bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid response of atmospheric BC to anthropogenic sources: observational evidence
Authors: Kompalli Sobhan Kumar , Moorthy K. Krishna , Babu S. Suresh
Published: December 2013

The response of Black Carbon (BC) concentrations to a near cut‐off of vehicular and industrial emissions favoured by a regional ‘strike call’ by organized trade unions, that brought to a halt of all industrial activities and commercial road traffic for 2 days is presented. In a dramatic, spectacular response to the seizure of emissions, BC concentrations dropped rapidly to ∼22% of the average concentrations that prevailed before the strike depicting the rapidity with which the concentrations deplete and the ‘rather slow’ replenishment as the emissions restart. These observations support the argument that controlling BC emissions yields quick results.
Prenatal effects of maternal consumption of polyphenol‐rich foods in late pregnancy upon fetal ductus arteriosus
Authors: Zielinsky Paulo , Busato Stefano
Published: December 2013

Fetal circulation has characteristic features, being morphologically and functionally different from extrauterine circulation. The ductus arteriosus plays a fundamental role in directing the blood flow to fetal inferior body parts. Basically, the ductus arteriosus directs 80–85% of the right ventricular output arising from the superior vena cava, coronary sinus, and a small part from the inferior vena cava to descending aorta. Its histological structure is made up predominantly by a thick muscular layer, differently from the aorta and the pulmonary artery, which increases with gestational age. The fibers have a circumferential orientation, especially at the external layers, facilitating and making effective ductal constriction. These factors may generate lumen alterations which may cause fetal and neonatal complications, such as heart failure, hydrops, neonatal pulmonary hypertension, and even death. Classically, maternal administration of indomethacin and/or other antiinflammatory drugs interfere in prostaglandins metabolism, causing ductal constriction. However, many cases of fetal ductal constriction, as well as of persistent neonatal pulmonary artery hypertension, remain without an established etiology, being referred as “idiopathic.” In recent years, a growing body of evidence has shown that herbs, fruits, nuts, and a wide diversity of substances commonly used in daily diets have definitive effects upon the metabolic pathway of inflammation, with consequent inhibition of prostaglandins synthesis. This antiinflammatory action, especially of polyphenols, when ingested during the third trimester of pregnancy, may influence the dynamics of fetal ductus arteriosus flow. The goal of this review is to present these new observations and findings, which may influence dietary orientation during pregnancy. Birth Defects Research (Part C) 99:256–274, 2013. © 2013 Wiley Periodicals, Inc.
Flavonoids, derived from traditional chinese medicines, show roles in the differentiation of neurons: Possible targets in developing health food products
Authors: Xu Sherry L. , Zhu Kevin Y. , Bi Cathy W.C. , Yan Lu , Men Simon W.X. , Dong Tina T.X. , Tsim Karl W.K.
Published: December 2013

Flavonoids, a family of phenolic compounds, are distributed in a variety of fruits, vegetables, tea, and wine. More importantly, many flavonoids are served as the active ingredients in traditional Chinese herbal medicines, which in general do not have side effects. Several lines of evidence support that flavonoids have impacts on many aspects of human health, including anti‐tumor, anti‐oxidation, and anti‐inflammation. Recently, there is significant attention focused on the neuronal beneficial effects of flavonoids, including the promotion of nervous system development, neuroprotection against neurotoxin stress, as well as the promotion of memory, learning, and cognitive functions. Here, the activities of flavonoids on the development of nervous system are being summarized and discussed. The flavonoids from diverse herbal medicines have significant effects in different developmental stages of nervous systems, including neuronal stem cell differentiation, neurite outgrowth, and neuronal plasticity. These findings imply that flavonoids are potential candidates for the development of health supplements in preventing birth defects and neuronal diseases. Birth Defects Research (Part C) 99:292–299, 2013. © 2013 Wiley Periodicals, Inc.
Fully semiparametric Bayesian approach for modeling survival data with cure fraction
Authors: Demarqui Fabio N. , Dey Dipak K. , Loschi Rosangela H. , Colosimo Enrico A.
Published: December 2013

In this paper, we consider a piecewise exponential model (PEM) with random time grid to develop a full semiparametric Bayesian cure rate model. An elegant mechanism enjoying several attractive features for modeling the randomness of the time grid of the PEM is assumed. To model the prior behavior of the failure rates of the PEM we assume a hierarchical modeling approach that allows us to control the degree of parametricity in the right tail of the survival curve. Properties of the proposed model are discussed in detail. In particular, we investigate the impact of assuming a random time grid for the PEM on the estimation of the cure fraction. We further develop an efficient collapsed Gibbs sampler algorithm for carrying out posterior computation. A Bayesian diagnostic method for assessing goodness of fit and performing model comparisons is briefly discussed. Finally, we illustrate the usefulness of the new methodology with the analysis of a melanoma clinical trial that has been discussed in the literature.
MiR‐92a mediates AZD6244 induced apoptosis and G1‐phase arrest of lymphoma cells by targeting Bim
Authors: Lv Xiao‐Bin , Zhang Xing , Deng Lan , Jiang Ling , Meng Wei , Lu Zhigang , Wang Xiuju
Published: December 2013

AZD6244, an ATP‐uncompetitive inhibitor of mitogen‐activated protein kinase 1/2 (MEK1/2), has shown activity in several malignant tumours. However, whether AZD6244 has a function in lymphoma cells is not known. We report that AZD6244 treatment represses the growth of Raji and MOLT4 cells by inducing apoptosis and G1‐phase arrest. Using miRNAs array and quantitative RT‐PCR, miR‐92a was downregulated byAZD6244 treatment through the ERK1/2‐AP1 signalling pathway. Overexpression of miR‐92a abrogated AZD6244‐induced apoptosis and G1‐phase arrest, indicating that it is involved in the cytotoxicity of AZD6244 in lymphoma cells. A luciferase reporter assay showed that miR‐92a directly targetsthe 3′‐UTRs of Bim. Overexpression of miR‐92a mimics downregulated Bim mRNA and protein expression level, indicating that miR‐92a negatively regulates its expression at both levels. Silencing Bim decreases AZD6244‐induced apoptosis and G1‐phase arrest, suggesting that Bim contributes to the growth arrest. Thus, miR‐92a mediates AZD6244‐induced cytotoxicity of lymphoma cells by targeting Bim. Downregulation of miR‐92a by AZD6244 is mediated by the ERK1/2‐AP1 signalling pathway.
Synthesis and Theoretical Investigation of a 1,8‐Bis(bis(diisopropylamino)cyclopropeniminyl)naphthalene Proton Sponge Derivative
Authors: Belding Lee , Dudding Travis
Published: December 2013

We report herein the synthesis and characterization of a new proton sponge derivative, 1,8‐bis(bis(diisopropylamino)cyclopropeniminyl)naphthalene 4 (DACN), as well as its bis‐protonated counterpart 6. A crystal structure of 6 is presented, along with variable temperature 1H NMR data on the BF4− salt (6⋅BF4). DFT calculations were performed to investigate the structure of the monoprotonated species 7 and to gain insight into the structural and electronic nature of all three species. The proton affinity (PA) of 4, calculated at the B3LYP/6‐311G++(d,p)//B3LYP/6‐31G(d,p) level, taking into account thermal corrections from the B3LYP/6‐31G(d,p) method, was 282.3 kcal mol−1, while its pKa was estimated at 27.0. NICS calculations were performed to examine the changes in aromaticity within these systems upon each successive protonation. Lastly, homodesmotic reaction schemes were used in order to estimate the factors contributing to the strong PA predicted for 4.
Streptococcal Hyaluronate Lyase Reveals the Presence of a Structurally Significant CH⋅⋅⋅O Hydrogen Bond
Authors: Moore Kevin B. , Migues Angela N. , Schaefer Henry F. , Vergenz Robert A.
Published: December 2013

Carbon‐donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5–1.0 kcal mol−1) that are difficult to detect, and thus their roles in the structure and functionality of chemical systems often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second‐order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing αHelix 3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of αHelix 3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of αHelix 3 observed from experiment. A strongly correlated motion between αHelix 3 and αHelices 2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just αHelix 3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena.
Cyclization‐Induced Turn‐On Fluorescence System Applicable to Dicarboxylate Sensing
Authors: Noguchi Takao , Roy Bappaditya , Yoshihara Daisuke , Tsuchiya Youichi , Yamamoto Tatsuhiro , Shinkai Seiji
Published: December 2013

A novel tetraphenylethene‐based fluorescence (FL) chemosensor exhibits nonlinear turn‐on FL switching though cooperative binding of L‐tartarate, where its convergent binding to form cyclic substructures is responsible for the FL increase. This binding scheme achieves selective detection of dicarboxylates over monocarboxylates, thus is potentially applicable to the preliminary screening for metabolic disorders.
Carbocations as Lewis Acid Catalysts in Diels–Alder and Michael Addition Reactions
Authors: Bah Juho , Franzén Johan
Published: December 2013

In general, Lewis acid catalysts are metal‐based compounds that owe their reactivity to a low‐lying empty orbital. However, one potential Lewis acid that has received negligible attention as a catalyst is the carbocation. We have demonstrated the potential of the carbocation as a highly powerful Lewis acid catalyst for organic reactions. The stable and easily available triphenylmethyl (trityl) cation was found to be a highly efficient catalyst for the Diels–Alder reaction for a range of substrates. Catalyst loadings as low as 500 ppm, excellent yields, and good endo/exo selectivities were achieved. Furthermore, by changing the electronic properties of the substituents on the tritylium ion, the Lewis acidity of the catalyst could be tuned to control the outcome of the reaction. The ability of this carbocation as a Lewis acid catalyst was also further extended to the Michael reaction.
Annual Report to the Nation on the status of cancer, 1975‐2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer
Authors: Edwards Brenda K. , Noone Anne‐Michelle , Mariotto Angela B. , Simard Edgar P. , Boscoe Francis P. , Henley S. Jane , Jemal Ahmedin , Cho Hyunsoon , Anderson Robert N. , Kohler Betsy A. , Eheman Christie R. , Ward Elizabeth M.
Published: December 2013

BACKGROUND

The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level.

METHODS

Data on cancer incidence were obtained from the NCI, the CDC, and the NAACCR; and data on mortality were obtained from the CDC. Long‐term (1975/1992‐2010) and short‐term (2001‐2010) trends in age‐adjusted incidence and death rates for all cancers combined and for the leading cancers among men and women were examined by joinpoint analysis. Through linkage with Medicare claims, the prevalence of comorbidity among cancer patients who were diagnosed between 1992 through 2005 residing in 11 Surveillance, Epidemiology, and End Results (SEER) areas were estimated and compared with the prevalence in a 5% random sample of cancer‐free Medicare beneficiaries. Among cancer patients, survival and the probabilities of dying of their cancer and of other causes by comorbidity level, age, and stage were calculated.

RESULTS

Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2001 through 2010. Overall incidence rates decreased in men and stabilized in women. The prevalence of comorbidity was similar among cancer‐free Medicare beneficiaries (31.8%), breast cancer patients (32.2%), and prostate cancer patients (30.5%); highest among lung cancer patients (52.9%); and intermediate among colorectal cancer patients (40.7%). Among all cancer patients and especially for patients diagnosed with local and regional disease, age and comorbidity level were important influences on the probability of dying of other causes and, consequently, on overall survival. For patients diagnosed with distant disease, the probability of dying of cancer was much higher than the probability of dying of other causes, and age and comorbidity had a smaller effect on overall survival.

CONCLUSIONS

Cancer death rates in the United States continue to decline. Estimates of survival that include the probability of dying of cancer and other causes stratified by comorbidity level, age, and stage can provide important information to facilitate treatment decisions. Cancer 2014;120:1290–1314. © 2013 American Cancer Society.
Micrometer‐Scale Mixing with Pickering Emulsions: Biphasic Reactions without Stirring
Authors: Zhang Wenjuan , Fu Luman , Yang Hengquan
Published: December 2013

A general strategy that avoids stirring for organic/aqueous reactions involving solid catalysts is reported. The strategy involves converting a conventional biphasic system into a Pickering emulsion phase with micrometer‐scale droplets ensuring good mixing. In test reactions, nitrotoluene reduction and epoxidation of allylic alcohols, the reaction efficiency is comparable to conventional stirrer‐driven biphasic catalysis reaction systems. Short diffusion distances, arising from the compartmentalization of densely packed droplets, play an important role in boosting the reaction efficiency.
Phragmites distribution relative to progressive water level decline in Lake Koronia, Greece
Authors: Crisman Thomas L. , Alexandridis Thomas K. , Zalidis George C. , Takavakoglou Vasileios
Published: December 2013

Lake Koronia is a hypertrophic Ramsar site in northern Greece. Water level dropped progressively from approximately 6 m in the mid‐1980s to 0·8 m in 2001 associated with over extraction of groundwater for agriculture, and the open water area has decreased from 4620 to 2930 ha, respectively. The resulting annual water level loss of 0·25–0·30 m year−1 was accompanied by expansion of Phragmites australis from a littoral fringe to dominance of exposed lake bottom areas from 97 ha in 1977 to 785 ha in 2005. The aim of this work was to apply an ecohydrological approach using remote sensing and geographic information system (GIS) to examine the movement of Phragmites relative to the water level retreat and to basin morphometry. Aerial expansion of Phragmites averaged 11–32 ha year−1 during the period of progressive water level decline but increased to 38–116 ha year−1 during a brief period of water level increase (2001–2003) as the plant colonized reflooded portions of the basin. The total area of Phragmites expanded 29% per annum during 1977–2005. Landward and lakeward margins of the Phragmites area followed water level retreat, moving 55 and 129 m, respectively, during the long period of progressive water level decline. Aerial movements of Phragmites in Lake Koronia are some of the highest reported in the literature. Mean water level within the Phragmites bed varied from 0·5 to 2·0 m during the period covered by this study. Very minor changes in basin slope, however, affected plant colonization rates, as evidenced by 200–250 ha/0·5 m water level drop at 0·18% basin slope to 360–1360 ha/0·5 m water level drop at 0·029% slope. The techniques applied to Lake Koronia for reconstructing past lake levels and associated distributions of Phragmites have broad application for understanding the dynamics of Phragmites elsewhere and anticipating periods of rapid plant expansion related to subtle changes in basin morphology. This study is useful for managing Phragmites populations in areas where efforts are being made to re‐establish populations as well as where elimination of invasive populations is sought. Copyright © 2013 John Wiley & Sons, Ltd.
The VH repertoire and clonal diversification of B cells in inflammatory myopathies
Authors: McIntyre Donna , Zuckerman Neta S. , Field Max , Mehr Ramit , Stott David I.
Published: December 2013

The contribution of antigen‐driven B‐cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin VH gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig VH gene repertoires of muscle‐infiltrating B cells deviate from the normal VH gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle‐infiltrating B cells and evidence for a chronic B‐cell response within the inflamed muscle. We conclude that muscle‐infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen‐driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders.
Parametric time‐domain identification of multiple‐input systems using decoupled output signals
Authors: Li Jian , Ruiz‐Sandoval Manuel , Spencer Billie F. , Elnashai Amr S.
Published: December 2013

Civil engineering structures are often subjected to multidirectional actions such as earthquake ground motion, which lead to complex structural responses. The contributions from the latter multidirectional actions to the response are highly coupled, leading to a MIMO system identification problem. Compared with single‐input, multiple‐output (SIMO) system identification, MIMO problems are more computationally complex and error prone. In this paper, a new system identification strategy is proposed for civil engineering structures with multiple inputs that induce strong coupling in the response. The proposed solution comprises converting the MIMO problem into separate SIMO problems, decoupling the outputs by extracting the contribution from the respective input signals to the outputs. To this end, a QR factorization‐based decoupling method is employed, and its performance is examined. Three factors, which affect the accuracy of the decoupling result, including memory length, input correlation, and system damping, are investigated. Additionally, a system identification method that combines the autoregressive model with exogenous input (ARX) and the Eigensystem Realization Algorithm (ERA) is proposed. The associated extended modal amplitude coherence and modal phase collinearity are used to delineate the structural and noise modes in the fitted ARX model. The efficacy of the ARX‐ERA method is then demonstrated through identification of the modal properties of a highway overcrossing bridge. Copyright © 2013 John Wiley & Sons, Ltd.
Expression, regulation and roles of miR‐26a and MEG3 in tongue squamous cell carcinoma
Authors: Jia Ling‐Fei , Wei Su‐Bi , Gan Ye‐Hua , Guo Yong , Gong Kai , Mitchelson Keith , Cheng Jing , Yu Guang‐Yan
Published: December 2013

MicroRNA miR‐26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR‐26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR‐26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC‐15 and CAL27 showed that miR‐26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR‐26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR‐26a or MEG3 in SCC‐15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR‐26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.
Long Noncoding RNAs Expression Profile of the Developing Mouse Heart
Authors: Zhu Jin Gai , Shen Ya Hui , Liu Hai Lang , Liu Ming , Shen Ya Qing , Kong Xiang Qing , Song Gui Xian , Qian Ling Mei
Published: December 2013

Long noncoding RNAs (lncRNAs) represent a sub‐group of noncoding RNAs that are longer than 200 nucleotides. The characterization of lncRNAs and their acceptance as crucial regulators of numerous developmental and biological pathways have suggested that the lncRNA study has gradually become one of the hot topics in the field of RNA biology. Many lncRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the lncRNA profile of the fetal mouse heart at three key time points (embryonic day E11.5, E14.5, and E18.5) in its development, by performing a microarray lncRNAs screen. Gene Ontology analysis and ingenuity pathway analysis showed some significant gene functions and pathways were altered in heart development process. We compared lncRNAs profile between the three points (E14.5 vs. E11.5 [early development]; E18.5 vs. E14.5 [later development]). A total of 1,237 lncRNAs were found to have consistent fold changes (>2.0) between the three time points. Among them, 20 dysregulated lncRNAs were randomly selected and confirmed by real‐time qRT‐PCR. Additionally, bioinformatics analysis of AK011347 suggested it may be involved in heart development through the target gene Map3k7. In summary, this study identified differentially expressed lncRNAs in the three time points studied, and these lncRNAs may provide a new clue of mechanism of normal heart development. J. Cell. Biochem. 115: 910–918, 2014. © 2013 Wiley Periodicals, Inc.
Transfection With Follicular Dendritic Cell Secreted Protein to Affect Phenotype Expression of Human Periodontal Ligament Cells
Authors: Xiang Lin , Ma Li , He Yao , Wei Na , Gong Ping
Published: December 2013

Follicular dendritic cell secreted protein (FDC‐SP), has been found to inhibit osteogenic differentiation of human periodontal ligament cells (hPDLCs) in recent studies. Based on these findings, we further investigate its effect on phenotype expression of hPDLCs in the present study, aiming to contribute to a better understanding of the biological functions governing FDC‐SP‐induced hPDLC differentiation. hPDLCs were firstly identified with immunocytochemical staining, followed by transfection with FDC‐SP lentiviral vector. Western blot analysis was used to confirm the expression of FDC‐SP. Then the influence of FDC‐SP transfection on hPDLC proliferation, osteogenic and fibrogenic phenotype expression was evaluated at the mRNA and protein level. Procollagen type I c‐peptide production was measured and alizarin red staining was then conducted to demonstrate effect of FDC‐SP on functional differentiation. We found that hPDLCs could be successfully transfected with FDC‐SP. Cell proliferation and cell cycle tests indicated that transfection with FDC‐SP did not affect hPDLC proliferation. Moreover, according to real‐time PCR and Western blot results, expression levels of type 1 collagen alpha 1, type 1 collagen alpha 2 and type 3 collagen were upregulated while that of osteocalcin, osteopontin, and bone sialoprotein were downregulated in FDC‐SP transfected cells. In addition, hPDLCs overexpressing FDC‐SP exhibited higher PIP production than the controls. Our findings demonstrate that transfection with FDC‐SP has negligible adverse effect on proliferation of hPDLCs and imply the biological function of FDC‐SP as a fibroblastic phenotype stabilizer by inhibiting hPDLCs differentiation into mineralized tissue‐forming cells, thus regulating regeneration in periodontal tissue engineering. J. Cell. Biochem. 115: 940–948, 2014. © 2013 Wiley Periodicals, Inc.
Locally instilled tumor necrosis factor α antisense oligonucleotide contributes to inhibition of TH2‐driven pulmonary fibrosis via induced CD4+CD25+Foxp3+ regulatory T cells
Authors: Luo Yi , Wang Min , Pang Zhonghua , Jiang Fengtao , Chen Jiangning , Zhang Junfeng
Published: December 2013

Background

Anti‐tumor necrosis factor α therapeutics has the potential to alleviate pulmonary fibrosis. However, the systemic administration of anti‐tumor necrosis factor α agents has brought about contradictory results and frequent adverse effects, such as infections, immunogenicity and malignancies, amongst others. In the present study, we attempted the local administration of tumor necrosis factor α antisense oligonucleotide and evaluated the treatment effects on pulmonary fibrosis in a bleomycin‐induced pulmonary fibrosis mouse model.

Methods

Flow cytometry for regulatory T cells, reverse transcriptase‐polymerase chain reaction for crucial gene expression, western blotting for crucial protein products, immunofluorescent analysis for TH2 cells and myofibroblasts, as well as histology analysis for pathological examination, were used.

Results

By local administration of tumor necrosis factor α antisense oligonucleotide, we investigated whether tumor necrosis factor α expression in epithelial cells was significantly inhibited and extracellular matrix overexpression was dramatically reduced. These treatment effects were associated with induced regulatory T cells, reduced TH2 cells and generally decreased TH2‐type cytokine expression. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of regulatory T cells in the blood, thymus or spleen was not affected.

Conclusions

These findings demonstrate that local administration of tumor necrosis factor α antisense oligonucleotide contributes to anti‐fibrotic action via a sustained up‐regulated level of regulatory T cells, which inhibits TH2‐biased responses, pro‐fibrotic mediator production and extracellular matrix deposition, with no systemic immunosupression associated with systemically induced regulatory T cells. Copyright © 2013 John Wiley & Sons, Ltd.
Polycyclic N‐Heterocyclic Compounds. Part 75: Synthesis of 2,4‐Disubstituted 5,6‐dihydro[1]benzoxepino[5,4‐d]pyrimidines and 12‐Substituted 1,2,4,5‐Tetrahydro[1]benzoxepino[4,5‐e]imidazo[1,2‐c]pyrimidines as Potential Antiplatelet Aggregators
Authors: Okuda Kensuke , Yamamoto Yuko , Hirota Takashi , Sasaki Kenji
Published: December 2013

Libraries of tricyclic 2‐substituted 4‐alkylamino‐5,6‐dihydro[1]benzoxepino[5,4‐d]pyrimidines and tetracyclic 12‐substituted 1,2,4,5‐tetrahydro[1]benzoxepino[4,5‐e]imidazo[1,2‐c]pyrimidines were synthesized as part of our research to develop new effective antiplatelet drugs. Several alkyl and aryl groups were used as substituents at the 2‐position. Evaluation of the effects of the newly synthesized compounds on collagen‐induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.
Application of Privileged Molecular Framework of 7‐Fluoro‐1,4‐benzodiazepin‐2‐one‐5‐methylcarboxylate to the Synthesis of Its 1‐ and 5‐Disubstituted Analogs of Medicinal Interest
Authors: Devi Pragati , Gupta Aarti , Kishore Dharma
Published: December 2013

Synthetic potential of the privileged molecular framework of 7‐fluoro‐1,4‐benzodiazepin‐2‐one containing a methyl carboxylate substituent at its 5‐position was exploited to develop efficient protocols to the synthesis of several novel 5‐(1′,3′,4′)oxadiazole ring incorporated analogs of medicinal interest, appended with the Mannich's base motifs at the nitrogen atom in its seven‐membered ring.
An Efficient Synthesis of 3‐Substituted Isoquinoline and Pyridine Derivatives by Gold Catalyzed Intramolecular Cyclization from o‐Alkynyloximes
Authors: Subbarao K. P. V. , Reddy G. Raveendra , Muralikrishna A. , Reddy K. V.
Published: December 2013

A one‐pot reaction was developed efficiently by AuCl3 catalyzed intramolecular cyclization of aromatic o‐alkynyloximes and 2‐alkynylcycloalkene‐1‐carbaldoximes leading to the formation of isoquinoline and pyridine derivatives with high yields. This methodology has been applied for aromatic as well as aliphatic systems. Aromatic o‐alkynyloximes are benzene and naphthalene, whereas electron‐donating groups are 4‐methoxybenzene, 4‐methylbenzene, and 4‐methoxy‐5‐methylbenzene. There are electron‐withdrawing groups such as chloro and nitrobenzene o‐alkynyl oximes, and the same methodology has been successfully applied to pyridine and piperonal, which is also extended to aliphatic rings such as five‐member, six‐member, seven‐member, and eight‐member 2‐alkynylcycloalkene‐1‐carbaldoximes.
Synthesis and Characterization of Geminally Dialkylsubstituted Tetraindanotetraoxa[8]circulenes
Authors: Mejlsøe Søren L. , Christensen Jørn B.
Published: December 2013

A synthetic methodology for the synthesis of 2,2‐dialkyl‐4,7‐dimethoxy‐2,3‐dihydro‐1H‐inden‐1‐ones from 4,7‐dimethoxy‐2,3‐dihydro‐1H‐inden‐1‐one has been developed, and some of these compounds were converted into the corresponding geminally dialkylsubstituted tetraindanotetraoxa[8]circulenes with the expectation of obtaining discotic liquid crystalline materials.
The Incremental Validity of a Short Form of the Ideational Behavior Scale and Usefulness of Distractor, Contraindicative, and Lie Scales
Authors: Runco Mark A. , Walczyk Jeffrey John , Acar Selcuk , Cowger Ernest L. , Simundson Melissa , Tripp Sunny
Published: December 2013

This article describes an empirical refinement of the Runco Ideational Behavior Scale (RIBS). The RIBS seems to be associated with divergent thinking, and the potential for creative thinking, but it was possible that its validity could be improved. With this in mind, three new scales were developed and the unique benefit (or “incremental validity”) of each was assessed. The three validity scales contained (a) distractor items, (b) contraindicative items, or (c) items constituting a lie scale. Step‐wise analyses using the three validity scales indicated very little incremental validity: They were interpreted in the light of psychometric theory, which suggests that their contribution may have been on a behavioral rather than on a statistical level. One additional analysis explored the possibility that a short form could be constructed. The short form of the RIBS was highly correlated with the long form (r = .94). Thus, most decisions made by the short form will be entirely compatible with decisions that would have been reached using the long form. A second significant result was that the RIBS was highly correlated with a check list of creative activities, supporting its concurrent validity.
Evaluation of the effects of systemic treatment with a sclerostin neutralizing antibody on bone repair in a rat femoral defect model
Authors: Alaee Farhang , Virk Mandeep S. , Tang Hezhen , Sugiyama Osamu , Adams Douglas J. , Stolina Marina , Dwyer Denise , Ominsky Michael S. , Ke Hua Zhu , Lieberman Jay R.
Published: December 2013

Systemic administration of a sclerostin neutralizing antibody (Scl‐Ab) has been shown to enhance fracture callus density and strength in several animal models. In order to further evaluate the potential of Scl‐Ab to improve healing in a bone defect model, we evaluated Scl‐Ab in a 3 mm femoral defect in young male outbred rats. Scl‐Ab was given either continuously for 6 or 12 weeks after surgery or with 2 weeks of delay for 10 weeks. Bone formation was assessed by radiographs, µ‐CT, and histology. Complete bony union was achieved in only a few defects after 12 weeks of healing (Scl‐Ab treated 5/30, vehicle treated 1/15). µ‐CT evaluation demonstrated a significant increase in the BV/TV in the defect in the delayed treatment group (65%, p < 0.05), but a non‐significant increase in the continuous group (35%, p = 0.11) compared to control. However, both regimens induced an anabolic response in the bone proximal and distal to the defect and in the un‐operated femurs. We demonstrate that treatment with Scl‐Ab can enhance bone repair in a bone defect and in the surrounding host bone, but lacks the osteoinductive activity to heal it. This agent seems to be most effective in bone repair scenarios where there is cortical integrity. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:197–203, 2014.
T2* MR relaxometry and ligament volume are associated with the structural properties of the healing ACL
Authors: Biercevicz Alison M. , Murray Martha M. , Walsh Edward G. , Miranda Danny L. , Machan Jason T. , Fleming Braden C.
Published: December 2013

Our objective was to develop a non‐invasive magnetic resonance (MR) method to predict the structural properties of a healing anterior cruciate ligament (ACL) using volume and T2* relaxation time. We also compared our T2*‐based structural property prediction model to a previous model utilizing signal intensity, an acquisition‐dependent variable. Surgical ACL transection followed by no treatment (i.e., natural healing) or bio‐enhanced ACL repair was performed in a porcine model. After 52 weeks of healing, high‐resolution MR images of the ACL tissue were collected. From these images, ligament volumes and T2* maps were established. The structural properties of the ligaments were determined via tensile testing. Using the T2* histogram profile, each ligament voxel was binned based on its T2* value into four discrete tissue sub‐volumes defined by specific T2* intervals. The linear combination of the ligament sub‐volumes binned by T2* value significantly predicted maximum load, yield load, and linear stiffness (R2 = 0.92, 0.82, 0.88; p < 0.001) and were similar to the previous signal intensity based method. In conclusion, the T2* technique offers a highly predictive methodology that is a first step towards the development of a method that can be used to assess ligament healing across scanners, studies, and institutions. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:492–499, 2014.
Immediate and Longer‐Term Stressors and the Mental Health of Hurricane Ike Survivors
Authors: Lowe Sarah R. , Tracy Melissa , Cerdá Magdalena , Norris Fran H. , Galea Sandro
Published: December 2013

Previous research has documented that individuals exposed to more stressors during disasters and their immediate aftermath (immediate stressors) are at risk of experiencing longer‐term postdisaster stressors. Longer‐term stressors, in turn, have been found to play a key role in shaping postdisaster psychological functioning. Few studies have simultaneously explored the links from immediate to longer‐term stressors, and from longer‐term stressors to psychological functioning, however. Additionally, studies have inadequately explored whether postdisaster psychological symptoms influence longer‐term stressors. In the current study, we aimed to fill these gaps. Participants (N = 448) were from population‐based study of Hurricane Ike survivors and completed assessments 2–5 months (Wave 1), 5–9 months (Wave 2) and 14–18 months (Wave 3) postdisaster. Through path analysis, we found that immediate stressors, assessed at Wave 1, were positively associated with Wave 2 and Wave 3 stressors, which in turn were positively associated with Wave 2 and Wave 3 posttraumatic stress and depressive symptoms. Wave 2 posttraumatic stress symptoms were positively associated with Wave 3 stressors, and Wave 1 depressive symptoms were positively associated with Wave 2 stressors. The findings suggest that policies and interventions can reduce the impact of disasters on mental health by preventing and alleviating both immediate and longer‐term postdisaster stressors.
Differential Effects of Exposure to Social Violence and Natural Disaster on Children's Mental Health
Authors: Kumar Manasi , Fonagy Peter
Published: December 2013

Disaster mental health, particularly postdisaster child mental health, is neglected in India. This study compares the impact of a natural disaster versus a spate of communal riots that occurred in Gujarat, India on January 26, 2001, and February 2002 to June 2002, respectively. Children aged 8–15 years from highly exposed earthquake sites (n = 128) and riot sites (n = 171) were approached for participation. A matching control sample of 351 nontrauma‐exposed children was sought to compare with the trauma groups. Trauma and postdisaster adversities were studied using the UCLA disaster trauma tool; Goodman's Strengths and Difficulties Questionnaire was used to assess adjustment difficulties. Spearman's correlations were calculated to find associations between trauma items on UCLA's brief trauma scale and Strengths and Difficulties Questionnaire items. Results suggest that 7.6% of the earthquake sample and 38.7% from the riots sample manifested clinically significant mental health problems. The earthquake sample had 24.8% of those above clinical cutoff for probable posttraumatic stress disorder and the riots sample had 27.3% children who displayed posttraumatic stress symptoms. Children exposed to violence were psychologically more affected and in the presence of postdisaster adversities, posttraumatic stress symptoms persisted long term. This finding should enable development of differential psychotherapeutic interventions for children exposed to extreme events.
Spatially explicit modeling of lesser prairie‐chicken lek density in Texas
Authors: Timmer Jennifer M. , Butler Matthew J. , Ballard Warren B. , Boal Clint W. , Whitlaw Heather A.
Published: December 2013

As with many other grassland birds, lesser prairie‐chickens (Tympanuchus pallidicinctus) have experienced population declines in the Southern Great Plains. Currently they are proposed for federal protection under the Endangered Species Act. In addition to a history of land‐uses that have resulted in habitat loss, lesser prairie‐chickens now face a new potential disturbance from energy development. We estimated lek density in the occupied lesser prairie‐chicken range of Texas, USA, and modeled anthropogenic and vegetative landscape features associated with lek density. We used an aerial line‐transect survey method to count lesser prairie‐chicken leks in spring 2010 and 2011 and surveyed 208 randomly selected 51.84‐km2blocks. We divided each survey block into 12.96‐km2quadrats and summarized landscape variables within each quadrat. We then used hierarchical distance‐sampling models to examine the relationship between lek density and anthropogenic and vegetative landscape features and predict how lek density may change in response to changes on the landscape, such as an increase in energy development. Our best models indicated lek density was related to percent grassland, region (i.e., the northeast or southwest region of the Texas Panhandle), total percentage of grassland and shrubland, paved road density, and active oil and gas well density. Predicted lek density peaked at 0.39 leks/12.96 km2(SE = 0.09) and 2.05 leks/12.96 km2(SE = 0.56) in the northeast and southwest region of the Texas Panhandle, respectively, which corresponds to approximately 88% and 44% grassland in the northeast and southwest region. Lek density increased with an increase in total percentage of grassland and shrubland and was greatest in areas with lower densities of paved roads and lower densities of active oil and gas wells. We used the 2 most competitive models to predict lek abundance and estimated 236 leks (CV = 0.138, 95% CI = 177–306 leks) for our sampling area. Our results suggest that managing landscapes to maintain a greater percentage of grassland and shrubland on the landscape with a greater ratio of grasses to shrubs in the northeast Panhandle should promote greater lek density. Furthermore, increases in paved road and active oil and gas well densities may reduce lek density. This information will be useful for future conservation planning efforts for land protection, policy decisions, and decision analyses. © 2013 The Wildlife Society
Enabling Open Innovation in Small and Medium Enterprises: A Dynamic Capabilities Approach
Authors: Grimaldi Michele , Quinto Ivana , Rippa Pierluigi
Published: December 2013

This paper aims at exploring the critical dynamic capabilities of small and medium enterprises (SMEs) in the innovation process and at identifying the dynamic capabilities that enable the implementation of open innovation practices. Building on qualitative data from the manufacturing industry deriving from an in‐depth investigation of the capabilities of four innovative case firms, the patterns between the firm's portfolio of dynamic capabilities and the different types of open innovation processes are mapped. This study makes three primary contributions to the body of knowledge. This is the first attempt to link dynamic capabilities to an open innovation approach undertaken by SMEs. Second, the study extends existing work on innovation in SMEs by identifying key dynamic capabilities in this context. Finally, the case‐based research provides empirical evidence of dynamic capabilities in practices, where analysis reveals that companies with strong sensing, seizing and reconfiguring capabilities are more inclined to develop open innovation approaches. Copyright © 2013 John Wiley & Sons, Ltd.
Horus and ERP‐Oriented Process Design—Overcoming Communication Lapses of Processes
Authors: Krone Oliver
Published: December 2013

This paper examines, on the basis of a mixed method approach, the potential of the Horus method for process engineering and its beneficial consequences for Enterprise Resources Planning (ERP) application Requirements Engineering (RE). The Horus method for process engineering is based on Petri nets. Process modeling is reduced to the elements of business objects and their processing in an organization. Horus works extensively with the principle of abstraction for process design. It disentangles process execution from organizational and strategic aims of the process engineering project. Communication gaps referred too are in relation to process design and understanding as both are important contributors for successful RE for ERP design and implementation. The focus in the description is on communicative weaknesses in the areas of business objects definition, the interface function inherent to them as processes cross‐departmental boundaries. Considered are project internal communication obstacles resulting from Tayloristic work distributions, too. Against these communicative weaknesses, the Horus method is matched. It is described how the tool‐kit approach ameliorates these challenges of process (re‐)engineering when conducted in relation with and for ERP implementation. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis of Molecularly Encoded Oligomers Using a Chemoselective “AB + CD” Iterative Approach
Authors: Trinh Thanh Tam , Oswald Laurence , Chan‐Seng Delphine , Lutz Jean‐François
Published: December 2013

A library of eight sequence‐defined model oligomers, whose sequence is based on a (0,1) binary code, is prepared through chemoselective repeating cycles of amidification and copper‐assisted alkyne‐azide cycloaddition reactions from a non‐modified Wang resin. This library is constructed from two AB (A = acid, B = alkyne) building blocks, i.e., 4‐pentynoic acid and 2‐methyl‐4‐pentynoic acid acting, respectively, as non‐coding (0) and coding (1) monomer, and 1‐amino‐11‐azido‐3,6,9‐trioxaundecane as complementary CD (C = amine, D = azide) spacer building block. In particular, encoded triads are synthesized by consecutive covalent attachment of five building blocks (i.e., three coding/non‐coding monomers and two spacers). In this communication, optimal protocols for the synthesis of the targeted oligomers are reported along with their full characterization by 1H NMR, MALDI‐TOF mass spectrometry, and size‐exclusion chromatography. It is found that all possible encoded triads (i.e., eight possibilities) could be synthesized using this approach. Indeed, monodisperse sequence‐defined oligomers are prepared and characterized in all cases.

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Bilinear Model for the Size‐Dependency of the CYP3A4 Inhibitory Activity of Structurally Diverse Compounds
Authors: Buchwald Peter , Yamashita Fumiyoshi
Published: December 2013

A quantitative structure‐activity relationship analysis of the inhibitory activity of structurally diverse compounds on recombinant human CYP3A4 is presented using a bilinear approach based on our previously developed LinBiExp model. Using only two main descriptors, molecular size and an indicator variable for the presence of triazole/imidazole moieties, this approach can account for close to 65 % of the variability in the inhibitory activity of more than 70 compounds and provides clear evidence that molecular size plays an important, but nonlinear role. Strongest inhibitory activity is likely to occur for compounds close to an optimal size, which is roughly that of the well‐know CYP3A4‐inhibitor ketoconazole. The activity‐limiting role of size was also confirmed on a large dataset of 3438 compounds (PubChem Bioassay AID 884). This model provides a simple, intuitive interpretation and can serve as the starting point for more complex descriptions of the CYP3A4 inhibitory activity.