bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Networks and Drug Discovery—Where Do We Stand?
Authors: Geppert Tim , Koeppen Herbert
Published: August 2014

Preclinical Research

The progress in genomics and molecular biology during the last decade has led to the insight that complex diseases are caused by defects in many genes and that cellular processes are organized in complex networks. In the search of new drugs, these findings have not yet been fully taken into account. The currently predominating drug discovery approach in pharmaceutical industry is still target‐centric, with the goal to optimize compounds toward high affinity and selectivity for a specific target. There is growing evidence that the successful development of effective disease‐modifying medications needs a network approach instead. This might also help to reduce the very high failure rate in the current drug development process. This review outlines concepts and applications of network biology and routes toward drugs that are designed to interact with several targets. Obstacles to the implementation of this approach in the pharmaceutical industry are discussed.
Activity Cliff Networks for Medicinal Chemistry
Authors: Stumpfe Dagmar , Bajorath Jürgen
Published: August 2014

Preclinical Research

Network representations are widely used in bioinformatics but have only been little explored in chemistry. Thus far, only a few attempts have been made to generate and analyze compound networks. Among these are the first activity cliff networks. In medicinal chemistry, activity cliffs are focal points of structure–activity relationships (SAR) analysis. Activity cliffs have generally been defined as pairs of structurally similar or analogous active compounds that have a large difference in potency against their target. However, most activity cliffs are not formed in isolation but in a coordinated manner involving multiple highly and weakly potent compounds. Recently, a comprehensive activity cliff network has been generated for current public domain bioactive compounds, hence providing a first global view of activity cliff formation. The design of activity cliff networks is discussed herein. From the global activity cliff network, local networks can be extracted for individual compound activity classes that provide graphical access to high‐level SAR information for compound optimization efforts.
Application of Chemometric Techniques in Search of Clinically Applicable Biomarkers of Disease
Authors: Kotłowska Alicja
Published: August 2014

Preclinical Research

Metabolomics deals with the global assessment of the metabolites present in a biological system to evaluate the progress of the disease, select potential biomarkers, and provide insights into the underlying pathophysiology. As metabolomic analysis generates large quantities of data, multivariate data analysis techniques and chemometrics are often used to interpret experimental results. The present overreview describes various chemometric methods that are frequently used in clinical biomarker studies, with emphasis on data analysis strategies and validation of classification and prognostic models. Moreover, an overview of most interesting recent biomarker discovery publications is provided to highlight the clinical applications of chemometric techniques used for bioanalytical data interpretation.
Network Pharmacology: A Rosetta Stone for Traditional Chinese Medicine
Authors: Hao Da Cheng , Xiao Pei Gen
Published: August 2014

Preclinical Research

Network pharmacology, based on the theory of systems biology, is a new discipline that analyzes the biological network and screens out the nodes of particular interest, with the aim of designing poly‐target drug molecule. It emphasizes maximizing drug efficacy and minimizing adverse effect via the multiple regulation of the signaling pathway. Coincidentally, almost all traditional Chinese medicine (TCM) and worldwide ethnomedicine exert therapeutic effect by targeting multiple molecules of the human body. In this overview, we offer a critique on the present perception of TCM and network pharmacology; illustrate the utility of network pharmacology in the study of single herb, medicine pair, and TCM formula; and summarize the recent progress of TCM‐based drug discovery inspired by network pharmacology. Network pharmacology could be of great help in decreasing drug attrition rate and thus is essential in rational and cost‐effective drug development. We also pinpoint the current TCM issues that could be tackled by the flexible combined use of network pharmacology and relevant disciplines.
Redox Regulation of Cancer Metastasis: Molecular Signaling and Therapeutic Opportunities
Authors: Yang Wenyong , Zou Linzhi , Huang Canhua , Lei Yunlong
Published: August 2014

Preclinical Research

Cancer metastasis is the major cause of cancer‐related mortality. Accumulated evidence has shown that high‐metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low‐metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis‐related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox‐sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.
Effects of person‐centred and integrated chronic heart failure and palliative home care. PREFER: a randomized controlled study
Authors: Brännström Margareta , Boman Kurt
Published: August 2014

Aims

We evaluated the outcome of person‐centred and integrated Palliative advanced home caRE and heart FailurE caRe (PREFER) with regard to patient symptoms, health‐related quality of life (HQRL), and hospitalizations compared with usual care.

Methods and results

From January 2011 to October 2012, 36 (26 males, 10 females, mean age 81.9 years) patients with chronic heart failure (NYHA class III–IV) were randomized to PREFER and 36 (25 males, 11 females, mean age 76.6 years) to the control group at a single centre. Prospective assessments were made at 1, 3, and 6 months using the Edmonton Symptom Assessment Scale, Euro Qol, Kansas City Cardiomyopathy Questionnaire, and rehospitalizations. Between‐group analysis revealed that patients receiving PREFER had improved HRQL compared with controls (57.6 ± 19.2 vs. 48.5 ± 24.4, age‐adjusted P‐value = 0.05). Within‐group analysis revealed a 26% improvement in the PREFER group for HRQL (P = 0.046) compared with 3% (P = 0.82) in the control group. Nausea was improved in the PREFER group (2.4 ± 2.7 vs. 1.7 ± 1.7, P = 0.02), and total symptom burden, self‐efficacy, and quality of life improved by 18% (P = 0.035), 17% (P = 0.041), and 24% (P = 0.047), respectively. NYHA class improved in 11 of the 28 (39%) PREFER patients compared with 3 of the 29 (10%) control patients (P = 0.015). Fifteen rehospitalizations (103 days) occurred in the PREFER group, compared with 53 (305 days) in the control group.

Conclusion

Person‐centred care combined with active heart failure and palliative care at home has the potential to improve quality of life and morbidity substantially in patients with severe chronic heart failure.

Trial registration: NCT01304381
Modified phospholipids: From detergents towards small molecular response modifiers
Authors: Hildmann Annette , Danker Kerstin
Published: August 2014

Natural living cell membrane phospholipids undergo rapid and continuous turnover that provides essential signalling pathways controlling cell survival. Derived from (lyso)phosphatidylcholine, alkylphopspholipids (APL) were synthesized as metabolically stable analogues 50 years ago. The nature of the chemical structure of APLs allows them to be inserted into membranes easily and partition into the membrane bilayers according to the degree of unsaturation of phospholipid alkyl chains. In an effort to overcome the severe side effects of existing anti‐tumour drugs, novel APLs with variations in alkyl side chain length, glycerol backbone, ester versus ether bonds, and different polar headgroups were developed to combine high anti‐proliferative capacity with reduced cytotoxicity. The platelet activating factor (PAF) is a natural alkylphospholipid. Substituting the sn‐2 position of platelet activating factor with an ether linked C2 spacer coupled to inositol created Inositol‐C2‐PAF. The effects of Inositol‐C2‐PAF can be divided into short‐term and long‐term effects. Short‐term effects include the inhibition of phosphorylation events, resulting in inhibition of cell proliferation and reduced cell migration. Long‐term effects of Inositol‐C2‐PAF, which are characterised by changes in gene expression, include up‐regulation of biological processes linked to cell differentiation or system development.

Inspired by the natural phospholipid platelet activating factor (PAF) derivatives are shown, that intercalate in plasma membranes and at sub‐toxic concentrations disturb plasma membrane microdomain composition and/or intracellular responses.
Phosphatidylinositol 3‐Phosphate Mimics Based on a Sulfoquinovose Scaffold: Synthesis and Evaluation as Protein Kinase B Inhibitors
Authors: Gabrielli Luca , Calloni Ilaria , Donvito Giulia , Costa Barbara , Arrighetti Noemi , Perego Paola , Colombo Diego , Ronchetti Fiamma , Nicotra Francesco , Cipolla Laura
Published: August 2014

New sulfoquinovose analogues of phosphatidylinositol 3‐phosphate have been synthesised based on a sulfoquinovose scaffold as potential protein kinase B (PKB) inhibitors. The synthetic strategy involved the introduction into glucose of a thioacetate group at the 6‐position and of an azide group at the anomeric position as precursors of the sulfonate and phosphoramidate moieties present in the final compounds. The synthesised compounds were tested in vitro on isolated PKB by means of ELISA assays and for their anti‐proliferative activity against the human ovarian carcinoma cell line IGROV‐1. Sulfoquinovose derivatives 2b and 2c showed inhibitory activity in the low micromolar range.
Real‐Time Pricing and Hedging of Options on Currency Futures with Artificial Neural Networks
Authors: von Spreckelsen Christian , von Mettenheim Hans‐Jörg , Breitner Michael H.
Published: August 2014

High‐frequency trading and automated algorithm impose high requirements on computational methods. We provide a model‐free option pricing approach with neural networks, which can be applied to real‐time pricing and hedging of FX options. In contrast to well‐known theoretical models, an essential advantage of our approach is the simultaneous pricing across different strike prices and parsimonious use of real‐time input variables. To test its ability for the purpose of high‐frequency trading, we perform an empirical run‐time trading simulation with a tick dataset of EUR/USD options on currency futures of 4 weeks. In very short non‐overlapping 15‐minute out‐of‐sample intervals, theoretical option prices derived from the Black model compete against nonparametric option prices through two different neural network topologies. We show that the approximated pricing function of learning networks is suitable for generating fast run‐time option pricing evaluation as their performance is slightly better in comparison to theoretical prices. The derivation of the network function is also useful for performing hedging strategies. We conclude that the performance of closed‐form pricing models depends highly on the volatility estimator, whereas neural networks can avoid this estimation problem but require market liquidity for training. Nevertheless, we also have to take particular enhancements into account, which give us useful hints for further research and steps. Copyright © 2014 John Wiley & Sons, Ltd.
Assessment of ovarian cancer conditions from exhaled breath
Authors: Amal Haitham , Shi Da‐You , Ionescu Radu , Zhang Wei , Hua Qing‐Ling , Pan Yue‐Yin , Tao Li , Liu Hu , Haick Hossam
Published: August 2014

We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor‐free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2‐butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor‐made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor‐free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor‐free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.
Association of symptoms and breast cancer in population‐based mammography screening in Finland
Authors: Singh Deependra , Malila Nea , Pokhrel Arun , Anttila Ahti
Published: August 2014

The study purpose was to assess association of symptoms at screening visits with detection of breast cancer among women aged 50–69 years during the period 2006–2010. Altogether 1.2 million screening visits were made and symptoms (lump, retraction, secretion etc.) were reported either by women or radiographer. Breast cancer risk was calculated for each symptom separately using logistic regression [odds ratio (OR)] and 95% confidence intervals (CIs). Of the 1,198,410 screening visits symptoms were reported in 298,220 (25%) visits. Breast cancer detection rate for women with and without symptoms was 7.8 per 1,000 and 4.7 per 1,000 screening visits, respectively, whereas lump detected 32 cancers per 1,000 screens. Women with lump or retraction had an increased risk of breast cancer, OR = 6.47, 95% CI 5.89−7.09 and OR = 2.19, 95% CI 1.92–2.49, respectively. The sensitivity of symptoms in detecting breast carcinoma was 35.5% overall. Individual symptoms sensitivity and specificity ranged from, 0.66 to 14.8% and 87.4 to 99.7%, respectively. Of 5,541 invasive breast cancers, 1,993 (36%) reported symptoms at screen. Breast cancer risk among women with lump or retraction was higher in large size tumors (OR = 9.20, 95% CI 8.08–10.5) with poorly differentiated grades (OR = 5.91, 95% CI 5.03–6.94) and regional lymph nodes involvement (OR = 6.47, 95% CI 5.67–7.38). This study was done in a setting where breast tumors size is generally small, and symptoms sensitivity and specificity in diagnosing breast tumors were limited. Importance of breast cancer symptoms in the cancer prevention and control strategy needs to be evaluated also in other settings.
DECREASING HARSH DISCIPLINE IN MOTHERS AT RISK FOR MALTREATMENT: A RANDOMIZED CONTROL TRIAL
Authors: Pereira Mariana , Negrão Mariana , Soares Isabel , Mesman Judi
Published: August 2014

This study tested the effectiveness of the attachment‐based program Video‐feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP‐SD; F. Juffer, M.J. Bakermans‐Kranenburg, & M.H. van IJzendoorn, 2008) in decreasing harsh discipline of 43 mothers and their 1‐ to 4‐year‐old‐children from severely deprived families. Based on previous studies, parenting stress was tested as a potential moderator of intervention effects on harsh discipline. Using a randomized control design, maternal harsh discipline was observed during home visits at the pretest and posttest, and mothers filled in questionnaires at both assessments. The VIPP‐SD proved to be effective in decreasing maternal harsh discipline, but only for mothers who experienced higher levels of parenting stress at intake. These findings provide support for the program's ability to improve parenting in families who are most at risk for harsh parenting and for potentially maltreating child–parent interactions. The results are discussed in terms of the VIPP‐SD elements most relevant to decreasing harsh discipline, and the challenges of parenting interventions in severely deprived populations.
PROGRESS ON THE PATERNAL BRAIN: THEORY, ANIMAL MODELS, HUMAN BRAIN RESEARCH, AND MENTAL HEALTH IMPLICATIONS
Authors: Swain J.E. , Dayton C.J. , Kim P. , Tolman R.M. , Volling B.L.
Published: August 2014

With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain‐imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby‐stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain‐imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father–child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance.
Good Practices for Whom? A Vital Question for Understanding the First Year of College
Authors: Goodman Kathleen M.
Published: August 2014

This chapter demonstrates that the effects of good teaching and academic challenge on leadership and psychological well‐being during the first year of college differ for African‐American and White students, which suggests that institutional researchers should disaggregate data by race or other relevant student characteristics when trying to understand the relationship between experiences and outcomes for first‐year students.
Programs and Practices That Retain Students From the First to Second Year: Results From a National Study
Authors: DeAngelo Linda
Published: August 2014

In this chapter findings from a nationally representative longitudinal study offer insights into how the experiences students have during their first college year affect their intention to be retained at their initial college for the second year.
Self‐Construal, Career Decision Self‐Efficacy, and Perceived Barriers Predict Mexican American Women's Life Satisfaction
Authors: Piña‐Watson Brandy , Jimenez Natalia , Ojeda Lizette
Published: August 2014

This study used the social cognitive theory of well‐being (SCTW; Lent, ) to examine the role of career decision self‐efficacy (CDSE), perceived educational barriers, and independent self‐construal on the life satisfaction of 176 Mexican American college women. A 3‐step hierarchical regression analysis indicated that independent self‐construal, CDSE, and fewer perceived educational barriers significantly predicted greater life satisfaction among Mexican American college women above and beyond the influence of socioeconomic status and generational status. These findings are consistent with SCTW and highlight the need for counselors and researchers to be aware of the role that self‐construal, CDSE, and perceived educational barriers can have on Mexican American women's life satisfaction. Implications for practice at the secondary‐school and university levels are discussed.
The Self‐Directed Search as a Stand‐Alone Intervention With College Students
Authors: Behrens Erica L. , Nauta Margaret M.
Published: August 2014

The Self‐Directed Search (SDS; Holland, ) is sometimes administered to large student groups outside of counseling to address common career development needs. This study evaluated the effectiveness of the SDS as a stand‐alone intervention by comparing a general sample of college students who completed the SDS (n = 39) with a no‐treatment control group (n = 41) on several outcomes. Completion of the SDS related to an increase in the number of career alternatives being considered 4 weeks later but did not relate to career exploration, career decision‐making self‐efficacy, career indecision, and seeking of career counseling services. If the SDS is used outside of counseling with broad student samples, the authors suggest providing additional intervention to ensure that it promotes exploration of any additional careers being considered.
Construction and Initial Validation of the Planned Happenstance Career Inventory
Authors: Kim Boram , Jung Sun Hwa , Jang Sun Hee , Lee Bohyun , Rhee Eunjeong , Cho Soo Hyun , Lee Sang Min
Published: August 2014

This study was conducted to develop and initially evaluate the psychometric properties of the Planned Happenstance Career Inventory (PHCI), which aims to assess skill in using chance events to develop career opportunities. After item generation and exploratory factor analysis, 130 original items were reduced to 25 items across 5 factors (5 items for each corresponding factor). Multigroup confirmatory factor analysis confirmed the validity of this 5‐factor structure, and the goodness of fit showed an adequate fit to the observed data for both women and men. Results showed that PHCI subscales correlated moderately and in expected directions with career preparation, career decision‐making self‐efficacy, and career stress. These findings suggest that the PHCI, which assesses 5 dimensions of career‐related planned happenstance skill, shows promise as a useful tool for facilitating understanding of the influence of chance events on career choice behavior.
A Framework for Promoting Women's Career Intentionality and Work–Life Integration
Authors: Tajlili Megan Hyland
Published: August 2014

Work–life integration is a major problem for today's working women, as the demands of full‐time work conflict with the relational factors of family life. Women feel they have to make difficult decisions that sacrifice their career or family, with little understanding of the influences that affect decision making. Career counselors may not be discussing the strain of Work–life integration with female college students, leading them to believe “having it all” is attainable. A framework blending the Kaleidoscope Career Model with the Systems Theory Framework to help women understand the environmental, societal, and personal influences on Work–life integration is proposed as a solution. This framework allows college women to make decisions with an intentional background of how these systems interact and sway perception. Using this framework, career counselors may help students identify goals, research the benefits and challenges, and clarify their authentic selves in personal and work realms.
Intrapreneurial Self‐Capital: A New Construct for the 21st Century
Authors: Di Fabio Annamaria
Published: August 2014

This article presents a new career construct, intrapreneurial self‐capital, and provides empirical evidence to verify it. Intrapreneurial self‐capital is defined as a core of individual intrapreneurial resources used to cope with career and life construction challenges and includes dimensions of core self‐evaluation, hardiness, creative self‐efficacy, resilience, goal mastery, decisiveness, and vigilance. The Intrapreneurial Self‐Capital Scale was developed to measure this new construct. It was administered to 171 Italian high school students, and confirmatory factor analysis supported the existence of the construct and its dimensions. Intrapreneurial self‐capital is a construct that will be useful for further research as well as for use in career interventions.
The Effects of Income and Skill Utilization on the Underemployed's Self‐Esteem, Mental Health, and Life Satisfaction
Authors: Roh Youn Hee , Chang Jae Yoon , Kim Myung Un , Nam Suk Kyung
Published: August 2014

This longitudinal study examined the effects of underemployment on psychological well‐being (i.e., self‐esteem, mental health, and life satisfaction) using a sample of 99 unemployed and 153 reemployed individuals in South Korea. Underemployment was determined by wage and skill utilization. The results indicated that when underemployment was determined by wage change, the underemployed showed a more favorable mental health level and more life satisfaction than the unemployed. However, when determined by wage difference, the underemployed were similar to the unemployed. For skill utilization‐based underemployment, no difference was observed between the underemployed and the unemployed. The implications for future research are discussed.
AKT as Locus of Cancer Phenotype
Authors: Radisavljevic Ziv
Published: August 2014

Cancer robustness is generated by the positive feedback loops. The positive loops hyperactivate AKT locus forming a cancer phenotype in leukemia, lymphoma, myeloma, plasmocytoma, sarcoma and carcinoma. The positive loops inducing AKT hyperphosphorylation increase activity of the AKT locus and the nodal associated and interconnected signaling genes. Only genes expressed above the threshold in the AKT signaling interactome networks, participate in the formation of the complex cancer phenotype. AKT is the switching locus for the cancer phenotype. The phenotype formation and maintenance is regulated by the AKT locus through an entropy/enthalpy processes. Targeting the AKT by locus chemotherapy, changing redox balance (antioxidant/oxidant), affects phosphorylation and activity of the AKT, inducing conversion of the positive feedback loops and disappearance of the malignant phenotype. J. Cell. Biochem. 116: 1–5, 2015. © 2014 Wiley Periodicals, Inc.
Glycogen Synthase Kinase 3 Regulates IL‐1β Mediated iNOS Expression in Hepatocytes by Down‐Regulating c‐Jun
Authors: Lakshmanan Jaganathan , Zhang Baochun , Nweze Ikenna C. , Du Yibo , Harbrecht Brian G.
Published: August 2014

Excessive nitric oxide from the inducible nitric oxide synthase (iNOS) increases shock‐induced hepatic injury, hepatic dysfunction, inflammation, and mortality in animal models. Cytokines increase the expression of iNOS in hepatocytes, but the signaling mechanisms involved are not completely understood. We have previously demonstrated that Akt mediates the inhibitory effect of cAMP and insulin on cytokine‐induced hepatocyte iNOS expression. We hypothesized that glycogen synthase kinase 3 (GSK3), a target of Akt phosphorylation, would regulate hepatocyte iNOS expression. In cultured rat hepatocytes, GSK3 inhibitors decreased IL‐1β mediated nitric oxide (NO) production and iNOS protein expression, while the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway inhibitor LY294002 increased the cytokine‐mediated NO production and iNOS expression. Over‐expression of the constitutively active form of GSK3β enhanced IL‐1β‐mediated iNOS expression. GSK3 catalyzes the phosphorylation of c‐Jun at the c‐terminal Thr239 that facilitates c‐Jun degradation. Inhibition of GSK3 with SB216763 and lithium chloride significantly reduced, whereas blocking PI3K/Akt increased phosphorylation of c‐Jun at Thr239. The levels of total‐c‐Jun and c‐Jun phosphorylated at Ser63 inversely correlated with c‐Jun phosphorylated at Thr239, GSK3 activation and iNOS expression. Over‐expression of a dominant negative c‐Jun not only caused an increase in IL‐1β‐mediated iNOS promoter activity and iNOS protein expression but was also able to reverse the SB216763‐mediated suppression of iNOS. These results demonstrate that GSK3, a downstream target of Akt, regulates IL‐1β‐stimulated iNOS expression in hepatocytes by directly phosphorylating c‐Jun in an inhibitory manner. J. Cell. Biochem. 116: 133–141, 2015. © 2014 Wiley Periodicals, Inc.
A Facile and One‐pot Synthetic Route to Functionalized Ethyl 3‐(Alkanoyl)‐2‐(alkyl imino)‐2,3‐dihydrothiazole‐4‐carboxylate Derivatives under Mild, Solventand Catalyst‐free Conditions
Authors: Iravani Nasir , Keshavarz Mosadegh , Haghnegahdar Tahereh , Salehi Maral
Published: August 2014

A new one‐pot, four‐component synthetic rout is reported for the preparation of functionalized N‐acyl‐2alkylimino‐2,3‐dihydrothiazole derivatives from the reaction between acid chlorides, ammonium thiocyanate, primary alkylamines, and ethyl bromopyruvate under mild, solvent‐ and catalyst‐free conditions at room temperature. This completely green and efficient straight forward procedure led to the desired products in good to high yields without any need to catalyst or solvent assistance and no by product was observed in all the reactions
One‐pot Solvent Free Synthesis of Some Tert‐indolylmethane Amine Derivatives by Fe(HSO4)3 as a Recyclable Catalyst
Authors: Rahimizadeh Mohammad , Eshghi Hossein , Mokaber‐Esfahani Majid , Gholizadeh Mostafa
Published: August 2014

Solvent‐free synthesis of 3‐substituted indole derivatives by a one‐pot three‐component coupling reaction between aldehyde, N‐alkyl aniline and indole by Fe(HSO4)3 catalyzed is described. The noticeable features of this protocol are the simplicity of the procedure, easy synthesized, recyclable and inexpensive catalyst, no organic solvent and high yields in relatively short reaction times.
Cubic Phase Formation from New Hexacatenar Metallomesogens Based on Cobalt 3,4,5‐Trialkoxybenzoate
Authors: Lin Chien‐Ho , Kao Hsien‐Chang , Sung Wen‐Te , Cheng Yao‐Wen , Wang Wen‐Jwu
Published: August 2014

Cobalt complexes of Co(3Cn)2(MeOH)4, derived from 3,4,5‐trialkyloxybenzoate ligand (noted as 3Cn) with n = 10, 12, 14 and 16, were synthesized and characterized. The crystal of Co(1C12)2(MeOH)4 were determined by means of x‐ray single crystal analysis. It crystallizes in the monoclinic P21/c space group with a = 24.3271(19) Å, b = 14.0058(11) Å, c = 6.4612(4) Å, α = γ = 90o, β = 94.368(4)o, and Z = 2. The phase texture and mesogenic properties were detected by polarized optical microscopic and powder x‐ray diffraction technique. It was found that these compounds display the cubic phases. Differential scanning calorimetric data indicated that these compounds were nearly room temperature liquid crystalline and with a very wide mesogenic phase range.
Development of a Sensitive Methodology for the Analysis of Chlorobenzenes in Water Samples by Combination of Homogeneous Liquid‐liquid Microextraction via Flotation Assistance and Gas Chromatography‐flame Ionization Detection
Authors: Khalilian Faezeh , Rezaee Mohammad
Published: August 2014

In this study, a simple, rapid and efficient method, homogeneous liquid‐liquid microextraction via flotation assistance (HLLME‐FA) combined with gas chromatography – flame ionization detection (GC‐FID), for the determination of chlorobenzenes (CBs) in water samples, has been described. In this research, a special extraction cell was designed to facilitate collection of the low‐density solvent extraction. No centrifugation was required in this procedure. The water sample solution was added into the extraction cell which contained an appropriate mixture of extraction and homogeneous solvents. By using air flotation, the organic solvent was collected at the conical part of the designed cell. Parameters affecting extraction efficiency were investigated and optimized. Under the optimum conditions, the detection limits, the precisions and the linearity of the method were found in the range of 0.2 to 1.5 µg L‐1, 5.7–9.3% (RSD, n =5) and 0.5–200 µg L‐1, respectively.
Initial Characterization of Osteoblast Differentiation and Loss of RUNX2 Stability in the Newly Established SK11 Human Embryonic Stem Cell‐Derived Cell Line
Authors: Yu Jia‐li , Adisetiyo Helty , Little Gillian H. , Vangsness C. Thomas , Jiang Jianjie , Sternberg Hal , West Michael D. , Frenkel Baruch
Published: August 2014

We describe a novel model for investigation of genetically normal human osteoblasts in culture. SK11 is a clonal progenitor cell line derived from human embryonic stem cells. Initially selected based on the expression of chondrogenic markers when differentiated in micromass culture, SK11 cells display typical mRNA expression patterns of bone phenotypic genes under osteogenic conditions. These include osterix, α1(I) collagen, alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. Similar to well‐characterized murine osteoblast cultures, the osteoblast master regulator RUNX2 was present during the first few days after plating, but the protein disappeared during the first week of culture. Loss of RUNX2 expression is considered an important regulatory feature for osteoblast maturation. Indeed, following ∼2 weeks of differentiation, SK11 cultures exhibited robust calcium deposition, evidenced by alizarin red staining. We also introduced a lentiviral vector encoding doxycycline (dox)‐inducible FLAG‐tagged RUNX2 into SK11 cells. Dox‐mediated enhancement of RUNX2 expression resulted in accelerated mineralization, which was further increased by co‐treatment with BMP‐2. Like the endogenous RUNX2, expression of the virally coded FLAG‐RUNX2 was lost during the first week of culture despite persistent dox treatment. By following RUNX2 decay after dox withdrawal from day‐5 versus day‐3 cultures, we demonstrated a developmentally regulated decrease in RUNX2 stability. Availability of culture models for molecular investigation of genetically normal human osteoblasts is important because differences between murine and human osteoblasts, demonstrated here by the regulation of matrix Gla Protein, may have significant biomedical implications. J. Cell. Physiol. 230: 237–241, 2015. © 2014 Wiley Periodicals, Inc.
Signaling Pathways Involved in Megakaryocyte‐Mediated Proliferation of Osteoblast Lineage Cells
Authors: Cheng Ying‐Hua , Streicher Drew A. , Waning David L. , Chitteti Brahmananda R. , Gerard‐O'Riley Rita , Horowitz Mark C. , Bidwell Joseph P. , Pavalko Fredrick M. , Srour Edward F. , Mayo Lindsey D. , Kacena Melissa A.
Published: August 2014

Recent studies suggest that megakaryocytes (MKs) may play a significant role in skeletal homeostasis, as evident by the occurrence of osteosclerosis in multiple MK related diseases (Lennert et al., 1975; Thiele et al., 1999; Chagraoui et al., 2006). We previously reported a novel interaction whereby MKs enhanced proliferation of osteoblast lineage/osteoprogenitor cells (OBs) by a mechanism requiring direct cell–cell contact. However, the signal transduction pathways and the downstream effector molecules involved in this process have not been characterized. Here we show that MKs contact with OBs, via beta1 integrin, activate the p38/MAPKAPK2/p90RSK kinase cascade in the bone cells, which causes Mdm2 to neutralizes p53/Rb‐mediated check point and allows progression through the G1/S. Interestingly, activation of MAPK (ERK1/2) and AKT, collateral pathways that regulate the cell cycle, remained unchanged with MK stimulation of OBs. The MK‐to‐OB signaling ultimately results in significant increases in the expression of c‐fos and cyclin A, necessary for sustaining the OB proliferation. Overall, our findings show that OBs respond to the presence of MKs, in part, via an integrin‐mediated signaling mechanism, activating a novel response axis that de‐represses cell cycle activity. Understanding the mechanisms by which MKs enhance OB proliferation will facilitate the development of novel anabolic therapies to treat bone loss associated with osteoporosis and other bone‐related diseases. J. Cell. Physiol. 230: 578–586, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Modulation of Mast Cell Proliferative and Inflammatory Responses by Leukotriene D4 and Stem Cell Factor Signaling Interactions
Authors: Al‐Azzam Nosayba , Kondeti Vinay , Duah Ernest , Gombedza Farai , Thodeti Charles K. , Paruchuri Sailaja
Published: August 2014

Mast cells (MCs) are important effector cells in asthma and pulmonary inflammation, and their proliferation and maturation is maintained by stem cell factor (SCF) via its receptor, c‐Kit. Cysteinyl leukotrienes (cys‐LTs) are potent inflammatory mediators that signal through CysLT1R and CysLT2R located on the MC surface, and they enhance MC inflammatory responses. However, it is not known if SCF and cys‐LTs cross‐talk and influence MC hyperplasia and activation in inflammation. Here, we report the concerted effort of the growth factor SCF and the inflammatory mediator LTD4 in MC activation. Stimulation of MCs by LTD4 in the presence of SCF enhances c‐Kit‐mediated proliferative responses. Similarly, SCF synergistically enhances LTD4‐induced calcium, c‐fos expression and phosphorylation, as well as MIP1β generation in MCs. These findings suggest that integration of SCF and LTD4 signals may contribute to MC hyperplasia and hyper‐reactivity during airway hyper‐response and inflammation. J. Cell. Physiol. 230: 595–602, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Determination of the distribution of electrical resistivity in reinforced concrete structures using electrical resistivity tomography
Authors: Reichling K. , Raupach M. , Klitzsch N.
Published: August 2014

Concrete resistivity is an important durability related material parameter. It correlates with various properties, e.g., the reinforcement corrosion rate, the water saturation degree and the porosity. The resistivity is typically determined on a structure by using the Wenner probe. Unfortunately the results can strongly be influenced by heterogeneities, e.g., reinforcement bars or inhomogeneous moisture distributions. Neglecting these effects can lead to significant misinterpretations. In order to consider these influences quantitatively the applicability of the electrical resistivity tomography (ERT) on reinforced concrete has been studied. The aim of the method is to determine the distribution of the concrete resistivity perpendicular to the concrete surface. Based on this data the spatial distribution of material properties can be derived and the influence of an inhomogeneous resistivity distribution on the corrosion rate of the reinforcement can be studied. ERT can be applied to determine the resistivity distribution of reinforced concrete within certain resolution limits. Within this work the influence of different electrode configurations and rebar positions as well as the improvement of the resolution by considering prior information are exemplarily shown. Compared to the Wenner configuration the resolution and accuracy can be improved significantly with dipole–dipole measurements.
Strategies for High Quality Injection Moulding of Polymer Nanopillars
Authors: Pedersen Rasmus H. , Xu Qian , Stormonth‐Darling John M. , Gadegaard Nikolaj
Published: August 2014

Injection moulding is a proven technology for high‐throughput production of nanostructures, but replication of raised structures is a considerable challenge, due to the complexities of cavity filling. We have developed a platform to systematically study the effects of nanostructures with aspect ratios up to 1.2:1. A master template containing nanostructures with a continuous variation in height is produced by a novel fabrication approach using a plasma polymerized hexane layer, deposited with a thickness gradient, as a sacrificial etch mask. Results show that a careful choice of process parameters can control the stretching of nanopillar replica dimensions, allowing a variety of final pattern heights using a single master.
Stable Cross‐linked Fluorescent Polymeric Nanoparticles for Cell Imaging
Authors: Li Haiyin , Zhang Xiqi , Zhang Xiaoyong , Yang Bin , Yang Yang , Wei Yen
Published: August 2014

Aggregation‐induced emission (AIE) dye‐based cross‐linked fluorescent polymeric nanoparticles (FPNs) are facilely prepared via a two‐step polymerization process including emulsion polymerization and subsequent anhydride cross‐linking. Then, a variety of characterization methods are carried out to determine the performance of the FPNs, which show high dispersibility and strong fluorescence in an aqueous solution due to the hydrophilic carboxyl groups on the surfaces and the AIE components as the cores. Biocompatibility evaluation and cell imaging results suggest that these FPNs are biocompatible for cell imaging. More importantly, this cross‐linking strategy is proven to overcome the issue of critical micelle concentration and opens the opportunity to develop more robust fluorescent bioprobes.

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Supramolecular Adhesives to Hard Surfaces: Adhesion Between Host Hydrogels and Guest Glass Substrates Through Molecular Recognition
Authors: Takashima Yoshinori , Sahara Taiga , Sekine Tomoko , Kakuta Takahiro , Nakahata Masaki , Otsubo Miyuki , Kobayashi Yuichiro , Harada Akira
Published: August 2014

Supramolecular materials based on host–guest interactions should exhibit high selectivity and external stimuli‐responsiveness. Among various stimuli, redox and photo stimuli are useful for its wide application. An external stimuli‐responsive adhesive system between CD host‐gels (CD gels) and guest molecules modified glass substrates (guest Sub) is focused. Here, the selective adhesion between host gels and guest substrates where adhesion depends on molecular complementarity is reported. Initially, it is thought that adhesion of a gel material onto a hard material might be difficult unless many guest molecules modified linear polymers immobilize on the surface of hard materials. However, reversible adhesion of the CD gels is observed by dissociating and re‐forming inclusion complex in response to redox and photo stimuli.

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Targeting the insulin‐like growth factor‐1 receptor by picropodophyllin for lung cancer chemoprevention
Authors: Zhang Qi , Pan Jing , Lubet Ronald A. , Wang Yian , You Ming
Published: August 2014

Insulin‐like growth factor‐1 receptor (IGF‐1R) is a transmembrane heterotetramer that is activated by Insulin‐like growth factor 1 and is crucial for tumor transformation and survival of malignant cells. Importantly, IGF‐1R overexpression has been reported in many different cancers, implicating this receptor as a potential target for anticancer therapy. Picropodophyllin (PPP) is a potent inhibitor of IGF‐1R and has antitumor efficacy in several cancer types. However, the chemopreventive effect of PPP in lung tumorigenesis has not been investigated. In this study, we investigated the chemopreventive activity of PPP in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and PPP was given by nasal inhalation to female A/J mice. Lung tumorigenesis was assessed by tumor multiplicity and tumor load. PPP significantly decreased tumor multiplicity and tumor load. Tumor multiplicity and load were decreased by 52% and 78% respectively by 4 mg/ml aerosolized PPP. Pharmacokinetics analysis showed good bioavailability of PPP in lung and plasma. Treatment with PPP increased staining for cleaved caspase‐3 and decreased Ki‐67 in lung tumors, suggesting that the lung tumor inhibitory effects of PPP were partially through inhibition of proliferation and induction of apoptosis. In human lung cancer cell lines, PPP inhibited cell proliferation, and also inhibited phosphorylation of IGF‐1R downstream targets, AKT and MAPK, ultimately resulting in increased apoptosis. PPP also reduced cell invasion in lung cancer cell lines. In view of our data, PPP merits further investigation as a promising chemopreventive agent for human lung cancer. © 2014 Wiley Periodicals, Inc.
Magnetic resonance imaging striatal volumes: A biomarker for clinical trials in Huntington's disease
Authors: Aylward Elizabeth H.
Published: August 2014

An abundance of research shows that magnetic resonance imaging (MRI) striatal volumes decrease long before diagnosis of Huntington's disease (HD) and closely track disease progression. Additional research indicates that these volumetric measures meet important criteria for a biomarker that can be used in clinical trials: They are 1) objectively measureable; 2) able to predict known endpoints; and 3) associated with known mechanisms of pathology of the disease. Researchers should consider formal application to regulatory agencies for biomarker status of volumetric MRI striatal measures, because these measures are anticipated to contribute significantly in the assessment of treatment effectiveness in HD. © 2014 International Parkinson and Movement Disorder Society
Huntingtin‐lowering strategies in Huntington's disease: Antisense oligonucleotides, small RNAs, and gene editing
Authors: Aronin Neil , DiFiglia Marian
Published: August 2014

The idea to lower mutant huntingtin is especially appealing in Huntington's disease (HD). It is autosomal dominant, so that expression of the mutant allele causes the disease. Advances in RNA and gene regulation provide foundations for the huntingtin gene (both normal and mutant alleles) and possibly the mutant allele only. There is much preclinical animal work to support the concept of gene and RNA silencing, but, to date, no clinical studies have been attempted in HD. Preventing expression of mutant huntingtin protein is at the cusp for a human trial. Antisense oligonucleotides delivered to patients with amyotrophic lateral sclerosis have been well tolerated; small RNAs administered to rodent and nonhuman primate brain knocked down huntingtin messenger RNA (mRNA); short‐hairpin complementary DNA of microRNAs can be expressed in adeno‐associated virus to provide long‐term silencing of huntingtin mRNA and protein. We expect that these approaches will be ready for clinical studies in the near future, once safety has been validated. Our understanding of gene editing—changing the huntingtin gene itself—is rapidly progressing. Harnessing our knowledge of transcription and translation should push scientific creativity to new and exciting advances that overcome the lethality of the mutant gene in HD. © 2014 International Parkinson and Movement Disorder Society
Effect of frying oils on the postprandial endoplasmic reticulum stress in obese people
Authors: Rangel‐Zuñiga Oriol A. , Haro Carmen , Perez‐Martinez Pablo , Delgado‐Lista Javier , Marin Carmen , Quintana‐Navarro Gracia M. , Tinahones Francisco J. , Malagón María M. , Lopez‐Segura Fernando , López‐Miranda Jose , Perez‐Jimenez Francisco , Camargo Antonio
Published: August 2014

The addition of antioxidants to frying oil reduces postprandial oxidative stress and the inflammatory response. ER stress may trigger both inflammation and oxidative stress processes. We aimed to determine the biological effects of the intake of four models of frying oils on postprandial ER stress in peripheral blood mononuclear cells. Twenty obese people received four breakfasts following a randomized crossover design, consisting of muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seed oils (SFO/canola oil) with either dimethylpolysiloxane (SOD) or natural antioxidants from olives (SOP) added), which were previously subjected to 20 heating cycles. ER stress was assessed by measuring the mRNA levels of sXBP1, BiP, CRT, and CNX in peripheral blood mononuclear cells. Our study showed that the intake of the muffins made with SFO induced the postprandial increase of the mRNA levels of the ER stress‐sensor sXBP1, and the ER stress related chaperones BiP and CRT (all p‐values <0.05). The harmful effects associated with the use of SFO as frying oil, in terms of inflammatory response and postprandial oxidative stress, may be partially mediated by the induction of postprandial ER stress.