bluuebunny/crossref_metadata_2025 huggingface dataset:
Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer
Authors: Tanaka Motofumi , Javle Milind , Dong Xiaoqun , Eng Cathy , Abbruzzese James L. , Li Donghui
Published: July 2010

BACKGROUND:

It has not been well established whether genetic variations can be biomarkers for clinical outcome of gemcitabine therapy. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) of gemcitabine metabolic and transporter genes that are associated with toxicity and efficacy of gemcitabine‐based therapy in patients with locally advanced pancreatic cancer.

METHODS:

The authors evaluated 17 SNPs of the CDA,dCK, DCTD, RRM1, hCNT1‐3, and hENT1 genes in 149 patients with locally advanced pancreatic cancer who underwent gemcitabine‐based chemoradiotherapy. The association of genotypes with neutropenia, tumor response to therapy, overall survival, and progression‐free survival (PFS) was analyzed by logistic regression, log‐rank test, Kaplan‐Meier plot, and Cox proportional hazards regression.

RESULTS:

The CDA A‐76C, dCK C‐1205T, RRM1 A33G, and hENT1 C913T genotypes were significantly associated with grade 3 to 4 neutropenia (P = .020, .015, .003, and .017, respectively).The CDA A‐76C and hENT1 A‐201G genotypes were significantly associated with tumor response to therapy (P = .017 and P = .019). A combined genotype effect of CDA A‐76C, RRM1 A33G, RRM1 C‐27A, and hENT1 A‐201G on PFS was observed. Patients carrying 0 to 1 (n = 64), 2 (n = 50), or 3 to 4 (n = 17) at‐risk genotypes had median PFS times of 8.3, 6.0, and 4.2 months, respectively (P = .002).

CONCLUSIONS:

The results indicated that some polymorphic variations of drug metabolic and transporter genes may be potential biomarkers for clinical outcome of gemcitabine‐based therapy in patients with locally advanced pancreatic cancer. Cancer 2010. © 2010 American Cancer Society.
Notch1 regulates the growth of human colon cancers
Authors: Zhang Yan , Li Bin , Ji Zong‐Zheng , Zheng Peng‐Sheng
Published: July 2010

BACKGROUND:

The aberrant activation of the Notch signaling has been associated with the development of colon cancers. However, the role of Notch1 in the pathogenesis of colon cancers is poorly understood.

METHODS:

The expression of Notch1 in colon cancer tissues and nontumor tissues and in colon cancer cell lines was examined by Western blot analysis and immunohistochemistry. The impact of small interfering RNA (siRNA)‐mediated Notch1 knockdown or Notch1 intracellular domain (NICD)‐based transgene‐induced Notch1 overexpression on the proliferation, cell cycling, apoptosis, colony formation, and tumorsphere formation in vitro and the development and growth of implanted tumors in vivo was characterized.

RESULTS:

Notch1 was overexpressed in colon cancer tissues, and the levels of Notch1 expression in different types of colon cancers were associated with the pathologic grade, progression, and metastasis of colon cancers. Furthermore, knockdown of Notch1 significantly inhibited the proliferation, colony formation, and tumorsphere formation of SW480 and HT‐29 cells, induced apoptosis and cell cycle arrest at G0/G1 phase, and mitigated the development and growth of implanted colon cancers in vivo. In contrast, Notch1 overexpression promoted the proliferation, colony formation, cell cycling, and tumorsphere formation of colon cancer cells in vitro and the development and growth of implanted colon cancers in vivo, but it inhibited spontaneous apoptosis.

CONCLUSIONS:

The current results indicated that Notch1 signaling positively regulates the growth of colon cancers. Conceivably, the modulation of Notch1‐related signaling may be a promising therapy for human colon cancers. Cancer 2010. © 2010 American Cancer Society.
Obesity adversely affects survival in pancreatic cancer patients
Authors: McWilliams Robert R. , Matsumoto Martha E. , Burch Patrick A. , Kim George P. , Halfdanarson Thorvardur R. , de Andrade Mariza , Reid‐Lombardo Kaye , Bamlet William R.
Published: July 2010

BACKGROUND:

Higher body‐mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia.

METHODS:

A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self‐reported diabetes and fasting blood glucose in the survival model.

RESULTS:

BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], P < .001) after adjustment for age, stage, and sex. In analysis by National Institutes of Health BMI category, BMIs of 30 to 34.99 kg/m2 (HR, 1.14; 95% confidence interval [CI], 0.98‐1.33), 35 to 39.99 kg/m2 (HR 1.32, 95% CI 1.08‐1.62), and ≥40 (HR 1.60, 95% CI 1.26‐2.04) were associated with decreased survival compared with normal BMI of 18.5 to 24.99 kg/m2 (overall trend test P < .001). Fasting blood glucose and diabetes did not affect the results.

CONCLUSIONS:

Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Cancer 2010. © 2010 American Cancer Society.
Microsatellite instability among individuals of Hispanic origin with colorectal cancer
Authors: Gupta Samir , Ashfaq Raheela , Kapur Payal , Afonso Bianca B. , Nguyen Thuy‐Phuong T. , Ansari Faryal , Boland C. Richard , Goel Ajay , Rockey Don C.
Published: July 2010

BACKGROUND:

Although the presence of microsatellite instability (MSI) in patients with colorectal cancer (CRC) may have implications for prognosis, therapy, and family counseling, to the authors' knowledge, the prevalence of MSI has not been well described among individuals of Hispanic origin with CRC residing in the United States.

METHODS:

A retrospective cohort study using a hospital‐based tumor registry to identify individuals of Hispanic origin who were diagnosed with CRC was conducted. Clinical data and tumor samples were retrieved. Molecular analyses included testing for MSI using a panel of 5 mononucleotide markers (BAT25, BAT26, NR21, NR24, and NR27) in a pentaplex polymerase chain reaction assay, as well as immunohistochemistry for the mismatch repair (MMR) proteins mutL homolog (MLH) 1, mutS homolog (MSH) 2, MSH6, and postmeiotic segregation increased 2 (PMS2) 2 on representative tissue.

RESULTS:

A total of 111 individuals of Hispanic origin with CRC were identified. Approximately 41.4% were women, and the median age was 57 years (interquartile range [IQR], 47.1‐63.5 years). Eleven patients (9.9%; 95% confidence interval [95% CI], 4.2%‐15.6%) had MSI CRC, whereas 14 patients (12.6%; 95% CI, 7.3%‐21.8%) had CRC with ≥1 MMR protein abnormality. Ten of 11 individuals with MSI had clinical or molecular characteristics suspicious for Lynch syndrome such as abnormal expression of MSH2 and/or MSH6 (n = 7) or age <50 years at the time of diagnosis (n = 7).

CONCLUSIONS:

The prevalence of MSI CRC among Hispanic individuals may be similar to that of other races and ethnicities, but clinicopathological characteristics, including age at diagnosis and pattern of abnormal MMR protein expression, suggest that sporadic MSI CRC may be less common in individuals of Hispanic origin, and that much of the MSI observed in this situation may be attributable to Lynch syndrome. Further exploration of the causes of disparate presentations of CRC by ethnicity and race is warranted. Cancer 2010. © 2010 American Cancer Society.
Fluorescence in situ hybridization for detecting urothelial carcinoma
Authors: Caraway Nancy P. , Khanna Abha , Fernandez Ricardo L. , Payne Linda , Bassett Roland L. , Zhang Hua‐Zhong , Kamat Ashish , Katz Ruth L.
Published: July 2010

BACKGROUND:

Because urothelial carcinoma (UC) is associated with a significantly high risk of disease recurrence and progression, patients with UC require long‐term surveillance. Fluorescence in situ hybridization (FISH) has been shown to be more sensitive than cytology in the detection of UC. The current study evaluated the use of FISH for detecting UC.

METHODS:

A pathology database was used to identify patients who had urine cytology and FISH performed at the study institution between 2004 and 2006. Urinary specimens were analyzed using UroVysion FISH probes for abnormalities in centromeric chromosomes 3, 7, and 17 and locus‐specific 9p21. FISH results were correlated with cytologic findings and a minimal clinical follow‐up of 24 months.

RESULTS:

A total of 1006 consecutive urinary specimens from 600 patients (448 men and 152 women) who were monitored for recurrent UC (915 specimens) or evaluated for urinary symptoms (91 specimens) were identified. On FISH analysis, 669 specimens were found to be negative for UC and 272 specimens were positive for UC. Sixty‐five (6%) specimens were insufficient for FISH analysis. The sensitivity and specificity of FISH for UC were 58% and 66%, respectively, and 59% and 63%, respectively, when FISH and cytology results were combined. Factors contributing to decreased FISH sensitivity included the paucity or absence of tumor cells, low‐grade tumors, degenerated cells, method of specimen collection, type of specimen, and obscuring inflammatory cells or lubricant.

CONCLUSIONS:

UroVysion FISH appeared to have good sensitivity and specificity for detecting UC in urinary specimens. It is important to correlate the FISH results with the cytologic findings. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Kinetics of Substituted Silylene Addition and Elimination in Silicon Nanocluster Growth Captured by Group Additivity
Authors: Adamczyk Andrew J. , Reyniers Marie‐Françoise , Marin Guy B. , Broadbelt Linda J.
Published: July 2010

Accurate rate coefficients for 40 bimolecular substituted silylene addition reactions for silicon hydrides containing up to nine silicon atoms are calculated using the G3//B3LYP method. The overall reactions exhibit two steps: the reactants first meet to form an adduct, which then converts into a saturated silicon hydride. Values for the single‐event Arrhenius pre‐exponential factor,${\tilde A}$, and the activation energy,Ea, are calculated from the G3//B3LYP rate coefficients corrected for internal rotations, and a group additivity scheme is developed to predict${\tilde A}$andEa. The values predicted by group additivity are more accurate than structure–reactivity relationships currently used in the literature, which rely on representative${\tilde A}$values and the Evans–Polanyi correlation. The structural factors that have the most pronounced effect on${\tilde A}$andEaare considered, and the presence of rings is shown to influence these values strongly.
Preparation and Electrochemical Behavior of PtRu(111) Alloy Single‐Crystal Surfaces
Authors: El‐Aziz Ahmed M. , Hoyer Rüdiger , Kibler Ludwig A.
Published: July 2010

The electrochemical behavior of a PtRu(111) single crystal with 1:1 bulk atomic ratio is investigated for the first time by means of cyclic voltammetry and scanning tunneling microscopy (STM). The electrode surfaces are enriched with either Ru or Pt, depending on the cooling conditions after inductive heating. Analysis of the surfaces by STM shows a typical topography with smooth terraces separated by monoatomic high steps. The voltammetric characterization of PtRu(111) in acid media clearly reveals an altered electrochemical behavior of the Pt and Ru surfaces compared to Pt(111) and Ru(0001), respectively. Systematic changes are observed for hydrogen adsorption and underpotential deposition of copper as test reactions. Based on theoretical calculations in the literature, it is experimentally verified that the Pt‐rich and the Ru‐rich surfaces of the PtRu(111) single‐crystal alloy bind adsorbates such as hydrogen significantly weaker and stronger than the pure single‐crystal electrode surfaces. Such changes in surface reactivity can be crucial for electrocatalytic reactions.
Supported and Free‐Standing Sulfonic Acid Functionalized Mesostructured Silica Films with High Proton Conductivity
Authors: Supplit Ralf , Sugawara Ayae , Peterlik Herwig , Kikuchi Ryuji , Okubo Tatsuya
Published: July 2010

Sulfonic acid functionalized silica films with 2D‐hexagonal mesostructures of various channel sizes are prepared in a one‐step synthesis. A successful combination of in situ oxidation of a mercapto‐functionalized silane with an evaporation induced self‐assembly (EISA) process in the presence of amphiphilic block copolymers allows the formation of a highly structured material with a sulfonation degree of 33 %. Analysis of the mesostructure by a combination of XRD, grazing‐incidence small‐angle X‐ray scattering (GI‐SAXS), and TEM shows that 2D‐hexagonally ordered mesostructured films are obtained by optimization of the surfactant to silica precursor ratio. The tuneability of the mesochannel size is demonstrated by the use of three different surfactants. The complete oxidation of the mercapto group to sulfonic acid is confirmed by Fourier transform infrared spectroscopy (FTIR). The thermal stability of the material is investigated by coupled thermogravimetric analysis, differential temperature analysis, and mass spectrometry (TGA‐DTA‐MS). Alternating current (AC) impedance analysis of humidified samples shows high proton conductivity of up to 0.18 S cm–1 at 60 °C and 95 % relative humidity.
Construction of a 2D Rectangular Grid and 3D Diamondoid Interpenetrated Frameworks and Their Functionalities by Changing the Second Spacers
Authors: Kanoo Prakash , Maji Tapas Kumar
Published: July 2010

Three new metal–organic ZnII frameworks, {[Zn(bipy)(1,4‐ndc)(H2O)2]·2H2O} (1), {[Zn(bpe)(1,4‐ndc)]2·2DMF} (2), {[Zn(bpee)(1,4‐ndc)]2·2DMF} (3) [bipy = 4,4′‐bipyridyl, 1,4‐ndc = 1,4‐naphthalenedicarboxylate, bpe = 1,2‐bis(4‐pyridyl)ethane, bpee = 1,2‐bis(4‐pyridyl)ethylene], have been synthesized by using mixed‐ligand systems under solvothermal conditions and characterized structurally by single‐crystal X‐ray diffraction. Compound 1 has a 2D structure with 44‐sql net topology, whereas 2 and 3 have a 3D diamondoid structure with interesting fourfold interpenetrated topology. Topological analyses of the diamondoid nets in compounds 2 and 3 reveal a 4‐connected net with 66 topology. Thermogravimetric experiments suggest that the solvent‐free compounds 1–3 are stable up to 370, 330, and 280 °C, respectively. The grids of 1 stack in –ABCD– fashion without any regular channel structure. Desolvated compound 2 (2′) selectively adsorbs CO2 over N2, and such discrimination is regulated by the restricted window dimension of the channels. Solvent vapor (H2O, MeOH, and EtOH) adsorption studies with 2′ suggest a hydrophobic nature of the pore surface. Gas and vapor adsorption studies with 3′ reveal no uptake, which can be correlated to a smaller pore size relative to the kinetic diameter of the respective adsorbates.
Fluorine Tagging of Polyoxometalates: The Cyclic [{MoV2O4(H2O)}4{O3PC(CF3)(O)PO3}4]12–
Authors: Banerjee Abhishek , Bassil Bassem S. , Röschenthaler Gerd‐Volker , Kortz Ulrich
Published: July 2010

We have discovered a simple and efficient strategy to incorporate fluorine into polyoxometalates by reaction of thefluorinated diphosphonate H2O3PC(CF3)(OH)PO3H2 with [MoV2O4(H2O)6]2+ in aqueous medium (pH = 6.4) resulting in [{MoV2O4(H2O)}4{O3PC(CF3)(O)PO3}4]12– (1), which was structurally characterized in solution by multinuclear NMR spectroscopy and in the solid state by single‐crystal X‐ray diffraction, infrared, thermogravimetric and elemental analyses. Polyanion 1 crystallizes as the mixed sodium/guanidinium salt Na6.5[(H2N)3C]5.5[{MoV2O4(H2O)}4{O3PC(CF3)(O)PO3}4]·8H2O (1a) in the monoclinic system, space groupC2/c with the unit‐cell parameters a = 34.0685(95) Å, b = 8.0874(19) Å, c = 34.4101(10) Å, β = 100.20(2)°, V = 9331.02(4) Å3 and Z = 2. The novel polyanion 1 has a cyclic, saddle‐like structure with four {Mo2O4(H2O)} units linked by four fully deprotonated diphosphonate moieties. In addition, the (CF3)C–OH moiety is deprotonated, due to the electronic effects of the neighboring CF3 group, leading to the formation of an Mo–O(C) bond. Solution 31P and 19F NMR studies of 1 indicate magnetic inequivalence of the two phosphorus atoms in each diphosphonate moiety. The solid‐state packing of the title polyanions in 1a by loosely bound Na+ counterions leads to an AAA‐type arrangement.
Flexible and Redox‐Active Coordination Polymer: Control of the Network Structure by Pendant Arms of a Macrocyclic Complex
Authors: Moon Hoi Ri , Suh Myunghyun Paik
Published: July 2010

The coordination polymer {[Ni(C20H32N8)]2[TCM]}·5DMF·8H2O (1) has been assembled from a NiII macrocyclic complex that contains two pyridyl pendant arms, [Ni(C20H32N8)](ClO4)2, and sodium tetrakis[4‐(carboxyphenyl)oxamethyl]methane (Na4TCM) in DMF/water. The X‐ray structure of 1 reveals that the pyridyl pendant arms in the macrocyclic complex play a crucial role in determining the network structure through the π–π interactions. Compound 1 forms doubly catenated rhombic grids that generate 1D channels. It exhibits flexible behavior upon desorption/resorption and exchange of organic guest molecules as well as temperature change. Solid 1 is redox active due to the incorporated NiII macrocyclic species, and reacts with Pd(NO3)2 dissolved in acetonitrile at room temperature to produce small Pd nanoparticles [(2.9 ± 0.4) nm in diameter] in the channels in the absence of extra reducing or capping agents.
PFG‐NMR on W1/O/W2‐emulsions: Evidence for molecular exchange between water phases
Authors: Guan Xiangzhen , Hailu Kidist , Guthausen Gisela , Wolf Frederik , Bernewitz Richard , Schuchmann Heike P.
Published: July 2010

A major question in the investigation of multiple emulsions of WOW‐type is that of stability and ripening, which is often reflected in the droplet‐size distribution (DSD). The DSD is an important parameter for judging product properties. Instability in multiple emulsions is often linked to molecular exchange between inner and outer water phases (W1, W2), which has to be taken into account. For example, coalescence phenomena and Ostwald ripening affect microscopic and/or macroscopic stability and therefore the multi‐dispersity of an emulsion. This is especially important as the inner compartment can act for encapsulating active agents. NMR investigations on emulsions are mainly based on the analysis of diffusion properties of molecules in the different compartments. For determination of the DSD of the inner and outer droplets, it is crucial to know the physical effects influencing the NMR‐signal. Depending on these effects, the NMR data are analyzed by different models, depending for example on the occurrence and time scale of molecular exchange between the phases. They are shown to yield correct DSDs. Evidence for the effect of diffusion between phases is given by using the phenomenon of driven diffusion, which allows a direct detection of the exchange by NMR. The exchange is confirmed by confocal laser scanning microscopy.
Metathesis and Macrocycles with Embedded Carbohydrates
Authors: Jarikote Dilip Venkatrao , Murphy Paul V.
Published: July 2010

Macrocycles containing embedded carbohydrates are found in nature. Tricholorin A and G, woodrosin, sophorolipid lactone, cycloviracin B1, glucolipsin A and ipomoeassins A–F are natural products with interesting biological properties. They have inspired synthesis of non‐natural macrocyclic structures which contain embedded carbohydrates. Glycophanes (hybrids of carbohydrates and cyclophanes) were prepared which show potential in host‐guest chemistry and which have been applied as rigid scaffolds for the synthesis of bivalent inhibitors of lectin binding to tumour cells. Macrocyclic neoglycoconjugates have also been prepared. These include macrocyclic neooligoaminodeoxysaccharides which bind to RNA regions containing either asymmetric internal loop or hairpin loop‐stem junctions, and vaccine candidates. Non‐natural macrolides having antibacterial and antifungal activity have been synthesised. Metathesis using Grubbs and Hoyveda‐Grubbs catalysts has been key to the successful generation of these compounds. Herein we review the recent application of metathesis to the synthesis of ipomoeassins A, B and F, glycophanes, neooligoaminodeoxysaccharides,macrolides and other macrocycles with embedded carbohydrates.
Pyrrolysine Analogs for Translational Incorporation into Proteins (Eur. J. Org. Chem. 22/2010)
Authors: Fekner Tomasz , Li Xin , Chan Michael K.
Published: July 2010

The cover picture shows the X‐ray crystal structure of the monomethylamine methyltransferase from Methanosarcina barkeri. It was central to the discovery of pyrrolysine, the 22nd genetically encoded amino acid. The picture is also decorated with the structures of pyrrolysine and some of its analogs. They can be incorporated into proteins in response to an otherwise non‐sense amber (UAG) codon upon action of pyrrolysyl‐tRNAPyl synthetases from various Methanosarcinaceae working in tandem with their cognate tRNAs. Details are presented in the Microreview by M. K. Chan et al. on p. 4171 ff. The scarlet‐and‐gray background represents the colors of The Ohio State University.
Separation of α‐lactalbumin grafted‐ and non‐grafted maghemite core/silica shell nanoparticles by capillary zone electrophoresis
Authors: Petr Jan , Teste Bruno , Descroix Stéphanie , Siaugue Jean‐Michel , Gareil Pierre , Varenne Anne
Published: July 2010

The use of nanoparticles (NPs) in immunodiagnostics is a challenging task for many reasons, including the need for miniaturization. In view of the development of an assay dedicated to an original, miniaturized and fully automated immunodiagnostics which aims to mimic in vivo interactions, magnetic zwitterionic bifunctional amino/polyethyleneoxide maghemite core/silica shell NPs functionalized with allergenic α‐lactalbumin were characterized by CE. Proper analytical performances were obtained through semi‐permanent capillary coating with didodecyldimethylammonium bromide (DDAB) or permanent capillary wall modification by hydroxypropylcellulose. The influence of experimental conditions (e.g. buffer component nature, pH, ionic strength, and electric field strength) on sample stability, electrophoretic mobility, and dispersion was investigated using either DDAB‐ or hydroxypropylcellulose‐coated capillaries. Adsorption to the capillary wall and aggregation phenomena were evaluated according to the CE conditions. The proper choice of experimental conditions, i.e. separation under −10 kV in a 25 mM ionic strength MES/NaOH (pH 6.0) with a DDAB‐coated capillary, allowed the separation of the grafted and the non‐grafted NPs.
Optimal design of superelastic‐friction base isolators for seismic protection of highway bridges against near‐field earthquakes
Authors: Ozbulut Osman E. , Hurlebaus Stefan
Published: July 2010

The seismic response of a multi‐span continuous bridge isolated with novel superelastic‐friction base isolator (S‐FBI) is investigated under near‐field earthquakes. The isolation system consists of a flat steel‐Teflon sliding bearing and a superelastic NiTi shape memory alloy (SMA) device. The key design parameters of an S‐FBI system are the natural period of the isolated bridge, the yielding displacement of the SMA device, and the friction coefficient of the sliding bearings. The goal of this study is to obtain optimal values for each design parameter by performing sensitivity analysis of a bridge isolated by an S‐FBI system. First, a three‐span continuous bridge is modeled as two‐degrees‐of‐freedom with the S‐FBI system. A neuro‐fuzzy model is used to capture rate‐ and temperature‐dependent nonlinear behavior of the SMA device. Then, a set of nonlinear time history analyses of the isolated bridge is performed. The variation of the peak response quantities of interest is shown as a function of design parameters of the S‐FBI system and the optimal values for each parameter are evaluated. Next, in order to assess the effectiveness of the S‐FBI system, the response of the bridge isolated by the S‐FBI system is compared with the response of the non‐isolated bridge and the same bridge isolated by pure‐friction (P‐F) sliding isolation system. Finally, the influence of temperature variations on the performance of the S‐FBI system is evaluated. The results show that the optimum design of a bridge with the S‐FBI system can be achieved by a judicious specification of design parameters. Copyright © 2010 John Wiley & Sons, Ltd.
Assessment indices for the seismic vulnerability of existing R.C. buildings
Authors: Thermou G. E. , Pantazopoulou S. J.
Published: July 2010

The seismic vulnerability of old multi‐storey reinforced concrete (R.C.) buildings reinforced with substandard details is assessed as a function of interstorey drift demand imposed by the design earthquake while considering brittle termination of elastic response of the critical members of the structure due to a premature shear failure. Interstorey drift demand is related to column and wall translational stiffnesses which are expressed through analytical derivations in terms of the floor area ratios of gravity and lateral load bearing members in the critical floor. Interstorey drift capacity is related to the available transverse reinforcement and the axial load ratio of the vertical members. The significance of the area ratio of vertical members in the typical floor as an index of vulnerability is explored with reference to the limitations in the value of axial load ratio used in R.C. design in order to secure ductile flexural behavior, and also with reference to the stability index of gravity load bearing members. Interstorey Drift Spectra are derived for the existing R.C. buildings suitable for rapid seismic vulnerability screening but also as a guide for rehabilitation of the existing structures. Lightly reinforced or substandard reinforced concrete buildings that reportedly collapsed during previous earthquakes are used as example case studies in order to calibrate the proposed methodology. Copyright © 2010 John Wiley & Sons, Ltd.
Incorporation of diffuse interface in smoothed particle hydrodynamics: Implementation of the scheme and case studies
Authors: Das A. K. , Das P. K.
Published: July 2010

An algorithm is proposed to incorporate diffuse interface (DI) modelling in the Lagrangian smoothed particle hydrodynamics (SPH) for the simulation of interface and its evolution. The model assumes a smooth variation of properties across the interface of two immiscible fluids. The conventional Cahn–Hilliard equation has been adopted to take care of the property variation across the DI. However, it has been recast to be compatible with the particle‐based formulation. The momentum equation has also been modified to account for the surface energy. Three different case studies namely evolution of gas bubbles at submerged orifice, drop deformation in shear flow and deformation of droplets in parabolic flow have been selected for the application of DI‐based SPH (DI‐SPH) method of solution. For the sake of comparison the predictions have been made for all the cases by DI‐SPH as well as by the basic SPH without incorporating DI. Results of these two simulations have been compared with those already reported in the literature. In all the cases DI‐SPH shows a definite improvement in the prediction of the complex interface and their dynamics. The present work demonstrates the strength of the technique in the simulation of diverse multiphase flow problems with evolving interfaces. Copyright © 2010 John Wiley & Sons, Ltd.
Nerve injury‐activated microglia engulf myelinated axons in a P2Y12 signaling‐dependent manner in the dorsal horn
Authors: Maeda Mitsuyo , Tsuda Makoto , Tozaki‐Saitoh Hidetoshi , Inoue Kazuhide , Kiyama Hiroshi
Published: July 2010

The mechanisms underlying neuropathic pain are poorly understood. However, several studies have implied a role for reactive microglia located in the dorsal horn in neuropathic pain. To clarify the roles of activated microglia in neuropathic pain, we investigated the interactions among microglia and other neural components in the dorsal horn using electron microscopy. Microglia were more abundantly localized in layers II–III of the dorsal horn than in other areas, and some of them adhered to and engulfed both injured and uninjured myelinated axons. This microglial engulfment was rarely observed in the normal dorsal horn, and the number of microglia attached to myelinated axons was markedly increased on postoperative day 7 on the operated side. However, after blocking the P2Y12 ATP receptor in microglia by intrathecal administration of its antagonist, AR‐C69931MX, the increase in the number of microglia attached to myelinated axons, as well as the development of tactile allodynia, were markedly suppressed, although the number of activated microglia did not change remarkably. These results indicate that engulfment of myelinated axons by activated microglia via P2Y12 signaling in the dorsal horn may be a critical event in the pathogenesis of neuropathic pain. © 2010 Wiley‐Liss, Inc.
Mental disorders affect older persons in Sweden – a register‐based study
Authors: Martinsson Gunilla , Wiklund‐Gustin Lena , Fagerberg Ingegerd , Lindholm Christina
Published: July 2010

Objective

The study aimed to estimate the prevalence of mental disorders based on pharmaceutical use among the old (age ≥ 65) in Sweden for the years 2006–2008.

Methods

Data on the mental health of older persons were approximated on the basis of recommended prescriptions for pharmaceuticals, gathered from the Swedish Register on Prescribed Pharmaceuticals (SRPP). Each disorder (ICD‐10, F20‐F42, and F60‐F61) was analyzed to identify associated recommended pharmaceuticals. Anatomical Therapeutic Chemical Classification codes were applied. The data covered 188 024 individuals who received 2 013 079 prescriptions for pharmaceuticals for mental disorders during a 3‐year period. Persons with pharmaceuticals for dementia disorders were excluded from the calculations of the prevalence of mental disorders.

Results

The prevalence of mental disorders among the old in Sweden, measured on the basis of pharmaceutical use, was 6.6% in 2006, 2007, and 2008, respectively. Men constituted one‐third of cases and women two‐thirds. Prevalence was lowest in the age group 65–69 and increased subsequently with age.

Conclusions

This fundamental register‐based study included a great number of older persons and shows that mental disorders affect every fifteenth older person in Sweden. The prevalence of mental disorders increases with increasing age. The results highlight the extent of mental disorders among older persons, which is important to know when planning care for these patients. This study, by investigating a large population, provides a solid basis for general planning as well as for future mental disorder research. Copyright © 2010 John Wiley & Sons, Ltd.
Hippocampal episode fields develop with learning
Authors: Gill Patrick R. , Mizumori Sheri J.Y. , Smith David M.
Published: July 2010

Several recent studies have shown that hippocampal neurons fire during the delay period in between trials and that these firing patterns differ when different behaviors are required, suggesting that the neuronal responses may be involved in maintaining the memories needed for the upcoming trial. In particular, one study found that hippocampal neurons reliably fired at particular times, referred to as “episode fields” (EFs), during the delay period of a spatial alternation task (Pastalkova et al. (2008) Science 321:1322–1327). The firing of these neurons resulted in distinct sequential firing patterns on left and right turn trials, and these firing patterns could be used to predict the upcoming behavioral response. In this study, we examined neuronal firing during the delay period of a hippocampus‐dependent plus maze task, which involved learning to approach two different reward locations (east and west), and we examined the development of these firing patterns with learning. As in the previous study, hippocampal neurons exhibited discrete periods of elevated firing during the delay (EFs) and the firing patterns were distinct on the east and west trials. Moreover, these firing patterns emerged and began to differentiate the east and west conditions during the first training session and continued to develop as the rats learned the task. The finding of similar firing patterns in different tasks suggests that the EFs are a robust phenomenon, which may occur whenever subjects must maintain distinct memory representations during a delay period. Additionally, in the previous study (Pastalkova et al. (2008) Science 321:1322–1327), the distinct firing patterns could have been due to the differing goal locations, behavioral responses (left or right turns), or trajectories. In this study, neuronal firing varied with the goal location regardless of the trajectories or responses, suggesting that the firing patterns encode the behavioral context rather than specific behaviors. ©2010 Wiley Periodicals, Inc.
Trend detection in water quality data using time series seasonal adjustment and statistical tests
Authors: Awadallah A. G. , Fahmy Hussam , Karaman H.G.
Published: July 2010

Detection of temporal and spatial trends can be considered one of the primary objectives of environmental monitoring networks. The overall goal of this paper is to make full use of water quality data available on Nile Delta drains in order to support the decision makers in managing the pollution problem. A more specific objective is to investigate several techniques in a systematic methodology to analyse water quality aimed at identifying temporal trends. Both seasonal adjustment time series analysis and statistical trend detection tests are used and compared. This approach was applied on two main drains in the Eastern Nile Delta (Bahr Hadus and Bahr El Baqar drains). The total dissolved salts (TDS) series was analysed as it has a length of 20 years from 1984 to 2004. The long time series gives an opportunity to apply both time series analysis and the statistical tests on the data and to compare the results of the two techniques. Both statistical techniques utilized arrived at the same results in general. The analysis showed improved (lower) salinity levels in the Bahr Hadus Drain. Although the Bahr El Baqar Drain belongs hydrobiologically to the same region, it is subject to fluctuations in salinity levels along the drain mainstream except near the outfall of the drain where the salinity level increased due to the reclamation activities taking place south of the Sahl El Hussania area. On the other hand, operation of the wastewater treatment plants of Greater Cairo have influenced the overall water quality conditions of the Bahr El Baqar Drain. Copyright © 2010 John Wiley & Sons, Ltd.
Prostate specific antigen reduction following statin therapy: Mechanism of action and review of the literature
Authors: Mener David J.
Published: July 2010

Prostate specific antigen (PSA) is a serine protease that is exclusively produced in the prostate, and its detection is the only laboratory test available for screening men for prostate cancer (PC). The interpretation of the assay is difficult since it is specific for prostate tissue and cellular growth, but not for PC. Pharmacologic therapy for hyperlipidemia, such as statins, may influence prostate cellular growth and subsequently PSA levels in patients. Dysregulated cellular growth in the prostate is mediated by inhibiting the rate‐limiting pathway step in cholesterol synthesis, thereby decreasing isoprenylate intermediates, decreasing cholesterol rich cellular membrane domains, and down‐regulating androgen and estrogen receptors. Statins, with variable efficacy, have been previously shown to inhibit cellular inflammation, angiogenesis, proliferation, migration/adhesion, and invasion, while promoting apoptosis in prostate cells by inhibiting the conversion of HMG‐CoA to mevalonate. An individual statin's molecular structure, need for enzymatic conversion, bioavailability, and peripheral tissue concentration may partially account for differing properties. By inhibiting prostatic cellular growth and promoting apoptosis, statins may subsequently decrease PSA levels, an effect recently observed in cohorts. There is scientific and clinical evidence supporting the observations that statins are associated with an overall reduction in serum PSA in men, when used for greater than 6 months, and especially when used for greater than 2 years. © 2010 IUBMB IUBMB Life, 62(8): 584–590, 2010.
How adhesion/growth‐regulatory galectins‐1 and ‐3 attain cell specificity: Case study defining their target on neuroblastoma cells (SK‐N‐MC) and marked affinity regulation by affecting microdomain organization of the membrane
Authors: Kopitz Jürgen , Bergmann Marion , Gabius Hans‐Joachim
Published: July 2010

Galectins are potent effectors with conspicuous cell‐type‐specific activity profile. Its occurrence poses the question on the nature of the underlying biochemical determinants, in human SK‐N‐MC neuroblastoma cells involved in negative growth regulation. Since increase of surface presentation of ganglioside GM1 and homodimeric galectin‐1 precedes growth inhibition, a direct interaction is suggested. We thus examined cell binding depending on glucosylceramide synthesis. It was drastically reduced by N‐butyldeoxynojirimycin and threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol, adding decisive evidence for the assumed galectin/ganglioside binding. Glycoproteins do not compensate ganglioside depletion which was verified by measuring lipid‐bound sialic acid. Binding affinity is significantly lowered by disrupting microdomain integrity, also effective for the competitive inhibitor galectin‐3. This was caused by cell treatment with either 2‐hydroxypropyl‐β‐cyclodextrin or filipin III. In this cell system, target specificity and topology of ligand presentation act together to enable high‐affinity binding. © 2010 IUBMB IUBMB Life, 62(8): 624–628, 2010.
Novel, UV‐curable coatings containing a tethered biocide: Synthesis, characterization, and antimicrobial activity
Authors: Chen Zhigang , Chisholm Bret. J. , Stafslien Shane , He Jie , Patel Sandeep
Published: July 2010

Cationic, UV ‐curable coatings containing the tethered biocide, triclosan, were produced and their antimicrobial activity toward Staphylococcus epidermidis and Escherichia coli determined. Two polysiloxanes functionalized with both cycloaliphatic epoxy and triclosan were synthesized using hydrosilylation. The functionalized polysiloxanes, with varied concentration of pendant triclosan, were used to produce UV‐curable coatings with reasonably good coating properties. Fourier transform (FT)‐Raman spectroscopy showed that the tethered triclosan moieties self‐concentrate on the coating surface. Using biological assays, it was determined that the coatings possessed nearly 100% antimicrobial activity toward the Gram‐positive bacterium, S. epidermidis, without leaching toxic components. For the Gram‐negative bacterium, E. coli, 60–80% reduction in biofilm retention was observed for all the coatings. Interestingly, the coatings were lesser effective in reducing E. coli cell viability suggesting that the tethered triclosan were able to substantially reduce the production of the biofilm extracellular matrix with minimal adverse affect on the bacterial cells attached to the coating surfaces. The high specificity of the coatings toward S. epidermidis indicates that a novel mode of contact‐active antimicrobial activity was achieved through the disruption of processes unique to the Gram‐positive cell wall. These novel UV‐curable coatings have potential applications in inhibiting implantable biomedical device associated infections. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Acute effects of microcystins exposure on the transcription of antioxidant enzyme genes in three organs (liver, kidney, and testis) of male Wistar rats
Authors: Xiong Qian , Xie Ping , Li Huiying , Hao Le , Li Guangyu , Qiu Tong , Liu Ying
Published: July 2010

Microcystins (MCs) induce the production of reactive oxygen species (ROS) in various tissues in mammals, whereas the endogenous antioxidant enzymes are responsible to scavenge the ROS. ROS can modulate the antioxidant enzyme activities by regulating the mRNA levels. The present study was undertaken to find out the relationship between the transcriptional alterations of antioxidant enzymes and MCs stimulation in rats. The time‐dependent changes of relative transcription abundance of catalase (CAT), Mn‐superoxide dismutase (Mn‐SOD), Cu,Zn‐superoxide dismutase (Cu,Zn‐SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and gamma‐glutamylcysteine synthetase (γ‐GCS) were investigated in three organs (liver, kidney, and testis) of male Wistar rats injected intravenously (i.v.) with 80 μg MC‐LRequivalent/kg body weight using the quantitative real‐time PCR (qPCR) method. We found that MCs could affect the transcriptional activities of these antioxidant enzymes in liver, kidney, and testis of MCs‐treated rats and we speculated the possible causation of the transcriptional change. The altered transcription of antioxidant enzymes may play an important role in counteracting the potential deleterious effects of elevated oxidative stress induced by MCs, and this will provide us new insights into the possible role of antioxidant enzymes in the toxicological mechanisms of MCs at molecular level. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:361–367, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20347
Characterization of photodynamic therapy responses elicited in A431 cells containing intracellular organelle‐localized photofrin
Authors: Hsieh Ya‐Ju , Yu Jau‐Song , Lyu Ping‐Chiang
Published: July 2010

Photodynamic therapy (PDT), a photochemotherapeutic regimen used to treat several diseases, including cancer, exerts its effects mainly through induction of cell death. Using human epidermoid carcinoma A431 cells as a model, we previously showed that distinct cell death types could be triggered by protocols that selectively delivered Photofrin (a clinically approved photosensitizer) to different subcellular sites (Hsieh et al. [2003] J Cell Physiol 194: 363–375]. Here, the responses elicited by PDT in A431 cells containing intracellular organelle‐localized Photofrin were further characterized. Two prominent cell phenotypes were observed under these conditions: one characterized by perinuclear vacuole (PV) formation 2–8 h after PDT followed by cell recovery or shrinkage within 48 h, and a second characterized by typical apoptotic features appearing within 4 h after PDT. DCFDA‐sensitive reactive oxygen species formed proximal to PVs during the response to PDT, covering areas in which both endoplasmic reticulum (ER) and the Golgi complex were located. Biochemical analyses showed that Photofrin‐PDT also induced JNK activation and altered the protein secretion profile. A more detailed examination of PV formation revealed that PVs were derived from the ER. The alteration of ER structure induced by PDT was similar to that triggered by thapsigargin, an ER Ca2+‐ATPase inhibitor that perturbs Ca2+ homeostasis, suggesting a role for Ca2+ in the formation of PVs. Microtubule dynamics did not significantly affect PV formation. This study demonstrates that cells in which intracellular organelles are selectively loaded with Photofrin mount a novel response to ER stress induced by PDT. J. Cell. Biochem. 111: 821–833, 2010. © 2010 Wiley‐Liss, Inc.
Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes
Authors: Arufe M.C. , De la Fuente A. , Fuentes I. , de Toro F.J. , Blanco F.J.
Published: July 2010

In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase‐polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte‐like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271+ subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271+ subpopulation than the other subpopulations. Spheroids formed from CD271‐enriched and CD73‐enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular matrix more closely than CD106+ MSCs and are possible candidates for use in cartilage tissue engineering. Both cell types have potential for promoting the differentiation of MSCs into chondrocytes, presenting new possibilities for achieving intrinsic cartilage repair. J. Cell. Biochem. 111: 834–845, 2010. © 2010 Wiley‐Liss, Inc.