bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element framework for describing dynamic wetting phenomena
Authors: Sprittles J. E. , Shikhmurzaev Y. D.
Published: July 2011

The finite element simulation of dynamic wetting phenomena, requiring the computation of flow in a domain confined by intersecting a liquid–fluid free surface and a liquid–solid interface, with the three‐phase contact line moving across the solid, is considered. For this class of flows, different finite element method (FEM) implementations have been used in the literature, and in some cases, these produced apparently contradictory results. In the present paper, a robust framework for the FEM simulation of dynamic wetting flows is developed, which, by consistently adhering to the FEM methodology, leaves no room for ad hoc ‘optional’ variations in the numerical handling of these flows. The developed approach makes it possible to conduct a convergence study, assess the spatial resolution required to achieve a preset accuracy and provide the corresponding benchmark calculations. This analysis allows one to identify numerical artefacts, which had previously been interpreted as physical effects, and demonstrates that suppressing numerical errors using a ‘strong’ implementation of a boundary condition creates bigger and less detectable errors elsewhere in the computational domain. We provide practical recommendations on the spatial resolution required by a numerical scheme for a given set of non‐dimensional similarity parameters and give a user‐friendly step‐by‐step guide specifying the entire implementation, which allows the reader to easily reproduce all presented results including the benchmark calculations. It is also shown how the developed framework accommodates generalizations of the mathematical model accounting for additional physical effects, such as gradients in surface tensions. Copyright © 2011 John Wiley & Sons, Ltd.
METHODS USED TO IDENTIFY AND MEASURE RESOURCE USE IN ECONOMIC EVALUATIONS: A SYSTEMATIC REVIEW OF QUESTIONNAIRES FOR OLDER PEOPLE
Authors: Martin Adam , Jones Alex , Mugford Miranda , Shemilt Ian , Hancock Ruth , Wittenberg Raphael
Published: July 2011

This paper presents the findings of a systematic review of full or partial economic evaluations that included questions to service users or their carers to elicit information on the types, amounts or costs of community‐based formal social care support provided to people 65 years and older. We have found that studies seldom report use of published validated questions for eliciting information from older people in the UK about their use of formal social care services. Given the political prominence of the debate over funding social care for older people, there remains a need for analysis of policy options. This requires reliable data on the receipt and payment for care. We recommend the development of improved questions on care that are clear, robust and up‐to‐date with developments in policy and practice. Copyright © 2011 John Wiley & Sons, Ltd.
Spontaneous Deracemization
Authors: Amabilino David B. , Kellogg Richard M.
Published: July 2011

Chirality can emerge spontaneously from racemizing samples in a remarkably efficient manner. The effect results from the stochastic generation of an excess of one enantiomer in the solid and subsequent amplification of the initial material to the bulk. In this review we shall give examples showing how this effect has proved to be an inspiration for the emergence of chirality from chiral materials, and even for the preparation of pharmaceutically important intermediates. While spontaneous deracemization should produce either enantiomer randomly, the kind of system that demonstrates the phenomenon is very prone to the induction of one handedness with extremely small quantities of chiral inducer, which makes the process exploitable in certain cases. This kind of deracemization is the epitome of the origin, transfer and amplification of chirality.
Molecular basis underlying LuxR family transcription factors and function diversity and implications for novel antibiotic drug targets
Authors: Zeng Li‐Rong , Xie Jian‐Ping
Published: July 2011

LuxR is a widespread and functional diverse transcription factors and belongs to TetR protein superfamily. It could both activate and inhibit the expression of many genes contingent on the contexts, thereby involving in many crucial physiological events, such as virulence factors production, biofilm formation, quorum sensing (QS), acetate metabolism, motility, bioluminescence, and ecological competition. We summarized the function diversity of LuxR and underlying mechanisms. The interchangeability of some transcriptional factors for secondary metabolites biosynthesis opens new avenue to obtain new chemical entities or higher yield of antibiotics via the manipulation of regulators instead of structural genes. Inhibitors of pathogen QS are under intensive screening for better new antibiotics against the drug resistance. A compendium of compounds capable of inhibiting LuxR family transcriptional factors is also presented. J. Cell. Biochem. 112: 3079–3084, 2011. © 2011 Wiley Periodicals, Inc.
Dose‐dependent effects of the caspase inhibitor Q‐VD‐OPh on different apoptosis‐related processes
Authors: Kuželová Kateřina , Grebeňová Dana , Brodská Barbora
Published: July 2011

The effects of the pan‐caspase inhibitor Q‐VD‐OPh on caspase activity, DNA fragmentation, PARP cleavage, 7A6 exposition, and cellular adhesivity to fibronectin were analyzed in detail in three different apoptotic systems involving two cell lines (JURL‐MK1 and HL60) and two apoptosis inducers (imatinib mesylate and suberoylanilide hydroxamic acid). Q‐VD‐OPh fully inhibited caspase‐3 and ‐7 activity at 0.05 µM concentration as indicated both by the measurement of the rate of Ac‐DEVD‐AFC cleavage and anti‐caspase immunoblots. Caspase‐8 was also inhibited at low Q‐VD‐OPh concentrations. On the other hand, significantly higher Q‐VD‐OPh dose (10 µM) was required to fully prevent the cleavage of PARP‐1. DNA fragmentation and disruption of the cell membrane functionality (Trypan blue exclusion test) were both prevented at 2 µM Q‐VD‐OPh while 10 µM inhibitor was needed to inhibit the drug‐induced loss of cellular adhesivity to fibronectin which was observed in JURL‐MK1 cells. The exposition of the mitochondrial antigen 7A6 occurred independently of Q‐VD‐OPh addition and may serve to the detection of cumulative incidence of the cells which have initiated the apoptosis. Our results show that Q‐VD‐OPh efficiency in the inhibition of caspase‐3 activity and DNA fragmentation in the whole‐cell environment is about two orders of magnitude higher than that of z‐VAD‐fmk. This difference is not due to a slow permeability of the latter through the cytoplasmic membrane. J. Cell. Biochem. 112: 3334–3342, 2011. © 2011 Wiley Periodicals, Inc.
Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production
Authors: Scheller Erica L. , Hankenson Kurt D. , Reuben Jayne S. , Krebsbach Paul H.
Published: July 2011

Suppressor of cytokine signaling‐3 (SOCS3) has multiple functions including inhibition of Janus kinase (Jak) activity, regulation of protein degradation, and suppression of cytokine signaling. SOCS3 modulates macrophage response to cytokines such as IL‐6 and leptin that are systemically induced in obesity. Obesity is a suspected risk factor for SOCS3‐related pathology such as rheumatoid arthritis and Crohn's disease as well as zoledronic acid (ZA)‐induced osteonecrosis of the jaw (ONJ). Thus, understanding the ability of bisphosphonates to modulate SOCS3 is necessary to qualify their contribution to these disorders. ONJ occurs in up to 10% of patients using intravenous bisphosphonates and has an unknown pathogenesis that may be linked to decreased bone turnover, altered vascularity, bacterial invasion, and compromised wound healing. Given the increased risk of ONJ with obesity and importance of macrophages in wound healing, we hypothesized that amino‐bisphosphonates could contribute to the pathogenesis of ONJ by regulating macrophage responses to cytokines such as leptin and IL‐6. We report that ZA is a novel inhibitor of SOCS3 in primary macrophages and human ONJ biopsy specimens. Inhibition of SOCS3 by ZA resulted in significant increases in IL‐6 production. SOCS3 transcription is regulated by nuclear accumulation of phosphorylated‐Stat3 (P‐Stat3). We found that ZA decreased phosphorylation of Stat3 in a mevalonate‐pathway dependent manner. However, restoration of P‐Stat3 was not sufficient to correct SOCS3 inhibition. We propose that disruption of macrophage SOCS3 expression by amino‐bisphosphonates such as ZA may be a novel contributor to inflammatory phenotypes in obesity and the pathogenesis of ONJ. J. Cell. Biochem. 112: 3364–3372, 2011. © 2011 Wiley Periodicals, Inc.
Dynamic compression of rabbit adipose‐derived stem cells transfected with insulin‐like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis
Authors: Li Jianjun , Zhao Qun , Wang Enbo , Zhang Chuanhui , Wang Guangbin , Yuan Quan
Published: July 2011

Articular cartilage is routinely subjected to mechanical forces and growth factors. Adipose‐derived stem cells (ASCs) are multi‐potent adult stem cells and capable of chondrogenesis. In the present study, we investigated the comparative and interactive effects of dynamic compression and insulin‐like growth factor‐I (IGF‐I) on the chondrogenesis of rabbit ASCs in chitosan/gelatin scaffolds. Rabbit ASCs with or without a plasmid overexpressing of human IGF‐1 were cultured in chitosan/gelatin scaffolds for 2 days, then subjected to cyclic compression with 5% strain and 1 Hz for 4 h per day for seven consecutive days. Dynamic compression induced chondrogenesis of rabbit ASCs by activating calcium signaling pathways and up‐regulating the expression of Sox‐9. Dynamic compression plus IGF‐1 overexpression up‐regulated expression of chondrocyte‐specific extracellular matrix genes including type II collagen, Sox‐9, and aggrecan with no effect on type X collagen expression. Furthermore, dynamic compression and IGF‐1 expression promoted cellular proliferation and the deposition of proteoglycan and collagen. Intracellular calcium ion concentration and peak currents of Ca2+ ion channels were consistent with chondrocytes. The tissue‐engineered cartilage from this process had excellent mechanical properties. When applied together, the effects achieved by the two stimuli (dynamic compression and IGF‐1) were greater than those achieved by either stimulus alone. Our results suggest that dynamic compression combined with IGF‐1 overexpression might benefit articular cartilage tissue engineering in cartilage regeneration. J. Cell. Physiol. 227: 2003–2012, 2012. © 2011 Wiley Periodicals, Inc.
Expression of receptors for VEGFs on normal human thyroid follicular cells and their role in follicle formation
Authors: Susarla Radhika , Gonzalez Ana‐Maria , Watkinson John C. , Eggo Margaret C.
Published: July 2011

Human thyroid follicular cells in culture expressed the mRNAs for the receptors for vascular endothelial growth factors (VEGFRs). The relative expression was neuropilin1 = neuropilin2 = VEGFR2 > VEGFR1 > VEGFR3. Western blotting for VEGFR2 showed labeling of proteins ∼200–230 kDa. Clonal follicular thyroid cell lines (FRTL5 and FTC133) also expressed mRNAs for the VEGFR1 and 2 obviating concerns of endothelial cell contamination. In the primary cultures, TSH, which is essential for expression of differentiated function, reduced VEGFR2 mRNA levels by 60%. Immunostaining for VEGFRs and neuropilin2 (NRP2), showed expression on the plasma membrane but with the exception of neuropilin1 (NRP1), all VEGFRs were also found in the cytoplasm and nucleus. Antibody specific for phosphotyrosine 1214 in VEGFR2 showed that the receptor was phosphorylated in the primary cultures and the cell lines. When VEGFR signaling was blocked with a specific inhibitor, follicle formation in the primary cultures was enhanced suggesting that VEGFR activation was detrimental to follicle formation. Immunostaining of sections of normal thyroids and various pathologies showed staining for VEGFR2 and pVEGFR2. We conclude that normal thyroid follicular cell express VEGFRs. For VEGFR2 its subcellular localization suggests functions additional to that of a cell surface receptor and a role in follicular integrity. J. Cell. Physiol. 227: 1992–2002, 2012. © 2011 Wiley Periodicals, Inc.
Essential role of ubiquitin C‐terminal hydrolases UCHL1 and UCHL3 in mammalian oocyte maturation
Authors: Mtango Namdori R. , Sutovsky Miriam , VandeVoort Catherine A. , Latham Keith E. , Sutovsky Peter
Published: July 2011

Ubiquitin C‐terminal hydrolases (UCHs) comprise a family of deubiquitinating enzymes that play a role in the removal of multi‐ubiquitin chains from proteins that are posttranslationally modified by ubiquitination to be targeted for proteolysis by the 26S proteasome. The UCH‐enzymes also generate free monomeric ubiquitin from precursor multi‐ubiquitin chains and, in some instances, may rescue ubiquitinated proteins from degradation. This study examined the roles of two oocyte‐expressed UCHs, UCHL1, and UCHL3 in murine and rhesus monkey oocyte maturation. The Uchl1 and Uchl3 mRNAs were highly expressed in GV and MII oocytes, and were associated with the oocyte cortex (UCHL1) and meiotic spindle (UCHL3). Microinjection of the UCH‐family enzyme inhibitor, ubiquitin‐aldehyde (UBAL) to GV oocytes prevented oocyte meiotic progression beyond metaphase I in a majority of treated oocytes and caused spindle and first polar body anomalies. Injection of antibodies against UCHL3 disrupted oocyte maturation and caused meiotic anomalies, including abnormally long meiotic spindles. A selective, cell permeant inhibitor of UCHL3, 4, 5, 6, 7‐tetrachloroidan‐1, 3‐dione also caused meiotic defects and chromosome misalignment. Cortical granule localization in the oocyte cortex was disrupted by UBAL injected after oocyte maturation. We conclude that the activity of oocyte UCHs contributes to oocyte maturation by regulating the oocyte cortex and meiotic spindle. J. Cell. Physiol. 227: 2022–2029, 2012. © 2011 Wiley Periodicals, Inc.
Up‐regulation of heat shock protein 70‐1 (Hsp70‐1) in human limbo‐corneal epithelial cells cultivated on amniotic membrane: A proteomic study
Authors: Ma David Hui‐Kang , Lai Jui‐Yang , Yu Szu‐Tzu , Liu Jia‐Ye , Yang Unique , Chen Hung‐Chi Jesse , Yeh Lung‐Kung , Ho Yi‐Ju , Chang Grace , Wang Su‐Fang , Chen Jan‐Kan , Lin Ken‐Kuo
Published: July 2011

Transplantation of cultivated human limbo‐corneal epithelial (HLE) cells has been recognized as an effective stem cell (SC) therapy for treating corneal epithelial SC deficiency caused by burn or other diseases. With this technique, cryo‐preserved human intact amniotic membrane (IAM) has been successfully used as a cell culture substrate and carrier, and is reported to preferentially preserve HLE stem/progenitor cells in vitro. However, little is known about what factors released by HLE cells are involved in the progenitor cell‐preserving mechanism. Using proteomic method, we identified 13 proteins over‐expressed by HLE cells cultured on IAM, which included heat shock protein 70‐1 (Hsp70‐1), Hsp‐27, glutathione (GSH) S‐transferase, annexin A2, galectin‐7, and protein S100‐A9. Increased Hsp70‐1 expression was confirmed by Western blot and real‐time PCR. The role of Hsp70‐1 in promoting HLE cell survival was demonstrated by increased apoptosis index and increased cleaved poly ADP‐ribose polymerase (CPARP) formation in hsp70‐1‐silenced, but not normal HLE cells after exposure to sublethal UVB irradiation or hydrogen peroxide. To understand the regulatory mechanism of Hsp70‐1 expression in HLE cells, the role of transcription factor deltaNp63 (a well‐recognized HLE stem cell; SC marker) was studied. We found that over‐expression of deltaNp63α by plasmid vector induced a corresponding increase in Hsp70‐1 protein production. Likewise, Hsp70‐1 expression decreased in HLE cells after addition of deltaNp63α SiRNA. Immunoconfocal microscopy also revealed a paralleled expression of both proteins in corneal specimens. Thus, deltaNp63α‐associated Hsp70‐1 over‐expression may promote HLE progenitor cell survival on IAM, possibly through the cytoprotective and anti‐apoptotic effect of Hsp70‐1. J. Cell. Physiol. 227: 2030–2039, 2012. © 2011 Wiley Periodicals, Inc.
Efficient generation of functional hepatocyte‐like cells from human fetal hepatic progenitor cells in vitro
Authors: Zhang Weitao , Li Weihong , Liu Baoqing , Wang Ping , Li Wen , Zhang Haiyan
Published: July 2011

Differentiation of human hepatic progenitor cells to functional hepatocytes holds great potential to develop new therapeutic strategies for liver disease and to provide a platform for drug toxicity screens and identification of novel pharmaceuticals. We report here that human fetal hepatic progenitor cells (hFHPCs) efficiently differentiate to hepatocyte‐like cells by continuous exposure to a combination of soluble factors for 7 days in vitro. We compared the effect of hepatocyte growth factor (HGF), oncostatin M (OSM), dexamethasone (DEX), or a combination on the expression of a liver‐specific marker, albumin (ALB). Real‐time RT‐PCR analysis showed that, upon exposure to a combination of OSM, DEX, and HGF, the expression of ALB gradually increased in a time‐dependent manner. In contrast, the level of the hepatic progenitor cell marker alpha‐fetoprotein (AFP) decreased as differentiation progressed. Moreover, cells exposed to the combination of OSM, DEX, and HGF gradually featured highly differentiated hepatic functions, including ALB secretion, glycogen storage, urea production, and cytochrome P450 (CYP) activity. The effect of these factors on the differentiation of hFHPCs may be blocked by U0126, an inhibitor of the ERK1/2 signaling pathway. In conclusion, we demonstrate that a combination of soluble factors facilitates the efficient generation of highly differentiated hepatocyte‐like cells from hFHPCs and ERK1/2 signaling pathway involved in this process. Results suggest that this system will be useful for generating functional hepatocytes and, hence, may serve as a cell source suitable for preclinical pharmacological research and testing. J. Cell. Physiol. 227: 2051–2058, 2012. © 2011 Wiley Periodicals, Inc.
Gastric volume changes in response to a meal: Validation of magnetic resonance imaging versus the barostat
Authors: Haans Jeoffrey J.L. , de Zwart Ingrid M. , Eilers Paul H.C. , Reiber Johan H.C. , Doornbos Joost , de Roos Albert , Masclee Ad A.M.
Published: July 2011

Purpose:

To determine the accuracy of magnetic resonance imaging (MRI) volume scans: 1) to measure known meal volumes in vitro, and 2) to compare volume changes in response to a meal measured with the barostat with those measured with MRI in vivo.

Materials and Methods:

Polyethylene bags were filled with known volumes and MRI volume scans were performed to determine the accuracy of the volume measurements. Barostat measurements and MRI volume scans were performed simultaneously in 14 healthy subjects before and up to 90 minutes after ingestion of a liquid meal.

Results:

In vitro MRI‐determined volumes showed an excellent linear relationship (r = 0.995, P < 0.001) with actual meal volumes. Although fasting gastric volume, postprandial gastric volume, and relaxation volume measured with MRI were significantly larger compared to volumes measured with the barostat, volumes determined with both techniques showed excellent correlation.

Conclusion:

Volumes in the range of postprandial meal volumes are accurately measured with MRI. MRI is a noninvasive technique to measure stomach volumes and volume changes in response to a meal. Volume changes in response to a meal measured with MRI correlate perfectly with those measured with the barostat device. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Diagnostic possibility of diffusion tensor imaging for the evaluation of myometrial invasion in endometrial cancer: An ex vivo study
Authors: Toba Mikayo , Miyasaka Naoyuki , Sakurai Urara , Yamada Ichiro , Eishi Yoshinobu , Kubota Toshiro
Published: July 2011

Purpose:

To investigate the feasibility of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) for evaluating the myometrial invasion of uterine endometrial cancer.

Materials and Methods:

Twelve specimens of uterine endometrial cancer were obtained. The depth of myometrial invasion was classified as stage E (limited to the endometrium; n = 4), stage S (superficial invasion of less than 50% of the myometrium; n = 5), or stage D (deep invasion of greater than 50% of the myometrium; n = 3). The specimens were fixed in 10% formalin and stored at 4°C before imaging. At 15 hours after fixation, MRI was performed using a 4.7‐T experimental imager/spectrometer system.

Results:

We found a high fractional anisotropy (FA) value zone (anisotropic zone) at the myometrium adjacent to the tumor on FA maps of histopathological stage S and stage D cancers, whereas the anisotropic zone did not exist in stage E cancers. Histopathological analysis showed that compared to the other regions, the anisotropic zone had tightly packed stromal tissue. The disruption of the anisotropic zone was consistent with myometrial invasion.

Conclusion:

Our ex vivo study suggests that DTI might be a useful tool for the diagnosis of myometrial invasion of uterine endometrial cancer ex vivo. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
In situ active control of noise in a 4 T MRI scanner
Authors: Li Mingfeng , Rudd Brent , Lim Teik C. , Lee Jing‐Huei
Published: July 2011

Purpose:

To evaluate the effectiveness of the proposed active noise control (ANC) system for the reduction of the acoustic noise emission generated by a 4 T MRI scanner during operation and to assess the feasibility of developing an ANC device that can be deployed in situ.

Materials and Methods:

Three typical scanning sequences, EPI (echo planar imaging), GEMS (gradient echo multislice), and MDEFT (modified driven equilibrium Fourier transform), were used for evaluating the performance of the ANC system, which was composed of a magnetic compatible headset and a multiple reference feedforward filtered‐x least mean square controller.

Results:

The greatest reduction, about 55 dB, was achieved at the harmonic at a frequency of 1.3 kHz in the GEMS case. Approximately 21 dB and 30 dBA overall reduction was achieved for GEMS noise across the entire audible frequency range. For the MDEFT sequence, the control system achieved 14 dB and 14 dBA overall reduction in the audible frequency range, while 13 dB and 14 dBA reduction was obtained for the EPI case.

Conclusion:

The result is highly encouraging because it shows great potential for treating magnetic resonance imaging noise with an ANC application during real‐time scanning. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Test–retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C
Authors: Shire Norah J. , Yin Meng , Chen Jun , Railkar Radha A. , Fox‐Bosetti Sabrina , Johnson Stephanie M. , Beals Chan R. , Dardzinski Bernard J. , Sanderson Schuyler O. , Talwalkar Jayant A. , Ehman Richard L.
Published: July 2011

Purpose:

To conduct a rigorous evaluation of the repeatability of liver stiffness assessed by MR elastography (MRE) in healthy and hepatitis‐C‐infected subjects.

Materials and Methods:

A biopsy‐correlated repeatability study using four‐slice MRE was conducted in five healthy and four HCV‐infected subjects. Subjects were scanned twice on day 1 and after 7–14 days. Each slice was acquired during a 14‐s breath‐hold with a commercially available acquisition technique (MR‐Touch, GE Healthcare). Results were analyzed by two independent analysts.

Results:

The intraclass correlation coefficient (ICC) was 0.85 (90% confidence interval [CI]: 0.71 to 0.98) for the between‐scan average of maximum stiffness within each slice and 0.88 (90% CI: 0.78 to 0.99) for the average of mean stiffness within each slice for the primary analyst. For both analysts, the average of the mean liver stiffness within each slice was highly reproducible with ICC of 0.93 and 0.94. Within‐subject coefficients of variation ranged from 6.07% to 10.78% for HCV+ and healthy subjects.

Conclusion:

MRE is a highly reproducible modality for assessing liver stiffness in HCV patients and healthy subjects and can discriminate between moderate fibrosis and healthy liver. MRE is a promising modality for noninvasive assessment of liver fibrosis (Clinicaltrials.gov identifier: NCT00896233). J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.
Morphine studied by vibrational spectroscopy and DFT calculations
Authors: Baranska M. , Kaczor A.
Published: July 2011

Morphine is a highly potent opiate analgesic drug considered to be the prototypical opioid. It is metabolized in the body to morphine‐3‐O‐glucuronide, which is antagonistic to the analgesic effects of the drug. Other forms of morphine of biological activity are salts used in medical dosing. In order to investigate morphine, its metabolite and salts and as well as pharmaceutical product, Fourier transform (FT) infrared and Raman spectroscopy were used. Experimental spectra of morphine were interpreted with the help of quantum‐chemical calculations performed at the B3LYP/6‐311 + + G(d,p) level. The results presented in this study provide clear evidence of the benefits of Raman and IR spectroscopy in alkaloid analysis, which can be used for efficient quality control, forensic analysis and analytical chemistry. Copyright © 2011 John Wiley & Sons, Ltd.
A planetary environment and analysis chamber (PEACh) for coordinated Raman–LIBS–IR measurements under planetary surface environmental conditions
Authors: Sobron Pablo , Wang Alian
Published: July 2011

A planetary environment and analysis chamber (PEACh) has been developed at Washington University in St. Louis, in order to perform in situ multiple spectroscopic measurements on geological samples under relevant planetary environmental conditions and to support future planetary missions, with particular interest on Mars. The pressure in the chamber can range from ambient to 3 × 10−2 mbar. The simulated atmospheric composition and pressure are regulated via a combination of needle and ball valves connecting the chamber with containers filled with premixed gas. The temperature of the samples can be controlled in a range from ambient to − 100 °C. The in situ analytical techniques implemented (and to be implemented) are laser Raman spectroscopy, laser‐induced breakdown spectroscopy (LIBS), near‐IR reflectance spectroscopy, mid‐IR attenuated total reflectance spectroscopy, and microscopic imaging. The coordinated spectroscopic sensing on the same geological sample under well‐controlled atmospheric conditions in the PEACh establishes a way to link the results from the laboratory experiments to the spectral data obtained by landed and orbital planetary exploration missions, which will facilitate understanding the surface processes by which mineral phases occur and their association with atmospheric changes. Copyright © 2011 John Wiley & Sons, Ltd.
Transcriptional upregulation of MT2‐MMP in response to hypoxia is promoted by HIF‐1α in cancer cells
Authors: Zhu Shikai , Zhou Yu , Wang Lin , Zhang Jianjun , Wu Hanqing , Xiong Jiongxin , Zhang Jinghui , Tian Yuan , Wang Chunyou , Wu Heshui
Published: July 2011

Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia‐inducible factor‐1α (HIF‐1α) through coordinated regulation of hypoxia‐responsive genes. In this study, we found that membrane type‐2 matrix metalloproteinase (MT2‐MMP), one of the matrix metalloproteinase (MMP) family members, was a novel hypoxia‐responsive gene and was upregulated by HIF‐1α under hypoxia. When cancer cells were subjected to hypoxia (1% O2) treatment, the mRNA and protein levels of MT2‐MMP were significantly increased in a time‐dependent manner in all three tested cancer cell lines including pancreatic cancer cells (PANC‐1), nonsmall cell lung cancer cells (A‐549), and cervix cancer cells (HeLa). Further analyses indicated that there were two hypoxia‐responsive elements (HREs) in the MT2‐MMP promoter, and HRE1 but not HRE2 was essential for MT2‐MMP transcriptional activation under hypoxia. HIF‐1α specifically and directly bound to MT2‐MMP promoter was analyzed by HIF‐1α binding/competition and chromatin immunoprecipitation (ChIP) assays. Furthermore, we found that upregulation of MT2‐MMP under hypoxia could confer resistance to hypoxia‐induced apoptosis and increase invasiveness of cancer cells. These findings provided a new insight into how cancer cells overcome hypoxic stress and trend to survive and invade, demonstrated a new regulatory mechanism of MT2‐MMP expression in caner cells, and also revealed that MT2‐MMP was a novel hypoxia‐responsive gene and was upregulated by HIF‐1α under hypoxia. © 2011 Wiley‐Liss, Inc.
A Novel cyano derivative of 11‐Keto‐β‐Boswellic acid causes apoptotic death by disrupting PI3K/AKT/Hsp‐90 cascade, mitochondrial integrity, and other cell survival signaling events in HL‐60 cells
Authors: Khan Sheema , Kaur Rajbir , Shah Bhahwal A. , Malik Fayaz , Kumar Ajay , Bhushan Shashi , Jain S.K. , Taneja Subhash C. , Singh Jaswant
Published: July 2011

Intervention of apoptosis is a promising strategy for discovery of novel anti‐cancer therapeutics. In this study, we examined the ability of a novel cyano derivative of 11‐keto‐β‐boswellic acid, that is, butyl 2‐cyano‐3,11‐dioxours‐1,12‐dien‐24‐oate (BCDD) to induce apoptosis in cancer cells. BCDD inhibited cell proliferation with 48 h IC50 of 0.67 µM in HL‐60, 1 µM in Molt4, and 1.5 µM in THP1 cells. The mechanism of cell death was investigated in HL‐60 cells where it caused apoptosis by acting against several potential apoptosis suppressive targets. It inhibited phosphatidylinositol‐3‐kinase (PI3K)/AKT activity, NF‐κB, Hsp‐90, and survivin which may enhance the sensitivity of cells to apoptosis. Also, BCDD decreased the activity of Bid and Bax in cytosol, caused ΔΨmt loss, releasing pro‐apoptotic cytochrome c, SMAC/DIABLO leading to caspase‐9‐mediated down stream activation of caspase‐3, ICAD, and PARP1 cleavage. Translocation of apoptotis‐inducing factor (AIF) from mitochondria to the nucleus indicated some caspases‐independent apoptosis. Though it upregulated DR‐5 and caspase‐8, the caspase inhibitor yet had no effect on apoptosis as against 75% inhibition by caspase‐9 inhibitor. Attempts were made to examine any acclaimed role of AIF in the activation of caspase‐8 using siRNA where it had no effect on caspase‐8 activity while the Bax‐siRNA inhibited caspase‐3 activation suggesting predominance of intrinsic signaling. Our studies thus demonstrated that BCDD exerts multi‐focal action in cancer cells while it required 10‐fold higher the concentration to produce cytotoxicity in normal human PBMC and gingival cell line, and therefore, may find usefulness in the management of human leukemia. © 2011 Wiley Periodicals, Inc.
Vessel size index measurements in a rat model of glioma: comparison of the dynamic (Gd) and steady‐state (iron‐oxide) susceptibility contrast MRI approaches
Authors: Pannetier Nicolas , Lemasson Benjamin , Christen Thomas , Tachrount Mohamed , Troprès Irène , Farion Régine , Segebarth Christoph , Rémy Chantal , Barbier Emmanuel L.
Published: July 2011

Vessel size index (VSI), a parameter related to the distribution of vessel diameters, may be estimated using two MRI approaches: (i) dynamic susceptibility contrast (DSC) MRI following the injection of a bolus of Gd‐chelate. This technique is routinely applied in the clinic to assess intracranial tissue perfusion in patients; (ii) steady‐state susceptibility contrast with USPIO contrast agents, which is considered here as the standard method. Such agents are not available for human yet and the steady‐state approach is currently limited to animal studies. The aim is to compare VSI estimates obtained with these two approaches on rats bearing C6 glioma (n = 7). In a first session, VSI was estimated from two consecutive injections of Gd‐Chelate (Gd1 and Gd2). In a second session (4 hours later), VSI was estimated using USPIO. Our findings indicate that both approaches yield comparable VSI estimates both in contralateral (VSI{USPIO} = 7.5 ± 2.0 µm, VSI{Gd1} = 6.5 ± 0.7 µm) and in brain tumour tissues (VSI{USPIO} = 19.4 ± 7.1 µm, VSI{Gd1} = 16.6 ± 4.5 µm). We also observed that, in the presence of BBB leakage (as it occurs typically in brain tumours), applying a preload of Gd‐chelate improves the VSI estimate with the DSC approach both in contralateral (VSI{Gd2} = 7.1 ± 0.4 µm) and in brain tumour tissues (VSI{Gd2} = 18.5 ± 4.3 µm) but is not mandatory. VSI estimates do not appear to be sensitive to T1 changes related to Gd extravasation. These results suggest that robust VSI estimates may be obtained in patients at 3 T or higher magnetic fields with the DSC approach. Copyright © 2011 John Wiley & Sons, Ltd.
In vivo MR studies of glycine and glutathione metabolism in a rat mammary tumor
Authors: Thelwall Peter E. , Simpson Nicholas E. , Rabbani Zahid N. , Clark M. Daniel , Pourdeyhimi Roxana , Macdonald Jeffrey M. , Blackband Stephen J. , Gamcsik Michael P.
Published: July 2011

The metabolism of glycine into glutathione was monitored noninvasively in vivo in intact rat mammary adenocarcinomas (R3230Ac) by MRI and MRS. Metabolism was tracked by following the isotope label from intravenously infused [2‐13C]‐glycine into the glycinyl residue of glutathione. Signals from [2‐13C]‐glycine and γ‐glutamylcysteinyl‐[2‐13C]‐glycine (13C‐glutathione) were detected by nonlocalized 13C spectroscopy, as these resonances are distinct from background signals. In addition, using spectroscopic imaging methods, heterogeneity in the in vivo tumor distribution of glutathione was observed. In vivo spectroscopy also detected isotope incorporation from [2‐13C]‐glycine into both the 2‐ and 3‐carbons of serine. Analyses of tumor tissue extracts showed single‐ and multiple‐label incorporation from [2‐13C]‐glycine into serine from metabolism through the serine hydroxymethyltransferase and glycine cleavage system pathways. Mass spectrometric analysis of extracts also showed that isotope‐labeled serine is further metabolized via the trans‐sulfuration pathway, as 13C isotope labels appear in both the glycinyl and cysteinyl residues of glutathione. Our studies demonstrate the use of MRI and MRS for the monitoring of tumor metabolic processes central to oxidative stress defense. Copyright © 2011 John Wiley & Sons, Ltd.
Meta‐analysis of interstitial pneumonia in studies evaluating iodine‐131‐labeled lipiodol for hepatocellular carcinoma using exact likelihood approach
Authors: Oger Emmanuel , Lavenu Audrey , Bellissant Eric , Garin Etienne , Polard Elisabeth
Published: July 2011

Purpose

Iodine‐131‐labeled lipiodol is currently licensed for unresectable hepatocellular carcinoma with portal thrombosis. It is thought to be well tolerated. Cases of interstitial pneumonia have been reported, but their frequency (≈2%) has not been well estimated. Quantifying adverse drug event frequency requires an appropriate statistical approach because standard methods are biased.

Methods

To estimate the frequency of interstitial pneumonia in patients with hepatocellular carcinoma receiving iodine‐131‐labeled lipiodol, we conducted a systematic review of English articles using MEDLINE and EMBASE. All types of articles were considered except case reports. Primary outcome measure was symptomatic interstitial pneumonia based on investigators' judgment. All pooled analyses were based on a random effects meta‐analysis model using an exact likelihood approach based on the binomial within‐study distribution.

Results

Ten studies, including 142 patients, used low activity per dose, ranging from 0.3 to 1.1 GBq. No respiratory adverse event was noticed in these studies. Eighteen studies, including 542 patients, evaluated higher activity per dose, around 2.2 GBq; 24 cases of interstitial pneumonia were reported in these studies. Estimated frequency of interstitial pneumonia was 1.6% (95%CI, 0.4–6.4%) after one high dose and 4.1% (95%CI, 1.0–16.0%) after two or more high doses.

Conclusions

The frequency of interstitial pneumonia appears higher and more precise than previously estimated. The risk appears to be related to the number of injections and the dose level per injection. Generalized linear mixed models using the exact binomial within‐study distribution initially described to summarize data on diagnostic evaluation could be relevant for drug‐related adverse reaction frequency assessment. Copyright © 2011 John Wiley & Sons, Ltd.
Components of asthma control and treatment response of individual control criteria in children: Analysis of the PEACE study
Authors: Pedersen Søren , Maspero Jorge , Gul Nadeem , Sharma Raj
Published: July 2011

Background

The aim of asthma management is to achieve and maintain clinical control. Control data for children is sparse.

Objective

This analysis evaluated factors associated with not achieving well‐controlled (WC) asthma using data from a study in 548 children with uncontrolled asthma.

Methods

Post hoc analysis of factors affecting the probability of not achieving WC asthma in children receiving salmeterol/fluticasone propionate 50/100 µg bd (SFC) or montelukast 5 mg od (MON), included: reasons for patients failing the asthma control criteria; achievement of overall asthma control; time course of improvement in individual outcomes and composite score; factors associated with not achieving WC asthma.

Results

The proportion of patients failing individual control criteria at baseline was: β2‐agonist rescue use: 96%, peak expiratory flow (PEF): 91%, symptoms: 78%, and night‐time awakenings: 66%. Most patients failed the composite control score for more than one reason with 482 (99%), 387 (80%), and 249 (52%) failing 2, 3, or 4 control criteria, respectively. Overall asthma control was achieved by 166 (59%) patients in the SFC group and 96 (36%) in the MON group (P < 0.001). Time course of control differed between individual control components with symptoms responding most rapidly and PEF most slowly. Factors significantly influencing the probability of not achieving WC asthma were treatment with MON, country, and night‐time awakenings at baseline, treatment being the most important.

Conclusion

Different outcomes improve at different rates. Assessment of one or a few outcomes over‐estimates the level of asthma control. An overall composite score in combination with the proportion of patients failing on three or more criteria seemed to most accurately reflect the level of control. Compared with SFC treatment, MON was three times less likely to result in good asthma control. Pediatr Pulmonol. 2011; 46: 1182–1188. © 2011 Wiley Periodicals, Inc.
Do international surveys and censuses exhibit ‘Dry Season’ bias?
Authors: Wright Jim A. , Yang Hong , Walker Kate
Published: July 2011

This study aims to assess whether Demographic and Health Surveys (DHS) and population censuses in developing countries are predominantly conducted during drier months and are therefore subject to seasonal bias. We examined field implementation dates of 176 DHS conducted in 64 countries and enumeration dates of the latest population censuses in 59 of those countries. We compared dry versus wet season implementation rates, distinguishing seasons using mean precipitation estimates and Koppen climate classes for each country. For countries with seasonal precipitation climates, 23% of 39 censuses were conducted in the wet season compared with an expected 47%. In the same countries, 43.3% of DHS fieldwork took place in the wet season compared with an expected 45.4%. There was thus a slight tendency for DHS and a greater, statistically significant tendency for censuses to be implemented in drier months. Thus, the recent censuses analysed exhibit greater ‘dry season’ bias than DHS when viewed internationally. Because past studies have identified seasonal patterns in diarrhoea incidence, water source, and malarial bednet use, care should be taken when comparing census and survey results for these variables internationally. Copyright © 2011 John Wiley & Sons, Ltd.
Urinary 1H‐NMR Metabonomics Study on Intervention Effects of Soya Milk in Africans
Authors: Ogegbo Olumuyiwa L. , Dissanyake Wimal , Crowder John , Asekun Olayinka , Familoni Oluwole , Branford‐White Christopher J. , Annie Bligh S. W.
Published: July 2011

Metabonomics is an important tool in understanding the toxicological or therapeutic effects of interventions by analysing metabolic profiles and interpreting complex multi‐dimensional spectroscopic/spectrometric data using multivariate data analysis. The objectives of this study were to evaluate the metabolic changes following a short‐term 5 day soya milk intervention, and to investigate factors that influence soy‐phytoestrogen metabolism focused on Africans based in either UK or Nigeria. 1H‐NMR metabonomics was applied to analyse urine samples collected at four phases I–IV (pre, days 3 and 5, and post) of the soy‐intervention from African volunteers (n = 40 in total). Individual proton NMR spectra were visually and statistically assessed using multivariate analyses (MVA): principal component analysis (PCA) and (orthogonal‐) partial‐least square–discriminant analysis ((O‐) PLS‐DA). In addition, 22 endogenous metabolites were quantified using a Chenomx NMR suite. The results showed the levels of analysed endogenous metabolites (creatinine adjusted) present ranged from 4 µ m to 12 m m with large inter‐subject variances in acetate, acetone, lactate and trimethylamine. The MVA results showed high inter‐individuality and sampling variances based on PCA score plots, and demonstrated soy metabolism to be significantly influenced by location and gender by both PLS‐DA and O‐PLS‐DA. Copyright © 2011 John Wiley & Sons, Ltd.
The Marine‐derived, Multi‐mineral formula, Aquamin, Enhances Mineralisation of Osteoblast Cells In Vitro
Authors: O'Gorman Denise M. , Tierney Claire M. , Brennan Orlaith , O'Brien Fergal J.
Published: July 2011

Osteoporosis is a global health problem characterized by low bone mass and an increase in bone fragility. It is now well accepted that dietary factors play a central role in bone development and health. Diet that lacks adequate minerals is considered to be a risk factor for osteoporosis. The food supplement, Aquamin, is a natural, multi‐mineral derived from the red algae Lithothamnion corallioides, rich in calcium, magnesium and 72 other trace minerals. The aim of this study was to evaluate the effect of Aquamin on osteoblastic behaviour and mineralisation in a pre‐osteoblastic cell line. Cell number and metabolic activity were assessed using Hoescht DNA and AlamarBlue assays respectively. Osteogenic differentiation was measured using an alkaline phosphatase assay while mineralisation was determined using von Kossa and alizarin red staining. It is reported here that Aquamin promotes increased mineralisation in osteoblast cell culture. These data suggest that the nutritional supplement Aquamin plays an important role in promoting bone formation and may be useful in treating bone diseases such as osteoporosis. Copyright © 2011 John Wiley & Sons, Ltd.
Global exponential stability analysis for a class of neural networks with time delays
Authors: Guo Yingxin , Liu Shu Tang
Published: July 2011

Employing Brouwer's fixed point theorem, matrix theory, we made a further investigation of a class of neural networks with delays in this paper. A family of sufficient conditions were given for checking global exponential stability. These results have important leading significance in the design and applications of globally stable neural networks with delays. Our results extended and improved some earlier publications. Copyright © 2011 John Wiley & Sons, Ltd.
DEVELOPMENT OF AN INFLOW‐CONTROLLED ENVIRONMENTAL FLOW REGIME FOR A NORWEGIAN RIVER
Authors: Alfredsen K. , Harby A. , Linnansaari T. , Ugedal O.
Published: July 2011

Hydropower produces 99% of the electricity in Norway, and a large number of rivers are regulated. Currently, static minimum flow regimes are used as a mitigation measure for most of these developments, usually having fixed values for winter and summer flow. Improved knowledge on the importance of variability in flow regimes has led to research on alternative solutions to the static minimum flow regimes. This paper describes the development of an environmental flow regime that is designed to follow the variation in natural inflow. The flow regime is designed using an adaptation of the building block methodology and linked to high, normal and low natural flow conditions. The work is focused on the river Daleelva in western Norway where Atlantic salmon is the key species. The paper also describes how the variable environmental flow regime can be implemented in practice as it pertains to current Norwegian legislation. Copyright © 2011 John Wiley & Sons, Ltd.
A joint model of recurrent events and a terminal event with a nonparametric covariate function
Authors: Zhangsheng Yu , Liu Lei
Published: July 2011

We extend the shared frailty model of recurrent events and a dependent terminal event to allow for a nonparametric covariate function. We include a Gaussian random effect (frailty) in the intensity functions of both the recurrent and terminal events to capture correlation between the two processes. We employ the penalized cubic spline method to describe the nonparametric covariate function in the recurrent events model. We use Laplace approximation to evaluate the marginal penalized partial likelihood without a closed form. We also propose the variance estimates for regression coefficients. Numerical analysis results show that the proposed estimates perform well for both the nonparametric and parametric components. We apply this method to analyze the hospitalization rate of patients with heart failure in the presence of death. Copyright © 2011 John Wiley & Sons, Ltd.
A business model‐based design of a damage control support system for naval ships
Authors: Kang Hee Jin , Shin Jong‐Gye , Lee Jong Kap
Published: July 2011

When a ship is hit, cutting‐edge damage control systems are used to mitigate the problem, but most onboard recovery activities are carried out by the crew. Therefore, the key to damage control rests with the activity of the crew. To design a new damage control support system, a reasonable design process is required. Systems engineering has been applied in the development of many defense systems, and the effectiveness of its contribution has been proven. However, the success of a project also depends on other factors, such as “user involvement,” “concern of executive,” and “expectation”; contemporary systems engineering process do not consider these factors enough. This paper uses a systems engineering approach to guide the development of a new business model‐based design method. To guarantee success of the project in the design phase, a business model is used as the “system analysis and control” tool. A new system for damage control support is developed using the proposed design process. The proposed design process makes it possible to design a reasonable system for damage control support with a minimal number of physical components, at affordable cost. The method also makes it possible to validate a given system's effectiveness and technological feasibility. © 2011 Wiley Periodicals, Inc. Syst Eng