bluuebunny/crossref_metadata_2025 huggingface dataset:
Negotiating Uncertainty: Jamaican Small Farmers’ Adaptation and Coping Strategies, Before and After Hurricanes—A Case Study of Hurricane Dean
Authors: Campbell Donovan , Beckford Clinton
Published: December 2009

In recent years, Jamaica has been seriously affected by a number of extreme meteorological events. The one discussed here, Hurricane Dean, passed along the south coast of the island in August 2007, damaging crops and disrupting livelihood activities for many small-scale farmers. This study is based on detailed ethnographic research in the southern coastal region of St. Elizabeth parish during the passage of Hurricane Dean, and explores the ways in which small farmers negotiate the stressors associated with hurricane events. The study employed a mix methods approach based on a survey of 282 farming households. The paper documents coping strategies employed by farmers in the immediate period of Hurricane Dean to reduce damage to their farming systems, and highlights the positive correlation between farmers’ perceptions of hurricanes and degree of damage to local farming systems. In addition, through an analysis of socio-economic and environmental data, the paper provides an understanding of the determinants of adaptive capacity and strategy among farmers in the area. The study indicated that despite high levels of vulnerability, farmers have achieved successful coping and adaptation at the farm level.
Unresponsiveness to Colchicine Therapy in Patients with Familial Mediterranean Fever Homozygous for the M694V Mutation
Authors: SOYLEMEZOGLU OGUZ , ARGA MUSTAFA , FIDAN KIBRIYA , GONEN SEVIM , EMEKSIZ HAMDI CIHAN , HASANOGLU ENVER , BUYAN NECLA
Published: December 2009

Objective.

More than 50 disease-associated mutations of the Mediterranean fever gene (MEFV) have been identified in familial Mediterranean fever (FMF), some of which were shown to have different clinical, diagnostic, prognostic, and therapeutic implications. The aim of our study was to define the frequency of mutation type, genotype-phenotype correlation, and response to colchicine treatment in patients with FMF.

Methods.

This study included 222 pediatric FMF patients. All patients were investigated for 6 MEFV mutations. Then patients were divided into 3 groups according to the presence of M694V mutation on both of the alleles (homozygotes), on only 1 allele (heterozygotes), and on none of the alleles, and compared according to their phenotypic characteristics and response to treatment. M694V/M694V was denoted Group A, M694V/Other Group B, and Other/Other, Group C.

Results.

Complete colchicine response was significantly lower while the rate of unresponsiveness was significantly higher in Group A compared to Groups B and C (p = 0.031, p < 0.001 and p = 0.005, p = 0.029, respectively). No differences except proteinuria were found between the phenotypic features of 3 groups. Group C had the lowest rate of proteinuria development (p = 0.024). All the amyloidosis patients were in Group A.

Conclusion.

Our results indicate that the M694V/M694V mutation is associated with lower response to colchicine treatment. Therefore, patients homozygous for M694V/M694V may be carrying an increased risk for development of amyloidosis.
Can Tumor Necrosis Factor Inhibitors Be Safely Used in Pregnancy?
Authors: ALI YASER M. , KURIYA BINDEE , OROZCO CATALINA , CUSH JOHN J. , KEYSTONE EDWARD C.
Published: December 2009

Objective.

We review available safety data for use of currently approved tumor necrosis factor (TNF) inhibitors during pregnancy and lactation and suggest guidelines for use of these agents among women of reproductive age.

Method.

Although regulatory agencies encourage the inclusion of pregnant women and those of child-bearing age in randomized controlled trials, pregnant and lactating women have universally been excluded from studies because of unknown or potential risks to the fetus. Thus, strong evidence-based treatment recommendations during pregnancy are usually lacking and safety information is derived from voluntary reports of adverse events during postmarketing surveillance or via uncontrolled, observational studies, reviewed here.

Results.

Uncommon adverse pregnancy outcomes observed with TNF inhibitor therapy appear to approximate those seen in women not receiving such therapy and may include premature birth, miscarriage, low birthweight, hypertension, and preeclampsia. There are rare reports of fetal malformations or congenital anomalies in patients exposed to TNF inhibitors during conception or pregnancy. However, the incidence of these events appears to be far below the 3% rate of congenital anomalies in the general population.

Conclusion.

If the activity or disease severity precludes the cessation of a TNF inhibitor and/or DMARD, uncontrolled observations suggest that conception and early pregnancy are not adversely affected by use of TNF inhibitors. Nearly 70% of pregnant patients can discontinue their TNF inhibitor early in the pregnancy (or with determination of pregnancy) without augmenting maternal or fetal risks.
Trp64Arg Polymorphism of the ADRB3 Gene Predicts Hyperuricemia Risk in a Population from Southern Spain
Authors: MORCILLO SONSOLES , ROJO-MARTÍNEZ GEMMA , MARTÍN-NÚÑEZ GRACIA MARÍA , GÓMEZ-ZUMAQUERO JUAN MIGUEL , GARCÍA-FUENTES EDUARDO , de ADANA MARISOL RUIZ , de la CRUZ ALMARAZ MARÍA , SORIGUER FEDERICO
Published: December 2009

Objective.

To study the role of Trp64Arg polymorphism of the ADRB3 gene in the risk of developing hyperuricemia in 1051 subjects from southern Spain, with a followup of 6 years. The inclusion of plasma levels of uric acid as a diagnostic criterion to define the metabolic syndrome is under discussion. Genes responsible for insulin resistance could contribute to the development of hyperuricemia. Previous cross-sectional studies have suggested ADRB3 as a possible candidate gene in the development of hyperuricemia and insulin resistance.

Methods.

A prospective, population-based, cohort study of 1051 persons examined in 1997–98 and reassessed at a second examination 6 years later. The metabolic phenotype was assessed at baseline and again at the followup. Insulin resistance was measured by homeostasis model assessment. The Trp64Arg polymorphism of ADRB3 was detected by real-time polymerase chain reaction. Subjects were considered normouricemic if their serum uric acid levels were ≤7 mg/dl for men or ≤ 6 mg/dl for women.

Results.

Carriers of the Arg64 allele who were normouricemic at baseline had a higher risk of developing hyperuricemia 6 years later (p = 0.017, OR 2.3, 95% CI 1.1–4.6). Multivariate logistic regression analysis showed that the OR of having hyperuricemia at the 6-year followup was significantly associated with the Arg64 allele, after adjusting for age, weight gain, baseline levels of triglycerides, serum uric acid, and insulin resistance (OR 3.1, 95% CI 1.3–7.1).

Conclusion.

Trp64Arg polymorphism of the ADRB3 gene predicted the risk of developing hyperuricemia in this adult population.
The story of the Red Sea as a theological framework of interpretation
Authors: Song Young M. , Du Rand Jan A.
Published: December 2009

The exodus motif is widely agreed to be one of the central frameworks illustrating the salvational acts of God in both the Old and New Testaments. According to the Old Testament, the exodus motif was, to Israel, the paradigm of redemptive historical renewal. For this reason, the exodus motif provided the typological expression for all future hope of salvation and served as a theological paradigm to be used by Old and New Testament authors. In this article, the exodus theme in the Book of Revelation, chapters 12 to 13, is discussed in the following order: (1) Christ�s crucif xion and resurrection as the archetypal exodus; (2) the chronological fulf llment of the exodus theme in the Bible; and (3) the exodus theme in Revelation 12 to 13. To investigate the exodus theme in Revelation 12 to 13, the intertextual interpretation, as based on the redemptive historical interpretation, will be highlighted.�
Inviting and initiating youth into a life of discipleship
Authors: Nel Malan
Published: December 2009

The research question/problem with which this article deals is whether we have lost the radical nature of the faith community as disciples of Jesus and seekers of the Kingdom of God? In youth ministry children and adolescents are often invited to make a decision for Christ as if such a decision comprises the totality of being a Christian. Being a Christian, as with being a disciple, consists of more than a mere decision. Both the Old and New Testaments reveal greater depth to such a commitment. Discipleship involves following Christ in a more considered way. Such a commitment requires the willingness to be initiated and guided into the acquisition of wisdom which enables one to discern what the more appropriate options are for a Christian to make. Given such a positioning, the role of the faith community as a people demands consideration. This article argues that we are the invitation and recommends how to frame the invitation.�
Manichaeism: Its sources and influences on Western Christianity
Authors: Van Oort Johannes
Published: December 2009

The aim of this paper is twofold. First, it will discuss the origins of Manichaeism, a gnostic-Christian world religion that was founded by the prophet Mani (216-276). My discussion of the origins of Manichaeism may serve as an excellent example to illustrate what �Gnosis� or �Gnosticism� actually was. Second, the paper will outline how Manichaeism, being an alternative form of Christianity and even an alternative Christian Church, seemed to have exercised a considerable infuence on Catholic Christianity.
A rapid and simple chemiluminescence method for screening levels of inosine and hypoxanthine in non‐traumatic chest pain patients
Authors: Farthing Don E. , Sica Domenic , Hindle Michael , Edinboro Les , Xi Lei , Gehr Todd W.B. , Gehr Lynne , Farthing Christine A. , Larus Terri L. , Fakhry Itaf , Karnes H. Thomas
Published: December 2009

A rapid and simple chemiluminescence method was developed for detection of inosine and hypoxanthine in human plasma. The method utilized a microplate luminometer with direct injectors to automatically dispense reagents during sample analysis. Enzymatic conversions of inosine to hypoxanthine, followed by hypoxanthine to xanthine to uric acid, generated superoxide anion radicals as a useful metabolic by‐product. The free radicals react with Pholasin®, a sensitive photoprotein used for chemiluminescence detection, to produce measurable blue‐green light. The use of Pholasin® and a chemiluminescence signal enhancer, Adjuvant‐K™, eliminated the need for plasma clean‐up steps prior to analysis. The method used 20 μL of heparinized plasma, with complete analysis of total hypoxanthine levels (inosine is metabolized to hypoxanthine using purine nucleoside phosphorylase) in approximately 3.7 min. The rapid chemiluminescence method demonstrated the capability of differentiating total hypoxanthine levels between healthy individuals, and patients presenting with non‐traumatic chest pain and potential acute cardiac ischemia. The results support the potential use of chemiluminescence methodology as a diagnostic tool to rapidly screen for elevated levels of inosine and hypoxanthine in human plasma, potential biomarkers of acute cardiac ischemia.Copyright ©2009 John Wiley & Sons, Ltd.
Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules
Authors: Li Wenkui , Tse Francis L. S.
Published: December 2009

The collection of whole blood samples on paper, known as dried blood spot (DBS), dates back to the early 1960s in newborn screening for inherited metabolic disorders. DBS offers a number of advantages over conventional blood collection. As a less invasive sampling method, DBS offers simpler sample collection and storage and easier transfer, with reduced infection risk of various pathogens, and requires a smaller blood volume. To date, DBS‐LC‐MS/MS has emerged as an important method for quantitative analysis of small molecules. Despite the increasing popularity of DBS‐LC‐MS/MS, the method has its limitations in assay sensitivity due to the small sample size. Sample quality is often a concern. Systematic assessment on the potential impact of various blood sample properties on accurate quantification of analyte of interest is necessary. Whereas most analytes may be stable on DBS, unstable compounds present another challenge for DBS as enzyme inhibitors cannot be conveniently mixed during sample collection. Improvements on the chemistry of DBS card are desirable. In addition to capturing many representative DBS‐LS‐MS/MS applications, this review highlights some important aspects of developing and validating a rugged DBS‐LC‐MS/MS method for quantitative analysis of small molecules along with DBS sample collection, processing and storage. Copyright © 2009 John Wiley & Sons, Ltd.
Systematic LC‐MS/MS bioanalytical method development that incorporates plasma phospholipids risk avoidance, usage of incurred sample and well thought‐out chromatography
Authors: Jemal Mohammed , Ouyang Zheng , Xia Yuan‐Qing
Published: December 2009

This treatise summarizes the underlying principle and the road map for systematic LC‐MS/MS bioanalytical method development. The three themes that have recently emerged as central to building quality during method development—phospholipids, incurred sample and sound chromatographic considerations—are the main focus of this article. In order to reduce the bioanalytical risk associated with plasma phospholipids, a dual approach involving extraction and chromatography is recommended. The use of incurred sample during method development is essential to avoid interference arising from drug‐related components. This is different from the current practice of incurred sample reanalysis, which tests reproducibility during method application. LC column/mobile phase optimization is needed to achieve appropriate peak shape, sensitivity and the separation of the analyte from interfering metabolites and phospholipids. Related to sound chromatographic considerations, we lay out facts and myths related to UPLC, vis‐à‐vis HPLC. Incorporation of quality during method development avoids the costly experience of finding out by chance about the invalidity of a method after it has been used in support of a number of pivotal clinical and non‐clinical studies. To this end, we put forth an outline of a protocol for a systematic LC‐MS/MS bioanalytical method development. Copyright © 2009 John Wiley & Sons, Ltd.
Endothelial IQGAP1 regulates efficient lymphocyte transendothelial migration
Authors: Nakhaei‐Nejad Maryam , Zhang Qiu‐Xia , Murray Allan G.
Published: December 2009

Leukocyte movement from the blood to the tissues is a fundamental process in acute and chronic inflammatory diseases. While the role of endothelial cells (EC) to recruit leukocytes to sites of inflammation is well known, the mechanisms that control remodeling of EC shape and adhesive contacts during leukocyte transendothelial migration (TEM) are not completely understood. We studied the role of IQGAP1, an adaptor protein that binds to filamentous‐actin and microtubules (MT) at interendothelial junctions, during lymphocyte TEM. EC IQGAP1 knockdown decreases MT tethered to the adherens junction, and decreases lymphocyte TEM to ∼70% (p<0.05) versus control. Similarly, loss of adherens junction‐associated MT induced by brief nocodazole (ND) treatment decreases lymphocyte TEM to ∼65% of control (p<0.01). Confocal microscopy imaging indicates that EC IQGAP1 knockdown and MT depolymerization both result in lymphocyte accumulation above the vascular endothelial cadherin (VE‐cadherin) junctions and reduces the fraction of adherent lymphocytes that complete diapedesis across interendothelial cell junctions. However, we observe no change in VE‐cadherin gap formation underlying adherent lymphocytes among control, IQGAP1 knockdown, or MT depolymerised EC monolayers. These data indicate that IQGAP1 contributes to MT stability at endothelial junctions. Further, IQGAP1 is involved in junction remodeling required for efficient lymphocyte diapedesis, independent of VE‐cadherin gap formation.
C5a receptor‐deficient dendritic cells promote induction of Treg and Th17 cells
Authors: Weaver Donald J. , Reis Edimara S. , Pandey Manoj K. , Köhl Gabriele , Harris Nathaniel , Gerard Craig , Köhl Jörg
Published: December 2009

C5a is a proinflammatory mediator that has recently been shown to regulate adaptive immune responses. Here we demonstrate that C5a receptor (C5aR) signaling in DC affects the development of Treg and Th17 cells. Genetic ablation or pharmacological targeting of the C5aR in spleen‐derived DC results in increased production of TGF‐β leading to de novo differentiation of Foxp3+ Treg within 12 h after co‐incubation with CD4+ T cells from DO11.10/RAG2−/− mice. Stimulation of C5aR−/− DC with OVA and TLR2 ligand Pam3CSK4 increased TGF‐β production and induced high levels of IL‐6 and IL‐23 but only minor amounts of IL‐12 leading to differentiation of Th cells producing IL‐17A and IL‐21. Th17 differentiation was also found in vivo after adoptive transfer of CD4+ Th cell into C5aR−/− mice immunized with OVA and Pam3CSK4. The altered cytokine production of C5aR−/− DC was associated with low steady state MHC class II expression and an impaired ability to upregulate CD86 and CD40 in response to TLR2. Our data suggest critical roles for C5aR in Treg and Th17‐cell differentiation through regulation of DC function.
Intrathecal immune responses to EBV in early MS
Authors: Jaquiéry Emilie , Jilek Samantha , Schluep Myriam , Meylan Pascal , Lysandropoulos Andreas , Pantaleo Giuseppe , Du Pasquier Renaud A.
Published: December 2009

EBV has been consistently associated with MS, but its signature in the CNS has rarely been examined. In this study, we assessed EBV‐specific humoral and cellular immune responses in the cerebrospinal fluid (CSF) of patients with early MS, other inflammatory neurological diseases (OIND) and non‐inflammatory neurological diseases (NIND). The neurotropic herpesvirus CMV served as a control. Virus‐specific humoral immune responses were assessed in 123 consecutive patients and the intrathecal recruitment of virus‐specific antibodies was expressed as antibody indexes. Cellular immune responses tested in the blood of 55/123 patients were positive in 46/55. The CD8+ CTL responses of these 46 patients were assessed in the blood and CSF using a CFSE‐based CTL assay. We found that viral capsid antigen and EBV‐encoded nuclear antigen‐1, but not CMV IgG antibody indexes, were increased in early MS as compared with OIND and NIND patients. There was also intrathecal enrichment in EBV‐, but not CMV‐specific, CD8+ CTL in early MS patients. By contrast, OIND and NIND patients did not recruit EBV‐ nor CMV‐specific CD8+ CTL in the CSF. Our data, showing a high EBV‐, but not CMV‐specific intrathecal immune response, strengthen the association between EBV and MS, in particular at the onset of the disease.
Synthesis and GC–MS analysis of angelates and tiglates as an aid to identification of these components in essential oils
Authors: Adams Robert P. , Dev Vasu
Published: December 2009

One‐hundred‐and‐forty‐one angelates and tiglates were synthesized and their Kováts retention indices and mass spectra are presented. It is anticipated that the publication of these data will aid in the identification of angelates and tiglates from natural sources. Copyright © 2009 John Wiley & Sons, Ltd.
Nanoscale Transport Dynamics inside a Hydrated Nafion Membrane with Electric Field Effects
Authors: Chen P. Y. , Hong C. W.
Published: December 2009

Atomistic simulations were performed to investigate the effects of electric field on the transport dynamics inside a hydrated Nafion membrane. An electric field, varied from 2.5 × 103 to 7.5 × 103 V m–1 simulating the operating voltage from 0.25 to 0.75 V and the membrane thickness of 100 μm was applied along the proton transport direction in the simulation cell. A significant change in the membrane morphology can be observed when the electric field was considered. With increase in the electric field strength, mobilities of hydronium ions and water molecules are enhanced. The difference in the transport phenomena, with and without the electric field, can be visualised from the molecular trajectory diagrams. The distribution of water clusters and their sizes under the influence of the electric field can also be investigated using this molecular analysis technique.
Microsurgical free flap in head and neck reconstruction
Authors: Wong Chin‐Ho , Wei Fu‐Chan
Published: December 2009

Microsurgical free flaps are today considered state of the art in head and neck reconstruction after composite tumor resections. Free flaps provide superior functional and aesthetic restoration with less donor‐site morbidity. This article details our approach to this challenging and complex procedure. Free tissue transfer can be viewed as consisting of 4 essential stages: (1) defect assessment, (2) preparation of recipient vessels, (3) flap selection and harvest, and (4) flap inset and microsurgical anastomoses. The essential details of each step are highlighted. Meticulous attention to each step is important because each plays a crucial role in the overall success of the procedure. Workhorse flaps in our practice are the anterolateral thigh, radial forearm, fibula, and jejunum flaps. Unique issues related to postoperative care and monitoring of head and neck free flaps are discussed. The management of complications, in particular those threatening flap survival, are reviewed in detail. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Core 2 N‐acetylglucosaminyltransferase‐1 expression induces aggressive potential of testicular germ cell tumor
Authors: Hatakeyama Shingo , Kyan Atsushi , Yamamoto Hayato , Okamoto Akiko , Sugiyama Naoki , Suzuki Yuichiro , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Yamada Shigeyuki , Saito Hideo , Arai Yoichi , Fukuda Minoru , Ohyama Chikara
Published: December 2009

We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anti‐core 2 N‐acetylglucosaminyltransferase‐1 (C2GnT‐1) antibody. The incidence of C2GnT‐1 positivity in stage I disease (29.5%, 21/71) was significantly lower than that in higher stages (84.7%, 50/59) (P < 0.001, χ2 test). This significant difference was also found when the cases were divided into seminoma and NSGCT according to histopathological classification. Kaplan‐Meier plots and the log rank test showed that in the patients with stage I seminoma, C2GnT‐1‐positive cases had a higher risk for recurrence (P < 0.001). This was also the case with the patients with stage I NSGCT (P < 0.001). To determine whether C2GnT‐1 promotes aggressive behavior of cancer cells, a C2GnT‐1‐negative human TGCT cell line, JKT‐1, was stably transfected with a mammalian expression vector containing C2GnT‐1 cDNA. In vitro assays revealed that JKT‐1‐C2 cells are more invasive than mock transfectants, although there are no differences in proliferation activity. When orthotopically inoculated into athymic nude mice, JKT‐1‐C2 cells produced larger testicular tumors extending to the retroperitoneum with mesenteric metastasis, while mock transfectants produced small tumors without metastasis (P < 0.01, Mann‐Whitney's U‐test). When injected via the tail vein, JKT‐1‐C2 cells produced a number of metastatic lung foci. In contrast, mock transfectants produced a small number of nodules (p < 0.01, Mann‐Whitney's U‐test). These results strongly suggest that C2GnT‐1 enhances the metastatic potential of TGCT and may be a reliable biomarker for aggressive potential of TGCT.
Cooperation of tumor‐derived HBx mutants and p53‐249ser mutant in regulating cell proliferation, anchorage‐independent growth and aneuploidy in a telomerase‐immortalized normal human hepatocyte‐derived cell line
Authors: Jiang Weidong , Wang Xin Wei , Unger Tamar , Forgues Marshonna , Kim Jin Woo , Hussain S. Perwez , Bowman Elise , Spillare Elisa A. , Lipsky Michael M. , Meck Jeanne M. , Cavalli Luciane R. , Haddad Bassem R. , Harris Curtis C.
Published: December 2009

Hepatocellular carcinoma (HCC) is a common cancer, and hepatitis B virus (HBV) is a major etiological agent. Convincing epidemiological and experimental evidence also links HCC to aflatoxin, a naturally occurring mycotoxin that produces a signature p53‐249ser mutation. Recently, we have reported that tumor‐derived HBx variants encoded by HBV exhibited attenuated transactivation and proapoptotic functions but retained their ability to block p53‐mediated apoptosis. These results indicate that mutations in HBx may contribute to the development of HCC. In this study, we determined whether tumor‐derived HBx mutants along, or in cooperation with p53‐249ser, could alter cell proliferation and chromosome stability of normal human hepatocytes. To test this hypothesis, we established a telomerase immortalized normal human hepatocycte line HHT4 that exhibited a near diploid karyotype and expressed many hepatocyte‐specific genes. We found that overexpression one of the tumor‐derived HBx mutants, CT, significantly increased colony forming efficiency (CFE) while its corresponding wild‐type allele CNT significantly decreased CFE in HHT4 cells. p53‐249ser rescued CNT‐mediated inhibition of colony formation. Although HHT4 cells lacked an anchorage independent growth capability as they did not form any colonies in soft agar, the CT‐expressing HHT4 cells could form colonies, which could be significantly enhanced by p53‐249ser. Induction of aneuploidy could be observed in HHT4 cells expressing CT, but additionally recurring chromosome abnormalities could only be detected in cells coexpressing CT and p53‐249ser. Our results are consistent with the hypothesis that certain mutations in HBx and p53 at codon 249 may cooperate in contributing to liver carcinogenesis.
Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1
Authors: Wang Lei , Kuang Lisha , Pan Xinhua , Liu Junchen , Wang Qian , Du Bing , Li Dali , Luo Jian , Liu Mingyao , Hou Aijun , Qian Min
Published: December 2009

Isoalvaxanthone (IAX) is a bioactive xanthone isolated from Cudrania cochinchinensis (Lour.). However, the function and mechanism of this compound in cancer migration and invasion have not been elucidated to date. In this study, we found that IAX could suppress various steps of tumor metastasis including proliferation, migration and invasion in a dose‐dependent manner on colorectal cancer cells. Especially matrix metalloproteinase 2 (MMP‐2), the pivotal factor in cancer invasion, was suppressed both on activation and expression after treated with IAX. To understand the underlying mechanism of IAX on the inhibitory effect of proliferation, migration and invasion, we demonstrated that IAX could significantly inhibit the activation of Rac1 but has undetectable effect on GTP‐RhoA, GTP‐Cdc42 and the phosphorylation of ERK1/2, p38 MAPK and JNK. Moreover, IAX showed little influence on the transcriptional activity of nuclear transcription factor κB (NF‐κB) but strongly inhibited that of activator protein‐1 (AP‐1), which is the downstream transcriptional factor of Rac1. Together, our results indicate that IAX exerts anticancer effect in SW620 cells by targeting MMP‐2 via regulating the activity of Rac1 and AP‐1. These results are the first to reveal the function of IAX in tumor metastasis and its underlying molecular mechanism, thus suggest IAX to be a promising antimetastatic agent.
Determination of side‐chain‐rotamer and side‐chain and backbone virtual‐bond‐stretching potentials of mean force from AM1 energy surfaces of terminally‐blocked amino‐acid residues, for coarse‐grained simulations of protein structure and folding. II. Results, comparison with statistical potentials, and implementation in the UNRES force field
Authors: Kozłowska Urszula , Maisuradze Gia G. , Liwo Adam , Scheraga Harold A.
Published: December 2009

Using the harmonic‐approximation approach of the accompanying article and AM1 energy surfaces of terminally blocked amino‐acid residues, we determined physics‐based side‐chain rotamer potentials and the side‐chain virtual‐bond‐deformation potentials of 19 natural amino‐acid residues with side chains. The potentials were approximated by analytical formulas and implemented in the UNRES mesoscopic dynamics program. For comparison, the corresponding statistical potentials were determined from 19,682 high‐resolution protein structures. The low free‐energy region of both the AM1‐derived and the statistical potentials is determined by the valence geometry and the L‐chirality, and its size increases with side‐chain flexibility and decreases with increasing virtual‐bond‐angle θ. The differences between the free energies of rotamers are greater for the AM1‐derived potentials compared with the statistical potentials and, for alanine and other residues with small side chains, a region corresponding to the C conformation has remarkably low free‐energy for the AM1‐derived potentials, as opposed to the statistical potentials. These differences probably result from the interactions between neighboring residues and indicate the need for introduction of cooperative terms accounting for the coupling between side‐chain rotamer and backbone interactions. Both AM1‐derived and statistical virtual‐bond‐deformation potentials are multimodal for flexible side chains and are topologically similar; however, the regions of minima of the statistical potentials are much narrower, which probably results from imposing restraints in structure determination. The force field with the new potentials was preliminarily optimized using the FBP WW domain (1E0L) and the engrailed homeodomain (1ENH) as training proteins and assessed to be reasonably transferable. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Selective oxidation of styrene on an oxygen‐adsorbed Cu(111): A comparison with Au(111)
Authors: Pang Xian‐Yong , Xing Bin , Xue Li‐Qin , Wang Gui‐Chang
Published: December 2009

The reaction mechanism for the styrene selective oxidation on the oxygen preadsorbed Cu(111) surface has been studied by the density functional theory calculation with the periodic slab model. The calculated result indicated that the process includes two steps: forming the oxametallacycle intermediate (OMMS) and then producing the products. In addition, it was found that the second step, from OMMS to the product, is the rate‐controlling step, which is similar to the previous work of ethylene selective oxidation. The present result indicated that the selectivity towards the formation of styrene epoxide on Cu(111) is much higher than that on Au(111). More importantly, we found that the mechanism via the OMMS (2) (i.e., the preadsorbed atomic oxygen bound to the CH2 group involved in C6H5CHCH2) to produce styrene epoxide is kinetically favored than that of OMMS (1). We also found that the selectivity toward the styrene epoxide formation on Cu2O is similar to that of Cu(111). © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Hepatic ablation for neuroendocrine tumor metastases
Authors: Maithel Shishir K. , Fong Yuman
Published: December 2009

The indolent nature of neuroendocrine tumors and their proclivity to be hormonally active warrant aggressive treatment for advanced stage disease with hepatic metastases. Cytoreduction has been associated with improved symptom control as well as prolonged survival compared with those treated with medical therapy. The primary modalities of cytoreduction employed are resection, ablation, and embolization. In particular, radiofrequency ablation has been utilized with good results and minimal morbidity for treating patients with advanced neuroendocrine disease. J. Surg. Oncol. 2009;100:635–638. © 2009 Wiley‐Liss, Inc.
Resected colorectal liver metastases: Does the survival differ according to postoperative chemotherapy regimen?
Authors: Kim Sun Young , Kim Hee Jun , Hong Yong Sang , Jung Kyung Hae , Park Ji Won , Choi Hyo Seong , Oh Jae Hwan , Park Sang‐Jae , Kim Seong Hoon , Nam Byung‐Ho , Chang Hee Jin , Kim Dae Yong
Published: December 2009

Background and Objectives

We compared clinical outcomes in patients who were treated with different chemotherapeutic regimens after resection of hepatic metastases from colorectal cancer (CRC).

Methods

Between August 2001 and June 2008, 156 patients who entered into chemotherapy of adjuvant intent after hepatic metastasectomy were reviewed retrospectively.

Results

Of the 156 patients, 58 patients were treated with oxaliplatin/fluoropyrimidines (group I), 48 with irinotecan/fluoropyrimidines (group II), and 50 with fluoropyrimidines alone (group III). In the univariate analysis, there was a marginally significant difference among the three groups with respect to the disease‐free survival (DFS); 23.4 months in group I, 14.1 months in group II, and 16.3 months in group III, P = 0.088). Group I showed better DFS when compared to the other two groups combined (group II and III) (P = 0.03). Multivariable analysis showed a marginally significant gain in the DFS for group I (P = 0.068). Multiple metastases (P = 0.045) and positive resection margin (P = 0.003) were significantly associated with poorer DFS.

Conclusion

Postoperative combination chemotherapy of oxaliplatin/fluoropyrimidines seemed to show better DFS when compared to fluoropyrimidine monotherapy or irinotecan‐based combination in patients who underwent liver metastasectomy. J. Surg. Oncol. 2009;100:713–718. © 2009 Wiley‐Liss, Inc.
3D compressed sensing for highly accelerated hyperpolarized 13C MRSI with in vivo applications to transgenic mouse models of cancer
Authors: Hu Simon , Lustig Michael , Balakrishnan Asha , Larson Peder E. Z. , Bok Robert , Kurhanewicz John , Nelson Sarah J. , Goga Andrei , Pauly John M. , Vigneron Daniel B.
Published: December 2009

High polarization of nuclear spins in liquid state through hyperpolarized technology utilizing dynamic nuclear polarization has enabled the direct monitoring of 13C metabolites in vivo at a high signal‐to‐noise ratio. Acquisition time limitations due to T1 decay of the hyperpolarized signal require accelerated imaging methods, such as compressed sensing, for optimal speed and spatial coverage. In this paper, the design and testing of a new echo‐planar 13C three‐dimensional magnetic resonance spectroscopic imaging (MRSI) compressed sensing sequence is presented. The sequence provides up to a factor of 7.53 in acceleration with minimal reconstruction artifacts. The key to the design is employing x and y gradient blips during a fly‐back readout to pseudorandomly undersample kf‐kx‐ky space. The design was validated in simulations and phantom experiments where the limits of undersampling and the effects of noise on the compressed sensing nonlinear reconstruction were tested. Finally, this new pulse sequence was applied in vivo in preclinical studies involving transgenic prostate cancer and transgenic liver cancer murine models to obtain much higher spatial and temporal resolution than possible with conventional echo‐planar spectroscopic imaging methods. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.
An unsaturated soil model with minimal number of parameters based on bounding surface plasticity
Authors: Morvan M. , Wong H. , Branque D.
Published: December 2009

This paper presents a constitutive model for unsaturated soils with only 13 parameters. Its development is based on the concept of bounding surface plasticity under a critical state framework. The definition of effective stress via an equivalent pore pressure and the introduction of suction effects into a general plastic hardening mechanism are inspired from the work of Pereira et al. (Ph.D. Thesis, 2005) and that of a few others. Despite the minimal number of parameters, this model can simulate correctly complex volumetric behaviour and post‐peak softening, as well as a few other classic typical behaviours of unsaturated soils. The model is validated using experimental data both on saturated and unsaturated soils. Its efficiency has been highlighted by comparing its outputs with those from the Barcelona Basic Model and from another advanced model CJS‐NS. The numerical studies revealed the necessity of additional experimental data for a more complete validation of the model and its future improvement. Copyright © 2009 John Wiley & Sons, Ltd.
Membrane protein analysis using an improved peptic in‐solution digestion protocol
Authors: Rietschel Benjamin , Bornemann Sandra , Arrey Tabiwang N. , Baeumlisberger Dominic , Karas Michael , Meyer Bjoern
Published: December 2009

In the proteomic analysis of membrane proteins, less‐specific proteases have become a promising tool to overcome fundamental limitations of trypsin with its unique specificity for basic residues. Pepsin is well‐known to be utilized for specific applications that require acidic conditions, but in terms of membrane protein identification and characterization, it has been disregarded for the most part. This work presents an optimization of an existing peptic digest protocol for the analysis of membrane proteins using bacteriorhodopsin from purple membranes as reference.
Molecular characteristics and physiological functions of major royal jelly protein 1 oligomer
Authors: Tamura Shougo , Amano Shizuka , Kono Toru , Kondoh Jun , Yamaguchi Kikuji , Kobayashi Seiichi , Ayabe Tokiyoshi , Moriyama Takanori
Published: December 2009

Royal jelly contains numerous components, including proteins. Major royal jelly protein (MRJP) 1 is the most abundant protein among the soluble royal jelly proteins. In its physiological state, MRJP 1 exists as a monomer and/or oligomer. This study focuses the molecular characteristics and functions of MRJP 1 oligomer. MRJP 1 oligomer purified using HPLC techniques was subjected to the following analyses. The molecular weight of MRJP 1 oligomer was found to be 290 kDa using blue native‐PAGE. MRJP 1 oligomer was separated into 55 and 5 kDa spots on 2‐D blue native/SDS‐PAGE. The 55 kDa protein was identified as MRJP 1 monomer by proteome analysis, whereas the 5 kDa protein was identified as Apisimin by N‐terminal amino acid sequencing, and this protein may function as a subunit‐joining protein within MRJP 1 oligomer. We also found that the oligomeric form included noncovalent bonds and was stable under heat treatment at 56°C. Furthermore, MRJP 1 oligomer dose dependently enhanced and sustained cell proliferation in the human lymphoid cell line Jurkat. In conclusion, MRJP 1 oligomer is a heat‐resistant protein comprising MRJP 1 monomer and Apisimin, and has cell proliferation activity. These findings will contribute to further studies analyzing the effects of MRJP 1 in humans.
Mechanism of glyceraldehyde‐3‐phosphate dehydrogenase inactivation by tyrosine nitration
Authors: Palamalai Vikram , Miyagi Masaru
Published: December 2009

Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a multifaceted protein that is involved in numerous processes including glycolysis, translational silencing, transcriptional regulation of specific genes, and acting as a nitric oxide sensor. The precise mechanism on how GAPDH is targeted to these different roles is unclear but believed to involve specific posttranslational modification to the protein. Numerous studies have demonstrated that GAPDH is a target for tyrosine nitration. However, the site of modification and the molecular consequence have not been defined. Rabbit GAPDH with a reversibly protected catalytic cysteine was nitrated in vitro with tetranitromethane, resulting in complete loss of GAPDH catalytic activity. Nitration was estimated as 0.32 mol of nitrotyrosine residue per mole of GAPDH. Mass spectrometry analysis of nitrated GAPDH indicated that Tyr311 and Tyr317 were the sole sites of nitration. The X‐ray crystal structure revealed that the distances between Tyr311 and Tyr317 and the cofactor nicotinamide adenine dinucleotide (NAD+) were less than 7.2 and 3.7 Å, respectively, implying that nitration of these two residues may affect NAD+ binding. This possibility was assessed using an NAD+ binding assay, which showed that nitrated GAPDH was incapable of binding NAD+. Thus, these results strongly suggest that Tyr311 and Tyr317 nitration prohibits NAD+ binding, leading to the loss of catalytic activity.
On the problem of renormalizability in non‐commutative gauge field models – a critical review
Authors: Blaschke D.N. , Kronberger E. , Rofner A. , Schweda M. , Sedmik R.I.P. , Wohlgenannt M.
Published: December 2009

When considering quantum field theories on non‐commutative spaces one inevitably encounters the infamous UV/IR mixing problem. So far, only very few renormalizable models exist and all of them describe non‐commutative scalar field theories on four‐dimensional Euclidean Groenewold‐Moyal deformed space, also known as ‘θ‐deformed space’ ℝ4θ. In this work we discuss some major obstacles of constructing a renormalizable non‐commutative gauge field model and sketch some possible ways out.
Controversies in the treatment of high‐risk prostate cancer—what is the optimal combination of hormonal therapy and radiotherapy: a review of literature
Authors: Al‐Mamgani Abrahim , Lebesque Joos V. , Heemsbergen Wilma D. , Tans Lisa , Kirkels Wim J , Levendag Peter C. , Incrocci Luca
Published: December 2009

BACKGROUND

In high‐risk prostate carcinoma, there is controversy whether these patients should be treated with escalated‐dose (≥74 Gy) or conventional‐dose radiotherapy (<74 Gy) combined with hormonal therapy. Furthermore, the issue of the optimal duration and timing of hormonal therapy are not well crystallized.

PATIENTS AND METHODS

A search for evidence from randomized‐ and large non‐randomized studies in order to address these issues, was therefore initiated. For this purpose, MedLine, EMbase, and PubMed and the data base of the Dutch randomized dose‐escalation trial, were consulted.

RESULTS AND CONCLUSIONS

From this search it was concluded that the benefit of hormonal therapy in combination with conventional‐dose radiotherapy (<74 Gy) in high‐risk prostate cancer is evident (Level 2 evidence); Levels 2 and 3 evidence were provided by several studies supporting the use of escalated‐dose radiotherapy in high‐risk prostate cancer. For the combination of hormonal therapy with escalated‐dose radiotherapy in these patients, there is Level 2 evidence for moderately escalated dose (74 Gy) and high escalated dose (≥78 Gy). The optimal duration and timing of hormonal therapy are not well defined. More randomized‐controlled trials and meta‐analyses are therefore needed to clearly determine the independent role of dose‐escalation in high‐risk patients treated with hormonal therapy and the optimal duration and timing of hormonal therapy. Prostate 70: 701–709, 2010. © 2009 Wiley‐Liss, Inc.
Femoral fracture following knee ligament reconstruction surgery due to an unpredictable complication of bioabsorbable screw fixation: a case report and review of literature
Authors: Konan Sujith , Haddad Fares Sami
Published: December 2009

We report an unusual case of femoral fracture from minimal trauma, due to the rapid disappearance of a bioabsorbable interference screw used for reconstruction of the posterolateral corner of the knee. The literature on bone tunnel fractures following knee ligament reconstruction surgery is also reviewed.
Objectives, criteria and methods for the design of the SmartHand transradial prosthesis
Authors: Cipriani Christian , Controzzi Marco , Carrozza Maria Chiara
Published: December 2009

This paper presents the requirements, design criteria and methodology used to develop the design of a new self-contained prosthetic hand to be used by transradial amputees. The design is based on users' needs, on authors background and knowledge of the state of the art, and feasible fabrication technology with the aim of replicating as much as possible the functionality of the human hand. The paper focuses on the design approach and methodology which is divided into three steps: (i) the mechanical actuation units, design and actuation distribution; (ii) the mechatronic development and finally (iii) the controller architecture design. The design is presented here and compared with significant commercial devices and research prototypes.
Rebuilding Government for the 21st Century: Can China Incrementally Reform the Public Sector?
Authors: Wong Christine
Published: December 2009

After three decades of spectacular economic successes, China is facing a significant challenge. The string of recent scandals – environmental degradation, melamine-tainted milk powder, fake drugs and chemicals – have all pointed to government weakness in protecting public safety, exposing an enormous gap between China's growing economic prowess and its capacity to govern. With the leadership now focused on improving the regulatory regime, will China “catch up” and build the public institutions needed? This article argues that the reactive, incremental retrenchment of government in the 1980s and 1990s, combined with inadequate finance, had broken the intergovernmental fiscal system and created large distortions in the incentive structure facing government agencies and public institutions (shiye danwei事业单位). Until the intergovernmental fiscal system is repaired and incentives are fundamentally reformed for the public sector, the top-down programme to redirect China's development and build a service-oriented government will have limited effect.
Between Owner and Regulator: Governing the Business of China's Telecommunications Service Industry
Authors: Yeo Yukyung
Published: December 2009

This study explains the institutional structure and mechanism of economic regulation in China's telecommunications basic service industry. The case of telecoms basic service provides an excellent window to explore how Chinese leadership governs strategic state sectors whose assets and profits are central to the national economy. Challenging the ideational model of independent regulator, this study argues that the State-owned Assets Supervision and Administration Commission (SASAC) explains much of the telecoms business regulation, as the authority of the Ministry of Information Industry has been circumscribed by other party-state institutions. The SASAC's regulatory power suggests that the primary goal of the Chinese industrial economy is the best protection of state assets through the creation of large and strong state firms, not the protection of consumers' interests by breaking up the monopoly in markets.
Communist Modernisation and Gender: The Experience of Bulgarian Muslims, 1970–1990
Authors: NAHODILOVA LENKA
Published: December 2009

This article, which is part of a wider project, ‘Experiences of Communist Modernisation in a Bulgarian Muslim Village, 1945–2005’, examines the assimilation of Bulgarian-speaking Muslims in the Rhodope Mountains in the 1970s. By analysing communist efforts to ‘modernise’ Bulgarian Muslims, it sheds light on the relationship between modernity and the views of the communist state on such cultural categories as ‘nation’, ‘ethnicity’, ‘gender’ and ‘religion’. It argues that this particular campaign was not simply the latest chapter in an ongoing effort by the Bulgarian authorities to assimilate such populations, but should rather be seen as a specific response by the communist regime to ideas of modernity. Despite national and patriotic elements, the aim of the communist assimilation campaign was to introduce ‘modernity’ and ‘civilisation’ to the whole of Bulgarian society, especially those living at the social, cultural and political peripheries. In Bulgaria, as elsewhere in communist eastern Europe, gender and ethnic policy merged. Gender equality was one of the essential aims of the modernisation programme, but for the communist modernisers introducing gender equality among ethnically marginal groups, such as the rural Muslim group of Pomaks, was even more important. ‘Emancipating’ Muslim women was more significant than the ‘struggle against religion’ or the ‘fight for national homogeneity’.