bluuebunny/crossref_metadata_2025 huggingface dataset:
On testing for genetic association in case‐control studies when population allele frequencies are known
Authors: Antonyuk A. , Holmes C.
Published: April 2009

With the emergence of Biobanks alongside large‐scale genome‐wide association studies (GWAS) we will soon be in the enviable situation of obtaining precise estimates of population allele frequencies for SNPs which make up the panels in standard genotyping arrays, such as those produced from Illumina and Affymetrix. For disease association studies it is well known that for rare diseases with known population minor allele frequencies (pMAFs) a case‐only design is most powerful. That is, for a fixed budget the optimal procedure is to genotype only cases (affecteds). In such tests experimenters look for a divergence from allele distribution in cases from that of the known population pMAF; in order to test the null hypothesis of no association between the disease status and the allele frequency. However, what has not been previously characterized is the utility of controls (known unaffecteds) when available. In this study we consider frequentist and Bayesian statistical methods for testing for SNP genotype association when population MAFs are known and when both cases and controls are available. We demonstrate that for rare diseases the most powerful frequentist design is, somewhat counterintuitively, to actively discard the controls even though they contain information on the association. In contrast we develop a Bayesian test which uses all available information (cases and controls) and appears to exhibit uniformaly greater power than all frequentist methods we considered. Genet. Epidemiol. 33:371–378, 2009. © 2009 Wiley Liss, Inc.
A modified forward multiple regression in high‐density genome‐wide association studies for complex traits
Authors: Gu Xiangjun , Frankowski Ralph F. , Rosner Gary L. , Relling Mary , Peng Bo , Amos Christopher I.
Published: April 2009

Genome‐wide association studies (GWAS) have been widely used to identify genetic effects on complex diseases or traits. Most currently used methods are based on separate single‐nucleotide polymorphism (SNP) analyses. Because this approach requires correction for multiple testing to avoid excessive false‐positive results, it suffers from reduced power to detect weak genetic effects under limited sample size. To increase the power to detect multiple weak genetic factors and reduce false‐positive results caused by multiple tests and dependence among test statistics, a modified forward multiple regression (MFMR) approach is proposed. Simulation studies show that MFMR has higher power than the Bonferroni and false discovery rate procedures for detecting moderate and weak genetic effects, and MFMR retains an acceptable‐false positive rate even if causal SNPs are correlated with many SNPs due to population stratification or other unknown reasons. Genet. Epidemiol. 33:518–525, 2009. © 2009 Wiley‐Liss, Inc.
A novel haplotype‐sharing approach for genome‐wide case‐control association studies implicates the calpastatin gene in Parkinson's disease
Authors: Allen Andrew S. , Satten Glen A.
Published: April 2009

The large number of markers considered in a genome‐wide association study (GWAS) has resulted in a simplification of analyses conducted. Most studies are analyzed one marker at a time using simple tests like the trend test. Methods that account for the special features of genetic association studies, yet remain computationally feasible for genome‐wide analysis, are desirable as they may lead to increased power to detect associations. Haplotype sharing attempts to translate between population genetics and genetic epidemiology. Near a recent mutation that increases disease risk, haplotypes of case participants should be more similar to each other than haplotypes of control participants; conversely, the opposite pattern may be found near a recent mutation that lowers disease risk. We give computationally simple association tests based on haplotype sharing that can be easily applied to GWASs while allowing use of fast (but not likelihood‐based) haplotyping algorithms and properly accounting for the uncertainty introduced by using inferred haplotypes. We also give haplotype‐sharing analyses that adjust for population stratification. Applying our methods to a GWAS of Parkinson's disease, we find a genome‐wide significant signal in the CAST gene that is not found by single‐SNP methods. Further, a missing‐data artifact that causes a spurious single‐SNP association on chromosome 9 does not impact our test. Genet. Epidemiol. 33:657–667, 2009. Published 2009 Wiley‐Liss, Inc.
A note on permutation tests for genetic association analysis of quantitative traits when variances are heterogeneous
Authors: Posthuma Danielle , de Koning Dirk‐Jan , Dolan Conor , Goddard Michael E. , Visscher Peter M.
Published: April 2009

The genetic dissection of quantitative traits, or endophenotypes, usually involves genetic linkage or association analysis in pedigrees and subsequent fine mapping association analysis in the population. The ascertainment procedure for quantitative traits often results in unequal variance of observations. For example, some phenotypes may be clinically measured whilst others are from self‐reports, or phenotypes may be the average of multiple measures but with the number of measurements varying. The resulting heterogeneity of variance poses no real problem for analysis, as long as it is properly modelled and thereby taken into account. However, if statistical significance is determined using an empirical permutation procedure, it is not obvious what the units of sampling are. We investigated a number of permutation approaches in a simulation study of an association analysis between a quantitative trait and a single nucleotide polymorphism. Our simulations were designed such that we knew the true p‐value of the test statistics. A number of permutation methods were compared from the regression of true on empirical p‐values and the precision of the empirical p‐values. We show that the best procedure involves an implicit adjustment of the original data for the effects in the model before permutation, and that other methods, some of which seemed appropriate a priori, are relatively biased. Genet. Epidemiol. 33:710–716, 2009. © 2009 Wiley‐Liss, Inc.
Simultaneously recorded EEG–fMRI: Removal of gradient artifacts by subtraction of head movement related average artifact waveforms
Authors: Sun Limin , Hinrichs Hermann
Published: April 2009

Electroencephalograms (EEGs) recorded simultaneously with functional magnetic resonance imaging (fMRI) are corrupted by large repetitive artifacts generated by the switched MR gradients. Several methods have been proposed to remove these distortions by subtraction of averaged artifact templates from the ongoing EEG. Here, we present a modification of this approach which accounts for head movements to improve the extracted template. Using the fMRI analysis package statistical parametric mapping (SPM; FIL London) the head displacement is determined at each half fMRI‐volume. The basic idea is to apply a moving average algorithm for template extraction but to include only epochs that were obtained at the same head position as the artefact to be removed. This approach was derived from phantom EEG measurements demonstrating substantial variations of the artefact waveform in response to movements of the phantom in the MRI magnet. To further reduce the residual noise, we applied a resampling algorithm which aligns the EEG samples in a strict adaptive manner to the fMRI timing. Finally, we propose a new algorithm to suppress residual artifacts such as those occasionally observed in case of brief strong movements, which are not reflected by the movement indicator because of the limited temporal resolution of the fMRI sequence. On the basis of EEG recordings of six subjects these measures combined reduce the residual artefact activity quantified in terms of the spectral power at the gradient repetition rate and its harmonics by roughly 20 to 50% (depending on the amount of movement) predominantly in frequencies beyond 30 Hz. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Lateralization of the arcuate fasciculus from childhood to adulthood and its relation to cognitive abilities in children
Authors: Lebel Catherine , Beaulieu Christian
Published: April 2009

The arcuate fasciculus is a major white matter tract involved in language processing that has also been repeatedly implicated in intelligence and reasoning tasks. Language in the human brain is lateralized in terms of both function and structure, and while the arcuate fasciculus reflects this asymmetry, its pattern of lateralization is poorly understood in children and adolescents. We used diffusion tensor imaging (DTI) and tractography to examine arcuate fasciculus lateralization in a large (n = 183) group of healthy right‐handed volunteers aged 5–30 years; a subset of 68 children aged 5–13 years also underwent cognitive assessments. Fractional anisotropy and number of streamlines of the arcuate fasciculus were both significantly higher in the left hemisphere than the right hemisphere in most subjects, although some subjects (10%) were right lateralized. Age and gender effects on lateralization were not significant. Children receiving cognitive assessments were divided into three groups: a “left‐only” group in whom only the left side of the arcuate fasciculus could be tracked, a left‐lateralized group, and a right‐lateralized group. Scores on the Peabody Picture Vocabulary Test (PPVT) and NEPSY Phonological Processing task differed significantly among groups, with left‐only subjects outperforming the right‐lateralized group on the PPVT, and the left‐lateralized children scoring significantly better than the right‐lateralized group on phonological processing. In summary, DTI tractography demonstrates leftward arcuate fasciculus lateralization in children, adolescents, and young adults, and reveals a relationship between structural white matter lateralization and specific cognitive abilities in children. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
A quantitative identification technique for a two‐dimensional subsurface defect based on surface temperature measurement
Authors: Fan Chunli , Sun Fengrui , Yang Li
Published: April 2009

The inverse identification of a subsurface defect boundary is an important part of an inverse heat conduction problem, and is also the basis for the quantitative development of a nondestructive thermographic inspection technique. For the commonly encountered quantitative thermographic defect identification problem when the test piece is heated from one part of the outer boundary, our previous study showed that some parts of the defect boundary are sensitive to the initial defect boundary prediction of the conjugate gradient method. In this paper, the heat transfer mechanism inside a test piece with this problem is analyzed by building a two‐dimensional model. A new method, the multiple measurements combination method (MMCM), is also presented which combines the identification algorithm study with the optimization of the thermographic detection technique to solve the problem. Numerical experiments certified the effectiveness of the present method. The temperature measurement error and the initial prediction of the defect boundary shape have little effect on the identification result. © 2009 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20251
Kinetic analysis on the drying of high moisture MSW
Authors: Chen Mei‐Qian , Chen Yun‐Xuan , Jia Li , Zhang Yan‐Guo , Li Qing‐Hai , Meng Ai‐Hong
Published: April 2009

Experiments on the drying of high moisture municipal solid waste (MSW) were carried out in a muffle incinerator, and a series of lost‐mass rate curves were obtained. The results show that lost mass is already over 80% for a castock, but only 30% for a potato block after 25 minutes when the drying temperature is higher than 120°C. Arrhenius equations and the activation energies of the drying process of castock and a potato block from a drying temperature of 100°C to 200°C were obtained from experimental data. The results show that lower energy is required for completely drying castock and a potato block. © 2009 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/htj.20252
Numerical study of the intensified heat transfer of an internally longitudinal ridged finned tube under pulsating flow
Authors: Wu Feng , Wang Qiu‐Wang
Published: April 2009

The turbulent pulsating flow and heat transfer in an internally longitudinal protuberant finned tube was numerically investigated by solving unsteady three‐dimensional elliptical Navier–Stokes equations. The realized k–ϵ turbulent model was adopted. The dynamic behaviors of velocity field, average Nusselt number, and friction number of the internally longitudinal protuberant finned tube were numerically analyzed in a pulsating period, and it was further investigated by changing the frequency of the pulsating flow. It was found that the intensity of heat transfer enhancement increases with an increase of pulsating frequency, while the pressure drop will be increased simultaneously, the intensification of heat transfer in internally longitudinal protuberant finned tubes are gradually better than the pressure drop with an increase of pulsating frequency. © 2009 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20253
Common genetic variants and risk for non‐Hodgkin lymphoma and adult T‐cell lymphoma/leukemia in Jamaica
Authors: Wang Sophia S. , Carreon J. Daniel , Hanchard Barrie , Chanock Stephen , Hisada Michie
Published: April 2009

We evaluated whether risk of non‐Hodgkin lymphoma (NHL), particularly adult T‐cell leukemia/lymphoma (ATL) related to human T‐lymphotropic virus (HTLV) infection was associated with 63 single nucleotide polymorphisms (SNPs) from 38 candidate genes. The 395 NHL cases registered in Jamaica were matched by age, sex, calendar‐year and HTLV serostatus to 309 controls from the same population. Interleukin 13 (IL13) Ex4+98A>G SNP (rs20541) was associated with decreased NHL risk (ORAG/AA = 0.62,95% CI = 0.44–0.87, p = 0.006), as was vascular cell adhesion molecule‐1, VCAM1 Ex9+149G>A SNP (rs1041163) (ORCT = 0.77, 95% CI = 0.54–1.10, ORCC=0.35, 95% CI = 0.16–0.76, p‐trend = 0.007). Both results were stronger in analyses restricted to ATL cases and HTLV‐positive controls, suggesting a role for these genes in ATL etiology (IL13 ORAG/AA = 0.54, 95% CI = 0.36–0.84, p = 0.005; VCAM1 ORCT = 0.65, 95% CI = 0.42–1.01, ORCC = 0.20, 95% CI = 0.08–0.54, p‐trend = 0.001). Confirmation of these results in Caribbean and other populations is needed. © 2009 UICC
The role of diet and other environmental factors in the causation of gastric cancer in Iran—A population based study
Authors: Pourfarzi Farhad , Whelan Anna , Kaldor John , Malekzadeh Reza
Published: April 2009

Despite a declining trend in the incidence of gastric cancer (GC), it is still a major global public health concern of the 21st century. The rates of GC reported from Ardabil Province, Iran, are among the highest in the world. To investigate risk factors for GC in Ardabil, we undertook a population‐based case‐control study. The study aimed to recruit all Ardabil residents newly diagnosed with GC in the time period of 2004–2005, and 2 controls per case. Participants were interviewed using a structured questionnaire. Ten milliliters of blood was collected for blood grouping and investigating the presence of IgG antibodies against Helicobacter pylori. During the study period, 217 people with GC and 394 controls were recruited. In multivariate analysis, diet and Helicobacter pylori infection (OR = 2.41; 95% CI: 1.35–4.32) were found to be the factors that were most strongly related to GC. High intake of Allium vegetables (OR = 0.35) and fruit, especially citrus fruit (OR = 0.31) and consumption of fresh fish (OR = 0.37) were significantly protective. On the other hand, consumption of red meat (OR = 3.40) and dairy products (OR = 2.28) were positively associated with the risk of GC. People who had a preference for higher salt intake (OR = 3.10) and drinking strong and hot tea (OR = 2.64 and 2.85, respectively) were at higher risk. In conclusion, Helicobacter pylori infection as measured by serum IgG as well as the consumption of red meat and dairy products increases the risk of GC in Ardabil, while the intake of fresh fruit and fresh fish decrease the risk. © 2009 UICC
Autophagy—A double‐edged sword in oncology
Authors: Apel Anja , Zentgraf Hanswalter , Büchler Markus W. , Herr Ingrid
Published: April 2009

Autophagy or “self‐eating” digests proteins and functionless cell organelles to reuse. This cell‐own recycling system attracts much attention in tumour biology. One of the major functions of autophagy is maintaining cellular homeostasis. Thus, it is constitutive active in all living cells. Damaged or dispensable proteins and organelles are removed to regulate composition and size of the cytoplasm. Many therapeutic treatments have been shown to modulate autophagy signalling although it is still unclear if autophagy represents a survival or a suicide mechanism for tumour cells. Tumour growth in response to blocked autophagy as well as tumour growth in response to induced autophagy has been described. Several recent review articles address the differential effect of autophagy manipulation to apoptosis signalling. However, less has been reported about interactions of autophagy manipulation to the outcome of cancer therapy and tumour growth. Therefore, this review tries to fill this gap. We discuss data demonstrating that cellular decisions to autophagy manipulation depend on tumour type, stage, microenvironment, autophagy initiator or inhibitor and combined tumour treatment. Finally, we come to the conclusion that further analyses are necessary before manipulation of autophagic mechanisms can find its way into tumour therapy for improved treatment of patients. © 2009 UICC
Mutations of NFKBIA, encoding IκBα, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non‐EBV‐associated cases
Authors: Lake Annette , Shield Lesley A. , Cordano Pablo , Chui Daniel T.Y. , Osborne Julie , Crae Shauna , Wilson Katherine S. , Tosi Sabrina , Knight Samantha J.L. , Gesk Stefan , Siebert Reiner , Hay Ron T. , Jarrett Ruth F.
Published: April 2009

A consistent feature of the Hodgkin and Reed‐Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF‐κB transcription factors. In Epstein‐Barr virus (EBV)‐associated cases of cHL, expression of viral antigens most probably leads to NF‐κB activation but for non‐EBV‐associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding IκBα, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non‐EBV‐associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non‐EBV‐associated cases but the majority of these cases had wild‐type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF‐κB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series. © 2009 UICC
Novel drug‐loaded gelatin films and their sustained‐release performance
Authors: Lin Mei , Meng Sheng , Zhong Wei , Cai Rui , Du Qiangguo , Tomasik Piotr
Published: April 2009

A new particulate drug delivery system with gelatin matrix containing Ibuprofen as a model drug molecule was developed for an epidermis drug prolonged release. Gelatin films containing Ibuprofen‐loaded poly‐ε‐caprolactone (PCL) microspheres have been developed on evaporation of organic solvent from an oil‐in‐water emulsion followed by cross‐linking. The microspheres were characterized for particle size, encapsulation efficiency, and surface morphology. Water uptake, matrix erosion, and drug release profile of the microsphere‐film system were investigated. The results indicated that drug‐loaded microspheres introduced in this system successfully prolonged drug release time. This kind of microsphere‐film system combined good adhesion, typical for gelatin films, with the sustained release performance of PCL microspheres. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
TRALI risk reduction: Donor and component management strategies
Authors: Eder Anne F. , Benjamin Richard J.
Published: April 2009

Transfusion‐related lung injury (TRALI) occurs in ∼1 in 5,000 transfusions and may cause considerably more morbidity and mortality that is not recognized in clinical practice. Based on the current understanding of the etiology of TRALI, blood centers have implemented or are evaluating various donor and component management strategies in an effort to mitigate the risk of TRALI. Many cases of TRALI are likely caused by antibodies to leukocyte antigens (HLA or HNA) in blood components. Approximately 10 to 20% of female blood donors with a history of pregnancy and 1 to 5% of male blood donors harbor these antibodies. Alternatively, TRALI may be mediated by other bioactive lipids or substances that accumulate during storage and cause a reaction when transfused to susceptible patients. The complex interplay among various donor‐, component‐, and patient‐related factors underlying TRALI guarantees that effective prevention will not be a single or simple intervention but rather will require a multifaceted approach. Perhaps, the most important risk reduction strategy is the effort to ensure appropriate use of blood products and eliminate unnecessary transfusions. Blood collection agencies, however, have more proximate control over donor selection and component management than transfusion practice. AABB has provided some guidance on deferring donors implicated in TRALI and minimizing the preparation of high plasma volume components from donors who have anti‐leukocyte antibodies or are at increased risk of leukocyte alloimmunization. Blood centers have taken various approaches to mitigate the risk of TRALI, and the possible benefit and the inherent limitations of the current strategies will be reviewed. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.
Stem cell research in Asia: A critical view
Authors: Sipp Douglas
Published: April 2009

Stem cell research stands as a high‐priority field in many countries across the Asia‐Pacific region, and the past decade has seen remarkable investment into facilities and programs intended to increase competitiveness in the drive to find clinical applications. In the years roughly framed by Korean cloner Woo‐Suk Hwang's meteoric ascent and fall, speculation was rampant that Asia was poised to overtake the West in this field of science. But that potential remains unfulfilled. In this article, I will look at some of the deficits in infrastructure and governance that underlie the East–West stem cell gap, and suggest a number of measures that might be taken to remedy them. J. Cell. Biochem. 107: 853–856, 2009. © 2009 Wiley‐Liss, Inc.
Evidence for direct effects of prolactin on human osteoblasts: Inhibition of cell growth and mineralization
Authors: Seriwatanachai Dutmanee , Krishnamra Nateetip , van Leeuwen J.P.T.M.
Published: April 2009

Hyperprolactinemia is one of the risk factor of decrease in bone mass which has been believed to be mediated by hypogonadism. However, the presence of prolactin receptor in human osteosarcoma cell line and primary bone cell culture from mouse calvariae supported the hypothesis of a direct prolactin (PRL) action on bone cells. Therefore, the aim of this study was to investigate the role of PRL and its signal transduction pathway in the regulation of bone metabolism via osteoblast differentiation. Human pre‐osteoblasts (SV‐HFO) that differentiate in a 3‐week period from proliferating pre‐osteoblasts (days 2–7) to extracellular matrix producing cells (days 7–14) which is eventually mineralized (days 14–21) were used. Concentration of PRL mimicked a lactating period (100 ng/ml) was used to incubate SV‐HFO for 21 days in osteogenic medium. Human prolactin receptor mRNA and protein are expressed in SV‐HFO. PRL significantly decreased osteoblast number (DNA content) which was due to a decrease in proliferation. PRL increased osteogenic markers, RUNX2 and ALP in early stage of osteoblast differentiation while decreasing it later suggesting a bi‐directional effect. Calcium measurement and Alizarin red staining showed a reduction of mineralization by PRL while having neither an effect on osteoblast activity nor RANKL/OPG mRNA ratio. We also demonstrated that PRL action on mineralization was not via PI‐3 kinase pathway. The present study provides evidence of a direct effect of prolactin on osteoblast differentiation and in vitro mineralization. J. Cell. Biochem. 107: 677–685, 2009. © 2009 Wiley‐Liss, Inc.
Contact inhibition revisited
Authors: Heckman Carol A.
Published: April 2009

Contact inhibition of cell movement was originally defined in the 1950s as a way of interpreting studies that were ethological and statistical in nature. Research done in succeeding decades provided a more detailed study of the initial contact and its consequences for the cell. The behavior called contact inhibition is characterized by the cessation of ruffling and forward movement in the lamellipodium of the cell making the contact. A new ruffling membrane then arises elsewhere on the cell perimeter. A comparison between the contact behavior described in the early literature and that of the nerve growth cone, described recently by Steketee and Tosney, suggests that filopodia mediate the sensing function in both cases. Since transformed cells have fewer filopodia than normal cells, the contact behavior may decline in direct response to the degraded function of filopodia. This new “filopodia focal signal transduction” hypothesis of contact inhibition elevates the filopodia sensing function and the cessation of lamellipodial advance to the highest importance as phenomena underlying the altered behavior of cancer cells. J. Cell. Physiol. 220: 574–575, 2009. © 2009 Wiley‐Liss, Inc.
NESCA: A new NEMO/IKKgamma and TRAF6 interacting protein
Authors: Napolitano Gennaro , Mirra Serena , Monfregola Jlenia , Lavorgna Alfonso , Leonardi Antonio , Ursini Matilde Valeria
Published: April 2009

NEMO/IKKγ is the essential regulatory subunit of the IkB Kinase (IKK) complex, required for the activation of Nuclear Factor kB (NF‐kB) in many physiological processes such as inflammation, immunity, apoptosis, or development. NEMO works at a converging point of the NF‐kB pathway as it interacts with upstream signaling molecules to orchestrate its activation. Here we report on the identification of a novel NEMO‐interacting protein, NESCA, an adapter molecule previously shown to be involved in the NGF‐pathway via the TrkA receptor. We demonstrated that NESCA and NEMO interact by their N‐terminal region. Beside to NEMO, we revealed that NESCA directly associates to the E3 ubiquitin ligase TRAF6, which in turn catalyzes NESCA polyubiquitination. Finally, we demonstrated that NESCA overexpression strongly inhibits TRAF6‐mediated polyubiquitination of NEMO. In summary, our results highlight that NESCA represents a novel missing link in the NEMO‐mediated NF‐kB activation pathway. J. Cell. Physiol. 220: 410–417, 2009. © 2009 Wiley‐Liss, Inc.
Proteasome inhibitors impair RANKL‐induced NF‐κB activity in osteoclast‐like cells via disruption of p62, TRAF6, CYLD, and IκBα signaling cascades
Authors: Ang Estabelle , Pavlos Nathan J. , Rea Sarah L. , Qi Ming , Chai Tracy , Walsh John P. , Ratajczak Thomas , Zheng Ming H. , Xu Jiake
Published: April 2009

Proteasome inhibitors represent a promising therapy for the treatment of relapsed and/or refractory multiple myeloma, a disease that is concomitant with osteolysis and enhanced osteoclast formation. While blockade of the proteosome pathway has been recently shown to influence osteoclast formation and function, the precise molecular cascade underlying these effects is presently unclear. Here, we provide evidence that proteasome inhibitors directly impair osteoclast formation and function via the disruption of key RANK‐mediated signaling cascades. Disruption of the proteosome pathway using selective inhibitors (MG‐132, MG‐115, and epoxomicin) resulted in the accumulation of p62 and CYLD, and altered the subcellular targeting and distribution of p62 and TRAF6 in osteoclast‐like cells. Proteosome inhibition also blocked RANKL‐induced NF‐κB activation, IκBα degradation and nuclear translocation of p65. The disruption in RANK‐signaling correlated dose‐dependently with an impairment in osteoclastogenesis, with relative potency epoxomicin > MG‐132 > MG‐115 based on equimolar concentrations. In addition, these inhibitors were found to impact osteoclastic microtubule organization and attenuate bone resorption. Based on these data we propose that deregulation of key RANK‐mediated signaling cascades (p62, TRAF6, CYLD, and IκBα) underscores proteasome‐mediated inhibition of osteolytic bone conditions. J. Cell. Physiol. 220: 450–459, 2009. © 2009 Wiley‐Liss, Inc.
Rainbow faces in edge‐colored plane graphs
Authors: Jendrol' Stanislav , Miškuf Jozef , Soták Roman , Škrabul'áková Erika
Published: April 2009

A face of an edge‐colored plane graph is called rainbow if the number of colors used on its edges is equal to its size. The maximum number of colors used in an edge coloring of a connected plane graph Gwith no rainbow face is called the edge‐rainbowness of G. In this paper we prove that the edge‐rainbowness of Gequals the maximum number of edges of a connected bridge face factor H of G, where a bridge face factor H of a plane graph Gis a spanning subgraph H of Gin which every face is incident with a bridge and the interior of any one face f∈F(G) is a subset of the interior of some face f′∈F(H). We also show upper and lower bounds on the edge‐rainbowness of graphs based on edge connectivity, girth of the dual graphs, and other basic graph invariants. Moreover, we present infinite classes of graphs where these equalities are attained. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 84–99, 2009
Spanning even subgraphs of 3‐edge‐connected graphs
Authors: Jackson Bill , Yoshimoto Kiyoshi
Published: April 2009

By Petersen's theorem, a bridgeless cubic graph has a 2‐factor. H. Fleischner extended this result to bridgeless graphs of minimum degree at least three by showing that every such graph has a spanning even subgraph. Our main result is that, under the stronger hypothesis of 3‐edge‐connectivity, we can find a spanning even subgraph in which every component has at least five vertices. We show that this is in some sense best possible by constructing an infinite family of 3‐edge‐connected graphs in which every spanning even subgraph has a 5‐cycle as a component. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 37–47, 2009
The complexity of the matching‐cut problem for planar graphs and other graph classes
Authors: Bonsma Paul
Published: April 2009

The Matching‐Cut problem is the problem to decide whether a graph has an edge cut that is also a matching. Previously this problem was studied under the name of the Decomposable Graph Recognition problem, and proved to be
${\cal{NP}}$‐complete when restricted to graphs with maximum degree four. In this paper it is shown that the problem remains
${\cal{NP}}$‐complete for planar graphs with maximum degree four, answering a question by Patrignani and Pizzonia. It is also shown that the problem is
${\cal{NP}}$‐complete for planar graphs with girth five. The reduction is from planar graph 3‐colorability and differs from earlier reductions. In addition, for certain graph classes polynomial time algorithms to find matching‐cuts are described. These classes include claw‐free graphs, co‐graphs, and graphs with fixed bounded tree‐width or clique‐width. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 109–126, 2009
On uniqueness of a general factorization of graph properties
Authors: Drgas‐Burchardt Ewa
Published: April 2009

A graph property is any class of simple graphs, which is closed under isomorphisms. Let H be a given graph on vertices v1, …, vn. For graph properties
𝒫1, …, 𝒫n, we denote by H[𝒫1, …, 𝒫n] the class of those (𝒫1, …, 𝒫n) ‐partitionable graphs G, with a corresponding vertex partition (V1, …, Vn), for which an edge {xi, xj} with xi∈Vi and xj∈Vj implies the existence of the edge {vi, vj} in the graph H. The problem of the unique description of a graph property 𝒫 in the form H[𝒫1, …, 𝒫n] is investigated for 𝒫, 𝒫1, …, 𝒫n being from the class La of all graph properties closed under taking disjoint unions and subgraphs. The unique factorization theorems obtained in the paper generalize known results of this type bringing together ∘ ‐reducibility over La and ∨ ‐reducibility in the lattice (La, ⊆). There is also offered a new insight into the modular decomposition tree for a graph. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 48–64, 2009
A local tournament contains a vertex whose out‐arcs are pseudo‐girth‐pancyclic
Authors: Meng Wei , Li Shengjia , Guo Yubao , Xu Gaokui
Published: April 2009

An arc leaving a vertex x in a digraph is called an out‐arc of x. Thomassen (J Combin Theory Ser B 28 (1980), 142–163) proved that every strong tournament contains a vertex whose every out‐arc is contained in a Hamiltonian cycle. In 2000, Yao et al. (Discrete Appl Math 99 (2000), 245–249) improved the result of Thomassen and confirmed that every strong tournament contains a vertex whose out‐arcs are pancyclic. In this article, we extend the result of Yao et al. to local tournaments and obtain a best possible result in some sense. © 2009 Wiley Periodicals, Inc. J Graph Theory 62: 346–361, 2009
Regioselective synthesis and bioactivity of new 5‐amino‐6‐arylamino‐pyrazolo[3,4‐d]‐pyrimidin‐4(5H)‐one derivatives
Authors: Wang Hong‐Qing , Zhou Wei‐Ping , Wang Yu‐Yuan , Lin Can‐Rong , Liu Zhao‐Jie
Published: April 2009

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A novel approach to regioselective synthesis of new 5‐amino‐6‐arylamino‐1H‐pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one 5 derivatives via a tandem aza‐wittig and annulation reaction of iminophosphorance 2, aromatic isocyanates and hydrazine in 69.6–94.7% isolated yields is reported. The compound 5 reacted with triethyl orthoformate to give compound 6 in good yield (65.8–82.8%). Their structure was clearly confirmed by spectroscopy data (IR, 1H NMR, MS, elemental analysis) and the results of preliminary bioassay indicated that compounds 5 and 6 possess high antifungal activity against Botrytis cinerea Pers and Sclerotinia sclerotiorum, and compound 5h showed 100, 96.4, and 90.2% inhibitory rate to Botrytis cinerea Pers, Pyricularia oryzae, and Sclerotinia sclerotiorum at the concentration of 50 mg/L. The antifungal activities of compound 6 were generally higher than those of compound 5. J. Heterocyclic Chem., (2009).
Bis(enaminones): Key intermediates for novel α,ω‐bis(pyrazolylphenoxy), bis(pyranylphenoxy), and bis(benzo[b]furanylphenoxy) alkanes
Authors: Abbas Ashraf A.
Published: April 2009

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New bis(enaminone) derivatives, 5a, 5b and 9a, 9b, were prepared in good yields. Their synthetic utilities as key intermediates for the synthesis of novel bis(pyrazole) 12a ,12b, bis(pyrane) 17a ,17b, and bis(benzo[b]furan) 20a, 20b, 20c, 20d derivatives were also investigated. J. Heterocyclic Chem., 46, 340 (2009).
Synthesis and antimicrobial activity of novel analogs of trifenagrel
Authors: Nagarapu Lingaiah , Aneesa  , Satyender Apuri , Chandana G. , Bantu Rajaskaker
Published: April 2009

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Novel analogs of trifenagrel were synthesized by using inexpensive and reusable phosphotungstic acid, H3[PW12O40] (3 mol %) catalyst under classical heating. Two of the newly synthesized triaryl imidazoles exhibited moderate antibacterial activity. J. Heterocyclic Chem.,46, 195 (2009).
Preparation of 2H‐spiro[benzo[d]isothiazole‐3,3′‐pyrazole]‐1, 1‐dioxide‐2′(4′H)‐carboxylates from dilithiated C(α),N‐carboalkoxyhydrazones and methyl 2‐(aminosulfonyl)benzoate
Authors: Dawsey Anna C. , Potter Chandra , Knight John D. , Kennedy Zachary C. , Smith Ellyn A. , Acevedo‐Jake Amanda M. , Puciaty Andrew J. , Metz Clyde R. , Beam Charles F. , Pennington William T. , VanDerveer Donald G.
Published: April 2009

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A variety of substituted spiro(benzoisothiazole‐pyrazoles) have been prepared by the condensation of dilithiated C(α),N‐carboalkoxyhydrazones with lithiated methyl 2‐(aminosulfonyl)benzoate followed by the cyclization of intermediates with acetic anhydride, which also resulted in spiro N‐acetylated products when carbomethoxyhydrazones or carboethoxyhydrazones were used, and spiro NH products when carbo‐tert‐butoxyhydrazones were used. J. Heterocyclic Chem., 46, 231 (2009).
A new synthetic route to 2H‐benzo[g]chromene‐5,10‐diones involving ring closing metathesis
Authors: Song Young Seok , Lee Kee‐Jung
Published: April 2009

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A simple synthesis of several 2H‐benzo[g]chromene‐5,10‐diones via the ring closing metathesis reaction of prerequisite bisolefins, prepared from the α‐vinylnaphthoquinones, is described. J. Heterocyclic Chem., 46, 207 (2009).
An efficient synthesis of pyrimido[4,5‐b]quinoline derivativesviathree‐component reaction in aqueous media
Authors: Shi Da‐Qing , Niu Li‐Hui , Yao Hao , Jiang Hong
Published: April 2009

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A series of pyrimido[4,5‐b]quinoline derivatives was synthesized by three‐component reaction of 6‐aminopyrimidine, aromatic aldehydes and 1,3‐cyclohexanedione or 5,5‐dimethyl‐1,3‐cyclohexanedione in aqueous media in the presence of triethylbenzylammonium chloride. This protocol has the advantages of higher yields, lower lost, easy work‐up, and environmentally friendly procedure. J. Heterocyclic Chem.,46, 237 (2009).
Facile, microwave‐assisted parallel syntheses of N‐substituted 1,4‐dihydropyridines of biological interest
Authors: Kumar B. R. Prashantha , Masih Pankaj , Lukose Chris Raju , Abraham Nimmy , Priya D. , Xavier Rinu Mary , Saji Kesiya , Adhikary Laxmi
Published: April 2009

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A solventless parallel synthesis of some novel, N‐substituted dihydropyridines by the application of microwaves is reported. The synthetic methodology adopted to synthesize the titled compounds and their antioxidant activity is described. J. Heterocyclic Chem., 46, 336 (2009).
Microwave‐assisted, solvent‐free, parallel syntheses and elucidation of reaction mechanism for the formation of some novel tetraaryl imidazoles of biological interest
Authors: Kumar B. R. Prashantha , Sharma Gyanendra Kumar , Srinath S. , Noor Mohamed , Suresh B. , Srinivasa B. R.
Published: April 2009

The microwave assisted, solvent free, parallel syntheses of title compounds is described in this protocol. Twelve new tetraaryl imidazoles, which are incorporated with the chemotherapeutic pharmacophores, have been synthesized by adopting one pot multicomponent reaction. Attempt has been made to investigate the mechanism behind the formation of tetraaryl imidazoles by product identification method. The synthesized compounds were analyzed by physical and analytical data. The synthesized compounds were evaluated for their antibacterial, antitubercular, and short‐term anticancer activity. Compound 13 was found to be the candidate compound to investigate further for its potential anticancer activity. J. Heterocyclic Chem., 46, 278 (2009).
Symmetrical diamides based on 2,6‐bis(methoxycarbonyl)pyridine: Syntheses and metal ion binding studies
Authors: Napitupulu Mery , Griggs Brendan L. , Luo Shi‐Xia , Turner Peter , Maeder Marcel , Lawrance Geoffrey A.
Published: April 2009

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Symmetrically‐armed molecules based on a 2,6‐diamidopyridine core, 2,6‐bis[N‐(1′‐piperidinylethyl)carbamyl]pyridine (1), 2,6‐bis[N‐(1′‐piperazinylethyl)carbamyl]pyridine (2), 2,6‐bis[N‐2′‐(5′′‐nitropyridine)‐1′‐azapropyl)carbamyl]pyridine (3), 2,6‐bis[N‐(3′‐hydroxypropyl)carbamyl]pyridine (4), 2,6‐bis[N‐(5′‐hydroxy‐3′‐azapentyl)carbamyl]pyridine (5), 2,6‐bis[N‐2′‐oxo‐2′,3′‐dihydropyrimidin‐4′‐yl)carbamyl]‐pyridine (6) as well as the thioamide analogue 2,6‐bis[(S‐2′‐pyridinyl)carbothiyl]pyridine (7) have been prepared and characterized. An X‐ray crystal structure of 1 confirms its formation. These molecules are potentially multidentate ligands for metal ions, and complexation has been probed through spectroscopic characterization, particularly by electrospray ionization mass spectrometry, and isolation of some first‐row transition metal complexes. The ligands, with potentially coordinating arms extending from each amide, dominantly form simple 1:1 M:L complexes. They show no tendency toward polynuclear helicate formation. J. Heterocyclic Chem., 46, 243 (2009).
Reaction of 2‐[(2‐Oxo‐2‐arylethyl)anilino]‐1‐aryl‐1‐ethanones with o‐phenylenediamine: Formation of quinoxalines
Authors: Ravindran Gurusamy , Muthusubramanian Shanmugam , Perumal Subbu
Published: April 2009

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Unexpected quinoxalines (3) have been obtained from a one‐pot reaction of 2‐[(2‐oxo‐2‐arylethyl)anilino]‐1‐aryl‐1‐ethanones (1) with o‐phenylenediamine (2) in the presence of a catalytic amount of p‐toluene sulfonic acid. The reaction presumably involves a tandem carbonyl addition—eliminative cyclization—air oxidation sequence. J. Heterocyclic Chem., 46, 332 (2009).
Investigation on the reactions of o‐hydroxybenzyl alcohols with vinyl ethers under acidic and/or thermal conditions
Authors: Kumbaraci Volkan , Ergunes Duygu , Midilli Melike , Begen Seckin , Talinli Naciye
Published: April 2009

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The reaction of vinyl ethers with o‐hydroxybenzyl alcohols under different reaction conditions was investigated. The aim of this attempt was to find out whether the protection reactions or the hetero Diels–Alder reaction of quinone methide in situ generated from o‐hydroxybenzyl alcohol is more likely to occur. o‐hydroxybenzyl alcohols can give hetero Diels–Alder reactions with dihydro‐2H‐pyran at high temperatures but only when used with acid catalysts. At room temperature, even in the presence of acid catalyst, reactions yielded regular protection products. However, butyl vinyl ether and 4‐methoxy‐3‐butenone could not give intermolecular cycloaddition reactions under the acidic conditions, because both decomposed to the new products with acids. Hetero‐Diels–Alder products obtained only under thermal conditions but in low yields. J. Heterocyclic Chem., 46, 226 (2009).
A simple and novel eco‐friendly process for the synthesis of cyclic dithiocarbonates from epoxides and carbon disulfide in water
Authors: Halimehjani Azim Ziyaei , Ebrahimi Forogh , Azizi Najmedin , Saidi Mohammad R.
Published: April 2009

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The reaction of oxiranes with carbon disulfide for preparation of cyclic dithiocarbonates was carried out in water under catalytic amount of an organic base such as dimethylaminopyridine or triethylamine. The reaction conditions are simple and give high yields of desired products. J. Heterocyclic Chem., 46, 347 (2009).
A novel method for the synthesis of 1(2H)‐phthalazinones using silica‐supported perchloric acid
Authors: Heravi Majid M. , Baghernejad Bita , Oskooie Hossein A.
Published: April 2009

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A simple and efficient synthesis of 1(2H)‐phthalazinone derivatives was achieved via reaction of phthalaldehydic acid and various phenyl hydrazines in acetonitrile using HClO4‐SiO2 as a catalyst in very good yields. J. Heterocyclic Chem., 46, 351 (2009).
Synthesis of pyrone carbaldehydes, pyrone sulfonium ylides and related epoxides
Authors: Shahrisa Aziz , Saraei Mahnaz
Published: April 2009

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Hexaminium salts of 4‐pyrones 3a, 3b were synthesized by treatment of 2‐(4‐bromomethylphenyl)‐6‐methyl‐4H‐pyran‐4‐one 2a and 2‐(4‐bromomethylphenyl)‐6‐phenyl‐4H‐pyran‐4‐one 2b with hexamethyl‐enetetramine in chloroform in 71 and 84% yields respectively. Hydrolysis of 3a and 3b in EtOH:H2O produced the corresponding aldehydes 4a and 4b in 43 and 58% yields respectively. The reaction of bromopyrones 2b and 2c with dimethylsulfide in MeOH: CH2Cl2 afforded the corresponding sulfonium salts 5b and 5c in 66 and 65% yields respectively. Treatment of 5b and 5c with arene carbaldehydes such as (Ar = p‐ClC6H4, o‐ClC6H4, p‐NO2C6H4, o‐NO2C6H4, p‐FC6H4, 2‐naphthyl, p‐MeOC6H4, C6H5CHCH, p‐MeC6H4, C6H5 and 4‐(4‐oxo‐6‐phenyl‐4H‐pyran‐2‐yl)‐benzaldehyde 4b) in the presence of sodium hydroxide in CH3CN:H2O afforded eleven trans‐epoxides in 61–93% yields. J. Heterocyclic Chem., 46, 268 (2009).
New dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines based on arylidene derivatives of 5‐acetylbarbituric and dehydroacetic acids
Authors: Rudenko Roman V. , Komykhov Sergey A. , Musatov Vladimir I. , Desenko Sergey M.
Published: April 2009

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The reaction of 3‐amino‐1,2,4‐triazole (1) with arylidene‐5‐acetyl barbituric acid (2b, 2c) or dehydroacetic acid (2a) by refluxing in butanol leads to the formation of dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines 3a, 3b, 3c. J. Heterocyclic Chem., 46, 285 (2009).
Isolated limb infusion: A review
Authors: Kroon Hidde M. , Thompson John F.
Published: April 2009

Isolated limb perfusion is the preferred treatment option for locally advanced melanoma and sarcoma confined to a limb. This treatment results in high response rates with a satisfying duration of response in both tumours. A drawback of isolated limb perfusion, however, is the invasive and complex character of the procedure.

Isolated limb infusion has been designed as a minimally invasive alternative to isolated limb perfusion. Treatment results of this simple technique, reported by various centres worldwide, show comparable response rates for melanoma and sarcoma. Therefore isolated limb infusion may replace isolated limb perfusion in the future as the preferred treatment option for these locally advanced limb tumours. J. Surg. Oncol. 2009;100:169–177. © 2009 Wiley‐Liss, Inc.
Radiofrequency ablation treatment of soft palate for patients with snoring: A systematic review of effectiveness and adverse effects
Authors: Bäck Leif J. J. , Hytönen Maija L. , Roine Risto P. , Malmivaara Antti O. V.
Published: April 2009

Objective:

To assess the effectiveness and adverse effects of radiofrequency ablation (RFA) of soft palate (SP) in snoring.

Study Design:

Systematic search of electronic databases. Only articles published in peer‐reviewed journals were evaluated. Included were controlled or prospective studies with at least 10 adults (≥18 years of age) without moderate/severe obstructive sleep apnea.

Results:

Of the 159 articles identified, 30 met the inclusion criteria: two randomized controlled trials (RCT), four clinical controlled trials, and 24 prospective uncontrolled studies. The only placebo controlled RCT indicated SP RFA to be superior compared to placebo. The other RCT, comparing different radiofrequency ablation generators, showed no evidence of differences in snoring treatment efficacy, and only minor differences in patient discomfort. In two of the controlled trials snoring relief obtained by SP RFA was comparable, and in three of them associated with less postoperative pain than other interventions. Radiologic results were contradictory with some trials reporting significant changes of the upper airways, whereas others did not. Neither long‐term side effects nor major adverse events have been reported after.

Conclusions:

The review provides evidence that SP RFA is an intervention causing less postoperative pain than others, and the risk of adverse effects for the patient seems to be small. It may reduce symptoms of snoring, at least in the short term. However, most of the published SP RFA literature is based on observational studies with a short follow‐up time, which precludes solid conclusions about the effectiveness of the procedure. Laryngoscope, 2009