bluuebunny/crossref_metadata_2025 huggingface dataset:
Faites un roi, ou faites la guerre : les organisations de l’Action française pendant la Grande Guerre (1914-1918)
Authors: Audet-Vallée Kevin
Published: September 2012

Peu approfondie dans l’historiographie de l’Action française, la période de la Grande Guerre n’en reste pas moins déterminante dans l’histoire de ce mouvement néoroyaliste et nationaliste français dont le parcours va de l’affaire Dreyfus au régime de Vichy. Tandis que ses maîtres à penser appelèrent leurs troupes à se rallier sans condition à « l’Union sacrée » du monde politique en faveur de la défense nationale, les militants du mouvement s’exilèrent en masse vers les tranchées. L’Action française, qui dans l’avant-guerre était structurée en un ensemble d’organisations présentes partout en France sous la forme de sections, se retrouva donc dépourvue entre 1914 et 1918 de sa force militante publique. Néanmoins, grâce aux efforts de quelques-uns de ses animateurs restés à « l’arrière front » et maintenant les activités du quotidien qu’il publiait, les idées du mouvement néoroyaliste avaient atteint à la fin de la guerre une notoriété inédite.
A Dosimetric Analysis of Tomotherapy Based Intensity Modulated Radiation Therapy with and without Bone Marrow Sparing in Gynecologic Malignancies
Authors: Platta Christopher S. , Bayliss Adam , McHaffie Derek , Tomé Wolfgang A. , Straub Margaret R. , Bradley Kristin A.
Published: September 2012

Whole pelvic radiotherapy with concurrent chemotherapy is the standard of care for locally advanced cervical carcinoma. Published literature reports that the pelvic bone marrow (BM) dosimetric parameters of V10 > 90% and V20 > 80% are associated with higher rates of hematologic toxicities using this approach. Here, we investigate the ability of Tomotherapy based intensity modulated radiation therapy (IMRT) to reduce dose to pelvic BM while evaluating dose distribution to critical structures and planning target volume (PTV) coverage. Ten patients were selected for analysis. Normal structures, whole pelvic BM, PTV contours, and IMRT objects were standardized. Two whole pelvis Tomotherapy plans were created for each patient, one standard plan, and one with the addition of a BM sparing (BMS) constraint (V10<85%, V20 < 80%). Data were calculated from multiple points with regard to BM dose, normal structure dose, and PTV coverage. Differences in dose distributions between the two sets of plans were analyzed using a paired t-test. The addition of a BMS planning constraint resulted in significant decreases in pelvic BM dose at the following dosimetric points: V5, V10, V15, V20, V30, V40, V50, and mean dose ( p < 0.05 for all points). There were no significant differences in dose to small bowel, bladder or rectum, with the exception of one data point (small bowel V30, p = 0.004) between the two sets of plans. There was no sacrifice of PTV coverage or loss of homogeneity with the addition of a BMS planning constraint. BMS-IMRT significantly reduces radiation dose to the pelvic BM while maintaining the ability to spare dose to the small bowel, bladder and rectum. The planning constraints were met without violation of study criteria, and without sacrifice of PTV coverage. Further investigation is warranted to determine if rates of hematologic toxicity improve with utilization of Tomotherapy based BMS-IMRT.
Purification and Concentration of Nucleic Acids
Authors: Dowhan Dennis H.
Published: September 2012

The purification and concentration of nucleic acids have become routine procedures in most biology and molecular biology laboratories. This unit covers the basic principles and procedures for the isolation, purification, and manipulation of solutions of DNA or RNA. The basic DNA protocol, using phenol extraction and ethanol precipitation, is appropriate for the purification of DNA from small volumes (<0.4 ml) at concentrations ≤1 mg/ml. Purification of DNA using commercially available silica membrane spin columns is presented as an alternate protocol. Isolation and purification of RNA from mammalian cells or tissues is also examined. Use of the protein denaturant guanidine thiocyanate and water‐saturated phenol, followed by concentration by isopropanol precipitation, for producing small samples of RNA, is illustrated in the basic RNA protocol. Curr. Protoc. Essential Lab. Tech. 6:5.2.1‐5.2.21. © 2012 by John Wiley & Sons, Inc.
A Pilot Study of Electrocortical Activity in Dysfunctional Anger: Decreased Frontocortical Activation, Impaired Attention Control, and Diminished Behavioral Inhibition
Authors: Jaworska Natalia , Berrigan Lindsay , Fisher Derek , Ahmed Adekunle G. , Gray Jonathan , Bradford John , Korovessis Athanassia , Fedoroff Paul , Knott Verner
Published: September 2012

Dysfunctional anger, though not a primary clinical diagnosis per se, does present clinically as a pathological mood for which treatment is sought. Few studies have probed the neurocortical correlates of dysfunctional anger or assessed if cognitive processes, such as attention, are altered in dysfunctional anger. Though dysfunctional and high trait anger appears to be associated with biased processing of anger‐eliciting information, few studies have examined if dysfunctional anger modulates attention more generally. This is a notable gap as volitional attention control is associated with effective emotive regulation, which is impaired in dysfunctional anger and in associated acts of aggression. In this pilot study, we examined performance and electroencephalographic (EEG) profiles during a 12‐min continuous performance task (CPT) of sustained attention in 15 adults with dysfunctional anger (Anger group) and 14 controls (control group). The Anger group had fewer hits at the end of the CPT, which correlated with decreased frontocortical activation, suggesting decreased engagement of frontal circuits when attention is taxed. The Anger group had more false alarms overall indicating impaired response inhibition. Increased right cortical activation during the initial portion of CPT existed in the Anger group, perhaps reflecting greater engagement of frontal circuits (i.e. effort) during initial stages of the task compared to controls. Finally, increased overall beta1 power, suggesting increased cortical activation, was noted in the Anger group. These EEG patterns suggest a hypervigilant state in dysfunctional anger, which may interfere with effective attention control and decrease inhibition. Such impairments likely extend beyond the laboratory setting, and may associate with aggressive acts in real life. Aggr. Behav. 38:469‐480, 2012. © 2012 Wiley Periodicals, Inc.
Highly Conductive Nanocomposites with Three‐Dimensional, Compactly Interconnected Graphene Networks via a Self‐Assembly Process
Authors: Wu Chao , Huang Xingyi , Wang Genlin , Lv Libing , Chen Gan , Li Guangyv , Jiang Pingkai
Published: September 2012

Polymer‐based materials with high electrical conductivity are of considerable interest because of their wide range of applications. The construction of a 3D, compactly interconnected graphene network can offer a huge increase in the electrical conductivity of polymer composites. However, it is still a great challenge to achieve desirable 3D architectures in the polymer matrix. Here, highly conductive polymer nanocomposites with 3D compactly interconnected graphene networks are obtained using a self‐assembly process. Polystyrene (PS) and ethylene vinyl acetate (EVA) are used as polymer matrixes. The obtained PS composite film with 4.8 vol% graphene shows a high electrical conductivity of 1083.3 S/m, which is superior to that of the graphene composite prepared by a solvent mixing method. The electrical conductivity of the composites is closely related to the compact contact between graphene sheets in the 3D structures and the high reduction level of graphene sheets. The obtained EVA composite films with the 3D graphene structure not only show high electrical conductivity but also exhibit high flexibility. Importantly, the method to fabricate 3D graphene structures in polymer matrix is facile, green, low‐cost, and scalable, providing a universal route for the rational design and engineering of highly conductive polymer composites.
Chaperone discovery
Authors: Quan Shu , Bardwell James C. A.
Published: September 2012

Molecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including the development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery.
Design of Cyclic Peptides Featuring Proline Predominantly in the cis Conformation under Physiological Conditions
Authors: Malešević Miroslav , Schumann Michael , Jahreis Günther , Fischer Gunter , Lücke Christian
Published: September 2012

Turns are secondary‐structure elements that are omnipresent in natively folded polypeptide chains. A large variety of four‐residue β‐turns exist, which differ mainly in the backbone dihedral angle values of the two central residues i+1 and i+2. The βVI‐type turns are of particular biological interest because the i+2 residue is always a proline in the cis conformation and might thus serve as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed cyclic hexapeptides containing two proline residues that predominantly adopt the cis conformation in aqueous solution. NMR data and MD calculations indicated that the cyclic peptide sequences c‐(‐DXaa‐Ser‐Pro‐DXaa‐Lys‐Pro‐) result in highly symmetric backbone structures when both prolines are in the cis conformation and the D‐amino acids are either alanine or phenylalanine residues. Replacement of the serine residue either by phosphoserine or by tyrosine compromises this symmetry, but further increases the cis conformation content of both prolines. As a result, we obtained a cyclic hexapeptide that exists almost exclusively as the cis‐Pro/cis‐Pro conformer but shows no cis/trans interconversion even in the presence of the PPIase Pin1, apparently due to an energetically quite favorable but highly restricted conformational space.
Asymmetric Total Synthesis of (−)‐Stenine and 9a‐epi‐Stenine
Authors: Fujioka Hiromichi , Nakahara Kenji , Kotoku Naoyuki , Ohba Yusuke , Nagatomi Yasushi , Wang Tsung‐Lung , Sawama Yoshinari , Murai Kenichi , Hirano Kie , Oki Tomohiro , Wakamatsu Shintaro , Kita Yasuyuki
Published: September 2012

A route for the asymmetric synthesis of (−)‐stenine, a member of the Stemona alkaloid family used as folk medicine in Asian countries, is described. The key features of the sequence employed include stereoselective transformations on a cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular Mitsunobu reaction to construct the perhydroindole ring system. By using an intermediate in the route to (−)‐stenine, an asymmetric synthesis of 9a‐epi‐stenine was also executed. The C(9a) stereocenter in 9a‐epi‐stenine was installed by using a Staudinger/aza‐Wittig reaction of a keto–azide precursor followed by reduction of the resulting imine. The results of this effort demonstrate the applicability of the chiral auxiliary based strategy to the preparation of naturally occurring alkaloids that contain highly functionalized cyclohexane cores.
Red‐Emitting Rhodamines with Hydroxylated, Sulfonated, and Phosphorylated Dye Residues and Their Use in Fluorescence Nanoscopy
Authors: Kolmakov Kirill , Wurm Christian A. , Hennig René , Rapp Erdmann , Jakobs Stefan , Belov Vladimir N. , Hell Stefan W.
Published: September 2012

Fluorescent dyes emitting red light are frequently used in conventional and super‐resolution microscopy of biological samples, although the variety of the useful dyes is limited. We describe the synthesis of rhodamine‐based fluorescent dyes with absorption and emission maxima in the range of 621–637 and 644–660 nm, respectively and demonstrate their high performance in confocal and stimulated emission depletion (STED) microscopy. New dyes were prepared by means of reliable chemical transformations applied to a rhodamine scaffold with three variable positions. They feature polarity, water solubility, variable net charges, improved stabilities of N‐hydroxysuccinimidyl (NHS) esters, as well as large fluorescence quantum yields in dye solutions and antibody conjugates. The photophysical and imaging properties of dyes containing three different polar groups, namely primary phosphate, sulfonic acid (in two different positions), and hydroxyl were compared. A dye with two primary phosphate groups was explored as a valuable alternative to dyes with “classical” sulfonic acid groups. Due to the increased net charge of the phosphorylated dye (q=−4 at pH 8), it demonstrated a far better electrophoretic mobility compared with analogues with two sulfonic acid groups (q=−2). As an example, one fluorescent dye was designed to be especially convenient for practical use. It is characterized by sufficiently high chemical stability of the NHS ester, its simple isolation, handling, and solubility in aqueous buffers, as well as in organic solvents. All these features, accompanied by a zero net charge in conjugates, were accomplished by the introduction of hydrophilic groups of two types: two hydroxyl groups and one sulfonic acid residue.
Multiple States of Dimeric Aggregates Formed by (Amido–ethynyl)helicene Bidomain Compound and (Amido–ethynyl–amido)helicene Tridomain Compound
Authors: Ichinose Wataru , Shigeno Masanori , Yamaguchi Masahiko
Published: September 2012

An (amido–ethynyl)helicene bidomain compound and an (amido–ethynyl–amido)helicene tridomain compound were synthesized. The multidomain compounds were designed on the basis of previous findings that amido and ethynyl oligomers form dimeric aggregates with properties orthogonal to each other. Four aggregate states of multidomain compounds, namely, all‐dimer, amido‐dimer, ethynyl‐dimer, and random‐coil states, were obtained in different solvents, which were analyzed by circular dichroism (CD), UV/Vis, 1H NMR, and IR spectroscopy; vapor pressure osmometry (VPO); dynamic light scattering (DLS); and atomic force microscopy (AFM). The amido and ethynyl domains independently aggregated and disaggregated in a two‐state manner. Reversible structural changes occurred for a tridomain compound between the ethynyl‐dimer/random‐coil state and the all‐dimer/amido‐dimer state with heating and cooling. Two structural change processes with different properties were obtained using a single compound.
Application of Supramolecular Bidentate Hybrid Ligands in Asymmetric Hydroformylation
Authors: Bellini Rosalba , Reek Joost N. H.
Published: September 2012

In this study we report a novel class of supramolecular bidentate hybrid ligands in which the two inequivalent phosphorus units and pyridine moieties are covalently attached to a chiral scaffold and the supramolecular interactions are used as a second handle to control the coordination sphere around the transition‐metal centre. The coordination chemistry of these ligands was investigated under hydroformylation conditions by high‐pressure NMR and IR spectroscopy, revealing the formation of a single active species in which the phosphane ligand is in the axial position and the phosphoramidite adopts the equatorial position. These ligands were applied in the asymmetric Rh‐catalysed hydroformylation of styrene and para‐substituted analogues. In these hydroformylation reactions, modification of the electronic and steric properties of the zinc(II)‐templates appear to have a significant influence on the activity and selectivity of the catalysis. In particular, zinc(II)‐templates bearing more electron‐withdrawing substituents led to an increase in enantioselectivity.
Application of Dispersive Liquid–Liquid Microextraction Based on Solidification of Floating Organic Droplet Multi‐residue Method for the Simultaneous Determination of Polychlorinated Biphenyls, Organochlorine, and Pyrethroid Pesticides in Aqueous Sample
Authors: Zuo Mei , Cheng Jing , Matsadiq Guzalnur , Liu Lu , Li Man‐Liang , Zhang Miao
Published: September 2012

Dispersive liquid–liquid microextraction based on solidification of floating organic droplet (DLLME‐SFO) technique was successfully applied for simultaneous assay of eight polychlorinated biphenyls, two organochlorine, and four pyrethroid pesticides multi‐residue in aqueous samples by using GC‐electron capture detection. The effects of various parameters such as kind of extractant and dispersant and volume of them, extraction time, effect of salt addition, and pH were optimized. As a result, 5.0 µL 1‐dodecanol was chosen as extraction solvent, 600 µL methanol were used as dispersive solvent without salt addition, pH was adjusted to 7. Under the optimized conditions, the limits of detection (LOD) were ranged from 1.4 to 8.3 ng L−1. Satisfactory linear range was observed from 5.0 to 2000 ng L−1 with correlation coefficient better than 0.9909. Good precisions were also acquired with RSD better than 13.6% for all target analytes. The enrichment factors of the method were ranged from 786 to 1427. The method can be successfully applied to simultaneous separation and determination of three class residues in real water samples and good recoveries were obtained ranging from 76 to 130, 73 to 129, and 78 to 130% for tap water, lake water, and industrial waste water, respectively.
Distribution and Contamination Assessment of Heavy Metals in Water and Soils from the College Town in the Pearl River Delta, China
Authors: Xiao Rong , Bai Junhong , Gao Haifeng , Wang Junjing , Huang Laibin , Liu Peipei
Published: September 2012

The accumulation of heavy metals such as Cu, Zn, Pb, Cd, Cr, and Ni in water and soils in a new‐built college town was investigated to demonstrate the effects of city construction on wetland ecosystem. Three sampling sites were chosen in wetland park (A), constructed wetland (B), and construction site (C), respectively. The results showed that the construction site C presented the highest accumulation levels of all six studied metals along soil profiles and hence had the highest eco‐toxicity to environment. Sites A and B showed similar accumulation levels, whereas their concentrations were significantly lower than those at site C though seriously high Cd were also found in soils from both sites A and B and dangerous concentration of Pb in water was observed at site A based on several standards or background concentration values. However, when compared with other regions in Pearl River Delta, this college town could be counted as “clean island” which may be benefit from its isolate location away from urban center and the effective management to avoid pollution.
Relation between Enzyme Activity of Sediments and Lake Eutrophication in Grass‐Type Lakes in North China
Authors: Zhang Yu , Cui Baoshan , Wang Shengrui , Chu Zhaosheng , Fan Xiaoyun , Hua Yanyan , Lan Yan
Published: September 2012

In order to discover the biochemistry mechanism of sediments in eutrophic grass‐type lakes, this study selected four grass‐type lakes in north China to explore the relation between enzyme activities of sediments and lake eutrophication condition. By applying the assessment method of organic nitrogen (ON) and total phosphorus (TP), the nutrition of lake sediments were assessed. As the results show, Hengshui (HS) Lake and Baiyangdian (BY) Lake, suffering severe pollution, have much higher urease activity in comparison with Nansi (NS) Lake and Dongping (DP) Lake. In addition, there is significant positive correlation between the urease activity and the contents of total nitrogen (TN) and organic matter (OM) of sediments (r = 0.805, p < 0.01; r = 0.840, p < 0.01). It's the same case between alkaline phosphatase (APA) activity and TP content (r = 0.876, p < 0.01). The activities of both cellulase and protease in HS Lake and BY Lake are weaker than those of NS Lake and DP Lake. The changes in the activities of polyphenol oxidase and peroxidase tend to be similar and their distributions are closely related to the degree of pollution and disruption caused by human activities. The enzymatic activity of lake sediments can serve as an indicator that reflects how serious lake eutrophication is.
Changes in Water Birds Habitat Suitability Following Wetland Restoration in the Yellow River Delta, China
Authors: Hua Yanyan , Cui Baoshan , He Wenjie
Published: September 2012

It has been 10 years since the 2002 implementation of a wetland restoration project in the Yellow River Delta, China. The project mainly aimed to improve natural habitat for rare birds by modifying hydrological processes. Integrated multi‐criteria evaluation methods and cartographic modeling based on long‐term field monitoring and surveying were used to determine habitat suitability for the critical bird species that belong to five orders in the study area. Results showed that the habitat suitability index (E) increased in the first 6 years but declined recently as vegetation coverage increased. Future wetland restoration efforts should consider the influence of vegetation coverage on the development of potential habitats. The results of this study will be of value in further restoration designs in the Yellow River Delta and other similar wetlands.
Systematic Structure–Activity Study on Potential Chaperone Lead Compounds for Acid α‐Glucosidase
Authors: Bruckmann Chiara , Repo Heidi , Kuokkanen Elina , Xhaard Henri , Heikinheimo Pirkko
Published: September 2012

Acid α‐glucosidase (GAA) is a lysosomal enzyme and a pharmacological target for Pompe disease, an inherited lysosomal storage disorder (LSD). An emerging treatment for LSDs is the use of pharmacological chaperones, small molecules that enhance total cellular activity of the target lysosomal protein. We have systematically studied thirteen inhibitors, which provide good lead compounds for the development of GAA chaperones. We have verified binding on GAA at low and neutral pH, mapping the range of pH during transport to lysosomes. These ligands inhibit GAA competitively and reversibly, and a few of the compounds show higher molecular stabilisation capacity than would be expected from their binding affinity. These molecules also increase lysosomal localisation of GAA variants in cells. In order to understand the specific molecular mechanism of the interactions, we docked the compounds to a homology model of the human GAA. Three factors contribute to the tightness of binding. Firstly, well‐positioned hydroxy groups are essential to orient the ligand and make the binding specific. Secondly, the open nature of the GAA active site allows both large and small ligands to bind. The third and most important binding determinant is the positive charge on the ligand, which is neutralised by Asp 518 or Asp 616 on GAA. Our study creates a firm basis for the design of drugs to treat Pompe disease, as it provides a comparable study of the ligand properties. Our analysis suggests a useful drug design framework for specific pharmacological chaperones for human GAA.
The combination of alisertib, an investigational Aurora kinase A inhibitor, and docetaxel promotes cell death and reduces tumor growth in preclinical cell models of upper gastrointestinal adenocarcinomas
Authors: Sehdev Vikas , Katsha Ahmed , Ecsedy Jeffrey , Zaika Alexander , Belkhiri Abbes , El‐Rifai Wael
Published: September 2012

BACKGROUND:

Upper gastrointestinal adenocarcinomas (UGCs) respond poorly to current chemotherapeutic regimes. The authors and others have previously reported frequent Aurora kinase A (AURKA) gene amplification and mRNA and protein overexpression in UGCs. The objective of the current study was to determine the therapeutic potential of alisertib (MLN8237) alone and in combination with docetaxel in UGCs.

METHODS:

After treatment with alisertib and/or docetaxel, clonogenic cell survival, cell cycle analyses, Western blot analyses, and tumor xenograft growth assays were carried out to measure cell survival, cell cycle progression, apoptotic protein expression, and tumor xenograft volumes, respectively.

RESULTS:

By using the AGS, FLO‐1, and OE33 UGC cell lines, which have constitutive AURKA overexpression and variable tumor protein 53 (p53) status, significantly enhanced inhibition of cancer cell survival was observed with alisertib and docetaxel treatment in combination (P < .001), compared with single‐agent treatments. Cell cycle analyses, after 48 hours of treatment with alisertib, produced a significant increase in the percentage of polyploidy in UGC cells (P < .01) that was further enhanced by docetaxel (P < .001). In addition, an increase in the percentage of cells in sub‐G1‐phase observed with alisertib (P < .01) was significantly enhanced with the combination treatment (P < .001). Western blot analysis demonstrated higher induction of cleaved caspase 3 protein expression with the combined treatment compared with single‐agent treatments. In addition, FLO‐1 and OE33 cell xenograft models demonstrated enhanced antitumor activity for the alisertib and docetaxel combination compared with single‐agent treatments (P < .001).

CONCLUSIONS:

The current study demonstrated that alisertib combined with docetaxel can mediate a better therapeutic outcome in UGC cell lines. Cancer 2013. © 2012 American Cancer Society.
Chemotherapy use and patient treatment preferences in advanced colorectal cancer
Authors: Zafar S. Yousuf , Malin Jennifer L. , Grambow Steven C. , Abbott David H. , Kolimaga Jane T. , Zullig Leah L. , Weeks Jane C. , Ayanian John Z. , Kahn Katherine L. , Ganz Patricia A. , Catalano Paul J. , West Dee W. , Provenzale Dawn ,   for the Cancer Care Outcomes Research & Surveillance (CanCORS) Consortium
Published: September 2012

BACKGROUND:

The objective of this study was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer.

METHODS:

Eligible patients with metastatic colorectal cancer (mCRC) were enrolled nationwide in a prospective, population‐based cohort study. Data were obtained through medical record abstraction and patient surveys. Logistic regression analysis was used to evaluate patient characteristics associated with visiting medical oncology and receiving chemotherapy and patient characteristics, beliefs, and preferences associated with receiving >1 line of chemotherapy and receiving combination chemotherapy.

RESULTS:

Among 702 patients with mCRC, 91% consulted a medical oncologist; and among those, 82% received chemotherapy. Patients ages 65 to 75 years and aged ≥75 years were less likely to visit an oncologist, as were patients who were too sick to complete their own survey. In adjusted analyses, patients aged ≥75 years who had moderate or severe comorbidity were less likely to receive chemotherapy, as were patients who were too sick to complete their own survey. Patients received chemotherapy even if they believed that chemotherapy would not extend their life (90%) or that chemotherapy would not likely help with cancer‐related problems (89%), or patients preferred treatment focusing on comfort even if it meant not living as long (90%). Older patients were less likely to receive combination first‐line therapy. Patient preferences and beliefs were not associated with receipt of >1 line of chemotherapy or combination chemotherapy.

CONCLUSIONS:

The majority of patients received chemotherapy even if they expressed negative or marginal preferences or beliefs regarding chemotherapy. Patient preferences and beliefs were not associated with the intensity or number of chemotherapy regimens. Cancer 2013. © 2012 American Cancer Society.
Molecular profiling of synovial joints: Use of microarray analysis to identify factors that direct the development of the knee and elbow
Authors: Pazin Dorothy E. , Gamer Laura W. , Cox Karen A. , Rosen Vicki
Published: September 2012

Background: Synovial joints develop from the interzone, a dense layer of mesenchymal progenitor cells that marks the site of the future joint. During the morphogenic events that follow, joints attain their distinct shape and organization. The molecular mechanisms controlling the initial specification of synovial joints has been studied, but the question of how individual joints attain the specific structure required for their unique functions remains largely unresolved. Here, we use microarray analysis to compare knee and elbow formation to identify factors involved in the development of specific joints. Results: The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor‐beta/bone morphogenetic protein (TGFβ/BMP) and Wnt signaling. Consistent with these findings, we show that TGFβ signaling directs knee morphogenesis, and is necessary for meniscus development. The tissue surrounding the elbow is highly enriched for genes involved in muscle specification and differentiation, and in splotch‐delayed muscleless mutants, elbow, but not knee morphogenesis is disrupted. Conclusions: Our results suggest there are fundamental differences in how individual joints develop after interzone formation. Our microarray analyses provides a new resource for further investigation of the pathways involved in the morphogenesis of specific synovial joints. Developmental Dynamics 241:1816–1826, 2012. © 2012 Wiley Periodicals, Inc.
The regulation of endogenous retinoic acid level through CYP26B1 is required for elevation of palatal shelves
Authors: Okano Junko , Kimura Wataru , Papaionnou Virginia E. , Miura Naoyuki , Yamada Gen , Shiota Kohei , Sakai Yasuo
Published: September 2012

Background: In previous studies, we investigated the effects of excess retinoic acid (RA) during palatogenesis by RA administration to pregnant mice. In the present study, we deleted Cyp26b1, one of the RA‐degrading enzymes, to further study the effects of excess RA in the normal developing palate and to understand how endogenous levels of RA are regulated. Results: Excess RA, due to the absence of Cyp26b1, targets cells in the bend region of the palatal shelves and inhibits their horizontal elevation, leading to cleft palate. An organ culture of Cyp26b1−/− palatal shelves after tongue removal did not rescue the impaired elevation of the palatal shelves. The expression of Fgf10, Bmp2, and Tbx1, important molecules in palatal development, was down‐regulated. Cell proliferation was decreased in the bend region of palatal shelves. Tongue muscles were hypoplastic and/or missing in Cyp26b1−/− mice. Conclusions: We demonstrated that CYP26B1 is essential during palatogenesis. Excess RA due to the lack of Cyp26b1 suppresses the expression of key regulators of palate development in the bend region, resulting in a failure in the horizontal elevation of the palatal shelves. The regulation of RA signaling through CYP26B1 is also necessary for the development of tongue musculature and for tongue depression. Developmental Dynamics 241:1744–1756, 2012. © 2012 Wiley Periodicals, Inc.
Copper(II) Cubane Complexes Built from Electro‐ and Photosensitive β‐Aminovinyl Trifluoromethyl Ketone Ligands
Authors: Chopin Nicolas , Chastanet Guillaume , Le Guennic Boris , Médebielle Maurice , Pilet Guillaume
Published: September 2012

A new family of [Cu4L4] cubane complexes have been synthesized by the self‐assembly of CuII salts and β‐aminovinyl trifluoromethyl ketone ligands. The resulting polynuclear architectures were especially designed to exhibit magnetic properties arising from the metallic cubane architecture as well as electro‐ or photosensitive properties arising from the ligands. The optical and electrochemical behaviours of the compounds were measured in solution to confirm that the properties of the free ligands were retained within the elaborated complexes. DFT investigations of the organic moieties were conducted with the aim of assigning the observed electronic processes to the different redox steps and absorption bands. The crystal structures of the polynuclear complexes were solved and refined by single‐crystal X‐ray diffraction analysis and correlated to variable‐temperature magnetic susceptibility data. The overall expected ferromagnetic behaviour of the [Cu4L4] complexes is weakly influenced by the ligand substitutions. Ab initio configuration interaction calculations helped us to detail the variations of the various magnetic exchange pathways.
Asymmetric Synthesis of Potent and Selective σ1 Receptor Ligands with Tetrahydro‐3‐benzazepine Scaffold
Authors: Sarkar Soumya , Schepmann Dirk , Köhler Jens , Fröhlich Roland , Wünsch Bernhard
Published: September 2012

A new strategy for the synthesis of tetrahydro‐3‐benzazepinones 6 by reductive amination of keto acid 3 and subsequent carbonyl diimidazole (CDI) mediated cyclization was developed. Use of enantiomerically pure (R)‐1‐phenylethylamine led to the formation of diastereomeric lactams (Rα‐R)‐6d and (Rα‐S)‐6e in a 80:20 ratio. Diastereoselective alkylation of (Rα‐R)‐6d, BH3‐mediated reduction and exchange of the N‐phenylethyl substituent provided enantiomerically pure tetrahydro‐3‐benzazepines with various substituents in the 1‐, 3‐, and 4‐positions. High σ1 affinity was achieved with a benzyl, cyclohexylmethyl, or 1‐phenylethyl moiety at the N‐atom. Whereas (R)‐configuration of the N‐substituent is crucial for high σ1 affinity, the configuration of the 3‐benzazepine ring system does not influence the σ1 affinity considerably. Introduction of additional substituents in the 1‐position led to almost complete loss of σ1 affinity. Potent σ1 ligands show high selectivity against the σ2 subtype and the NMDA receptor.
Advances in automated detection of sand dunes on Mars
Authors: Bandeira Lourenço , Marques Jorge S. , Saraiva José , Pina Pedro
Published: September 2012

This paper describes advances in an automatic approach for the detection of sand dunes of Mars, based on supervised learning techniques. A set of features (gradient histogram) is extracted from the remotely sensed images and two classifiers (Support Vector Machine and Random Forests) are trained from this data. The evaluation is conducted on 230 MOC‐NA images (spatial resolution between 1·45 and 6·80 m/pixel) leading to about 89% of correct detections. A detailed analysis of the detection results (dune/non‐dune) is performed by dune type or bulk shape, confirming high performances independently of the way the dataset is analysed. This demonstrates the robustness and adequacy of the automated approach to deal with the large variety of aeolian structures present on the surface of Mars. Copyright © 2012 John Wiley & Sons, Ltd.
The Effects of School Bonding on High School Seniors’ Academic Achievement
Authors: Bryan Julia , Moore‐Thomas Cheryl , Gaenzle Stacey , Kim Jungnam , Lin Chia‐Huei , Na Goeun
Published: September 2012

The authors examine the effects of school bonding on academic achievement (measured by math achievement scores) in a sample of 12th graders from the Educational Longitudinal Study of 2002 (Ingels, Pratt, Rogers, Siegel, & Stutts, 2005). Components of school bonding have proximal and distal effects on academic achievement. Attachment to school and school involvement had direct effects on achievement; attachment to teachers and school commitment behaviors had indirect effects on achievement through school‐related delinquency and prior achievement. Implications for counselors are discussed.
Multiobjective optimization design of concentric ring arrays with 3D beam scanning using differential evolution algorithm
Authors: Zhang Li , Jiao Yong‐Chang , Chen Bo , Weng Zi‐Bin
Published: September 2012

This paper presents a multiobjective differential evolution (MODE) algorithm for designing concentric ring arrays with three‐dimensional (3D) beam scanning. The problem formulation of the concentric ring arrays with 3D beam scanning based on the optimization of the array geometry is a constrained multiobjective optimization problem. To obtain 3D beam scanning, concentric ring array geometries are optimized. The design tradeoffs, namely, the directivity, peak sidelobe level, and the total number of elements of the concentric ring array, are captured by using MODE. MODE adopts an external archive to retain nondominated solutions that are found during the evolutionary process. The method yields the distribution of the objective function values and the corresponding array configurations. In addition, the nondominated sorting genetic algorithm‐II (NSGA‐II), which is a well‐known multiobjective evolutionary algorithm, is also employed to optimize the proposed problems. The comparison with the results of NSGA‐II reveals the superiority of the MODE approach and confirms its potential for the array synthesis problems. Copyright © 2012 John Wiley & Sons, Ltd.
Climate impact of deforestation over South Sudan in a regional climate model
Authors: Salih Abubakr A. M. , Körnich Heiner , Tjernström Michael
Published: September 2012

This study examines the sensitivity of climate to changes in vegetation cover and land use in South Sudan. The focus lies on the effect of deforestation on precipitation and surface temperature especially during the rainy season. Sensitivity experiments are performed with the third version of the Abdus Salam International Centre for Theoretical Physics Regional Climate Model (RegCM3) where the present forest and vegetation cover south of 10°N in Sudan are replaced by either grass or, as an extreme case, desert. The model experiments were conducted for a time period of almost 21 years, from January 1989 to August 2009, and were preceded by a control experiment to ascertain the fidelity of the model simulations. The experiments indicate that the vegetation changes affect precipitation and surface temperature in both Southern and Central Sudan significantly although the land cover changes were imposed only in the south. The precipitation during the rainy season (June through September) was reduced in the perturbed region by about 0.1–2.1 mm d−1 for the desert scenario and by 0.1–0.9 mm d−1 for the grass scenario. The surface temperature increases by about 1.2 and 2.4 °C in the grass and desert scenario, respectively. The precipitation reduction is thus not only local but also extends to Central Sudan and neighbouring regions. The study demonstrates significant dependency for Southern and Central Sudan precipitation on the land use in Southern Sudan and indicates that the deforestation has both local and non‐local regional climatic effects.
Atmospheric circulation types and winter daily precipitation in Iran
Authors: Raziei Tayeb , Bordi Isabella , Santos João A. , Mofidi Abbas
Published: September 2012

The relationship between daily large‐scale atmospheric circulation types (CTs) and wintertime daily precipitation over Iran during the period 1965–2000 is investigated. Twelve atmospheric CTs identified in a previous study, which applied the K‐means clustering technique to the rotated principal components (RPCs) of the 500 hPa geopotential height fields, are also considered in this study. The leading spatial modes of daily precipitation variability over Iran are extracted by a PC analysis, with Varimax rotation, applied to the APHRODITE (Asian Precipitation‐Highly Resolved Observational Data Integration Towards Evaluation of the Water Resources) gridded precipitation dataset; six Iranian sub‐regions with independent precipitation variability are identified. The relationships between the CTs and the daily precipitation are investigated by computing: (1) the spatial patterns of the performance index (PI) for each CT and (2) the cross tabulations between the frequencies of occurrence of the CTs and the RPC scores of the daily precipitation, associated with each of the six sub‐regions. Results suggest that two particular CTs affect the precipitation occurrence over most of the country, while the remaining ten provide more regional or negligible contributions to precipitation. The more (less) influencing CTs in each precipitation sub‐region are then identified and a characterization of the main large‐scale atmospheric features governing the winter precipitation fields is provided.
ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma
Authors: Power Patricia F. , Mak Isabella W. Y. , Singh Shalini , Popovic Snezana , Gladdy Rebecca , Ghert Michelle
Published: September 2012

Chondrosarcoma is a unique type of bone cancer in that it does not respond to chemotherapy or radiation therapy, and therefore many affected patients die from metastatic disease. Metastasis has been correlated with the upregulation of the matrix metalloproteinase (MMP) family of proteases, which can degrade extracellular components. ETV5 is a transcription factor which has shown to be overexpressed in various types of invasive tumors. We hypothesized that ETV5 regulates MMP2 in human chondrosarcoma with the protease acting as a downstream effector. Gene knock‐down of ETV5 in human chondrosarcoma cells reduces MMP2 mRNA expression as well as decreased protein production and significantly decreased MMP2 activity. With plasmid transfected ETV5 upregulation, MMP2 expression is similarly upregulated at the gene expression and protein levels. Data from our bone resorption studies revealed that when a matrix metalloproteinase‐2 inhibitor is added to the growth media of chondrosarcoma cells, collagen released from bone chips incubated with the cells decreased by 27%. This data suggests that ETV5 has a significant role in regulating MMP2 expression and therefore matrix resorption in human chondrosarcoma, and thus may be a targetable upstream effector of the metastatic cascade in this cancer. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 493–501, 2013
GOSH – a graphical display of study heterogeneity
Authors: Olkin Ingram , Dahabreh Issa J. , Trikalinos Thomas A.
Published: September 2012

Estimates from individual studies included in a meta‐analysis often are not in agreement, giving rise to statistical heterogeneity. In such cases, exploration of the causes of heterogeneity can advance knowledge by formulating novel hypotheses. We present a new method for visualizing between‐study heterogeneity using combinatorial meta‐analysis. The method is based on performing separate meta‐analyses on all possible subsets of studies in a meta‐analysis. We use the summary effect sizes and other statistics produced by the all‐subsets meta‐analyses to generate graphs that can be used to investigate heterogeneity, identify influential studies, and explore subgroup effects. This graphical approach complements alternative graphical explorations of data. We apply the method to numerous biomedical examples, to allow readers to develop intuition on the interpretation of the all‐subsets graphical display. The proposed graphical approach may be useful for exploratory data analysis in systematic reviews. Copyright © 2012 John Wiley & Sons, Ltd.
Nutritional content of fresh and canned peaches
Authors: Durst Robert W , Weaver George W
Published: September 2012

BACKGROUND: The objective of this study was to assess whether canned peaches could deliver nutrient levels comparable to fresh peaches. Fresh freestone peaches, fresh cling peaches and canned cling peaches were analyzed for vitamins A, C and E, folate, antioxidants, total phenolics and total carotenoids to assess how these nutrients were affected by the canning process and whether storage further changed these components.

RESULTS: The vitamins and phytochemicals measured in this study were found to be present in canned cling peaches versus fresh freestone at statistically significantly higher levels (vitamin C, antioxidants and folate); higher but not statistically different levels (vitamin A); or lower, but not statistically different levels (vitamin E, total phenolics and total carotenoids). There were no statistically significant changes in nutrient content during storage for 3 months.

CONCLUSIONS: The nutritional content of canned peaches has been shown in this study to be comparable to that of fresh peaches. There were no statistically significant decreases in those nutritional parameters measured in this study between fresh freestone peaches and canned cling peaches. Vitamins A and E along with total carotenoids decrease immediately upon processing, but appear to stabilize after the processing step, showing minimal additional changes upon storage for 3 months. This study shows that canned peaches can provide comparable nutrient levels to the consumer as fresh peaches, meaning that consumers can enjoy peaches year round without worrying about loss of nutrients in their diet. © 2012 Society of Chemical Industry
Identification of flavonoids with trypsin inhibitory activity extracted from orange peel and green tea leaves
Authors: Shahwar Durre , Raza Muhammad A , Atta‐Ur‐Rahman
Published: September 2012

Background

Orange peel (Citrus sinensis) and green tea (Camellia sinensis) leaves, rich sources of food flavonoids, were analyzed for their trypsin inhibitory potential. Hesperetin, rutin and hesperidin from orange peel, and catechin from green tea leaves, were isolated and their chemical structures were analyzed. All four compounds were evaluated for their trypsin inhibitory potential.

Results

Among all the isolated compounds, rutin exhibited the highest protease inhibition activity (75.4 ± 0.9%) with IC50 = 16 ± 2 µmol L−1, followed by catechin (65.3 ± 1.4%; IC50 = 83 ± 9 µmol L−1), hesperetin (62.1 ± 1.3%; IC50 = 104 ± 12 µmol L−1) and hesperidin (59.7 ± 1.1%; IC50 = 127 ± 14 µmol L−1). Lineweaver–Burk and Dixon plots and their secondary replots indicated that all four compounds possessed non‐competitive inhibition. The Ki values of hesperetin, rutin, hesperidin and catechin were calculated as 90.2 ± 1.1, 17.5 ± 0.6, 84.2 ± 1.5 and 65.1 ± 1.5 µmol L−1 respectively.

Conclusion

The present results suggest that the four isolated flavonoids can be used as a supplement in food for the treatment of pathologies associated with the degradation of a specific protein. © 2012 Society of Chemical Industry
A potential biodegradable lubricant from castor biodiesel esters
Authors: da Silva José André Cavalcanti , Habert Alberto Cláudio , Freire Denise Maria Guimarães
Published: September 2012

Worldwide, 12 million tonnes per year of lubricants are disposed of in the environment through leakages, exhausted gas, incorrect disposal, water–oil emulsions and so on. Some are resistant to biodegradation, representing an environmental threat. One solution to modify this situation is the replacement of mineral oils by biodegradable synthetic lubricants. Esters, whose chemical structures are similar to natural triglycerides, are excellent substitutes for mineral oils. Castor oil contains around 90% ricinoleic acid, and as a result, castor oil has a higher viscosity and a lower viscosity index, compared with other vegetable oils. This work was based on the production of biodegradable lubricant base fluids from castor biodiesel esters, using various chemical catalysts to yield products with interesting properties, such as high viscosity index and good oxidation stability, compared with mineral oils. This route to lubricants is safer, more economical and more efficient. Copyright © 2012 John Wiley & Sons, Ltd.
Cultivating wisdom
Authors: Garvey Berger Jennifer
Published: September 2012

Berger believes that with dizzying change, leaders have an almost unprecedented scope to shape and create the future. They must move beyond good judgment to cultivating wisdom. She explains how our minds and emotions develop, leading to a goal of a “self‐transforming” form of mind, even higher than the highly evolved “self‐authored” one: “These leaders can use the tension of very different stakeholders to create innovation rather than discord. They see the biggest picture and reach far into the future in their vision. They hold the often‐conflicting requirements of health of individuals, organization, community, and the planet simultaneously.”