bluuebunny/crossref_metadata_2025 huggingface dataset:
A midcrustal ramp‐fault structure beneath the Taiwan tectonic wedge illuminated by the 2013 Nantou earthquake series
Authors: Chuang Ray Y. , Johnson Kaj M. , Wu Yih‐Min , Ching Kuo‐En , Kuo Long‐Chen
Published: October 2013

Taiwan's active mountain belt is a spotlight for orogenic studies and was first used to test the critical‐taper wedge mechanics. The concept of an orogenic wedge above a shallow detachment surface has been highly influential on current understanding of orogenic processes in Taiwan. However, the recent ML 6.2 and ML 6.5 2013 Nantou reverse‐faulting earthquakes in central Taiwan have nucleated below the proposed detachment, indicating that active mountain building is occurring below the orogenic wedge. We estimate the coseismic slip distributions and fault geometry using the uniform stress drop slip inversions. The earthquakes occur on essentially the same 30° dipping fault plane ramping up from ~20 km depth near a cluster of 1999 Chi‐Chi earthquake aftershocks to the shallow detachment and the Chi‐Chi fault plane. The fault could be a deep extension of a mature shallow fault or a newly developed deep ramp fault that is not reflected in the surface geology.
The role of anterior midcingulate cortex in cognitive motor control
Authors: Hoffstaedter Felix , Grefkes Christian , Caspers Svenja , Roski Christian , Palomero‐Gallagher Nicola , Laird Angie R. , Fox Peter T. , Eickhoff Simon B.
Published: October 2013

The rostral cingulate cortex has been associated with a multitude of cognitive control functions. Recent neuroimaging data suggest that the anterior midcingulate cortex (aMCC) has a key role for cognitive aspects of movement generation, i.e., intentional motor control. We here tested the functional connectivity of this area using two complementary approaches: (1) resting‐state connectivity of the aMCC based on fMRI scans obtained in 100 subjects, and (2) functional connectivity in the context of explicit task conditions using meta‐analytic connectivity modeling (MACM) over 656 imaging experiment. Both approaches revealed a convergent functional network architecture of the aMCC with prefrontal, premotor and parietal cortices as well as anterior insula, area 44/45, cerebellum and dorsal striatum. To specifically test the role of the aMCC's task‐based functional connectivity in cognitive motor control, separate MACM analyses were conducted over “cognitive” and “action” related experimental paradigms. Both analyses confirmed the same task‐based connectivity pattern of the aMCC. While the “cognition” domain showed higher convergence of activity in supramodal association areas in prefrontal cortex and anterior insula, “action” related experiments yielded higher convergence in somatosensory and premotor areas. Secondly, to probe the functional specificity of the aMCC's convergent functional connectivity, it was compared with a neural network of intentional movement initiation. This exemplary comparison confirmed the involvement of the state independent FC network of the aMCC in the intentional generation of movements. In summary, the different experiments of the present study suggest that the aMCC constitute a key region in the network realizing intentional motor control.Hum Brain Mapp 35:2741–2753, 2014. ©2013 Wiley Periodicals, Inc.
SELF‐PERCEIVED JOB INSECURITY AND THE DEMAND FOR MEDICAL REHABILITATION: DOES FEAR OF UNEMPLOYMENT REDUCE HEALTH CARE UTILIZATION?
Authors: Reichert Arndt R. , Augurzky Boris , Tauchmann Harald
Published: October 2013

An inverse relationship between job insecurity and sickness absence has been established in the literature, which is explained by employees avoiding to send signals of both poor health and uncooperative behavior towards the employer. In this paper, we focus on whether the same mechanism applies to the demand for medical rehabilitation measures. This question has recently gained much interest in the context of the current public debate on presenteeism. Using county‐level unemployment rates as instrument for the employees' fear of job loss on the individual level, we find that an increase in subjective job insecurity substantially decreases the probability of participating in medical rehabilitation. Copyright © 2013 John Wiley & Sons, Ltd.
EFFECTS OF BICYCLE HELMET LAWS ON CHILDREN'S INJURIES
Authors: Markowitz Sara , Chatterji Pinka
Published: October 2013

In recent years, many states and localities in the USA have enacted bicycle helmet laws. We estimate the effects of these laws on injuries requiring emergency department treatment. Using hospital‐level panel data and triple difference models, we find helmet laws are associated with reductions in bicycle‐related head injuries among children. However, laws also are associated with decreases in non‐head cycling injuries, as well as increases in head injuries from other wheeled sports. Thus, the observed reduction in bicycle‐related head injuries may be due to reductions in bicycle riding induced by the laws. Copyright © 2013 John Wiley & Sons, Ltd.
HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells
Authors: Hah J. Hun , Zhao Mei , Pickering Curtis R. , Frederick Mitchell J. , Andrews Genevieve A. , Jasser Samar A. , Fooshee David R. , Milas Zvonimir L. , Galer Chad , Sano Daisuke , William William N. , Kim Edward , Heymach John , Byers Lauren A. , Papadimitrakopoulou Vali , Myers Jeffrey N.
Published: October 2013

Background

The purpose of this study was to identify mechanisms of innate resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib resistance.

Methods

Erlotinib sensitivity was determined by methyl thiazolyl‐tetrazolium (MTT) assays. Molecular signaling pathways and somatic mutations were examined. Changes in sensitivity after modulation of HRAS expression were evaluated.

Results

All 7 cell lines were wild‐type for EGFR and KRAS regardless of erlotinib sensitivity; however, 1 erlotinib‐resistant cell line (HN31) harbored an HRAS G12D mutation. Downregulation of HRAS expression by small interfering RNA (siRNA) or short hairpin RNA (shRNA) in HN31 led to increased erlotinib sensitivity in vitro and in vivo. Transfection of activating HRAS‐mutant (G12D and G12V) constructs into erlotinib‐sensitive cell lines made them more resistant to erlotinib.

Conclusion

Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1547–1554, 2014
Preclinical safety and activity of recombinant VSV‐IFN‐β in an immunocompetent model of squamous cell carcinoma of the head and neck
Authors: Kurisetty Vittal V. S. , Heiber Joshua , Myers Rae , Pereira Guilherme S. , Goodwin Jarrard W. , Federspiel Mark J. , Russell Stephen J. , Peng Kah Whye , Barber Glen , Merchan Jaime R.
Published: October 2013

Background

Recombinant vesicular stomatitis virus expressing interferon‐β (VSV‐IFN‐β) has demonstrated antitumor activity in vitro and in vivo. In preparation for clinical testing in human squamous cell carcinoma (SCC) of the head and neck, we conducted preclinical studies of VSV‐IFN‐β in syngeneic SCC models.

Methods

In vitro, VSV‐IFN‐β (expressing rat or mouse interferon [IFN]‐β)‐induced cytotoxicity and propagated in rat (FAT‐7) or mouse (SCC‐VII) SCC cells during normoxia and hypoxia. In vivo, intratumoral administration of VSV‐rat‐IFN‐β or VSV‐human‐IFN‐β in FAT‐7 bearing or non‐tumor bearing immunocompetent rats did not result in acute organ toxicity or death.

Results

VSV‐r‐IFN‐β replicated predominantly in tumors and a dose dependent anti‐VSV antibody response was observed. Intratumoral or intravenous administration of VSV‐IFN‐β resulted in growth delay and improved survival compared with controls.

Conclusion

The above data confirm safety and feasibility of VSV‐IFN‐β administration in immunocompetent animals and support its clinical evaluation in advanced human head and neck cancer. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1619–1627, 2014
Clinical significance of intraparotid lymph node metastasis in primary parotid cancer
Authors: Lim Chwee Ming , Gilbert Mark R. , Johnson Jonas T. , Kim Seungwon
Published: October 2013

Background

The clinical utility of intraparotid lymph node metastasis in primary parotid cancer is unknown, and this study was undertaken to address this gap in knowledge.

Methods

A medical chart review was performed on 86 patients who underwent parotidectomy with neck dissection (39 cN+ and 47 cN0). The disease‐specific mortality and locoregional recurrence (LRR) were correlated with intraparotid lymph node metastasis status.

Results

Using intraparotid lymph node metastasis status to predict cervical nodal metastasis resulted in a sensitivity and specificity of 70% and 90.6%, respectively (positive predictive value [PPV] of 87.3%). Patients with positive intraparotid lymph node metastasis had a worse 3‐year disease‐specific mortality compared with patients with negative intraparotid lymph node metastasis (p = .0037). Patients with cN0 neck but positive intraparotid lymph node metastasis were more likely to develop locoregional recurrence than patients without intraparotid lymph node metastasis (p = .08).

Conclusion

In patients with cN0 neck but positive intraparotid lymph node metastasis, intraparotid lymph node metastasis presence was strongly associated with a worse disease‐specific survival and placed them at a higher risk of locoregional recurrence. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1634–1637, 2014
Association of vascular invasion with increased mortality in patients with minimally invasive follicular thyroid carcinoma but not widely invasive follicular thyroid carcinoma
Authors: Kim Hye Jeong , Sung Ji‐Youn , Oh Young Lyun , Kim Jung Han , Son Young‐Ik , Min Yong‐Ki , Kim Sun Wook , Chung Jae Hoon
Published: October 2013

Background

The association of vascular invasion with tumor aggressiveness and poor prognosis in follicular thyroid carcinoma (FTC) remains controversial.

Methods

We reviewed medical records of 204 patients with histologically confirmed FTC.

Results

The disease‐specific survival rates at 5 and 10 years were 94% and 85%, respectively. Using Cox proportional hazard model, the extent of invasiveness and the frequency of distant metastasis were found to be independent prognostic factors for survival in all patients with FTC. When we performed individual analyses stratified by the extent of invasiveness, vascular invasion was an independent predictor of disease‐specific survival in minimally invasive FTC, but that did not independently affect survival in widely invasive FTC.

Conclusion

This study suggests that vascular invasion is associated with aggressive features of FTC and independently influences outcomes in minimally invasive FTC. For patients aged <45 years with minimally invasive FTC without vascular invasion, thyroid lobectomy alone may be adequate. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1695–1700, 2014
TP53 single nucleotide polymorphism rs1042522 in salivary gland neoplasms
Authors: Gomes Carolina C. , Fonseca–Silva Thiago , Diniz Marina G. , Orsine Lissur A. , Gomez Ricardo S.
Published: October 2013

Background

The TP53 single nucleotide polymorphism (SNP) rs1042522 encodes arginine (Arg) or proline (Pro). The Arg variant is more effective at inducing apoptosis than the Pro.

Methods

We assessed this SNP through direct sequencing of benign and malignant salivary neoplasms of Brazilian patients and compared the results with healthy controls' data. BAX, BCL‐2, and CASPASE‐3 mRNA levels were assessed by quantitative polymerase chain reaction (qPCR) in a set of salivary tumors, and the results were correlated with the tumor genotype.

Results

We found a higher frequency of the Arg/Arg genotype in the malignant group. However, the SNP did not influence the age of onset in either benign or malignant tumors. The SNP was not associated with the transcription levels of apoptotic/antiapoptotic genes.

Conclusion

Malignant salivary neoplasms showed a higher frequency of the allele encoding Arg and a higher frequency of the Arg/Arg genotype. However, the different genotypes did not impact the transcription of genes involved in apoptosis. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1685–1688, 2014
p16 status, pathologic and clinical characteristics, biomolecular signature, and long‐term outcomes in head and neck squamous cell carcinomas of unknown primary
Authors: Keller Lanea M. , Galloway Thomas J. , Holdbrook Thomas , Ruth Karen , Yang Donghua , Dubyk Cara , Flieder Douglas , Lango Miriam N. , Mehra Ranee , Burtness Barbara , Ridge John A.
Published: October 2013

Background

The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).

Methods

Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC).

Results

A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known‐primary cancer.

Conclusion

The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1677–1684, 2014
Hepatitis C virus clearance correlates with HLA-DR expression on proliferating CD8+ T cells in immune-primed chimpanzees
Authors: Zubkova Iryna , Duan Hongying , Wells Frances , Mostowski Howard , Chang Esther , Pirollo Kathleen , Krawczynski Kris , Lanford Robert , Major Marian
Published: October 2013

Vaccination of chimpanzees against hepatitis C virus (HCV) using T-cell-based vaccines targeting nonstructural proteins has not resulted in the same levels of control and clearance as those seen in animals reexposed after HCV clearance. We hypothesized that the outcome of infection depends on the different subtypes of activated T cells. We used multicolor flow cytometry to evaluate activation (CD38+/HLA-DR+) and proliferation (Ki67+/Bcl-2-low) profiles of CD4+ and CD8+ T cells in peripheral blood before and after challenge in chimpanzees vaccinated using DNA/adenovirus, mock-vaccinated, and chimpanzees that had spontaneously cleared infection (rechallenged). The frequencies of activated or proliferating CD8+ T cells peaked at 2 weeks postchallenge in the vaccinated and rechallenged animals, coinciding with reductions in viral titers. However, the magnitude of the responses did not correlate with outcome or sustained control of viral replication. In contrast, proliferation of the CD8+ T cells coexpressing HLA-DR either with or without CD38 expression was significantly higher at challenge in animals that rapidly cleared HCV and remained so throughout the follow-up period. Conclusion: Our data suggest that the appearance of proliferating HLA-DR+/CD8+ T cells can be used as a predictor of a successfully primed memory immune response against HCV and as a marker of effective vaccination in clinical trials. (HEPATOLOGY 2014;59:803–813)
Opposing effects of prednisolone treatment on T/NKT cell- and hepatotoxin-mediated hepatitis in mice
Authors: Kwon Hyo-Jung , Won Young-Suk , Park Ogyi , Feng Dechun , Gao Bin
Published: October 2013

Prednisolone is a corticosteroid that has been used to treat inflammatory liver diseases such as autoimmune hepatitis and alcoholic hepatitis. However, the results have been controversial, and how prednisolone affects liver disease progression remains unknown. In the current study we examined the effect of prednisolone treatment on several models of liver injury, including T/NKT cell hepatitis induced by concanavalin A (ConA) and α-galactosylceramide (α-GalCer), and hepatotoxin-mediated hepatitis induced by carbon tetrachloride (CCl4) and/or ethanol. Prednisolone administration attenuated ConA- and α-GalCer-induced hepatitis and systemic inflammatory responses. Treating mice with prednisolone also suppressed inflammatory responses in a model of hepatotoxin (CCl4)-induced hepatitis, but surprisingly exacerbated liver injury and delayed liver repair. In addition, administration of prednisolone also enhanced acetaminophen-, ethanol-, or ethanol plus CCl4-induced liver injury. Immunohistochemical and flow cytometric analyses demonstrated that prednisolone treatment inhibited hepatic macrophage and neutrophil infiltration in CCl4-induced hepatitis and suppressed their phagocytic activities in vivo and in vitro. Macrophage and/or neutrophil depletion aggravated CCl4-induced liver injury and impeded liver regeneration. Finally, conditional disruption of glucocorticoid receptor in macrophages and neutrophils abolished prednisolone-mediated exacerbation of hepatotoxin-induced liver injury. Conclusion: Prednisolone treatment prevents T/NKT cell hepatitis but exacerbates hepatotoxin-induced liver injury by inhibiting macrophage- and neutrophil-mediated phagocytic and hepatic regenerative functions. These findings may not only increase our understanding of the steroid treatment mechanism but also help us to better manage steroid therapy in liver diseases. (HEPATOLOGY 2014;59:1094–1106)
Interferon regulatory factor 3 constrains IKKβ/NF-κB signaling to alleviate hepatic steatosis and insulin resistance
Authors: Wang Xin-An , Zhang Ran , She Zhi-Gang , Zhang Xiao-Fei , Jiang Ding-Sheng , Wang Tao , Gao Lu , Deng Wei , Zhang Shu-Min , Zhu Li-Hua , Guo Sen , Chen Ke , Zhang Xiao-Dong , Liu De-Pei , Li Hongliang
Published: October 2013

Obesity and related metabolic diseases associated with chronic low-grade inflammation greatly compromise human health. Previous observations on the roles of interferon regulatory factors (IRFs) in the regulation of metabolism prompted investigation of the involvement of a key family member, IRF3, in metabolic disorders. IRF3 expression in the liver is decreased in animals with diet-induced and genetic obesity. The global knockout (KO) of IRF3 significantly promotes chronic high-fat diet (HFD)-induced hepatic insulin resistance and steatosis; in contrast, adenoviral-mediated hepatic IRF3 overexpression preserves glucose and lipid homeostasis. Furthermore, systemic and hepatic inflammation, which is increased in IRF3 KO mice, is attenuated by the overexpression of hepatic IRF3. Importantly, inhibitor of nuclear factor kappa B kinase beta subunit / nuclear factor kappa B (IKKβ/NF-κB) signaling is repressed by IRF3, and hepatic overexpression of the inhibitor of κB-α (IκBα) reverses HFD-induced insulin resistance and steatosis in IRF3 KO mice. Mechanistically, IRF3 interacts with the kinase domain of IKKβ in the cytoplasm and inhibits its downstream signaling. Moreover, deletion of the region of IRF3 responsible for the IRF3/IKKβ interaction inhibits the capacity of IRF3 to preserve glucose and lipid homeostasis. Conclusion: IRF3 interacts with IKKβ in the cytoplasm to inhibit IKKβ/NF-κB signaling, thus alleviating hepatic inflammation, insulin resistance, and hepatic steatosis. (HEPATOLOGY 2014;59:870–885)
Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data
Authors: Trépo Eric , Nahon Pierre , Bontempi Gianluca , Valenti Luca , Falleti Edmondo , Nischalke Hans-Dieter , Hamza Samia , Corradini Stefano Ginanni , Burza Maria Antonella , Guyot Erwan , Donati Benedetta , Spengler Ulrich , Hillon Patrick , Toniutto Pierluigi , Henrion Jean , Franchimont Denis , Devière Jacques , Mathurin Philippe , Moreno Christophe , Romeo Stefano , Deltenre Pierre
Published: October 2013

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model = 1.77; 95% confidence interval [CI]: 1.42-2.19; P = 2.78 × 10−7). This association was more pronounced in ALD (OR = 2.20; 95% CI: 1.80-2.67; P = 4.71 × 10−15) than in CHC patients (OR = 1.55; 95% CI: 1.03-2.34; P = 3.52 × 10−2). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. Conclusion: Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development. (Hepatology 2014;59:2170–2177)
Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver
Authors: Wieland Stefan , Makowska Zuzanna , Campana Benedetta , Calabrese Diego , Dill Michael T. , Chung Josan , Chisari Francis V. , Heim Markus H.
Published: October 2013

Approximately 50% of patients with chronic hepatitis C (CHC) have ongoing expression of interferon stimulated genes (ISGs) in the liver. It is unclear why this endogenous antiviral response is inefficient in eradicating the infection. Several viral escape strategies have been identified in vitro, including inhibition of interferon (IFN) induction and ISG messenger RNA (mRNA) translation. The in vivo relevance of these mechanisms is unknown, because reliable methods to identify hepatitis C virus (HCV)-infected cells in human liver are lacking. We developed a highly sensitive in situ hybridization (ISH) system capable of HCV RNA and ISG mRNA detection in human liver biopsies and applied it to study the interaction of HCV with the endogenous IFN system. We simultaneously monitored HCV RNA and ISG mRNA using HCV isolate- and ISG mRNA-specific probes in liver biopsy sections from 18 CHC patients. The signals were quantified at the single-cell resolution in a series of random high-power fields. The proportion of infected hepatocytes ranged from 1%-54% and correlated with viral load, but not with HCV genotype or ISG expression. Infected cells occurred in clusters, pointing to cell-to-cell spread as the predominant mode of HCV transmission. ISG mRNAs were readily detected in HCV-infected cells, challenging previously proposed mechanisms of viral interference with the immune system. Conversely, infected cells and neighboring cells showed increased ISG mRNA levels, demonstrating that the stimulus driving ISG expression originates from HCV-infected hepatocytes. Conclusion: HCV infection in human hepatocytes during CHC does not efficiently interfere with IFN induction, IFN signaling, or transcription of ISG mRNA. (Hepatology 2014;59:2121–2130)
Tri-iodothyronine induces hepatocyte proliferation by protein kinase a-dependent β-catenin activation in rodents
Authors: Fanti Maura , Singh Sucha , Ledda-Columbano Giovanna M. , Columbano Amedeo , Monga Satdarshan P.
Published: October 2013

Thyroid hormone (T3), like many other ligands of the steroid/thyroid hormone nuclear receptor superfamily, is a strong inducer of liver cell proliferation in rats and mice. However, the molecular basis of its mitogenic activity, which is currently unknown, must be elucidated if its use in hepatic regenerative medicine is to be considered. F-344 rats or C57BL/6 mice were fed a diet containing T3 for 2-7 days. In rats, administration of T3 led to an increased cytoplasmic stabilization and nuclear translocation of β-catenin in pericentral hepatocytes with a concomitant increase in cyclin-D1 expression. T3 administration to wild-type (WT) mice resulted in increased hepatocyte proliferation; however, no mitogenic response in hepatocytes to T3 was evident in the hepatocyte-specific β-catenin knockout mice (KO). In fact, T3 induced β-catenin-TCF4 reporter activity both in vitro and in vivo. Livers from T3-treated mice demonstrated no changes in Ctnnb1 expression, activity of glycogen synthase kinase-3β, known to phosphorylate and eventually promote β-catenin degradation, or E-cadherin-β-catenin association. However, T3 treatment increased β-catenin phosphorylation at Ser675, an event downstream of protein kinase A (PKA). Administration of PKA inhibitor during T3 treatment of mice and rats as well as in cell culture abrogated Ser675-β-catenin and simultaneously decreased cyclin-D1 expression to block hepatocyte proliferation. Conclusion: We have identified T3-induced hepatocyte mitogenic response to be mediated by PKA-dependent β-catenin activation. Thus, T3 may be of therapeutic relevance to stimulate β-catenin signaling to in turn induce regeneration in selected cases of hepatic insufficiency. (Hepatology 2014;59:2309–2320)
Small proline rich protein 2a in benign and malignant liver disease
Authors: Mizuguchi Yoshiaki , Isse Kumiko , Specht Susan , Lunz John G. , Corbitt Natasha , Takizawa Toshihiro , Demetris Anthony J.
Published: October 2013

STAT3-driven expression of small proline rich protein 2a (SPRR2a), which acts as an src homology 3 (SH3) domain ligand, induces biliary epithelial cell (BEC) epithelial-mesenchymal transition (EMT), which, in turn, promotes wound healing. SPRR2a also quenches free radicals and protects against oxidative stress and DNA damage in nonneoplastic BEC. Sprr2a-induced EMT also increases local invasiveness of cholangiocarcinomas (CC), but prevents metastases. Understanding SPRR2a regulation of EMT has potential for therapeutic targeting in both benign and malignant liver disease. Molecular mechanisms responsible for SPRR2a-induced EMT were characterized, in vitro, and then evidence for utilization of these pathways was sought in human intrahepatic CC, in vivo, using multiplex labeling and software-assisted morphometric analysis. SPRR2a complexes with ZEB1 and CtBP on the microRNA (miR)-200c/141 promoter resulting in synergic suppression of miR-200c/141 transcription, which is required for maintenance of the BEC epithelial phenotype. SPRR2a induction promotes dephosphorylation and nuclear translocation of the SH3-domain containing protein GRB2 and an SH3-domain ligand in ZEB1 is required for SPRR2a-induced synergic suppression of miR-200c/141. Multiplex protein labeling of CC and morphometric analyses showed: 1) up-regulation of ZEB-1, and 2) down-regulation of CK19 in intrahepatic CC compared to nonneoplastic BEC, consistent with previous CC proteomic studies showing EMT during cholangiocarcinogenesis. Conclusion: SPRR2a modulates ZEB-1 signaling by way of miR-200c/141-associated EMT through SH3-domain networks and contributes to benign and malignant BEC wound-healing responses. (HEPATOLOGY 2014;59:1130–1143)
Development of an Energy‐Economic Model with Endogenous Technological Progress and Feasibility Study of CCS Systems
Authors: Kusunoki Tomoya , Furubayashi Takaaki , Nakata Toshihiko , Usui Takafumi
Published: October 2013

The main objective of this research is to develop a bottom‐up energy‐economic model considering endogenous technological development. The designed model analyzes the feasibility of CCS technologies in the Japanese electricity market to derive an optimum carbon reduction scenario. Two factors, a learning curve based on learning‐by‐doing and public R&D investment, precede technological progress. The analysis is calculated with a set of scenarios, which is based on alternative assumptions for technological characteristics: chemical and physical carbon absorptive technology. From modeling estimation, we conclude that technological progress reduces the generation costs of conversion technologies with CCS, as a CCS system acquires an additional unit of installation. Generation cost with chemical absorption remarkably reduces its marginal unit cost through a learning mechanism. The supply fraction from a gas‐fired power plant increases over the analytical time period. The introduction of CCS reduces carbon emission level 17% compared to the baseline scenario in 2050. Technological progress has little impact on the total system costs; however, learning‐by‐doing pushes the introduction of CCS into the market rather than into a R&D activity. Research and development efforts in the private sector or knowledge spillover are not modeled in the study; however, they have the potential to contribute to the mitigation of carbon emission as well. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(4): 332–351, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21078
Modeling of a Solar Water Collector with Water‐Based Nanofluid Using Nanoparticles
Authors: Nasrin Rehena , Alim M.A.
Published: October 2013

The pressure‐velocity form of the Navier–Stokes equations, energy equation, and concentration equation are used to represent the mass, momentum, energy, and concentration conservations of the nanofluid medium in the solar collector. The governing equations and corresponding boundary conditions are converted to dimensionless form and solved numerically by the finite element method. The physical domain is discretized by triangular mesh elements with six nodes. The working fluid is water‐based nanofluid with two nanoparticles, namely, silver (Ag) and copper oxide (CuO). The study includes computations for different values of buoyancy ratio (Nr) and Schmidt number (Sc). Flow, heat, and mass transfer characteristics are presented in the forms of streamlines, isotherms, and iso‐concentrations. In addition, results for the average radiative, convective heat and mass transfer, mean temperature and concentration of nanofluid, mid‐height horizontal‐vertical velocities, and subdomain average velocity field are offered and discussed for the above‐mentioned parametric conditions. Results show that the effects of Nr and Sc on the convective‐radiative heat and mass transfer phenomenon inside the collector are significant for all values of Nr and Sc studied. Comparison and validation with the standard experimental/numerical data is given in brief. The variation of the obtained result is presented as 34% with the result of experimental data. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(3): 270–287, 2014; Published online 30 September 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21080
Thermophoretic Deposition Effect on Transient Free Convection Hydromagnetic Flow Along an Accelerated Inclined Permeable Surface with Time‐Dependent Temperature and Concentration
Authors: Alam M.S. , Rahman M.M.
Published: October 2013

This work investigates the thermophoretic deposition effect on a transient free convection hydromagnetic flow along an accelerated infinite inclined permeable surface in the presence of heat generation, suction (or injection), thermal diffusion, and diffusion‐thermo taking into account that the surface temperature and concentration are time dependent. The governing partial differential equations are transformed into a set of nonlinear coupled ordinary differential equations, which are then solved numerically by applying the shooting method with a sixth‐order Runge–Kutta integration scheme. Graphical results for the dimensionless velocity, temperature, concentration distributions as well as wall thermophoretic velocity are reported and examined for the pertinent parameters showing the interesting aspects of the obtained solutions. The local skin‐friction coefficient, the local Nusselt number, and the local Sherwood number are also computed. The results show that higher flow rates can be obtained when the temperature and concentration are time independent. Smaller buoyancy is observed for higher temperature indexes. Wall thermophoretic velocity is decreased with the increasing values of the Prandtl number, the thermophoretic parameter, as well as heat generation parameter. The results further show that the presence of thermal diffusion and diffusion‐thermo intensify the shear stress but reduce the rate of heat as well as mass transfer. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(4): 352–367, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21081
Influence of Viscous Dissipation on Mixed Convection in a Non‐Darcy Porous Medium Saturated with a Nanofluid
Authors: Rashad A.M. , Chamkha A.J. , RamReddy C. , Murthy P.V.S.N.
Published: October 2013

In this study, the effects of viscous dissipation on mixed convection heat and mass transfer along a vertical plate embedded in a nanofluid‐saturated non‐Darcy porous medium have been investigated. The model used for the nanofluid incorporates the effects of Brownian motion and thermophoresis. The new far‐field thermal boundary condition that has been recently developed is employed to properly account for the effect of viscous dissipation in mixed convective transport in a porous medium. The nonlinear governing equations and the associated boundary conditions are transformed to a set of nonsimilar ordinary differential equations and the resulting system of equations is then solved numerically by an improved implicit finite‐difference method. The effect of the physical parameters on the flow, heat transfer, and nanoparticle concentration characteristics of the model are presented through graphs and the salient features are discussed. As expected, a significant improvement in the heat transfer coefficient is noticed because of the consideration of the nanofluid in the porous medium. With the increase in the value of the viscous dissipation parameter, a reduction in the non‐dimensional heat transfer coefficient is noted while an increase in the nanoparticle mass transfer coefficient is seen. Further, an increase in the mixed convection parameter lowered both the heat and nanoparticle mass transfer rates. Moreover, the increase in the Brownian motion parameter enhanced the nanoparticle mass transfer rate but it reduced the heat transfer rate in the boundary layer. A similar trend is also found with the thermophoresis parameter. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(5): 397–411, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21083
The Interfacial Layer and the Thermal Conductivity of Nanofluid
Authors: Pasrija Ritu , Srivastava Sunita
Published: October 2013

Nanofluids are a class of colloidal dispersion of nanosized particles which are found to exhibit anomalous heat conducting properties compared to other conventional heat transfer fluids. Among various factors responsible for this anomaly, the role of nanolayer thickness is found to be quite important. This article includes its effect by suggesting a new exponential form for the profile of thermal conductivity in the interfacial layer. The effect of nanoparticle size, the volume fraction, and the ratio of thermal conductivity of the nanoparticle to the base fluid form part of the discussion. The presented scheme predicts well the enhancement of thermal conductivity of two nanofluids, alumina/EG and CuO/water, used as an example. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(3): 288–296, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21084
Wall‐Confined Flow and Heat Transfer Around a Square Cylinder at Low Reynolds and Hartmann Numbers
Authors: Chatterjee Dipankar , Chatterjee Kanchan , Mondal Bittagopal , Hui Nirmal Baran
Published: October 2013

This article discusses the results obtained through a two‐dimensional numerical simulation following a finite volume approach on the forced convection heat transfer for the hydromagnetic flow around a square cylinder at low Reynolds and Hartmann numbers. The magnetohydrodynamic (MHD) flow of a viscous incompressible and electrically conducting fluid is assumed to take place in a rectangular channel subjected to externally imposed magnetic fields and the cylinder is fixed within the channel. The magnetic fields may be applied either along the streamwise or transverse directions. Simulations are performed for the range of kinetic Reynolds number 10 ≤ Re ≤ 60 with Hartmann number 0 ≤ Ha ≤ 15 and for different thermal Prandtl numbers, Pr = 0.02 (liquid metal), 0.71 (air), and 7 (water) for a blockage ratio β = 0.25. A steady flow can be expected for the above range of conditions. Besides the channel wall, the magnetic field imparts additional stability to the flow as a consequence of which the recirculation region behind the obstacle reduces with increasing magnetic field strength for a particular Re. The critical Hartmann numbers for the complete suppression of flow separation in the case of a transversely applied magnetic field are computed. The rate of heat transfer is found almost invariant at low Re whereas it increases moderately for higher Re with the applied magnetic field. The heat transfer increases in general with the Reynolds number for all Hartmann numbers. Finally, the influence of obstacle shape on the thermohydrodynamic quantities is noted. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(5): 459–475, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21091
Viscous Potential Flow Analysis of Kelvin–Helmholtz Instability of a Cylindrical Flow with Heat and Mass Transfer
Authors: Asthana Rishi , Awasthi Mukesh Kumar , Agrawal G.S.
Published: October 2013

A linear analysis of Kelvin–Helmholtz instability of a cylindrical interface has been carried out when there is heat and mass transfer across the interface, using viscous potential flow theory. Both fluids are considered as incompressible, viscous, and thermally conducting with different kinematic viscosities. Both axisymmetric as well as asymmetric disturbances are considered. Stability criterion is given by a critical value of relative velocity and stability is discussed theoretically as well as numerically. Various graphs with respect to physical parameters such as wave number, viscosity ratio, heat transfer coefficients, Reynolds number, etc., have been drawn and the effect of various parameters have been described. A comparison with the linear stability analysis of inviscid fluids (Lee [10]) has been made and it is observed that viscosity has a stabilizing effect on the stability of the system. © 2013 Wiley Periodicals, Inc. Heat Trans Asian Res, 43(6): 489–503, 2014; Published online 3 October 2013 in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21092
Prediction and structural equation model of sertraline treatment response in Japanese patients with major depressive disorder
Authors: Nishioka Gentaro , Yashima Hideaki , Kiuchi Yuji , Nakamura Sumiko , Oyamada Hideto , Ishii Masakazu , Kudo Ikuo
Published: October 2013

Objective

The aim of this study was to extract the factors possibly associated with sertraline treatment response and elucidate their interactions and extent of influence.

Methods

Demographic state, stress state, personality, and eight genetic polymorphisms at baseline and clinical symptoms at baseline and 8 weeks were analyzed and examined by logistic regression and a structural equation model in sertraline treatment study of 96 Japanese patients with major depressive disorder.

Results

Non‐responders were associated with higher scores of harm avoidance in Temperament and Character Inventory, higher scores (≥24) of 17‐item Hamilton Rating Scale for Depression at baseline, recurrence, and 12/12 genotype of the serotonin transporter variable number of tandem repeat polymorphism in intron 2 (5HTTSTin2). When we calculated the response index using four factors extracted, the mean response index value of non‐responders was significantly higher than that of responders. The symptoms at baseline, personality, recurrence, and polymorphism of 5HTTSTin2 showed significantly direct and positive influences on the symptoms at 8 weeks in our final structural equation model with a good model fit.

Conclusion

Considering the combination of four factors extracted may be useful for predicting a worse response to sertraline treatment and selecting different treatment other than sertraline. Copyright © 2013 John Wiley & Sons, Ltd.
River evaporation and corresponding heat fluxes in forested catchments
Authors: Maheu Audrey , Caissie Daniel , St‐Hilaire André , El‐Jabi Nassir
Published: October 2013

River water temperature is a very important variable in ecological studies, especially for the management of fisheries and aquatic resources. Temperature can impact on fish distribution, growth, mortality and community dynamics. River evaporation has been identified as an important heat loss and a key process in the thermal regime of rivers. However, its quantification remains a challenge, mainly because of the difficulty of making direct measurements. The objectives of this study were to characterize the evaporative heat flux at different scales (brook vs river) and to improve the estimation of the evaporative heat flux in a stream temperature model at the hourly timescale. Using a mass balance approach with floating minipans, we measured river evaporation at an hourly timescale in a medium‐sized river (Little Southwest Miramichi) and a small brook (Catamaran Brook) in New Brunswick, Canada. With these direct measurements of evaporation, we developed mass transfer equations to estimate hourly evaporation rates from microclimate conditions measured 2 m above the stream. During the summer 2012, river evaporation was more important for the medium‐sized river with a mean daily evaporation rate of 3.0 mm day−1 in the Little Southwest Miramichi River compared with that of 1.0 mm day−1 in Catamaran Brook. Evaporation was the main heat loss mechanism in the two studied streams and was responsible for 42% of heat losses in the Little Southwest Miramichi River and 34% of heat losses in Catamaran Brook during the summer. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of lakes and reservoirs on annual river nitrogen, phosphorus, and sediment export in agricultural and forested landscapes
Authors: Powers S. M. , Robertson D. M. , Stanley E. H.
Published: October 2013

Recently, effects of lakes and reservoirs on river nutrient export have been incorporated into landscape biogeochemical models. Because annual export varies with precipitation, there is a need to examine the biogeochemical role of lakes and reservoirs over time frames that incorporate interannual variability in precipitation. We examined long‐term (~20 years) time series of river export (annual mass yield, Y, and flow‐weighted mean annual concentration, C) for total nitrogen (TN), total phosphorus (TP), and total suspended sediment (TSS) from 54 catchments in Wisconsin, USA. Catchments were classified as small agricultural, large agricultural, and forested by use of a cluster analysis, and these varied in lentic coverage (percentage of catchment lake or reservoir water that was connected to river network). Mean annual export and interannual variability (CV) of export (for both Y and C) were higher in agricultural catchments relative to forested catchments for TP, TN, and TSS. In both agricultural and forested settings, mean and maximum annual TN yields were lower in the presence of lakes and reservoirs, suggesting lentic denitrification or N burial. There was also evidence of long‐term lentic TP and TSS retention, especially when viewed in terms of maximum annual yield, suggesting sedimentation during high loading years. Lentic catchments had lower interannual variability in export. For TP and TSS, interannual variability in mass yield was often >50% higher than interannual variability in water yield, whereas TN variability more closely followed water (discharge) variability. Our results indicate that long‐term mass export through rivers depends on interacting terrestrial, aquatic, and meteorological factors in which the presence of lakes and reservoirs can reduce the magnitude of export, stabilize interannual variability in export, as well as introduce export time lags. Copyright © 2013 John Wiley & Sons, Ltd.
Maximizing the accuracy of field-derived numeric nutrient criteria in water quality regulations
Authors: McLaughlin Douglas B
Published: October 2013

High levels of the nutrients nitrogen and phosphorus can cause unhealthy biological or ecological conditions in surface waters and prevent the attainment of their designated uses. Regulatory agencies are developing numeric criteria for these nutrients in an effort to ensure that the surface waters in their jurisdictions remain healthy and productive, and that water quality standards are met. These criteria are often derived using field measurements that relate nutrient concentrations and other water quality conditions to expected biological responses such as undesirable growth or changes in aquatic plant and animal communities. Ideally, these numeric criteria can be used to accurately “diagnose” ecosystem health and guide management decisions. However, the degree to which numeric nutrient criteria are useful for decision making depends on how accurately they reflect the status or risk of nutrient-related biological impairments. Numeric criteria that have little predictive value are not likely to be useful for managing nutrient concerns. This paper presents information on the role of numeric nutrient criteria as biological health indicators, and the potential benefits of sufficiently accurate criteria for nutrient management. In addition, it describes approaches being proposed or adopted in states such as Florida and Maine to improve the accuracy of numeric criteria and criteria-based decisions. This includes a preference for developing site-specific criteria in cases where sufficient data are available, and the use of nutrient concentration and biological response criteria together in a framework to support designated use attainment decisions. Together with systematic planning during criteria development, the accuracy of field-derived numeric nutrient criteria can be assessed and maximized as a part of an overall effort to manage nutrient water quality concerns. Integr Environ Assess Manag 2014;10:133–137. © 2013 SETAC