bluuebunny/crossref_metadata_2025 huggingface dataset:
Tritium: a coming of age for drug discovery and development ADME studies
Authors: Lockley W. J. S. , McEwen A. , Cooke R.
Published: June 2012

Owing to recent developments in tritium chemistry and analysis, high‐quality tritium‐labelled drugs can now be prepared simply, cheaply and in timescales commensurate with those needed for rapid drug discovery in adsorption, distribution, metabolism and excretion (ADME) projects. Such3H‐labelled drugs are enabling high‐quality decision‐making at key points in the drug discovery process, thus ensuring more effective research projects, a key issue in commercial success. In addition, tritium‐labelled compounds continue to play a significant role in ADME studies later in the pharmaceutical development process. This is especially so for highly potent and hence low‐dose agents, for drugs with complex structures and for those compounds that undergo molecular fragmentation as a result of metabolism.
Long‐term interferon monotherapy reduces the risk of HCV‐associated hepatocellular carcinoma
Authors: Takeyasu Makiko , Akuta Norio , Suzuki Fumitaka , Seko Yuya , Kawamura Yusuke , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu
Published: June 2012

The aims of this study were to evaluate the efficacy of long‐term interferon (IFN) monotherapy on hepatocellular carcinoma (HCC) in patients who showed no virological response to the first course of IFN therapy, define predictive factors for HCC in patients on long‐term IFN monotherapy, and evaluate the clinical impact of amino acid (aa) substitutions in the hepatitis C virus (HCV)‐1b core region on HCC rate. This retrospective study included 494 consecutive treatment‐naive patients infected with HCV‐1b who failed to achieve sustained virological response after ≥24‐week IFN monotherapy. Of 494 patients, 113 (22.9%) received another course of ≥48‐week IFN monotherapy (additional‐IFN group), while the remaining 381 (77.1%) received no such therapy (no‐additional‐IFN group), and 10 years have elapsed since the end of the first IFN monotherapy. The cumulative HCC rate was significantly higher in the no‐additional‐IFN group than additional‐IFN group, and in those with aa substitutions in the core region of Gln70(His 70) and Met 91 than those with Arg 70 and/or Leu 91. Multivariate analysis identified stage of liver fibrosis, liver enzymes, age, treatment group, aa substitution in the core region, low‐density lipoprotein cholesterol (LDL‐cholesterol), and gender as determinants of HCC, and that additional IFN treatment significantly lowered the cumulative rate of HCC, even in patients with cirrhosis. In conclusion, long‐term IFN monotherapy reduces the risk of HCC, even in patients with cirrhosis. Substitution of aa at position 70 and/or 91 in the core region and lipid metabolism are important predictors of HCC in long‐term IFN monotherapy. J. Med. Virol. 84: 1199–1207, 2012. © 2012 Wiley Periodicals, Inc.
Tumor‐specific and gender‐specific pre‐vaccination distribution of human papillomavirus types 6 and 11 in anogenital warts and laryngeal papillomas: A study on 574 tissue specimens
Authors: Komloš Kristina Fujs , Kocjan Boštjan J. , Košorok Pavle , Luzar Boštjan , Meglič Leon , Potočnik Marko , Hočevar‐Boltežar Irena , Gale Nina , Seme Katja , Poljak Mario
Published: June 2012

Anogenital warts and laryngeal papillomas are two most important benign tumors etiologically linked with HPV. In the study, which included both the largest number of laryngeal papilloma tissue specimens (152 specimens from 152 patients) to date and the largest number of prospectively collected and histologically confirmed tissue specimens of anogenital warts obtained from both genders (422 specimens from 315 patients), HPV DNA was detected in 413/422 (97.9%) of anogenital warts and 139/152 (91.4%) of laryngeal papillomas. HPV‐6 and/or HPV‐11 were detected in 291/315 (92.4%) patients with anogenital warts and in 138/152 (90.8%) patients with laryngeal papillomas, indicating that the great majority of both tumors could be prevented with prophylactic quadrivalent vaccine. The HPV‐6 gender‐specific distribution in both anogenital warts and laryngeal papillomas was not statistically significant. In contrast, HPV‐11 was found almost three times more often in males than in females with anogenital warts (16.5% vs. 6.3%; P = 0.008), with a gender neutral HPV‐11 type distribution in laryngeal papillomas. The overall HPV DNA prevalence in anogenital warts was significantly different from that in laryngeal papillomas (97.1% vs. 91.4%; P = 0.01). In the first comparison of the HPV‐6/HPV‐11 type‐specific distribution between patients suffering from anogenital warts and laryngeal papillomas with the same geographic and ethnic background, a significant imbalance in tumor‐specific distribution of HPV‐6 and HPV‐11 was identified: HPV‐6 was statistically more often present in anogenital warts than in laryngeal papillomas (79.0% vs. 59.2%; P = 0.000013), whereas HPV‐11 was statistically more frequent in laryngeal papillomas than in anogenital warts (28.9% vs. 12.4%; P = 0.00003). J. Med. Virol. 84: 1233–1241, 2012. © 2012 Wiley Periodicals, Inc.
Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: Does ethnicity matter?
Authors: Papastergiou Vasilios , Dimitroulopoulos Dimitrios , Skorda Lamprini , Lisgos Philippos , Ketikoglou Ioannis , Kostas Nikolaos , Karatapanis Stylianos
Published: June 2012

Hepatitis C virus genotype 4 (HCV‐4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV‐4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment‐naïve patients infected with HCV‐4 (subtype a) and to identify factors influencing response rates. One hundred seventy‐seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7‐year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135–0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816–0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933–0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482–0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV‐4. J. Med. Virol. 84: 1217–1223, 2012. © 2012 Wiley Periodicals, Inc.
Sequencing and phylogenetic analysis of the hexon, fiber, and penton regions of adenoviruses isolated from AIDS patients
Authors: Al Qurashi Yasir Mohammed A. , Alkhalaf Moustafa Alissa , Lim Lusiana , Guiver Malcolm , Cooper Robert J.
Published: June 2012

Sequencing and phylogenetic analysis of the hexon, fiber, and penton regions of adenoviruses isolated between 1986 and 1997 from AIDS patients has been performed. Sequencing the L2 part of the hexon gene of 51 adenoviruses isolated between 1986 and 1997 from AIDS patients revealed only one type each from species A and C and two types from species B with all the remaining isolates from species D. Further sequencing and phylogenetic analysis of the fiber knob region of these species D adenoviruses revealed that 28/46 were intermediate strains with conflicting hexon and fiber sequences. When the penton regions of these intermediate strains were sequenced, it became clear that some had originated from a third adenovirus type presumably by intergene recombination events. Evidence from sequencing the L1 hexon and fiber shaft regions showed no evidence of intragene recombination but penton sequences showed that recombination between the hypervariable region (HVR) and RGD regions was common. Six isolates appear to be from three new adenovirus types. Five AIDS patients showed sequential infection with different adenovirus variants and six such variants were isolated from a single patient in 2 years. J. Med. Virol. 84: 1157–1165, 2012. © 2012 Wiley Periodicals, Inc.
Gene expression profile in human skeletal muscle cells infected with human adenovirus type 36
Authors: Wang Zhong Q. , Yu Yongmei , Zhang Xian H. , Qin Jianhua , Floyd Elizabeth
Published: June 2012

Human adenovirus type‐36 (HAdV‐36) is a specific pathogen that may lead to increased adiposity and obesity. In order to evaluate the effects of HAdV‐36 on gene transcription, a microarray analysis of muscle cells infected with HAdV‐36 was performed. Gene expression profile was determined by microarray analysis in cultured human skeletal muscle cells with or without HAdV‐36 infection. Quantitative real‐time PCR (qPCR) assay was performed in selected 35 genes to verify the results of the microarray analysis. A total of 13,060 unique genes were detected in the HAdV‐36 infected muscle cells infected with HAdV‐36. Among them, 1,004 genes were significantly altered by using a cut‐off point at fold change ≥1.5 and P value <0.05. Most of the principal 100 altered genes were involved in development, immune response, signal transduction, transcriptional regulation as well as carbohydrate, lipid and protein metabolism. Thirty‐two genes (91.4%) from the 35 selected genes were confirmed by qPCR assay. In addition, HAdV‐36 altered 252 genes that are associated with cancer. The study showed HAdV‐36 infection upregulated host cell antiviral defense. HAdV‐36 also induces changes in gene expression related to cellular signaling pathways of signal transduction, transcriptional regulation as well as carbohydrate, lipid and protein metabolism. However, it remains to be investigated if HAdV‐36 infection could lead to oncogenesis. J. Med. Virol. 84: 1254–1266, 2012. © 2012 Wiley Periodicals, Inc.
Occurrence of human bocaviruses and parvovirus 4 in solid tissues
Authors: Norja Päivi , Hedman Lea , Kantola Kalle , Kemppainen Kaisa , Suvilehto Jari , Pitkäranta Anne , Aaltonen Leena‐Maija , Seppänen Mikko , Hedman Klaus , Söderlund‐Venermo Maria
Published: June 2012

Human bocaviruses 1‐4 (HBoV1‐4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2‐4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1‐4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1‐4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species‐specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus‐like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2‐4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. J. Med. Virol. 84: 1267–1273, 2012. © 2012 Wiley Periodicals, Inc.
Enhanced apoptotic effects by the combination of curcumin and methylseleninic acid: potential role of mcl‐1 and fak
Authors: Guo Xiao , Yin Shutao , Dong Yinhui , Fan Lihong , Ye Min , Lu Junxuan , Hu Hongbo
Published: June 2012

Curcumin and methylseleninic acid (MSeA) are well‐documented dietary chemopreventive agents. Apoptosis appears to be a major mechanism for both agents to exert anti‐cancer activity. The purpose of the present study was designed to determine whether the apoptotic effect on human cancer cells can be enhanced by combining curcumin with MSeA. Apoptosis was evaluated by Annexin V staining of externalized phosphatidylserine by flow cytometry. Expression of protein was analyzed by Western blotting. Localization of apoptosis‐inducing factor (AIF) was detected by immunocytochemistry. RNA interference was employed to inhibit expression of specific protein. We found here that combining curcumin with MSeA led to a significantly enhanced apoptosis in both MDA‐MB‐231 breast cancer cells and DU145 prostate cancer cells. Further mechanistic investigations revealed that curcumin treatment alone caused a concentration dependent upregulation of Mcl‐1, which can be overcome by combining it with MSeA. In line with the Mcl‐1 reduction, an enhanced mitochondrial permeability transition and AIF nuclear translocation by the combination were achieved. In addition, an increased suppression of focal adhesion kinase activity was observed in the combination‐treated cells which were associated with cell detachment‐induced apoptosis by the combination. Our findings suggest that curcumin/MSeA combination holds excellent potential for improving their efficacy against human breast and prostate cancer through enhanced apoptosis induction. © 2012 Wiley Periodicals, Inc.
Global well‐posedness of the compressible Euler with damping in Besov spaces
Authors: Jiu Quansen , Zheng Xiaoxin
Published: June 2012

In this paper, we consider the Cauchy problems for compressible Euler equations with damping. In terms of the Littlewood–Paley decomposition and Bony's para‐product formula, we prove the global existence, uniqueness and asymptotic behavior of the solution in the critical Besov space
comparing with previous results. Copyright © 2012 John Wiley & Sons, Ltd.
Quantification issues of in vivo1H NMR spectroscopy of the rat brain investigated at 16.4 T
Authors: Hong Sung‐Tak , Pohmann Rolf
Published: June 2012

The accuracy and precision of the quantification of metabolite concentrations in in vivo 1H NMR spectroscopy are affected by linewidth and signal‐to‐noise ratio (SNR). To study the effect of both factors in in vivo 1H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo 1H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation was found between most of the heavily overlapping metabolite peaks, indicating independent and reliable quantification. Two different approaches for the consideration of macromolecular signals were evaluated. The use of prior knowledge derived by parameterization of a metabolite‐nulled spectrum demonstrated improved fitting quality, with reduced Cramér–Rao lower bounds, compared to the calculation of a regularized spline baseline. Copyright © 2012 John Wiley & Sons, Ltd.
Understanding online donor behavior: the role of donor characteristics, perceptions of the internet, website and program, and influence from social networks
Authors: Shier Micheal L. , Handy Femida
Published: June 2012

Online donation platforms, albeit a recent phenomenon, are becoming more important for human service nonprofits, allowing them to reach a broader target population of donors at relatively little cost. In developing countries such as India, internet use is flourishing, and this has allowed fund‐raisers to reach a population hitherto difficult to reach. A cross‐sectional research design was utilized to survey donors of one online donation program in India (n = 479). This research was exploratory, investigating the factors that influence people's willingness to donate online, including the socio‐demographic characteristics of donors. Results show that gender, perception of the organization, and influence from others are variables that influence the likelihood of donating online. Further research and implications for human service nonprofits seeking to undertake online charitable campaigns are discussed.

Copyright © 2012 John Wiley & Sons, Ltd.
Sphingosine‐1‐phosphate activates chemokine‐promoted myeloma cell adhesion and migration involving α4β1 integrin function
Authors: García‐Bernal David , Redondo‐Muñoz Javier , Dios‐Esponera Ana , Chèvre Raphaël , Bailón Elvira , Garayoa Mercedes , Arellano‐Sánchez Nohemí , Gutierrez Norma C , Hidalgo Andrés , García‐Pardo Angeles , Teixidó Joaquin
Published: June 2012

Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1‐dependent myeloma cell adhesion is up‐regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine‐1‐phosphate (S1P) regulates immune cell trafficking upon binding to G‐protein‐coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up‐regulated the α4β1‐mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high‐affinity α4β1 that efficiently bound the α4β1 ligand VCAM‐1, a finding that was associated with S1P‐triggered increase in talin‐β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1‐dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2‐Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1‐dependent adhesion and migration of myeloma cells by CXCL12‐S1P combined activities might have important consequences for myeloma disease progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Synthesis, thermal polymerization, and properties of benzoxazine resins containing fluorenyl moiety
Authors: Fu Zien , Liu Huan , Cai Hualun , Liu Xin , Ying Guo , Xu Kai , Chen Mingcai
Published: June 2012

Three difunctional fluorene‐based benzoxazine compounds were synthesized via Mannich condensation and were characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR), and elementary analysis (EA). The polymerization of benzoxazine monomers were investigated with differential scanning calorimeter (DSC) method. Thermal properties of the polybenzoxazines were studied by thermogravimetric analysis (TGA) and DSC. Water absorption of the polybenzoxazines was tested. Contact angle measurement was employed to characterize the surface property of materials. The glass transition temperatures (Tgs) and thermal stability were improved significantly in comparison with bisphenol‐A‐based analogue because of the incorporation of rigid fluorenyl group. The fluorenyl‐based polybenzoxazines showed hydrophobic characteristics, which was ascribed to the low polarity of fluorenyl and pi–pi stacking interaction of fluorenyl on the surface. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Effect of titanium dioxide nanoparticles on polydimethylsiloxane/polyethersulfone composite membranes for gas separation
Authors: Madaeni S.S. , Badieh M. Moahamadi Sarab , Vatanpour V. , Ghaemi N.
Published: June 2012

Introducing inorganic nanoparticles into the structure of polymeric membranes is an interesting approach for the enhancement of physical, chemical, and separation properties of the membranes. In this article, the performance of a two‐layer nanocomposite membrane for gas separation was studied. Three different methods for embedding titanium dioxide (TiO2) nanoparticle were employed for the membrane preparation. The techniques include blending TiO2 in the polydimethylsiloxane (PDMS) coating layer, blending TiO2 in the polyethersulfone (PES) support and dip coating of PES support with TiO2 accompanied by PDMS coating. The aim of the current research was finding the optimum technique for introducing TiO2 into the membrane to obtain superior performance for gas separation. The results indicated that PES support containing TiO2 nanoparticles possessed favorable effect on gas separation capability. The optimum performance was obtained by PDMS‐coated membranes prepared with 7 wt% TiO2‐embedded PES support. Carbon dioxide (CO2) permeance, CO2/nitrogen, and CO2/methane selectivity were obtained as 188.7 GPU, 8.6, and 3.4, respectively. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Stretch‐induced molecular ordering in amorphous/crystalline polylactide blends
Authors: Lv Ruihua , Zou Shufen , Na Bing , Pan Huayan , Deng Huiyu
Published: June 2012

The effect of amorphous poly(D,L‐lactide) (PDLLA) on the molecular orientation and crystallization of crystalline poly(L‐lactide) (PLLA) on stretching is reported in this study. It is indicated that the presence of PDLLA in its miscible blends with PLLA is not favorable for either cohesive mesophase formation below Tg or strain‐induced crystallization above Tg at strains beyond the segmental extensibility limit. Because of lack of constraints imposed by cohesive mesophase or crystals, oriented segments are liable to slide each other or recoil, responsible for low‐molecular orientation in the stretched blends. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers
Preparation of 1,3‐Diazido‐2‐Nitro‐2‐Azapropane from Urea
Authors: Il'yasov Sergey G. , Danilova Elena O.
Published: June 2012

An alternative method to prepare 1,3‐diazido‐2‐nitro‐2‐azapropane (DANP), a promising liquid component for high‐energy condensed systems, is suggested and involves the following stages: (i) nitration of urea, (ii) condensation of the nitration product with formaldehyde, (iii) acylation (chlorination) of 1,3‐dihydroxy‐2‐nitro‐2‐azapropane, (iv) chlorination of 1,3‐diacetoxy‐2‐nitro‐2‐azapropane, and (v) azidation of the dichloro derivative to DANP. This synthesis method is selective and enables isolation of 1,3‐diazido‐2‐nitrazapropane devoid of impurities.
A novel set of β‐N‐biaryl ether sulfonamide hydroxamates as potential MMPs inhibitors: Molecular dynamics simulations and molecular properties evaluation
Authors: Turra Kely Medeiros , Pasqualoto Kerly Fernanda Mesquita , de Moraes Barros Silvia Berlanga
Published: June 2012

Matrix metalloproteinases (MMPs) constitute a family of zinc‐dependent proteases involved in the extracellular matrix degradation. MMP‐2 and MMP–9 are overexpressed in several human cancer types, including melanoma, thus the development of new compounds to inhibit MMPs' activity is desirable. Molecular dynamic simulation and molecular properties calculations were performed on a set of novel β‐N‐biaryl ether sulfonamide‐based hydroxamates, reported as MMP‐2 and MMP‐9 inhibitors, for providing data to develop an exploratory analysis. Thermodynamic, electronic, and steric descriptors have significantly discriminated highly active from moderately and less active inhibitors of MMP‐2 whereas apparent partition coefficient at pH 1.5 was also significant for the MMP‐9 data set. Compound 47 was considered an outlier in all analysis, indicating the presence of a bulky substituent group in R3 is crucial to this set of inhibitors for the establishment of molecular interactions with the S1 subsite of both enzymes, but there is a limit. © 2012 Wiley Periodicals, Inc.
Hydrogen site occupation and electronic structure in the La2Ni2In intermetallic and hydrides
Authors: Aburto Andrea , Orgaz Emilio
Published: June 2012

By means of electronic structure computation methods based on density functional theory, we investigated some properties of the intermetallic compounds R2Ni2In (R = La, Ce, Pr, Nd). We studied the hydrogen atom occupancy in the La2Ni2In intermetallic and we found that the available interstitial sites for hydrogen occupation can be clearly differentiated by the hydrogen site energy. Hydrogen atoms are stabilized by the NiH bonding interaction. This result indicates that the formation of a solid solution and eventually a hydride phase follow an enthalpic controlled order. With this information, we have investigated the formation of hydride phases in La2Ni2In. © 2012 Wiley Periodicals, Inc.
Information geometric security analysis of differential phase‐shift quantum key distribution protocol
Authors: Gyongyosi Laszlo , Imre Sandor
Published: June 2012

This paper analyzes the information‐theoretical security of the of Differential Phase Shift (DPS) Quantum Key Distribution (QKD) protocol, using efficient computational information geometric algorithms. The protocol was introduced for practical reasons, since the earlier QKD schemes were too complicated to implement in practice. The DPS QKD protocol can be an integrated part of current network security applications; hence its practical implementation is much easier with the current optical devices and optical networks. The proposed algorithm could be a very valuable tool to answer the still open questions related to the security bounds of the DPS QKD protocol. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of Egyptian bronze archaeological artifacts
Authors: Gouda V. K. , Youssef G. I. , Abdel Ghany N. A.
Published: June 2012

This paper presents the results of in situ non‐destructive X‐ray fluorescence determination of the chemical analysis of a collection of ten bronze statues that are on display at the Egyptian museum of Cairo. The statues are from the late period of the ancient Egyptian history. In addition, destructive technique X‐ray diffraction analysis was applied on 11 damaged archaeological objects to determine the corrosion products and the alloy compositions. Specimens of the latter objects were subjected to metallographic examinations to determine the microstructure of the alloy. Surprisingly, the results indicated that all ten statues and 10 of the 11 damaged objects were made of lead – bronze alloy; the percentage of the lead varied from 3.43 to 18.04, the tin varied from 2.53 to 10.67. The chemical composition of the patina on eight damaged objects is essentially composed of (Cu2O) cuprite for all objects in addition to other compounds such as (SnO2) cassiterite in two objects, (PbCO3) cerussite in three other objects and (Cu2(OH)3Cl) atacamite or (Cu(OH)3Cl) paratacamite in two other objects. The formation of chlorides and carbonate resulted from the interaction between surrounding environment and the alloy. The results of the metallographic examinations indicated a non‐homogenous structure and the increase of the lead content increases the globular lead particles. In spite of this condition, the galvanic corrosion tendency when the alloy is exposed to moist air or soil is not possible as lead compounds are electrically insulating. Another advantage for using leaded bronze in making statues is being heavy and thus leads to stability. Copyright © 2012 John Wiley & Sons, Ltd.
The initial effect of KCl deposit on alumina scales characterized by ToF‐SIMS and AES
Authors: Engkvist J. , Israelsson N. , Bexell U.
Published: June 2012

A FeCrAl alloy was preoxidized to form a protective alumina scale, and the effect of KCl deposits on the alumina scale was investigated while exposed during 1 and 24 h at 600 °C. However, impurity concentrations in the alumina scale change the ion conductivity and hence affect its protective properties. Therefore, Auger electron spectroscopy and time‐of‐flight secondary ion mass spectrometry were used to characterize the alumina scales and detect traces of K and Cl. The results showed that K and Cl existed as large sharp‐edged crystals surrounded by a dendritic network after 1 h. However, after 24 h, those were dissolved, and K together with Cl was detected only in the outer layer of the duplex alumina scale, which was formed during preoxidation. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of individual nano‐objects with nanoprojectile‐SIMS
Authors: Liang C.‐K. , Verkhoturov S. V. , Bisrat Y. , Dikler S. , DeBord J. D. , Fernandez‐Lima F. A. , Schweikert E. A. , Della‐Negra S.
Published: June 2012

Secondary ion mass spectrometry (SIMS) applied in the event‐by‐event bombardment/detection mode is uniquely suited for the characterization of individual nano‐objects. In this approach, nano‐objects are examined one‐by‐one, allowing for the detection of variations in composition. The validity of the analysis depends upon the ability to physically isolate the nano‐objects on a chemically inert support. This requirement can be realized by deposition of the nano‐objects on a Nano‐Assisted Laser Desorption/Ionization (NALDI™) plate. The featured nanostructured surface provides a support where nano‐objects can be isolated if the deposition is performed at a proper concentration. We demonstrate the characterization of individual nano‐objects on a NALDI™ plate for two different types of nanometric bacteriophages: Qβ and M13. Scanning electron microscope (SEM) images verified that the integrity of the phages is preserved on the NALDI™ substrate. Mass spectrometric data show secondary ions from the phages are identified and resolved from those from the underlying substrate. Copyright © 2012 John Wiley & Sons, Ltd.
Clinical trials for predictive medicine
Authors: Simon Richard
Published: June 2012

Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials. In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are Phase III clinical trials involving both genome‐wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction‐based approach to the analysis of randomized clinical trials that both preserves the Type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Copyright © 2012 John Wiley & Sons, Ltd.
Identifying comorbidity patterns of health conditions via cluster analysis of pairwise concordance statistics
Authors: Ng Shu Kay , Holden Libby , Sun Jing
Published: June 2012

Identification of comorbidity patterns of health conditions is critical for evidence‐based practice to improve the prevention, treatment and health care of relevant diseases. Existing approaches focus mainly on either using descriptive measures of comorbidity in terms of the prevalence of coexisting conditions, or addressing the prevalence of comorbidity based on a particular disease (e.g. psychosis) or a specific population (e.g. hospital patients). As coincidental comorbidity by chance increases with the prevalence rates of the conditions, which in turn depend heavily on the population under study, research findings on comorbidity patterns using those approaches may provide unreliable results. In this paper, we propose an asymmetric version of Somers’ D statistic to provide a quantitative measure of comorbidity that accounts for co‐occurrence of conditions by chance, and develop a unified clustering algorithm to identify comorbidity patterns with adjustment for multiple testing and control for the false discovery rate. We assess the applicability of the proposed comorbidity measure and investigate the performance of the proposed procedure for the adjustment of multiple testing by conducting a comparative study and a sensitivity analysis, respectively. The proposed method is illustrated using a national survey data set of mental health and wellbeing and a national health survey data set in Australia. Copyright © 2012 John Wiley & Sons, Ltd.
Decentralized model predictive‐based load‐frequency control in an interconnected power system concerning wind turbines
Authors: Mohamed Tarek Hassan , Morel Jorge , Bevrani Hassan , Abd‐Eltawwab Hassan Ahmed , Sayed Mohamed Yehia , Hiyama Takashi
Published: June 2012

This paper presents a load‐frequency control (LFC) design using the model predictive control (MPC) technique in a multi‐area power system in the presence of wind turbines (WTs). In the studied system, the controller of each local area is designed independently such that the stability of the overall closed‐loop system is guaranteed. A frequency response model of the multi‐area power system including WTs is introduced, and physical constraints of the governors and turbines are considered. The model was employed in the MPC structures. Digital simulations for a two‐area power system are provided to validate the effectiveness of the proposed scheme. The results show that with the proposed MPC technique the overall closed‐loop system performance shows robustness in the face of uncertainties due to governor and turbine parameter variation and load disturbances. A performance comparison between the proposed controller with WTs and MPC without WTs and a classical integral control scheme is carried out, confirming the superiority of the proposed MPC technique with WTs. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Augmented automatic choosing control of filter type for nonlinear systems and its application to power systems
Authors: Takata Hitoshi , Hachino Tomohiro , Motoyama Seiji , Yunokuchi Kazutomo , Kawabata Kimihisa
Published: June 2012

This paper deals with a feedback control using automatic choosing control and nonlinear filter for nonlinear systems with noise measurement. The state estimation of plants is carried out by the nonlinear filter. The control is designed by piecewise linear controls which are smoothly integrated into a single nonlinear feedback control by the automatic choosing functions. This is called an augmented automatic choosing control of filter type (AACCF) for nonlinear noisy measurement systems. This controller is applied to a transient stability problem of power systems, whose simulation results show that the new controller enables the expansion of the stable region well. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
A novel and simple model for estimating the hourly global solar radiation
Authors: Zang Haixiang , Xu Qingshan , Ichiyanagi Katsuhiro
Published: June 2012

This letter proposes a novel and simple method for estimating solar radiation, named the ‘three‐point method’. The three points used to form the model are sunrise, sunset, and the maximum radiation point. The issue of obtaining maximum radiation is performed with the weighting evaluation of the HOTTEL and ASHRAE models. The feasibility and effectiveness of the proposed model is shown by simulation results. This model is equally applicable in any part of the world with a reassessment of the weighting factors for the maximum radiation. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
The 22q11 deletion: DiGeorge and velocardiofacial syndromes and the role of TBX1
Authors: Papangeli Irinna , Scambler Peter
Published: June 2012

Hemizygous deletion of 22q11 affects approximately 1:4000 live births and may give rise to many different malformations but classically results in a constellation of phenotypes that receive a diagnosis of DiGeorge syndrome or velocardiofacial syndrome. Particularly affected are the heart and great vessels, the endocrine glands of the neck, the face, the soft palate, and cognitive development. Although up to 50 genes may be deleted, it is haploinsufficiency of the transcription factor TBX1 that is thought to make the greatest contribution to the disorder. Mouse embryos are exquisitely sensitive to varying levels of Tbx1 mRNA, and Tbx1 is required in all three germ layers of the embryonic pharyngeal region for normal development. TBX1 controls cell proliferation and affects cellular differentiation in a cell autonomous fashion, but it also directs non‐cell autonomous effects, most notably in the signaling between pharyngeal surface ectoderm and the rostral neural crest. TBX1 interacts with several signaling pathways, including fibroblast growth factor, retinoic acid, CTNNB1 (formerly known as β‐catenin), and bone morphogenetic protein (BMP), and may regulate pathways by both DNA‐binding and non‐binding activity. In addition to the structural abnormalities seen in 22q11 deletion syndrome (DS) and Tbx1 mutant mouse models, patients reaching adolescence and adulthood have a predisposition to psychiatric illness. Whether this has a developmental basis and, if so, which genes are involved is an ongoing strand of research. Thus, knowledge of the genetic and developmental mechanisms underlying 22q11DS has the potential to inform about common disease as well as developmental defect. WIREs Dev Biol 2013, 2:393–403. doi: 10.1002/wdev.75

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The Caenorhabditis elegans epidermis as a model skin. II: differentiation and physiological roles
Authors: Chisholm Andrew D. , Xu Suhong
Published: June 2012

The Caenorhabditis elegans epidermis forms one of the principal barrier epithelia of the animal. Differentiation of the epidermis begins in mid embryogenesis and involves apical–basal polarization of the cytoskeletal and secretory systems as well as cellular junction formation. Secretion of the external cuticle layers is one of the major developmental and physiological specializations of the epidermal epithelium. The four post‐embryonic larval stages are separated by periodic moults, in which the epidermis generates a new cuticle with stage‐specific characteristics. The differentiated epidermis also plays key roles in endocrine signaling, fat storage, and ionic homeostasis. The epidermis is intimately associated with the development and function of the nervous system, and may have glial‐like roles in modulating neuronal function. The epidermis provides passive and active defenses against skin‐penetrating pathogens and can repair small wounds. Finally, age‐dependent deterioration of the epidermis is a prominent feature of aging and may affect organismal aging and life span. WIREs Dev Biol 2012 doi: 10.1002/wdev.77

This article is categorized under:

Early Embryonic Development > Development to the Basic Body Plan

Invertebrate Organogenesis > Worms
Storage Age of Transfused Red Blood Cells During Liver Transplantation and Its Intraoperative and Postoperative Effects
Authors: Chen Jun , Singhapricha Terry , Memarzadeh Masood , Ziman Alyssa , Yuan Shan , Hu Ke‐qin , Steadman Randolph H. , Busuttil Ronald W. , Xia Victor W.
Published: June 2012

Background

Recent studies suggest that the storage age of red blood cells (RBCs) may be associated with morbidity and mortality in surgical patients. We studied perioperative effects of RBC storage age in patients undergoing orthotopic liver transplant (OLT).

Methods

Adult patients who received ≥5 U of RBCs during OLT between January 2004 and June 2009 were studied. The subjects were divided into two groups according to the mean storage age of RBCs they received: new or old RBCs (stored ≤14 or >14 days, respectively). Effects of storage age of transfused RBCs during OLT on intraoperative potassium (K+) concentrations, incidence of hyperkalemia (K+ ≥5.5 mmol/L), postoperative morbidity, and patient and graft survival were studied.

Results

The mean serum K+ concentrations and the incidence of hyperkalemia during OLT were significantly associated with storage age of the RBCs. Logistic analysis showed that storage age of RBCs was an independent risk factor for intraoperative hyperkalemia (odds ratios 1.067–1.085, p < 0.001) in addition to baseline K+ concentration and units of RBCs transfused. Patient and graft survival and postoperative morbidity including postoperative ventilation, reoperation, acute renal dysfunction defined by the RIFLE criteria was not associated with old RBCs.

Conclusions

Transfusion of RBCs stored for a longer time was associated with intraoperative hyperkalemia but not with postoperative adverse outcomes in adult OLT. Prevention and treatment of potentially harmful hyperkalemia should be considered when old RBCs are administered.
Substituted Thiadiazole, Oxadiazole, Triazole and Triazinone as Antimicrobial and Surface Activity Compounds
Authors: El‐Sayed R.
Published: June 2012

Stearic acid (1) was utilized as a new cheap starting material in the manufacture of important biologically active heterocycles as thiadiazole, oxadiazole, triazole and triazinone derivatives (2–11) by treating with different nucleophiles. These heterocycles bears active hydrogen atom (SH, NH and NH2) which could be propoxylated by different moles of propylene oxide (5, 10, 15 mol) to produce nonionic compounds (12–21)a–c having functions as surface and antimicrobial activities. The structural elucidation of these compounds is based on IR, 1H NMR, 13C NMR and elemental analysis. The surface properties (surface and interfacial tension, cloud point, witting time, foaming properties and emulsion stability) and the biodegradability were screened beside these compounds have been tested for their antimicrobial activity.
Pleckstrin homology (PH) like domains – versatile modules in protein–protein interaction platforms
Authors: Scheffzek Klaus , Welti Stefan
Published: June 2012

The initial reports on pleckstrin homology (PH) domains almost 20 years ago described them as sequence feature of proteins involved in signal transduction processes. Investigated at first along the phospholipid binding properties of a small subset of PH representatives, the PH fold turned out to appear as mediator of phosphotyrosine and polyproline peptide binding to other signaling proteins. While phospholipid binding now seems rather the exception among PH‐like domains, protein–protein interactions established as more and more important feature of these modules. In this review we focus on the PH superfold as a versatile protein–protein interaction platform and its three‐dimensional integration in an increasing number of available multidomain structures.
The imbibing idiot bias: Consuming alcohol can be hazardous to your (perceived) intelligence
Authors: Rick Scott I. , Schweitzer Maurice E.
Published: June 2012

Alcohol consumption and cognitive impairment frequently co‐occur. We propose that the relationship is so familiar that exposure to alcohol cues primes expectations of cognitive impairment. Across five studies, we find that in the absence of any evidence of reduced cognitive performance, people who hold an alcoholic beverage are perceived to be less intelligent than those who do not, a mistake we term the imbibing idiot bias. In fact, merely priming observers with alcohol cues causes them to judge targets who hold no beverage at all as less intelligent. The bias is not driven by a belief that less intelligent people are more likely to consume alcohol. We find that the bias may be costly in professional settings. Job candidates who ordered wine during an interview held over dinner were viewed as less intelligent and less hireable than candidates who ordered soda. However, prospective candidates believe that ordering wine rather than soda will help them appear more intelligent.
Candida Parapsilosis Total Hip Arthroplasty Infection: Case Report and Literature Review
Authors: Wang-Kei Chiu , Kwong-Yin Chung , Kin-Wing Cheung , Kwok-Hing Chiu
Published: June 2012

A 71 year-old male with a history of diabetes mellitus and right total hip arthroplasty (THA), received a revision surgery on the acetabulum cup of the THA because of loosening. The intraoperative culture yielded Candida parapsilosis. It was regarded as contamination initially. The patient had remained asymptomatic for 4 years after the revision surgery. The radiographs showed no evidence of loosening and the blood inflammatory markers were normal. The only abnormal finding was two subcutaneous swellings over the surgical scar. The patient then presented with right hip pain on walking and low-grade fever. A course of fluconazole had been given for 6 months, but the infection did not improve. Eventually, an excision arthroplasty of the right hip was performed. This case illustrates the rarity and the indolent pattern of presentation of fungal prosthetic infection. High index of suspicion and prompt treatment were needed. Literature on fungal prosthetic infection was also reviewed.
An Introduction to Catholicism
Authors: Cunningham Lawrence S.
Published: June 2012

The Vatican. The Inquisition. Contraception. Celibacy. Apparitions and miracles. Plots and scandals. The Catholic Church is seldom out of the news. But what do its one billion adherents really believe, and how do they put their beliefs into practice in worship, the family, and society? This down-to-earth account goes back to the early Christian creeds to uncover the roots of modern Catholic thinking. It avoids getting bogged down in theological technicalities, and throws light on aspects of the Church's institutional structure and liturgical practice that even Catholics can find baffling: why go to confession? How are people made saints? What is 'infallible' about the Pope? Topics addressed include:
• scripture and tradition
• sacraments and prayer
• popular piety
• personal and social morality
• reform, mission, and interreligious dialogue
Lawrence Cunningham, a theologian, prize-winning writer and university teacher, provides an overview of Catholicism today which will be indispensable for undergraduates and lay study groups.
A History of Modern Indonesia
Authors: Vickers Adrian
Published: June 2012

Although Indonesia has the fourth largest population in the world, its history is still relatively unfamiliar and understudied. Guided by the life and writings of the country's most famous author, Pramoedya Ananta Toer, Adrian Vickers takes the reader on a journey across the social and political landscape of twentieth-century Indonesia in this innovative and timely account. He begins by explaining the country's origins under the Dutch in the early part of that century, the subsequent anti-colonial struggle and revolution which led to independence in 1949. Thereafter the spotlight is on the 1950s, a crucial period in the formation of Indonesia as a new nation, which was followed by the Sukarno years, and the anti-communist massacres of the 1960s when General Suharto took over as president. The concluding chapters chart the fall of Suharto's New Order after thirty two years in power, and the subsequent political and religious turmoil which culminated in the Bali bombings in 2002. Drawing on insights from literature, art and anthropology, Adrian Vickers portrays a complex and resilient people borne out of a troubled past.