is proposed. The parasitics between the primary metal coils and the substrate are taken into consideration. The model parameters can be analytically extracted from open‐loaded S‐parameters measured from two‐port test structures. The modeling methodology renders excellent agreement with the data from both simulation and measurement over the frequency range of 0.1–20 GHz for a monolithic stacked transformer manufactured in 0.18‐µm Radio frequency Complementary Metal Oxide Semiconductor (RF CMOS) technology. Copyright © 2015 John Wiley & Sons, Ltd.
A facile high‐performance SERS substrate based on broadband near‐perfect optical absorption
Authors: Yan Zhendong , Du Wei , Tu Linlin , Gu Ping , Huang Zhong , Zhan Peng , Liu Fanxin , Wang Zhenlin
Published: June 2015

Plasmonic systems based on metal nanoparticles on a metal film with high optical absorption have generated great interests for surface‐enhanced Raman scattering (SERS). In this study, we prepare a broadband‐visible light absorber consisting Au nanotriangles on the surface of a continuous optically opaque gold film separated with a dielectric SiO2 layer, which is a typical metal‐insulator‐metal (MIM) system, and demonstrate it as an efficient SERS substrate. The MIM nanostructure, prepared using nanosphere lithography with a very large area, shows a broadband with absorption exceeding 90% in the wavelength regime of 630–920 nm. We observe an average SERS enhancement factor (EF) as large as 4.9 × 106 with a 22‐fold increase compared to a single layer of Au nanotriangles directly on a quartz substrate. A maximum SERS EF can be achieved by optimizing the thicknesses of the dielectric layer to control the optical absorption. Owing to the simple, productive, and inexpensive fabrication technique, our MIM nanostructure could be a potential candidate for SERS applications. Copyright © 2015 John Wiley & Sons, Ltd.
Physiological changes and sHSPs genes relative transcription in relation to the acquisition of seed germination during maturation of hybrid rice seed
Authors: Zhu Li‐Wei , Cao Dong‐Dong , Hu Qi‐Juan , Guan Ya‐Jing , Hu Wei‐Min , Nawaz Aamir , Hu Jin
Published: June 2015

BACKGROUND

During the production of early hybrid rice seed, the seeds dehydrated slowly and retained high moisture levels when rainy weather lasted for a couple of days, and the rice seeds easily occurred pre‐harvest sprouting (PHS) along with high temperature. Therefore it is necessary to harvest the seeds before the PHS occurred.

RESULTS

The seeds of hybrid rice (Oryza sativa L. subsp. indica) cv. Qianyou No1 that harvests from 19 to 28 days after pollination (DAP) all had high seed vigour. The seed moisture content at 10 DAP was 36.1%, and declined to 28.6% at 19 DAP; the contents of soluble sugar and total starch increased significantly with the development of seeds. The soluble protein content, the level of abscisic acid (ABA) and gibberellin (GA3), and ascorbate peroxidase (APX) activity continued to decrease from 10 DAP to 19 DAP. The seeds at 19 DAP had the highest peroxidase (POD) activity and lowest catalase (CAT) activity while the superoxide dismutase (SOD) activity had no significant difference among the different developing periods. The relative expressions of genes 64S Hsp18.0 and Os03g0267200 transcripts increased significantly from 10 to 19 DAP, and then decreased. However, no significant change was recorded in soluble protein, sugar and GA3 after 16 DAP, and they all significantly correlated with seed viability and vigour during the process of seed maturity.

CONCLUSION

The seeds of hybrid rice Qianyou No1 had a higher viability and vigour when harvested from 19 DAP to 28 DAP, the transcription levels of 64S Hsp18.0 and Os03g0267200 increased significantly from 10 DAP to 19 DAP and the highest value was recorded at 19 DAP. The seeds could be harvested as early as 19 DAP without negative influence on seed vigour and viability. © 2015 Society of Chemical Industry
Instructive Conductive 3D Silk Foam‐Based Bone Tissue Scaffolds Enable Electrical Stimulation of Stem Cells for Enhanced Osteogenic Differentiation
Authors: Hardy John G. , Geissler Sydney A. , Aguilar David , Villancio‐Wolter Maria K. , Mouser David J. , Sukhavasi Rushi C. , Cornelison R. Chase , Tien Lee W. , Preda R. Carmen , Hayden Rebecca S. , Chow Jacqueline K. , Nguy Lindsey , Kaplan David L. , Schmidt Christine E.
Published: June 2015

Stimuli‐responsive materials enabling the behavior of the cells that reside within them to be controlled are vital for the development of instructive tissue scaffolds for tissue engineering. Herein, we describe the preparation of conductive silk foam‐based bone tissue scaffolds that enable the electrical stimulation of human mesenchymal stem cells (HMSCs) to enhance their differentiation toward osteogenic outcomes.
Small perturbations of an indefinite elliptic equation
Authors: Ramos Quoirin Humberto
Published: June 2015

We investigate a perturbed semilinear indefinite elliptic equation and show that the results known for the unperturbed equation still hold if the perturbation is sufficiently small. To this end, we use a continuity argument that allows us to establish the existence of two positive solutions even in the case where the strong maximum principle does not apply.
Formation of Hexagonally Packed Hollow Hoops and Morphology Transition in RAFT Ethanol Dispersion Polymerization
Authors: Zhang Wen‐Jian , Hong Chun‐Yan , Pan Cai‐Yuan
Published: June 2015

Similar to the traditional self‐assembly strategy, polymerization induced self‐assembly and reorganization (PISR) can produce a myriad of polymeric morphologies through morphology transitions. Besides the chain length ratio (R) of the hydrophobic to the hydrophilic blocks, the chain mobility in the intermediate nano‐objects, which is a requisite for morphology transition, is a determining factor in the formation of the final morphology. Although various morphologies have been fabricated, hexagonally packed hollow hoops (HHHs) with highly ordered internal structure have not, to the best of our knowledge, been prepared by PISR. In this article, the fabrication of HHHs through morphology transition from large compound vesicles to HHHs is reported. HHHs with highly regular internal structure may have significance in theoretical research and practical applications of nanomaterials.

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Photoinduced Acrylate Polymerization: Unexpected Reduction in Chain Branching
Authors: Wenn Benjamin , Reekmans Gunter , Adriaensens Peter , Junkers Tanja
Published: June 2015

The branching stemming from midchain radical formation in n‐butyl acrylate polymerization is investigated via melt‐state 13C NMR measurements. The dependence of the degree of branching (DB) on the monomer conversion of the system is examined for photoinduced polymerizations, revealing a steady increase in branching with conversion. For polymerization at moderate light intensities, an increase in branching from 0.03% to 0.37% is observed for polymerizations at 60 °C, which is fivefold below the level of branching observed in thermally initiated poly­merizations under otherwise identical reaction conditions. The reason for this overall reduction in branching remains momentarily unclear; yet, a strong dependence of branching on light intensity is observed. While polymerization under a 1 W LED lamp results at almost full monomer conversion in branching degrees of 0.22%, polymerization under a 400 W lamp yields 1.81% of chain branches.

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Comparison of the substituent effects on the 13C NMR with the 1H NMR chemical shifts of CHN in substituted benzylideneanilines
Authors: Wang Linyan , Cao Chaotun , Cao Chenzhong
Published: June 2015

Fifty‐two samples of substituted benzylideneanilines XPhCHNPhYs (XBAYs) were synthesized, and their NMR spectra were determined in this paper. Together with the NMR data of other 77 samples of XBAYs quoted from literatures, the 1H NMR chemical shifts (δH(CHN)) and 13C NMR chemical shifts (δC(CHN)) of the CHN bridging group were investigated for total of 129 samples of XBAYs. The result shows that the δH(CHN) and δC(CHN) have no distinctive linear relationship, which is contrary to the theoretical thought that declared the δH(CHN) values would increase as the δC(CHN) values increase. With the in‐depth analysis, we found that the effects of σF and σR of X/Y group on the δH(CHN) and the δC(CHN) are opposite; the effects of the substituent specific cross‐interaction effect between X and Y (Δσ2) on the δH(CHN) and the δC(CHN) are different; the contributions of parameters in the regression equations of the δH(CHN) and the δC(CHN) [Eqns and 7), respectively] also have an obvious difference. Copyright © 2015 John Wiley & Sons, Ltd.
Recurrent DICER1 hotspot mutations in endometrial tumours and their impact on microRNA biogenesis
Authors: Chen Jiamin , Wang Yemin , McMonechy Melissa K , Anglesio Michael S , Yang Winnie , Senz Janine , Maines‐Bandiera Sarah , Rosner Jamie , Trigo‐Gonzalez Genny , Grace Cheng SW , Kim Jaeyeon , Matzuk Martin M , Morin Gregg B , Huntsman David G
Published: June 2015

DICER1 plays a critical role in microRNA (miRNA) biogenesis. Recurrent somatic 'hotspot' mutations at the four metal‐binding sites within the RNase IIIb domain of DICER1 were identified in ovarian sex cord‐stromal tumours and have since been described in other paediatric tumours. In this study, we screened the RNase IIIb domain of DICER1 in 290 endometrial tumours and identified six cases with hotspot mutations, including two cases affected by an atypical G1809R mutation directly adjacent to a metal‐binding site. Using Illumina and Sanger targeted resequencing, we observed and validated biallelic DICER1 mutations in several cases with hotspot mutations. Through in vitro DICER1 cleavage assays, small RNA deep sequencing and real‐time PCR, we demonstrated that mutations adding a positively charged side chain to residue 1809 have similar detrimental effects on 5p miRNA production to mutations at the metal‐binding sites. As expected, 5p miRNAs were globally reduced in tumours and cell lines with hotspot mutations. Pathway analysis of gene expression profiles indicated that genes de‐repressed due to loss of 5p miRNAs are strongly associated with pathways regulating the cell cycle. Using a Dicer1‐null mouse cell line model, we found that expression of DICER1 hotspot mutants promoted cell proliferation, whereas wild‐type (WT) DICER1 inhibited cell proliferation. Furthermore, targets of let‐7 family miRNAs are enriched among the up‐regulated genes, suggesting that loss of let‐7 may be impacting downstream pathways. Our results reveal that DICER1 hotspot mutations are implicated in common malignancies and may constitute a unique oncogenic pathway. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Diagnosis, Management, and Prevention in Critically Ill Patients
Authors: Dixit Deepali , Bridgeman Mary Barna , Andrews Liza Barbarello , Narayanan Navaneeth , Radbel Jared , Parikh Amay , Sunderram Jag
Published: June 2015

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate‐to‐severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid‐acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU.
Severity of personality disorders and domains of general personality dysfunction related to attachment
Authors: Hengartner Michael P. , von Wyl Agnes , Tanis Thachell , Halmi Winter , Galynker Igor , Cohen Lisa J.
Published: June 2015

This is the first study to link attachment to both severity of total DSM‐IV personality disorder (PD) traits and domains of general personality dysfunction, using a sample of 72 inpatients from New York City. We assessed a measure of global PD severity and the core domains of personality functioning using the severity indices of personality problems (SIPP‐118). Attachment was measured with the experience in close relationships‐revised (ECR‐R) and the relationship style questionnaire (RSQ). Global PD severity correlated most strongly with attachment anxiety (r = 0.65). Regression of the SIPP‐118 domains on attachment produced models that accounted for a substantial proportion of variance in those scales (R2 ranging from 28.2 to 54.2%). SIPP‐118 relational capacities were the strongest predictor of ECR‐R avoidance (β = −0.88) and anxiety (β = −0.58), as well as RSQ secure (β = 0.53) and fearful (β = −0.65). In conclusion, insecure attachment strongly related to the severity of global PD traits and specifically to relational capacities, which are a higher‐order domain of general personality dysfunction. These findings provide further evidence that interpersonal problems are at the core of PDs and that attachment could constitute an important mediator of the social dysfunction in persons with personality pathology. Copyright © 2015 John Wiley & Sons, Ltd.
Quantitative proteomics reveals differential regulation of protein expression in recipient myocardium after trilineage cardiovascular cell transplantation
Authors: Chang Ying‐Hua , Ye Lei , Cai Wenxuan , Lee Yoonkyu , Guner Huseyin , Lee Youngsook , Kamp Timothy J. , Zhang Jianyi , Ge Ying
Published: June 2015

Intramyocardial transplantation of cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) derived from human induced pluripotent stem cells (hiPSCs) has beneficial effects on the post‐infarction heart. However, the mechanisms underlying the functional improvements remain undefined. We employed large‐scale label‐free quantitative proteomics to identify proteins that were differentially regulated following cellular transplantation in a swine model of myocardial infarction (MI). We identified 22 proteins that were significantly up‐regulated after trilineage cell transplantation compared to both MI and Sham groups. Among them, 12 proteins, including adenylyl cyclase‐associated protein 1 and tropomodulin‐1, are associated with positive regulation of muscular contraction whereas 11 proteins, such as desmoplakin and zyxin, are involved in embryonic and muscular development and regeneration. Moreover, we identified 21 proteins up‐regulated and another 21 down‐regulated in MI, but reversed after trilineage cell transplantation. Proteins up‐regulated after MI but reversed by transplantation are related to fibrosis and apoptosis. Conversely, proteins down‐regulated in MI but restored after cell therapy are regulators of protein nitrosylation. Our results show that the functionally beneficial effects of trilineage cell therapy are accompanied by differential regulation of protein expression in the recipient myocardium, which may contribute to the improved cardiac function.
Proteomics, biomarkers, and HIV‐1: A current perspective
Authors: Donnelly Maire Rose , Ciborowski Pawel
Published: June 2015

Despite more than three decades of extensive research, HIV‐1 infection although well controlled with cART, remains incurable. Multifactorial complexity of the viral life‐cycle poses great challenges in understanding molecular mechanisms underlying this infection and the development of biomarkers, which we hope will lead us to its eradication. For a more in‐depth understanding of how the virus interacts with host target cells, T cells and macrophages, proteomic profiling techniques that offer strategies to investigate the proteome in its entirety were employed. Here, we review proteomic studies related to HIV‐1 infection and discuss perspectives and limitations of proteomic and systems biology approaches in future studies.
Electron‐capture dissociation and ion mobility mass spectrometry for characterization of the hemoglobin protein assembly
Authors: Cui Weidong , Zhang Hao , Blankenship Robert E. , Gross Michael L.
Published: June 2015

Native spray has the potential to probe biophysical properties of protein assemblies. Here we report an investigation using both ECD top‐down sequencing with an FTICR mass spectrometer and ion mobility (IM) measurements on a Q‐TOF to investigate the collisionally induced unfolding of a native‐like heterogeneous tetrameric assembly, human hemoglobin (hHb), in the gas phase. To our knowledge, this is the first report combining ECD and ion‐mobility data on the same target protein assembly to delineate the effects of collisional activation on both assembly size and the extent and location of fragmentation. Although the collision‐induced unfolding of the hemoglobin assembly is clearly seen by both IMMS and ECD, the latter delineates the regions that increasingly unfold as the collision energy is increased. The results are consistent with previous outcomes for homogeneous protein assemblies and reinforce our interpretation that activation opens the structure of the protein assembly from the flexible regions to make available ECD fragmentation, without dissociating the component proteins.
EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles
Authors: Fan Yao , Tan Kemin , Chhor Gekleng , Butler Emily K. , Jedrzejczak Robert P. , Missiakas Dominique , Joachimiak Andrzej
Published: June 2015

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (∼10 kDa), comprised of a helix‐loop‐helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for two alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero‐oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.
Structural genomics for drug design against the pathogen Coxiella burnetii
Authors: Franklin Matthew C. , Cheung Jonah , Rudolph Michael J. , Burshteyn Fiana , Cassidy Michael , Gary Ebony , Hillerich Brandan , Yao Zhong‐Ke , Carlier Paul R. , Totrov Maxim , Love James D.
Published: June 2015

Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high‐throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure‐based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25‐fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria. Proteins 2015; 83:2124–2136. © 2015 Wiley Periodicals, Inc.
Exploring mechanisms of resistance to dimethachlone in Sclerotinia sclerotiorum
Authors: Firoz Md. Jahangir , Xiao Xiang , Zhu Fu‐Xing , Fu Yan‐Ping , Jiang Dao‐Hong , Schnabel Guido , Luo Chao‐Xi
Published: June 2015

BACKGROUND

The dicarboximide fungicide dimethachlone has been widely used in China for more than 12 years to control the Sclerotinia stem rot caused by Sclerotinia sclerotiorum disease. First signs of resistance in the field are reported at low frequency. In this study, four resistant isolate/mutants were used to explore still unknown mechanisms leading to dimethachlone resistance.

RESULTS

The resistant isolate/mutants had significantly higher EC50 values compared with the sensitive control isolates. Cross‐resistance was confirmed between dimethachlone and procymidone, iprodione and fludioxonil. The resistant isolate/mutants revealed a decreased mycelial growth rate, were less pathogenic on leaves of oilseed rape, were more sensitive to osmotic pressure and oxidative stress and released more electrolytes compared with the sensitive isolates. Only in one lab mutant did we find a point mutation (V238A) in the SsOs1 gene of the high‐osmolarity glycerol (HOG) signalling pathway. The expression of this gene was lost in the field resistant isolate HN456‐1‐JBJ and decreased in mycelium that was subjected to either high osmotic pressure or dimethachlone; however, another key gene in the HOG pathway, SsHog1, could be induced in the resistant isolate and mutants with NaCl treatment.

CONCLUSION

This study demonstrates that resistance to dicarboximide fungicide dimethachlone in S. sclerotiorum is emerging in China. Several fitness parameters, including mycelial growth rate, sclerotia formed in vitro, aggressiveness on leaves and osmotic and H2O2 sensitivity, indicate that the resistant strains may not effectively compete with sensitive isolates in the field in the absence of selection pressure. Lost expression or the V238A point mutation in the SsOs1 gene may confer resistance to dicarboximide fungicide dimethachlone in S. sclerotiorum, but this study illustrates that other, yet unknown mechanisms also exist. © 2015 Society of Chemical Industry
Opportunity for integration lost in creation of new roles
Authors: Baines Darrin
Published: June 2015

Efforts to reorganise pharmacy to encourage the provision of medicines management and patient care created new roles for pharmacists but they remained outside mainstream primary care.
Collective Remittances and Development in Rural Mexico: a View from Chicago's Mexican Hometown Associations
Authors: Bada Xóchitl
Published: June 2015

This paper addresses the changing agendas of US‐based hometown associations (HTAs) in rural Mexico and the impact that these changes have on local government decisions to finance community development. The evidence that is offered in this paper confirms that local governments at the subnational state, municipal, and village levels are interested in maintaining the economic attachments of emigrant populations. These governments have created innovative state–society partnerships to reduce conflict with HTAs, maintain loyalties, and preserve the flow of remittances. Thus, one of the objectives of local governments is to sustain migrant collective remittance efforts in those sending regions that already have a critical mass of US‐based HTAs that demand government funds for development. The inclusion of organised migrant voices in community development debates has the potential to increase transnational democratic participation. However, when the allocation of public funds is based on an approach that privileges diaspora‐driven demands, this generates inequalities between international migrants and stay‐at‐home communities because it forces local sending communities to find HTAs across borders to solve infrastructure needs. As new hierarchies of place‐based citizen participation become more prevalent, the voices of stay‐at‐home communities risk being ignored by local government officials. Copyright © 2015 John Wiley & Sons, Ltd.
From flat graphene to bulk carbon nanostructures
Authors: Baimova Julia A. , Rysaeva Leysan Kh. , Liu Bo , Dmitriev Sergey V. , Zhou Kun
Published: June 2015

Studies on thin sheets and related materials are of high importance nowadays because of their great potential in various applications. The latest success in the production of graphene opens many new opportunities for the construction of novel three‐dimensional carbon nanostructures that exhibit good mechanical and electronic properties together with high specific surface area. Such novel nanostructures based on graphene sheets are very promising for energy storage devices, supercapacitors and stretchable electronics, to name a few. In this work, the mechanical responses of new bulk carbon nanostructures under hydrostatic pressure or shear strain are investigated, respectively, via molecular dynamics simulations. The size effect of the structural units on the strength of crumpled graphene is analyzed. The studied bulk carbon nanostructures are found to be extremely stable against diamondization. It is shown that the structures and mechanical properties of bulk carbon nanomaterials can be altered by severe plastic shear deformation. Shear strain leads to the formation of stable structures, even at relatively small strain.
New examples of three‐dimensional dilational materials
Authors: Milton Graeme Walter
Published: June 2015

Two‐dimensional dilational materials, for which the only easy mode of deformation is dilation are reviewed and connections are drawn between models previously proposed in the literature. Some models, which appear to be dilational materials, but which in fact are not, are also discussed. Finally, four new examples of three‐dimensional dilational materials are given.