bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicogenomics discrimination of potential hepatocarcinogenicity of non‐genotoxic compounds in rat liver
Authors: Yamada Fumihiro , Sumida Kayo , Uehara Takeki , Morikawa Yuji , Yamada Hiroshi , Urushidani Tetsuro , Ohno Yasuo
Published: July 2012

Long‐term carcinogenicity testing of a compound is exceedingly time‐consuming and costly, and requires many test animals, whereas the Ames test, which is based on the assumption that any substance that is mutagenic may also exert carcinogenic potential, is useful as a short‐term screening assay but has major drawbacks. Although, in fact, 90% of compounds that give a positive Ames test cause cancer in laboratory animals, a good proportion of compounds that give a negative Ames test are also carcinogens; that is, there is no good correlation between carcinogenicity and negative Ames test results. As an alternative to these two approaches, we have tried applying toxicogenomics to predict the carcinogenicity of a compound from the gene expression profile induced in vivo. To establish our model, male Sprague–Dawley rats were orally administered test compounds (12 hepatocarcinogens and 26 non‐hepatocarcinogens) for 28 days. Analysis of liver gene expression data by Support Vector Machines (SVM) dividing compounds into ‘for training’ and ‘for test’ (20 cases assigned randomly) allowed a set of marker genes to be tested for prediction of hepatocarcinogenicity. The developed prediction model was then validated with reference to the concordance rate with training data and test data, and a good performance was obtained. We will have new gene expression data and continue the validation of our model. Copyright © 2012 John Wiley & Sons, Ltd.
From molecular structure to tissue architecture: collagen organization probed by SHG microscopy
Authors: Cicchi Riccardo , Vogler Nadine , Kapsokalyvas Dimitrios , Dietzek Benjamin , Popp Jürgen , Pavone Francesco Saverio
Published: July 2012

Second‐harmonic generation (SHG) microscopy is a fantastic tool for imaging collagen and probing its hierarchical organization from molecular scale up to tissue architectural level. In fact, SHG combines the advantages of a non‐linear microscopy approach with a coherent modality able to probe molecular organization. In this manuscript we review the physical concepts describing SHG from collagen, highlighting how this optical process allows to probe structures ranging from molecular sizes to tissue architecture, through image pattern analysis and scoring methods. Starting from the description of the most relevant approaches employing SHG polarization anisotropy and forward – backward SHG detection, we then focus on the most relevant methods for imaging and characterizing collagen organization in tissues through image pattern analysis methods, highlighting advantages and limitations of the methods applied to tissue imaging and to potential clinical applications. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Paxillin contracts the osteoclast cytoskeleton
Authors: Zou Wei , DeSelm Carl J , Broekelmann Thomas J , Mecham Robert P , Vande Pol Scott , Choi Kyunghee , Teitelbaum Steven L
Published: July 2012

Osteoclastic bone resorption depends upon the cell's ability to organize its cytoskeleton via the αvβ3 integrin and osteoclastogenic cytokines. Because paxillin associates with αvβ3, we asked if it participates in skeletal degradation. Unlike deletion of other αvβ3-associated cytoskeleton-regulating molecules, which impairs the cell's ability to spread, paxillin-deficient (Pax−/−) osteoclasts, generated from embryonic stem cells, “superspread” in response to receptor activator of NF-κB ligand (RANKL) and form large, albeit dynamically atypical, actin bands. Despite their increased size, Pax−/− osteoclasts resorb bone poorly, excavating pits approximately one-third normal depth. Ligand-occupied αvβ3 or RANKL promotes paxillin serine and tyrosine phosphorylation, the latter via cellular sarcoma (c-Src). The abnormal Pax−/− phenotype is rescued by wild-type (WT) paxillin but not that lacking its LD4 domain. In keeping with the appearance of mutant osteoclasts, WT paxillin, overexpressed in WT cells, contracts the cytoskeleton. Most importantly, the abnormal phenotype of Pax−/− osteoclasts likely represents failed RANKL-mediated delivery of myosin IIA to the actin cytoskeleton via the paxillin LD4 domain but is independent of tyrosine phosphorylation. Thus, in response to RANKL, paxillin associates with myosin IIA to contract the osteoclast cytoskeleton, thereby promoting its bone-degrading capacity. © 2012 American Society for Bone and Mineral Research.
Deuterium nuclear magnetic resonance unambiguously quantifies pore and collagen-bound water in cortical bone
Authors: Ong Henry H , Wright Alexander C , Wehrli Felix W
Published: July 2012

Bone water (BW) plays a pivotal role in nutrient transport and conferring bone with its viscoelastic mechanical properties. BW is partitioned between the pore spaces of the Haversian and lacuno-canalicular system, and water predominantly bound to the matrix proteins (essentially collagen). The general model of BW is that the former predominantly experiences fast isotropic molecular reorientation, whereas water in the bone matrix undergoes slower anisotropic rotational diffusion. Here, we provide direct evidence for the correctness of this model and show that unambiguous quantification in situ of these two functionally and dynamically different BW fractions is possible. The approach chosen relies on nuclear magnetic resonance (NMR) of deuterium (2H) that unambiguously separates and quantifies the two fractions on the basis of their distinguishing microdynamic properties. Twenty-four specimens of the human tibial cortex from 6 donors (3 male, 3 female, ages 27–83 years) were cored and 2H spectra recorded at 62 MHz (9.4 Tesla) on a Bruker Instruments DMX 400 spectrometer after exchange of native BW with 2H2O. Spectra consisted of a doublet signal resulting from quadrupole interaction of water bound to collagen. Doublet splittings were found to depend on the orientation of the osteonal axis with respect to the magnetic field direction (8.2 and 4.3 kHz for parallel and perpendicular orientation, respectively). In contrast, the isotropically reorienting pore-resident water yielded a single resonance line superimposed on the doublet. Nulling of the singlet resonance allowed separation of the two fractions. The results indicate that in human cortical bone 60% to 80% of detectable BW is collagen-bound. Porosity determined as the difference between total BW and collagen bound water fraction was found to strongly parallel micro–computed tomography (µCT)-based measurements (R2 = 0.91). Our method provides means for direct validation of emerging relaxation-based measurements of cortical bone porosity by proton MRI. © 2012 American Society for Bone and Mineral Research © 2012 American Society for Bone and Mineral Research
One‐pot Three‐component Synthesis of Spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] Derivatives Catalyzed by Melamine Trisulfonic Acid
Authors: Yang Li‐Min , Sun Peng‐Li , Wu Li‐Qiang
Published: July 2012

Novel spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] derivatives were prepared by the three‐component reaction of isatins 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine and Meldrum's acid in the presence of a catalytic amount of melamine trisulfonic acid. This protocol provides a simple one‐step procedure with the advantages of easy work‐up, mild reaction conditions and environmentally benign.
Preparation and Enhanced Electrochemical Performance of MnO2 Nanosheets for Supercapacitors
Authors: Mondal Anjon Kumar , Wang Bei , Su Dawei , Wang Ying , Zhang Xiaogang , Wang Guoxiu
Published: July 2012

MnO2 nanosheets have been synthesized by using a redox reaction of manganese nitrate tetrahydrate and potassium permanganate without any surfactants. The morphology and microstructure of the as‐prepared material were characterized by field emission scanning electron microscopy, transmission electron microscopy and X‐ray diffraction (XRD). Electrochemical performances as electrode materials for supercapacitor were evaluated using cyclic voltammetry and galvanostatic charge‐discharge in 1 M Na2SO4 aqueous electrolyte. It was found that MnO2 nanosheets showed an excellent capacitive behaviour with good cycling stability. The specific capacitance of the MnO2 nanosheet electrode can reach up to 332.8 Fg−1 at a current density of 500 mA/g and a stable cycling performance.
TYPES OF SOCIAL SUPPORT PROVIDED BY PARENTS, TEACHERS, AND CLASSMATES DURING ADOLESCENCE
Authors: Hombrados‐Mendieta Ma Isabel , Gomez‐Jacinto Luis , Dominguez‐Fuentes Juan Manuel , Garcia‐Leiva Patricia , Castro‐Travé Margarita
Published: July 2012

This study investigated social support networks (father, mother, classmates, and teachers) in a sample of 447 adolescents aged between 12 and 18 years. Using a cross‐sectional design, the main aim was to analyze differences in the sources of family and school support during adolescence based on a multidimensional perspective, focusing on the frequency of and satisfaction with emotional, instrumental, and informational support provided by the sources. The results suggest that the mother is the main provider of support. Parents mainly provide emotional and instrumental support, classmates provide informational and emotional support, and teachers provide informational support. Informational support was provided significantly more frequently than any other type and satisfaction with informational support was greater. There was a trend for parental support to decrease as support from classmates increased. We also found gender differences; compared with boys, girls received less support from the father and more support from classmates.
IMPLEMENTATION OF A COMMUNITY‐BASED FAMILY‐CENTERED PROGRAM IN PORTUGAL: A MULTIPLE CASE STUDY EVALUATION
Authors: Teixeira de Melo Ana , Alarcão Madalena
Published: July 2012

Family‐centered, community‐based programs are particularly suited to support families with at‐risk children or maltreated children and achieve family preservation or reunification. In these child protection and child welfare cases, assessment is of great importance to inform decision making. But the implementation of services to support the families change and its evaluation in real settings is not without challenges. The Integrated Family Assessment and Intervention Model (IFAIM) was designed to conduct assessment and intervention with multichallenged families with at‐risk or maltreated children and support the activities of the child protection system. In this article, we describe a pragmatic, focused on improvement, action research multicase study of the process and outcome of IFAIM's first implementation. Multiple factors affected implementation, namely, factors related with the teams, the organizations, and the communities. An improved model of implementation based on the evaluation results is proposed.
TESTING A COMPREHENSIVE COMMUNITY PROBLEM‐SOLVING FRAMEWORK FOR COMMUNITY COALITIONS
Authors: Yang Evelyn , Foster‐Fishman Pennie , Collins Charles , Ahn Soyeon
Published: July 2012

Community problem solving is believed to help coalitions achieve community changes and subsequent population‐level reductions in targeted community health problems. This study empirically examined a community problem solving model used by CADCA, a national coalition training organization, to determine if the model explains how coalitions become effective community change agents and the extent to which it fits for different types of coalitions. The sample consisted of 551 substance abuse coalitions, and SEM was used to test the research questions. Results suggest the overall conceptual model fits the data and provides an adequate representation of the community problem solving process for coalitions. Additionally multi‐group modeling indicates the model fits for a variety of coalitions. CADCA's model appears to have wide utility and applicability and appears to have honed in on critical elements of community problem solving that may increase the likelihood of coalition success at reducing substance abuse within their community.
F‐actin and α‐actinin reorganization mediates initial fibroblast interaction with CoCr alloy particles in vitro
Authors: Madathil Bernadette K. , Damodaran Vinod , Thrikkovil Kumary V. , Mohanty Mira
Published: July 2012

Asceptic loosening remains the primary cause for failure of joint implant. The active role of fibroblasts in mediating asceptic loosening is however not well documented. In this study the initial interactions of fibroblasts with metal particles was studied by evaluating changes in the cytoskeletal structure and cytokine level. Murine L929 fibroblasts cultured with cobalt chromium particles were observed by phase contrast and scanning electron microscopy (SEM). Changes in the cytoskeletal rearrangement of F‐actin and α‐actinin focal adhesion plaques were studied by confocal microscopy. Expression of the proinflammatory cytokines IL‐6 and IL‐1α were analyzed by ELISA. The role of actin filaments and microtubules in particle uptake were determined at low temperature and in presence of colchicine and cytochalasin B. Phase contrast and SEM studies reveal that the metal particles adhere to the fibroblasts. The cellular cytoplasm was observed to grow over the particles and is suggestive of particle uptake. Confocal microscopy shows the presence of voids within the F‐actin cytoskeletal framework corresponding to areas occupied by the metal particles, indicating the possible uptake of these particles. Aggregates of α‐actinin into patches at the cell surface were also noted. Adherence and uptake of particles did not occur at low temperature and in presence of cytochalasin B, indicating that it is an active energy‐dependent process involving actin filaments. Changes in the levels of cytokine IL‐6 and IL‐1α were not observed suggesting the role of other cytokine molecules in mediating the inflammatory response to wear debri by fibroblasts. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Synthesis and Antibacterial Activity of Certain Fused Azoles and Oxazinones
Authors: El‐Saghier Ahmed M. , Alwedi Embarak F. , Fawzy Naglaa M.
Published: July 2012

2‐Phenyl‐4‐benzylidene‐5(4H)‐oxazolones (1a‐e) were used as versatile starting materials for the synthesis of fused compounds such as: 4H‐3,1‐benoxazin‐4‐ones (2a,b), imidazo[4,3‐b]benzimidazoles (3,4), imidazo[1,5‐b]1,2,4‐triazoles (5a,b), and 7.
Synthesis of 3,6‐Dibromopyrazine‐2,5‐dicarbonitrile [1]
Authors: Sato Nobuhiro , Fukuya Shunsuke
Published: July 2012

Symmetrically functionalized pyrazine of 3,6‐dibromopyrazine‐2,5‐dicarbonitrile was synthesized in three or four steps from 3‐aminopyrazinecarbonitrile or its 6‐bromo derivatives.
A Versatile Synthesis, PM3‐Semiempirical, Antibacterial, and Antitumor Evaluation of Some Bioactive Pyrazoles
Authors: Hamama Wafaa S. , El‐Gohary Hamada G. , Soliman Mamdouh , Zoorob Hanfi H.
Published: July 2012

This research work describes the synthesis and biological properties of some novel isolated or fused heterocyclic ring systems with pyrazole, for example; enaminones containing pyrazolone ring photochromic functional unit, 4‐[(4‐chlorophenylamino)methylene]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one (3) and some analogous derivatives 4, 9, and 10, also as pyrazolo[3,4‐b]pyridine, pyrazolo[3,4‐b]quinoline, pyrazolo[3′,4′:4,5]thieno[2,3‐c]pyrazoline and pyrazolo[3,4‐c]pyrazole were synthesized and characterized. Newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectral data and quantum mechanical calculations. Selected products were tested for their antibacterial and antitumor agents.
A Concise Diastereoselective Photochemical Synthesis of 3‐Hydroxyfuran‐2(3H)‐ones
Authors: Bondock Samir
Published: July 2012

The photocycloaddition of alkyl phenylglyoxylates to allylic alcohols leads to oxetanes 3a–h with high to moderate (2R∗,4R∗)‐diastereoselectivity that can be easily ring‐opened to give 3‐hydroxyfuran‐2(3H)‐ones 4a–b.
2,2′:6′,2″‐Terpyridines Functionalized with Thienyl Substituents: Synthesis and Applications
Authors: Husson Jérôme , Knorr Michael
Published: July 2012

This review deals with the synthesis and applications of 2,2′:6′,2″‐terpyridines which are functionalized with thiophene ring, directly linked to the terpyridine core or via a spacer. Two main methodologies were used, ring closure of diketo‐derivatives and cross coupling reactions. The obtained compounds find applications in various fields especially in material sciences such as solar cells or macromolecular sciences.
A Facile Synthesis of Novel Dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines Using HTIB
Authors: Prakash Om , Aneja Deepak Kumar , Wadhwa Deepak , Kumar Ravi , Arora Sanjiv
Published: July 2012

The synthesis of a series of 21 novel 3‐alkyl/aryl‐7/9‐methyl‐10,10a‐dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines (4) has been achieved by the cyclocondensation between 4/6‐methyl‐2‐tosyloxy‐1‐indanones (2) and 3‐alkyl/aryl‐4‐amino‐5‐mercapto‐1,2,4‐s‐triazoles (3). 4/6‐Methyl‐2‐tosyloxy‐1‐indanones (2) were readily accessible through hypervalent iodine oxidation of 4/6‐methyl‐1‐indanones using [(hydroxy)tosyloxyiodo]benzene (HTIB, Koser's reagent) in acetonitrile.
Synthesis and Biological Evaluation of Laxiflorin J Derivatives as Potential Antitumor Agents
Authors: Liu Jing‐Ping , Zhang Hong‐Bin , Huang Sheng‐Xiong , Pu Jian‐Xin , Xiao Wei‐Lie , Zhang Xue‐Ping , Xiao Wen‐Ding , Lei Chun , Sun Han‐Dong
Published: July 2012

Laxiflorin J, isolated from the leaves of Isodon eriocalyx var. laxiflora, showed significant inhibitory activity toward T‐24 cells. A series of laxiflorin J derivatives were synthesized and their in vitro activity was evaluated against BEL‐7402, A‐549, HT‐29, HL‐60, MOLT‐4 tumor cell lines, with IC50 values ranging from 1.3 to 42.2 μg mL−1.
Synthesis of New Substituted 1,2,4‐Triazines from Isonitrosoketones and Terephthalaldehydedihydrazone
Authors: Alici Onder , Karatas Ibrahim
Published: July 2012

This study describes a novel method for the synthesis of 1,2,4‐triazines. Firstly, isonitrosoacetophenone, p‐methylisonitrosoacetophenone, and isonitroso‐1‐acetylnaphthalene were synthesized from the reaction of butylnitrite with acetophenone, p‐methylisonitrosoacetophenone, and 1‐acetylnaphthalene, respectively. Then, symmetric derivatives of 1,2,4‐triazines were prepared from the condensation reaction of keto oximes with terephthalohydrazone. However, the heteroaromatic closure was not observed in the condensation reaction of pyruvic‐aldehyde‐1‐oxime(keto oxime) with terephthalohydrazone. Structures of the obtained products were confirmed by FTIR, 1H‐NMR, and elemental analyses techniques.
Lewis Acid Catalyzed Synthesis of 1‐Aryl‐1,2‐dihydro‐naphtho[1,2‐e][1,3]oxazin‐3‐ones under Solvent Free Conditions: A Mechanistic Approach
Authors: Sharma Mukul , Manohar Sunny , Rawat Diwan S.
Published: July 2012

Lewis acids catalyzed highly efficient one‐pot three component coupling of β‐naphthol, benzaldehydes and urea to produce 1‐aryl‐1,2‐dihydro‐naphtho[1,2‐e][1,3]oxazin‐3‐one derivatives under solvent free conditions is described. Mechanistic studies confirmed that product formation is possible only at very high temperature (140–150°C) and at lower temperature (90–100°C) formation of 14‐aryl‐14H‐dibenzo(a,j)xanthenes was observed. Among the nine Lewis acids screened, iodine, P2O5 and Yb(OTf)3 are found to be most effective catalyst for this multicomponent reaction.
N2O4 Chemisorbed onto n‐Propylsilica Kryptofix 21 and Kriptofix 22 as Two New Functional Polymers for the Fast Oxidation of Urazoles and 1,4‐Dihydropyridines
Authors: Chehardoli Gholamabbas , Zolfigol Mohammad Ali , Ghaemi Ezat , Madrakian Elaheh , Niknam Khodabakhsh , Mallakpour Shadpour
Published: July 2012

3‐Chloropropylsilica was reacted with Kriptofix 21 or 22 in the presence of triethylamine to form N‐propylsilica Kryptofix 21 and Kriptofix 22. Then N2O4 was added to each of these polymers to chemisorb onto cavity of aza‐crown ethers. These functionalized polymers were applied for the fast and simple oxidation of urazoles and 1,4‐dihydropyridines, respectively.
A Simple and Efficient One‐Pot Synthesis of Multifunctional 5‐Aryl‐5H‐thiazolo[3,2‐a]pyrimidines
Authors: Fatima Seerat , Sharma Anindra , Sharma Rahul , Tripathi Rama P.
Published: July 2012

One‐pot economical and efficient synthesis of multifunctional 5H‐thiazolo[3,2‐a]pyrimidines by the reaction of 4‐aryl dihydrothiopyrimidines with propargyl bromide in the presence of inorganic base has been reported in very short time.
Three‐Component Domino Reaction in PPG: An Easy Access to 4‐Thiazolidinone Derivatives
Authors: Prasad Davinder , Nath Mahendra
Published: July 2012

A simple, economical, and convenient synthesis of a new series of 4‐thiazolidinone derivatives using one‐pot three‐component condensation of aromatic amines, thioglycolic acid and aromatic aldehydes or cyclohexanone in polypropylene glycol (PPG), a recyclable and inexpensive solvent medium is reported. All the reactions are carried out at 110°C without using catalyst or additives. The products are obtained in good to excellent yields (60–97%) after easy workup and purification.
Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(as‐triazino[3,4‐b][1,3,4]thiadiazines)
Authors: Shaaban Mohamed R. , Elwahy Ahmed H. M.
Published: July 2012

A synthesis of bis(α‐bromo ketones) 5a‐c and 6b,c was accomplished by the reaction of bis(acetophenones) 3a‐c and 4b,c with N‐bromosuccinimide in the presence of p‐toluenesulfonic acid (p‐TsOH). Treatment of 5a‐c and 6b,c with each of 4‐amino‐3‐mercapto‐1,2,4‐triazoles 9a,b and 4‐amino‐6‐phenyl‐3‐mercapto‐1,2,4‐triazin‐5(4H)‐ones 13 in refluxing ethanol afforded the novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 10a‐d and 11a‐c as well as bis(as‐triazino[3,4‐b][1,3,4]thiadiazines) 14a‐c and 15, respectively, in good yields. Compounds 11b and 11c underwent NaBH4 reduction in methanol to give the target 1,ω‐bis{4‐(6,7‐dihydro‐3‐substituted‐5H‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)phenoxy}butanes 12a and 12b in 42 and 46% yields, respectively.
Synthesis of a New Class of Arylsulfonylethylsulfonylmethyloxazolines and Thiazolines
Authors: Padmavathi Venkatapuram , Venkatesh Bhumireddy Chinnachennaiahgari , Premakumari Chokkappagari , Padmaja Adivireddy
Published: July 2012

A new class of arylsulfonylethylsulfonylmethyl oxazolines and thiazolines were prepared using multistep, one‐pot methodologies exploiting lanthanide alkoxides and under microwave irradiation. The microwave method provides an excellent approach in a single step with high yields.
Multiple admissions for alcohol withdrawal
Authors: Larson Scott A. , Burton M. Caroline , Kashiwagi Deanne T. , Hugo Zachary P. , Cha Stephen S. , Lapid Maria I.
Published: July 2012

Objective

The objective was to identify risk factors for multiple admissions for alcohol withdrawal syndrome (AWS) in patients admitted to a general medicine service.

Methods:

A retrospective study was performed examining records of patients admitted for AWS between January 1, 2006 and December 31, 2008 to an academic tertiary referral hospital. Patients with a single admission were compared to patients with multiple admissions with respect to demographic and clinical variables.

Results:

Three hundred and twenty‐two patients accounted for 788 admissions. Of the 322 patients, 142 (44%) had multiple admissions. Compared to patients with a single admission, patients with multiple admissions were more likely to have a high school education or less (p=0.0071), a higher Charlson comorbidity index score (p=0.0010), a positive urine drug screen for non‐alcohol drug (p=0.0002), psychiatric comorbidity (p=0.0303) and a higher CIWA‐Ar maximum total score (p<0.0001).

Conclusion:

In patients with AWS, we identified demographic and clinical variables associated with multiple admissions to a general medicine service. Our results indicate areas for a targeted multidisciplinary and multispecialty approach at initial intervention, which is especially important given the high rates of recidivism in this patient population. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine.
RESEARCH CAPACITY‐BUILDING IN AFRICA: NETWORKS, INSTITUTIONS AND LOCAL OWNERSHIP
Authors: Marjanovic Sonja , Hanlin Rebecca , Diepeveen Stephanie , Chataway Joanna
Published: July 2012

Networked models are often proposed as a means to enhance health research capacity‐building in Africa. This paper addresses a knowledge gap on what works and does not in capacity‐building in African research settings. It provides an analysis of how multi‐partner networks are built and how their success depends on building institutional level capacity‐strengthening within partner institutions. To do this, the paper focuses on the Wellcome Trust's African Institutions initiative, drawing on initial learning and evaluation project data. We identify priority areas for policy attention and share emerging early insights on mechanisms and strategies being implemented by consortia to address key challenges. Copyright © 2012 John Wiley & Sons, Ltd.
Vascular space occupancy MRI during breathholding at 3 tesla
Authors: Hsu Yuan‐Yu , Chu Wen‐Cheng , Lim Kun‐Eng , Liu Ho‐Ling
Published: July 2012

Purpose:

To evaluate the vasodilatory response of normal human brain and meningiomas under repeated breathholding challenges using vascular space occupancy (VASO) MRI at 3 Tesla (T).

Materials and Methods:

Five normal volunteers and five patients with meningiomas were recruited for this study. For the normal group, VASO MRI during repeated breathholds of different duration (5 to 30 s) was acquired. Patients performed a 15‐s breathhold paradigm for VASO MRI. The maximum signal change and full‐width at half‐maximum (FWHM) were determined by curve fitting.

Results:

Significant VASO signal decreases in the gray matter could be detected for a breathhold period as short as 5 s. The fractional activation volume vs. breathhold duration reached a plateau around 34.21 ± 3.39% at 15 s. In the patient group, there were significant VASO signal decreases in normal gray matters and also in small areas of three large‐sized meningiomas.

Conclusion:

The 3T VASO MRI detected significant signal decreases in the gray matter, but not in the white matter, during short periods of breathholding. The fractional activation volume reached the plateau at 15‐s breathhold, which is recommended for clinical application. J. Magn. Reson. Imaging 2012;36:1179–1185. © 2012 Wiley Periodicals, Inc.
Revealing the glycation sites in synthetic neoglycoconjugates formed by conjugation of the antigenic monosaccharide hapten of Vibrio cholerae O1, serotype Ogawa with the BSA protein carrier using LC‐ESI‐QqTOF‐MS/MS
Authors: Jahouh Farid , Saksena Rina , Kováč Pavol , Banoub Joseph
Published: July 2012

In this manuscript, we present the determination of glycation sites in synthetic neoglycoconjugates formed by conjugation of the antigenic monosaccharide hapten of Vibrio cholerae O1 serotype Ogawa to BSA using nano‐ liquid chromatography electrospray ionization quadrupole time‐of‐flight tandem mass spectroscopy (LC‐ESI‐QqTOF‐MS/MS). The matrix‐assisted laser desorption/ionization‐TOF/TOF‐MS/MS analyses of the tryptic digests of the glycoconjugates having a hapten:BSA ratio of 4.3:1, 6.6:1 and 13.2:1 revealed only three glycation sites, on the following lysine residues: Lys 235, Lys 437 and Lys 455. Digestion of the neoglycoconjugates with the proteases trypsin and GluC V8 gave complementary structural information and was shown to maximize the number of recognized glycation sites. Here, we report identification of 20, 27 and 33 glycation sites using LC‐ESI‐QqTOF‐MS/MS analysis of a series of synthetic neoglycoconjugates with a hapten:BSA ratio of, respectively, 4.3:1, 6.6:1 and 13.2:1. We also tentatively propose that all the glycated lysine residues are located mainly near the outer surface of the protein. Copyright © 2012 John Wiley & Sons, Ltd.
Light and heavy dansyl reporter groups in food chemistry: amino acid assay in beverages
Authors: Mazzotti Fabio , Benabdelkamel Hicham , Donna Leonardo Di , Athanassopoulos Constantinos M. , Napoli Anna , Sindona Giovanni
Published: July 2012

5‐Dimethylamino‐1‐sulfonyl naphthalene (DNS, commonly referred as dansyl) is a functionality, bearing well‐established properties in directing the fragmentation, by mass spectrometry (MS), of the corresponding ionized sulfonylated derivatives. This property is shared also by its labeled analogs. The use of d0/d6 DNS derivatives is now exploited in the application of the well‐established isotope dilution mass spectrometric approach in the assay of complex mixtures. A new method for the quantitation of amino acids (AAs) in beverages is therefore presented, which relies on liquid chromatographic separation of their N‐dansylated derivatives followed by comparative electrospray tandem MS/MS of the d0/d6 isobaric mixtures.

Labeled and unlabeled DNS derivatives of the selected AAs are readily available by microwave‐assisted synthetic protocols. The novelty of the method is represented by the use of heavy and light DNS‐isotopologue providing suitable reporter groups. Multiple‐reaction monitoring has been applied in the assay of AAs in wine, pineapple juice and bergamot juice with good‐to‐excellent results as proved by both relative standard deviation, lower than 15%, and by the accuracy values in the range 90–110%. Copyright © 2012 John Wiley & Sons, Ltd.
Distillation of fermented sugarcane juice: fractions characterized by electrospray ionization mass spectrometry and multivariate data treatment
Authors: Canuto Marcus H. , Rosa Carlos A. , de Moura Fabiana , Augusti Rodinei , Siebald Helmuth G. L.
Published: July 2012

Direct infusion electrospray ionization mass spectrometry in the negative ion mode (ESI(−)‐MS) was employed to discriminate among fractions arising from the distillation of fermented sugarcane juice during the production of cachaça, a typical Brazilian alcoholic beverage. Aliquots were collected in the course of distillation and their ESI(−)‐MS shown to be almost indistinguishable by a simple visual inspection. However, when the ESI(−)‐MS data were treated by the principal component analysis (PCA) and hierarchical clustering analysis (HCA) statistical methods, four major groups were clearly determined, the so‐called head (two distinct clusters), heart and tail fractions. Furthermore, the recognition of diagnostic ions (and their respective intensities) enabled a more confident establishment of the cutoff position (i.e. the initial and final points of each fraction). In conclusion, ESI‐MS, in conjunction with PCA or HCA approaches, proved to be a quite efficient method that allowed for a prompt characterization of each fraction derived from the distillation of brewed sugarcane. The results described herein can, therefore, be useful not only to optimize the production of cachaça but also to improve the quality of the final product. Copyright © 2012 John Wiley & Sons, Ltd.
Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS)
Authors: Raju B. , Ramesh M. , Borkar Roshan M. , Padiya Raju , Banerjee Sanjay K. , Srinivas R.
Published: July 2012

In vivo metabolites of ketorolac (KTC) have been identified and characterized by using liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI‐HR‐MS/MS) in combination with online hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, blood urine and feces samples were collected after oral administration of KTC to Sprague–Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation and freeze liquid separation followed by solid‐phase extraction and then subjected to LC/HR‐MS/MS analysis. A total of 12 metabolites have been identified in urine samples including hydroxy and glucuronide metabolites, which are also observed in plasma samples. In feces, only O‐sulfate metabolite and unchanged KTC are observed. The structures of metabolites were elucidated using LC‐MS/MS and MSn experiments combined with accurate mass measurements. Online HDX experiments have been used to support the structural characterization of drug metabolites. The main phase I metabolites of KTC are hydroxylated and decarbonylated metabolites, which undergo subsequent phase II glucuronidation pathways. Copyright © 2012 John Wiley & Sons, Ltd.
Intracerebral transplantation of bone marrow stromal cells ameliorates tissue plasminogen activator‐induced brain damage after cerebral ischemia in mice detected by in vivo and ex vivo optical imaging
Authors: Liu Ning , Deguchi Kentaro , Yamashita Toru , Liu Wentao , Ikeda Yoshio , Abe Koji
Published: July 2012

Detection and protection of the neurovascular unit (NVU) are essential for treatment of acute stroke patients, especially the use of tissue plasminogen activator (tPA). In the present study, we conducted in vivo and ex vivo optical imaging for detecting activation of matrix metalloproteinases (MMPs) and evaluated the protective effect of intracerebral transplantation of bone marrow stromal cells (BMSCs) obtained from green fluorescent protein (GFP) transgenic (Tg) mice on the NVU in tPA‐mediated brain damage after transient middle cerebral artery occlusion (tMCAO) in mice. Compared with the tMCAO group, the tMCAO plus BMSC group showed significant reductions of in vivo and ex vivo fluorescent signals for MMPs at 48 hr after tMCAO, with a partial colocalization of BMSC–GFP signals. Intracerebrally transplanted BMSCs ameliorated MMP‐9 activation by immunohistochemistry and Western blot with differentiation into microglial and astroglial cells. Double‐immunofluorescence study revealed improved NVU disruption in the tMCAO plus BMSC group. The present study suggests that intracerebral BMSC transplantation reduced MMP activation and subsequent NVU disruption caused by tPA after tMCAO and that this MMP activation and BMSC effect were detectable with in vivo and ex vivo optical imaging. © 2012 Wiley Periodicals, Inc.
Neuronal injury induces microglial production of macrophage inflammatory protein‐1α in rat corticostriatal slice cultures
Authors: Okamura Toshiyuki , Katayama Takahiro , Obinata Chihiro , Iso Yukina , Chiba Yuzuho , Kobayashi Hayato , Yamada Yuma , Harashima Hideyoshi , Minami Masabumi
Published: July 2012

Chemokines are potent chemoattractants for immune and hematopoietic cells. In the central nervous system, chemokines play an important role in inflammatory responses through activation of infiltrating leukocytes and/or resident glial cells. We previously demonstrated that N‐methyl‐D‐aspartate (NMDA)‐evoked neuronal injury induced astrocytic production of monocyte chemoattractant protein‐1 (MCP‐1, CCL2) via sustained activation of extracellular signal‐regulated kinase (ERK) in rat organotypic slice cultures. In the present study, we examined mRNA expression and protein production of macrophage inflammatory protein‐1α (MIP‐1α, CCL3) induced by NMDA‐evoked neuronal injury in the slice cultures. MIP‐1α mRNA expression was transiently increased by NMDA treatment in a concentration‐dependent manner. Double‐fluorescence immunohistochemistry revealed that MIP‐1α was produced predominantly in microglia. Depletion of microglial cells from the slice cultures by pretreatment with liposome‐encapsulated clodronate abrogated the increase in MIP‐1α mRNA expression after NMDA treatment. NMDA‐induced MIP‐1α mRNA expression was partially but significantly inhibited by the c‐Jun N‐terminal kinase inhibitor SP600125; conversely, the p38 mitogen‐activated protein (MAP) kinase inhibitor SB203580 enhanced it. U0126, a MAP kinase/ERK kinase inhibitor, did not affect mRNA expression. These results, combined with our previous findings, demonstrate that NMDA‐evoked neuronal injury differentially induces MIP‐1α and MCP‐1 production in microglia and astrocytes, respectively, through activation of different intracellular signaling pathways. © 2012 Wiley Periodicals, Inc.
Recent and future climate extremes arising from changes to the bivariate distribution of temperature and precipitation in Bavaria, Germany
Authors: Estrella Nicole , Menzel Annette
Published: July 2012

This study assesses recent and future changes in joint temperature and precipitation regimes at 28 sites in Bavaria, based on statistical downscaling of the ECHAM4 B2 Scenario (WETTREG). Monthly meteorological data of three future decades (2021–2030, 2031–2040 and 2041–2050) were compared with modelled data for the reference period 1971–2000. The bivariate data were classified into four weather types or modes (cooler/drier, cooler/wetter, warmer/wetter and warmer/drier relative to the 1971–2000 reference period). For the three future decades, a systematic change at all locations throughout the year was revealed. Both the cooler modes are predicted to occur less frequently in future decades; changes in warmer modes differ seasonally: In winter months, they are predicted to occur in the warmer/wetter mode, whereas in spring and summer months in the warmer/drier mode. Climatological extremes were defined as monthly weather events outside the 90% confidence ellipse of a Gaussian model of events in the reference period. An increase of extremes in the decade 2041–2050 was striking for June, which is predicted to be warmer and drier for half of the years. The same decade is predicted to experience the most extreme warm and wet modes, one in three Februarys and one in two winters are likely to be in this mode. The magnitude of these future changes in climate was related to the present mean annual temperature of the stations by rank regression. Stations with currently cooler climates are more likely to retain the normal conditions of the baseline period in contrast to currently warmer stations where the increase of extreme warm and wet conditions in summer and winter is expected to be larger. Copyright © 2012 Royal Meteorological Society
The 2010–2011 drought in the Horn of Africa in ECMWF reanalysis and seasonal forecast products
Authors: Dutra Emanuel , Magnusson Linus , Wetterhall Fredrik , Cloke Hannah L. , Balsamo Gianpaolo , Boussetta Souhail , Pappenberger Florian
Published: July 2012

This study evaluates the use of European Centre for Medium‐Range Weather Forecasts (ECMWF) products in monitoring and forecasting drought conditions during the recent 2010–2011 drought in the Horn of Africa (HoA). The region was affected by a precipitation deficit in both the October–December 2010 and March–May 2011 rainy seasons. These anomalies were captured by the ERA‐Interim reanalysis (ERAI), despite its limitations in representing the March–May interannual variability. Soil moisture anomalies of ERAI also identified the onset of the drought condition early in October 2010 with a persistent drought still present in September 2011. This signal was also evident in normalized difference vegetation index (NDVI) remote sensing data. The precipitation deficit in October–December 2010 was associated with a strong La Niña event. The ECMWF seasonal forecasts for the October–December 2010 season predicted the La Niña event from June 2010 onwards. The forecasts also predicted a below‐average October–December rainfall, from July 2010 onwards. The subsequent March–May rainfall anomaly was only captured by the new ECWMF seasonal forecast system in the forecasts starting in March 2011. Our analysis shows that a recent (since 1999) drying in the region during the March–May season is captured by the new ECMWF seasonal forecast system and is consistent with recently published results. The HoA region and its population are highly vulnerable to future droughts, thus global monitoring and forecasting of drought, such as that presented here, will become increasingly important in the future. Copyright © 2012 Royal Meteorological Society
Are raccoons limited by the availability of breeding resources? Evidence of variability in fecundity at fine spatial scales
Authors: Beasley James C. , Rhodes Olin E.
Published: July 2012

Despite their behavioral plasticity, recent research suggests raccoons (Procyon lotor) exhibit variability in demography and genetic structure among individual habitat patches in landscapes heavily affected by anthropogenic land use. Consequently, elucidation of vital rates at fine‐spatial scales is needed to implement appropriate management strategies for this species. To evaluate the degree of variability in productivity that exists among individual habitat patches, we collected reproductive (n = 170) and cementum annuli age data (n = 383) for raccoons occupying 30 forest patches varying in local and landscape‐level habitat attributes within a highly fragmented agricultural ecosystem. Across all females sampled, pregnancy rates averaged 85% but were highly variable among ages (range: 47–100%). Average litter sizes ranged from 3.2 to 4.7, but did not differ as a function of age. At the landscape‐level, we observed significant variability among habitat patches in the total number of offspring produced (range: 0–80), indicating that individual patches vary in their contribution to the overall size and stability of the global (landscape‐level) population. Variability in productivity among habitat patches primarily was driven by local differences in the availability of denning resources, likely because of the influence of this variable on variability in the number, age structure, and reproductive rate of females. Our results suggest that in agricultural ecosystems, the reproductive potential and temporal stability of raccoons within individual habitat fragments is inextricably linked to the density of tree cavities. © 2012 The Wildlife Society.
Surface Modification of Gold Nanorods by Grafting Fluorene‐Based Conjugated Copolymers Containing Thiol‐Pendants
Authors: Sahu Duryodhan , Chu Hsuan‐Chih , Yang Po‐Jen , Lin Hong‐Cheu
Published: July 2012

Two conjugated surfactants of monomer TF and polymer PTF with pendant thiol groups are synthesized for surface modifications of gold nanorods (GNRs). Cetyltrimethylammonium bromide (CTAB)‐GNRs (without surface‐modification) in aqueous solutions are prepared, and the original CTAB surfactant is replaced with TF and PTF due to their thiol‐gold grafting reactions. Surface‐modified TF‐GNRs and PTF‐GNRs in THF are obtained. UV‐visible spectra provide the grafting evidence of TF and PTF. Compared with TF‐GNRs, the PTF‐GNRs show better solubility and stability against aggregations of nanorods in THF. TEM and XPS confirm the existence of binding bonds between the sulfur groups of PTF and the gold surface in PTF‐GNRs. Compared with polymer surfactant (PTF), the faster PL emission decay in PTF‐GNRs match well with the PL quenching of PTF‐GNRs. Surface modifications are verified by UV‐visible, TEM, XPS, PL and lifetime measurements.
An Advanced Class of Bio‐Hybrid Materials: Bionanocomposites of Inorganic Clays and Organic Stereocomplex Polylactides
Authors: Purnama Purba , Jung Youngmee , Kim Soo Hyun
Published: July 2012

Bio‐stereo nanocomposite polylactides are prepared by polymerization followed by stereocomplexation in scCO2/dichloromethane through in situ polymerization and master batch processes. The bio‐stereo nanocomposite polylactides show intercalated‐exfoliated and fully exfoliated nanoscale clay distribution in a perfect stereocomplex polylactide matrix. In situ polymerization proves better strategy to produce well‐exfoliated silicate layers in the stereocomplex matrix compared to the MB route that increases the melting temperature by up to ≈64 °C. The thermal properties of these materials maintain both stereocomplex and nanocomposite features simultaneously. The results open a new and versatile way to develop polylactide‐based materials.

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An Efficient Quantified Stereological Macrodispersion Analysis Approach for Determining Microscale Influences on Nanocomposite Material Properties
Authors: Lively Brooks , Zhong Wei‐Hong
Published: July 2012

A quantified stereological characterization approach is used to study the macrodispersion of polycarbonate/carbon nanotube nanocomposites with visually similar microstructures and differing material properties. Through the use of this stereological macrodispersion tool, observed agglomeration states are quantified from optical images of the nanocomposite cross‐sections and resulting data processed with Wicksell's corpuscle problem to estimate the volume macrodispersion state. This characterization method provides an industry friendly tool for performance and quality assessment. Through mechanical and rheological property correlation, it is found that the size of agglomerates and frequency of large agglomerates are clear indicators of nanocomposite performance.

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Brain perfusion anomalies in rapid eye movement sleep behavior disorder with mild cognitive impairment
Authors: Vendette Mélanie , Montplaisir Jacques , Gosselin Nadia , Soucy Jean‐Paul , Postuma Ronald B. , Dang‐Vu Thien Thanh , Gagnon Jean‐François
Published: July 2012

Rapid eye movement (REM) sleep behavior disorder is an important risk factor for Parkinson's disease and dementia with Lewy bodies. Approximately 50% of patients with REM sleep behavior disorder have mild cognitive impairment. Our objective was to investigate brain perfusion changes associated with mild cognitive impairment in REM sleep behavior disorder. Twenty patients with REM sleep behavior disorder, including 10 patients with mild cognitive impairment and 10 patients without mild cognitive impairment, and 20 healthy controls underwent a complete neuropsychological assessment and single‐photon emission computerized tomography using 99mcTc‐Ethylene Cysteinate Dimer. Compared with controls, both REM sleep behavior disorder groups had hypoperfusion in the frontal regions. In addition, patients with REM sleep behavior disorder and mild cognitive impairment showed cortical hypoperfusion in the occipital, temporal, and parietal regions compared with controls and patients with REM sleep behavior disorder without mild cognitive impairment. Both REM sleep behavior disorder groups had hyperperfusion in the right hippocampus and parahippocampal gyri. However, patients with REM sleep behavior disorder and mild cognitive impairment showed more pronounced anomalies in the right hippocampus and had increased perfusion in the putamen and the left paracentral gyrus. This study showed specific patterns of posterior cortical hypoperfusion and hyperperfusion in some brain areas in patients with REM sleep behavior disorder and mild cognitive impairment, similar to those found in Parkinson's disease dementia and dementia with Lewy bodies. This suggests the presence of an identifiable neuroimaging marker of synucleinopathy in REM sleep behavior disorder with mild cognitive impairment. © 2012 Movement Disorder Society
Newborn brachial plexus palsy: Evaluation of severity using quantitative ultrasound of muscle
Authors: Zaidman Craig M. , Holland Mark R. , Noetzel Michael J. , Park Tae Sung , Pestronk Alan
Published: July 2012

Introduction: We studied ultrasound features of muscle after nerve injury. Methods: We evaluated ultrasound measurements of muscle thickness and backscatter in injured and contralateral uninjured elbow flexors of 51 children with newborn brachial plexus palsy (NBPP) and compared the results to elbow flexor function (Active Movement Scale), defined as normal, moderate, or severe. Results: Compared with uninjured limbs, muscle in injured arms was 15% thinner with severe impairment, 17% thicker with moderate impairment, and no different with normal function. Relative to uninjured limbs, moderately impaired muscle was thicker than both severely impaired and normal strength muscle. Backscatter was higher in injured than in uninjured limbs regardless of function. In 17 patients with sequential measures, muscle thickness, but not backscatter, increased with function over time. Conclusions: Muscle thickness differentiates moderate from severe impairment after NBPP and increases with recovery over time. Muscle backscatter identifies prior injury regardless of function. Muscle Nerve, 2013