bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-Transjugular Intrahepatic Portosystemic Shunts (TIPS) Prediction of Post-TIPS Overt Hepatic Encephalopathy: The Critical Flicker Frequency Is More Accurate Than Psychometric Tests
Authors: Berlioux Pierre , Angèle Robic Marie , Poirson Hélène , Métivier Sophie , Otal Philippe , Barret Carine , Lopez Frédéric , Péron Jean Marie , Vinel Jean Pierre , Bureau Christophe
Published: August 2013

Transjugular intrahepatic portosystemic shunts (TIPS) is a second-line treatment because of an increased incidence of overt hepatic encephalopathy (OHE). A better selection of patients to decrease this risk is needed and one promising approach could be the detection of minimal hepatic encephalopathy (MHE). The aim of the present prospective study was to determine whether pre-TIPS minimal hepatic encephalopathy was predictive of post-TIPS OHE and to compare Psychometric Hepatic Encephalopathy Sum Score (PHES) and the Critical Flicker Frequency (CFF) in this setting. From May 2008 to January 2011, 54 consecutive patients treated with TIPS were included. PHES and CFF were performed 1 to 7 days before and after TIPS at months 1, 3, 6, 9, and 12 or until liver transplantation or death. Before TIPS, MHE was detected by PHES and CFF in 33% and 39% of patients, respectively. After the TIPS procedure, 19 patients (35%) experienced a total of 64 episodes of OHE. OHE developed significantly more often in patients for whom an indication for TIPS had been refractory ascites, with a history of OHE or of renal failure, lower hemoglobin level, or MHE as diagnosed by CFF. Post-TIPS OHE was more accurately predicted by CFF than by PHES. Absence of MHE at CFF had a good negative predictive value (91%) for the risk of post-TIPS recurrent OHE, defined as the occurrence of three or more episodes of OHE or of one episode which lasted more than 15 days. The absence of pre-TIPS history of OHE and a CFF value equal to or greater than 39 Hz had a 100% negative predictive value for post-TIPS recurrent OHE.

Conclusion

: Aiming to decrease the rate of post-TIPS HE, the use of CFF could help selecting patients for TIPS. (Hepatology 2014;59:622–629)
Structure-Guided Design Affirms Inhibitors of Hepatitis C Virus p7 as a Viable Class of Antivirals Targeting Virion Release
Authors: Foster Toshana L. , Thompson Gary S. , Kalverda Arnout P. , Kankanala Jayakanth , Bentham Matthew , Wetherill Laura F. , Thompson Joseph , Barker Amy M. , Clarke Dean , Noerenberg Marko , Pearson Arwen R. , Rowlands David J. , Homans Steven W. , Harris Mark , Foster Richard , Griffin Stephen
Published: August 2013

Current interferon-based therapy for hepatitis C virus (HCV) infection is inadequate, prompting a shift toward combinations of direct-acting antivirals (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are in the pipeline yet primarily target only three viral proteins, namely, NS3/4A protease, NS5B polymerase, and NS5A. With concerns growing over resistance, broadening the repertoire for DAA targets is a major priority. Here we describe the complete structure of the HCV p7 protein as a monomeric hairpin, solved using a novel combination of chemical shift and nuclear Overhauser effect (NOE)-based methods. This represents atomic resolution information for a full-length virus-coded ion channel, or “viroporin,” whose essential functions represent a clinically proven class of antiviral target exploited previously for influenza A virus therapy. Specific drug-protein interactions validate an allosteric site on the channel periphery and its relevance is demonstrated by the selection of novel, structurally diverse inhibitory small molecules with nanomolar potency in culture. Hit compounds represent a 10,000-fold improvement over prototypes, suppress rimantadine resistance polymorphisms at submicromolar concentrations, and show activity against other HCV genotypes.

Conclusion

: This proof-of-principle that structure-guided design can lead to drug-like molecules affirms p7 as a much-needed new target in the burgeoning era of HCV DAA. (Hepatology 2014;59:408–422)
Effects of lentivirus‐mediated CREB expression in the dorsolateral striatum: Memory enhancement and evidence for competitive and cooperative interactions with the hippocampus
Authors: Kathirvelu Balachandar , Colombo Paul J.
Published: August 2013

Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus‐mediated expression of the transcription factor CREB (LV‐CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV‐CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV‐CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV‐CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV‐CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV‐CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV‐CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus. © 2013 Wiley Periodicals, Inc.
Selective deficit in spatial memory strategies contrast to intact response strategies in patients with schizophrenia spectrum disorders tested in a virtual navigation task
Authors: Wilkins Leanne K. , Girard Todd A. , Konishi Kyoko , King Matthew , Herdman Katherine A. , King Jelena , Christensen Bruce , Bohbot Veronique D.
Published: August 2013

Spatial memory is impaired among persons with schizophrenia (SCZ). However, different strategies may be used to solve most spatial memory and navigation tasks. This study investigated the hypothesis that participants with schizophrenia‐spectrum disorders (SSD) would demonstrate differential impairment during acquisition and retrieval of target locations when using a hippocampal‐dependent spatial strategy, but not a response strategy, which is more associated with caudate function. Healthy control (CON) and SSD participants were tested using the 4‐on‐8 virtual maze (4/8VM), a virtual navigation task designed to differentiate between participants' use of spatial and response strategies. Consistent with our predictions, SSD participants demonstrated a differential deficit such that those who navigated using a spatial strategy made more errors and took longer to locate targets. In contrast, SSD participants who spontaneously used a response strategy performed as well as CON participants. The differential pattern of spatial‐memory impairment in SSD provides only indirect support for underlying hippocampal dysfunction. These findings emphasize the importance of considering individual strategies when investigating SSD‐related memory and navigation performance. Future cognitive intervention protocols may harness SSD participants' intact ability to navigate using a response strategy and/or train the deficient ability to navigate using a spatial strategy to improve navigation and memory abilities in participants with SSD. © 2013 Wiley Periodicals, Inc.
Synthesis of Monospiro‐2‐amino‐4H‐pyran Derivatives Catalyzed by Propane‐1‐sulfonic Acid‐Modified Magnetic Hydroxyapatite Nanoparticles
Authors: Jalili‐Baleh Leili , Mohammadi Narges , Khoobi Mehdi , Ma'mani Leila , Foroumadi Alireza , Shafiee Abbas
Published: August 2013

Various monospiro‐2‐amino‐4H‐pyran derivatives have been synthesized in high yields (via three‐component coupling of ninhydrin or different isatins with malononitrile and 1,3‐dicarbonyl compounds) in the presence of catalytic amount of propane‐1‐sulfonic acid‐modified magnetic hydroxyapatite nanoparticles in H2O. Due to easy magnetic removal of nanocatalyst and applying of H2O as solvent, this protocol enhanced product purity, and promised economic as well as environmental benefits, exemplifying a waste‐free chemistry. More importantly, the catalyst could be easily recycled for more than five times without loss of activity.
Synthetic Studies Toward (+)‐Spongidepsin
Authors: Venkateswar Reddy Guvvala , Satish Chandra Kumar Rotte , Shankaraiah Gundeti , Suresh Babu Katragadda , Madhusudana Rao Janaswamy
Published: August 2013

A convergent enantiomerically controlled synthetic effort toward (+)‐spongidepsin is reported. The synthesis benefits from the use of readily available and inexpensive starting materials like D‐mannitol and (−)‐β‐citronellene. Key transformations include Evans asymmetric methylation, Mitsunobu esterification, (1H‐benzotriazol‐1‐yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP)‐mediated amide formation for the preparation of a fully functionalized acyclic precursor, and ring‐closing metathesis (RCM).
First Stereoselective Total Synthesis of Oplopandiol
Authors: Kumar Bejjanki Naveen , Venkatesham Akkaladevi , Balraju Kammari , Nagaiah Kommu
Published: August 2013

The first stereoselective synthesis of the naturally occurring conjugated diyne oplopandiol is reported. The pivotal functionalities are derived from CadiotsChodkiewicz cross‐coupling reaction, OhiraBestmann alkynation, asymmetric Noyori reduction, and cis‐olefination reaction
A Transformation of N‐Alkylated Anilines to N‐Aryloxamates
Authors: Zhu Xiao‐He , Zhang Xin , Xin Hong‐Xing , Yan Hong
Published: August 2013

Transformation of N‐alkylated anilines to N‐aryloxamates was studied using ethyl 2‐diazoacetoacetate as an alkylating agent and dirhodium tetraacetate (Rh2(OAc)4) as the catalyst. The general applicability of the reaction as a synthetic method for N‐aryloxamates was studied with a number of substituted N‐alkylated anilines. The results revealed that the oxamate was formed by a radical reaction with molecular O2 and Rh2(OAc)4 as initiator.
One‐Pot Synthesis of 1,4‐Oxathiino[2,3‐b]quinoxalines or ‐pyrazines from 2,3‐Dichloroquinoxaline or ‐pyrazine and 1‐Aryl‐2‐bromoalkan‐1‐ones
Authors: Kobayashi Kazuhiro , Konishi Natsuki , Suzuki Teruhiko , Nakagawa Kazuhiro
Published: August 2013

An efficient one‐pot synthesis of novel heterocyclic derivatives, 2‐aryl‐1,4‐oxathiino[2,3‐b]quinoxalines or ‐pyrazines 5, via the reaction of 2,3‐dichloroquinoxaline or ‐pyrazine with Na2S⋅9 H2O, and subsequent treatment of the resulting 2‐chloro‐3‐sodiosulfanylquinoxaline or ‐pyrazine 2 with 1‐aryl‐2‐bromo‐1‐alkanones and then NaH under mild conditions is described.
Reactions of Acid Chlorides/Ketenes with 2‐Substituted 4,5‐Dihydro‐4,4‐dimethyl‐1,3‐thiazoles: Formation of Penam Derivatives
Authors: Shi Junxing , Linden Anthony , Heimgartner Heinz
Published: August 2013

Addition reactions of acid chlorides with various 2‐substituted 4,5‐dihydro‐4,4‐dimethyl‐5‐(methylsulfanyl)‐1,3‐thiazoles under basic conditions were studied. Two kinds of products were obtained from these additions, β‐lactams and non‐β‐lactam adducts. When the reaction was carried out with 4,5‐dihydro‐1,3‐thiazoles with a Ph substituent at C(2), the reaction proceeded via formal [2+2] cycloaddition and led to the correspoding β‐lactam. On the other hand, acid chlorides and 4,5‐dihydro‐1,3‐thiazoles bearing an α‐H‐atom at the C(2)‐substituent underwent C(α)‐ and/or N‐addition reactions and furnished non‐β‐lactam adducts, i.e., C(α)‐ and/or N‐acylated 1,3‐thiazolidines. The attempted transformations of sulfonyl esters of exo‐6‐hydroxy penams to endo‐6‐azido penams failed, although they were successful with mono‐β‐lactams under the same conditions.
Rainfall–runoff model parameter estimation and uncertainty evaluation on small plots
Authors: Kim Keewook , Whelan Gene , Purucker S. Thomas , Bohrmann Thomas F. , Cyterski Michael J. , Molina Marirosa , Gu Yin , Pachepsky Yakov , Guber Andrey , Franklin Dorcas H.
Published: August 2013

Four seasonal rainfall simulations in 2009 and 2010 were applied to a field containing 36 plots (0.75 × 2 m each), resulting in 144 runoff events. In all simulations, a constant rate of rainfall was applied then halted 60 min after initiation of runoff, with plot‐scale monitoring of runoff every 5 min during that period. Runoff was simulated with the Kinematic Runoff and Erosion/Simulator of Transport with Infiltration and Runoff (KINEROS2/STWIR) field‐scale model, whose hydrodynamics are based on the kinematic wave equation. Because of the non‐linear nature of the model and a highly parameterized model with respect to the available data, several approaches were investigated to upscale nine runoff‐related parameters from a series of small monitored plots to the field scale. Inverse modeling was performed using the model‐independent Parameter ESTimation (PEST) algorithm to individually calibrate the nine KINEROS2/STWIR parameters on 36 plots. The parameters were averaged, and bootstrapping was used to assess uncertainty of the parameters via estimation of confidence intervals (CI). A Monte Carlo simulation using the bootstrap results showed reasonable field‐scale representation of flow rates. Median values of calibrated parameters were within the 95% CI obtained with bootstrapping. The simulated results for the median values associated with the 90% CI flow rates produced similar trends as those exhibited with the observed data, suggesting that median values of the calibrated parameters from the PEST inverse modeling could be used to represent the field scale. Copyright © 2013 John Wiley & Sons, Ltd.
Application and evaluation of a snowmelt runoff model in the Tamor River basin, Eastern Himalaya using a Markov Chain Monte Carlo (MCMC) data assimilation approach
Authors: Panday Prajjwal K. , Williams Christopher A. , Frey Karen E. , Brown Molly E.
Published: August 2013

Previous studies have drawn attention to substantial hydrological changes taking place in mountainous watersheds where hydrology is dominated by cryospheric processes. Modelling is an important tool for understanding these changes but is particularly challenging in mountainous terrain owing to scarcity of ground observations and uncertainty of model parameters across space and time. This study utilizes a Markov Chain Monte Carlo data assimilation approach to examine and evaluate the performance of a conceptual, degree‐day snowmelt runoff model applied in the Tamor River basin in the eastern Nepalese Himalaya. The snowmelt runoff model is calibrated using daily streamflow from 2002 to 2006 with fairly high accuracy (average Nash–Sutcliffe metric ~0.84, annual volume bias < 3%). The Markov Chain Monte Carlo approach constrains the parameters to which the model is most sensitive (e.g. lapse rate and recession coefficient) and maximizes model fit and performance. Model simulated streamflow using an interpolated precipitation data set decreases the fractional contribution from rainfall compared with simulations using observed station precipitation. The average snowmelt contribution to total runoff in the Tamor River basin for the 2002–2006 period is estimated to be 29.7 ± 2.9% (which includes 4.2 ± 0.9% from snowfall that promptly melts), whereas 70.3 ± 2.6% is attributed to contributions from rainfall. On average, the elevation zone in the 4000–5500 m range contributes the most to basin runoff, averaging 56.9 ± 3.6% of all snowmelt input and 28.9 ± 1.1% of all rainfall input to runoff. Model simulated streamflow using an interpolated precipitation data set decreases the fractional contribution from rainfall versus snowmelt compared with simulations using observed station precipitation. Model experiments indicate that the hydrograph itself does not constrain estimates of snowmelt versus rainfall contributions to total outflow but that this derives from the degree‐day melting model. Lastly, we demonstrate that the data assimilation approach is useful for quantifying and reducing uncertainty related to model parameters and thus provides uncertainty bounds on snowmelt and rainfall contributions in such mountainous watersheds. Copyright © 2013 John Wiley & Sons, Ltd.
The usefulness of outcrop analogue air permeameter measurements for analyzing aquifer heterogeneity: quantifying outcrop hydraulic conductivity and its spatial variability
Authors: Rogiers Bart , Beerten Koen , Smeekens Tuur , Mallants Dirk , Gedeon Matej , Huysmans Marijke , Batelaan Okke , Dassargues Alain
Published: August 2013

Saturated hydraulic conductivity (K) is one of the most important parameters determining groundwater flow and contaminant transport in both unsaturated and saturated porous media. Although several well‐established laboratory methods exist for determining K, in situ measurements of this parameter remain very complex and scale dependent. Often, the limited accessibility of subsurface sediments for sampling means an additional impediment to our ability to quantify subsurface K heterogeneity. One potential solution is the use of outcrops as analogues for subsurface sediments.

This paper investigates the use of air permeameter measurements on outcrops of unconsolidated sediments to quantify K and its spatial heterogeneity on a broad range of sediment types. The Neogene aquifer in northern Belgium is used as a case study for this purpose. To characterize the variability in K, 511 small‐scale air permeability measurements were performed on outcrop sediments representative over five of the aquifer's lithostratigraphic units. From these measurements, outcrop‐scale equivalent K tensors were calculated using numerical upscaling techniques. Validation of the air permeameter‐based K values by comparison with laboratory constant head K measurements reveals a correlation of 0.93. Overall, the results indicate that hand‐held air permeameters are very efficient and accurate tools to characterize saturated K, as well as its small‐scale variability and anisotropy on a broad range of unconsolidated sediments. The studied outcrops further provided a qualitative understanding of aquifer hydrostratigraphy and quantitative estimates about K variability at the centimetre‐scale to metre‐scale. Copyright © 2013 John Wiley & Sons, Ltd.
Soil C and N response to changes in winter precipitation in a subalpine forest ecosystem, NW Italy
Authors: Viglietti Davide , Freppaz Michele , Filippa Gianluca , Zanini Ermanno
Published: August 2013

Among the potential effects of climate change on subalpine forest ecosystems during the winter season, the shift in snowline towards higher altitudes and the increase in frequency of rain events on the snowpack are of particular interest. Here, we present the results of a 2‐year field experiment conducted in a forest stand (Larix decidua) in NW Italy at 2020 m a.s.l. From 2009 to 2011, we monitored soil physical characteristics (temperature and moisture), and soil and soil solution chemistry, in particular carbon (C) and nitrogen (N) forms and their change in time, as affected by simulated late snowpack accumulation and rain on snow events. Late snowpack accumulation determined a stronger effect on soil thermal and moisture regimes than rain on snow events. Also soil chemistry was significantly affected by late snowfall simulation. Although microbial biomass C and N were not reduced by soil freezing, soil contents of the more labile dissolved organic carbon and inorganic N increased when the soil was affected by mild/hard freezing. Variations in the soil solution were shifted with respect to those observed in soil, with an increase in N‐NO3− concentrations occurring during spring and summer. This study highlights the potential N loss in subalpine soils under changing environmental conditions driven by a changing climate. Copyright © 2013 John Wiley & Sons, Ltd.
Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients
Authors: Mishra Dhruva K. , Creighton Chad J. , Zhang Yiqun , Gibbons Don L. , Kurie Jonathan M. , Kim Min P.
Published: August 2013

The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (four dimensional, 4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (two‐dimensional, 2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (three‐dimensional, 3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity and cell fate and development. Moreover, expression array analysis of 2D vs. 3D showed 1,006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (vs. 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D vs. 2D correlated with better survival in lung cancer patients with lung cancer. As patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.
Progression of anal high‐grade squamous intraepithelial lesions to invasive anal cancer among HIV‐infected men who have sex with men
Authors: Berry J. Michael , Jay Naomi , Cranston Ross D. , Darragh Teresa M. , Holly Elizabeth A. , Welton Mark L. , Palefsky Joel M.
Published: August 2013

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)‐infected men‐who‐have‐sex‐with‐men (MSM) compared to the general population. Anal high‐grade squamous intraepithelial lesions (HSIL) are common in HIV‐infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV‐infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high‐resolution anoscopy (HRA) and HRA‐guided biopsy. Although treatment for HSIL and follow‐up were recommended, not all were treated and some were lost to follow‐up. Prevalent cancer was found in 66 men. Seventy‐two HIV‐infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy‐proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV‐infected MSM. Early diagnosis is facilitated by careful follow‐up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.
BENEFITS IDENTIFICATION AND EVALUATION OF FLOODWATER UTILIZATION IN BAICHENG REGION, NORTH‐EASTERN CHINA
Authors: Lü Subing , Wang Wenchuan , Xu Shiguo
Published: August 2013

The utilization of small and medium magnitudes of floodwater has remarkable benefits when the supply of conventional water is scarce relative to demand. Conceptually correct and empirically accurate estimates of the benefits of floodwater utilization are essential for rational replenishment of scarce water in the fields of agriculture, industry, households, recreation and so on. This article raises several issues that should be considered in deriving sound evaluation of benefits of floodwater utilization. These include: (i) identifying and defining benefit categories according to flood loss analysis; (ii) establishing a universal benefits indices system and choosing the variable fuzzy pattern recognition model to evaluate the system; (iii) illustrating the benefits of floodwater utilization based on the floodwater utilization practices in the Baicheng Region of northeastern China. An integrated floodwater utilization benefits research framework suggests that a combination of direct economic benefit, eco‐environmental benefit and social benefit can provide complementary insights into sustainable water utilization. Evaluation of the comprehensive benefits of floodwater resources enables decision makers to make more informed choices on floodwater use safely and allocated soundly, in which the full extent of growing demands for these uses is seen in the face of increased scarcity. Copyright © 2013 John Wiley & Sons, Ltd.
Hypoxia preconditioning of mesenchymal stromal cells enhances PC3 cell lymphatic metastasis accompanied by VEGFR‐3/CCR7 activation
Authors: Huang Xin , Su Kunkai , Zhou Limin , Shen Guofang , Dong Qi , Lou Yijia , Zheng Shu
Published: August 2013

Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastases through the secretion of chemokines. MSCs have been reported to home toward the hypoxic tumor microenvironment in vivo. In this study, we investigated prostate cancer PC3 cell behavior under the influence of hypoxia preconditioned MSCs and explored the related mechanism of prostate cancer lymphatic metastases in mice. Transwell assays revealed that VEGF‐C receptor, VEGFR‐3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs. Knock‐in Ccr7 in PC3 cells also improved cell migration in vitro. Furthermore, when PC3 cells were labeled using the hrGfp‐lentiviral vector, and were combined with hypoxia preconditioned MSCs for xenografting, it resulted in an enhancement of lymph node metastases accompanied by up‐regulation of VEGFR‐3 and CCR7 in primary tumors. Both PI3K/Akt/IκBα and JAK2/STAT3 signaling pathways were activated in xenografts in the presence of hypoxia‐preconditioned MSCs. Unexpectedly, the p‐VEGFR‐2/VEGFR‐2 ratio was attenuated accompanied by decreased JAK1 expression, indicating a switching‐off of potential vascular signal within xenografts in the presence of hypoxia‐preconditioned MSCs. Unlike results from other studies, VEGF‐C maintained a stable expression in both conditions, which indicated that hypoxia preconditioning of MSCs did not influence VEGF‐C secretion. Our results provide the new insights into the functional molecular events and signalings influencing prostate tumor metastases, suggesting a hopeful diagnosis and treatment in new approaches. J. Cell. Biochem. 114: 2834–2841, 2013. © 2013 Wiley Periodicals, Inc.
The balance mediated by miRNAs and the heme oxygenase 1 feedback loop contributes to biological effects
Authors: Ma Ning , Xiang Ying , Zhang Yanfen , Zhao Xia , Zhou Lingyun , Gao Xu
Published: August 2013

Heme oxygenase‐1 (HMOX1) is a ubiquitously expressed inducible enzyme that degrades heme to carbon monoxide, biliverdin, and free iron ions. Since 1950, many studies have revealed the role of HMOX1 in reducing the impact of oxidative stress in many types of diseases, such as Alzheimer's disease, heart disease, and the development of tumors. These effects arise as a result of the removal of heme, the biological activities of the products of HMOX1 and the activity of HMOX1 itself. However, HMOX1 has some contradictory effects. The discovery of microRNAs (miRNAs) and their relationship with HMOX1 has provided a new direction for research in this field. Here, we discuss the role of a potential regulatory feedback loop between HMOX1 and miRNAs in pathological processes based on recently published data. We hope to describe a new mechanism for HMOX1 function based on miRNAs to address the contradictory results reported in the literature. J. Cell. Biochem. 114: 2637–2642, 2013. © 2013 Wiley Periodicals, Inc.
FBP1 and p27kip1 Expression After Sciatic Nerve Injury: Implications for Schwann Cells Proliferation and Differentiation
Authors: Yao Li , Cao Jianhua , Sun Huiqing , Guo Aisong , Li Aihong , Ben Zhiyun , Zhang Haiyan , Wang Xinxiu , Ding Zongmei , Yang Xiaojing , Huang Xianting , Ji Yuhong , Zhou Zhengming
Published: August 2013

Far Upstream Element (FUSE) Binding Protein 1 (FBP1), first identified as a single‐stranded DNA (ssDNA) binding protein that binds to the FUSE, could modulate c‐myc mRNA levels and also has been shown to regulate tumor cell proliferation and replication of virus. Typically, FBP1 could active the translation of p27kip1 (p27) and participate in tumor growth. However, the expression and roles of FBP1 in peripheral system lesions and repair are still unknown. In our study, we found that FBP1 protein levels was relatively higher in the normal sciatic nerves, significantly decreased and reached a minimal level at Day 3, and then returned to the normal level at 4 weeks. Spatially, we observed that FBP1 had a major colocation in Schwann cells and FBP1 was connected with Ki‐67 and Oct‐6. In vitro, we detected the decreased level of FBP1 and p27 in the TNF‐α‐induced Schwann cells proliferation model, while increased expression in cAMP‐induced Schwann cells differentiation system. Specially, FBP1‐specific siRNA‐transfected SCs did not show fine and longer morphological change after cAMP treatment and had a decreased motility compared with normal. At 3 days after cAMP treatment and SC/neuron co‐cultures, p27 was transported to cytoplasm to form CDK4/6‐p27 to participate in SCs differentiation. In conclusion, we speculated that FBP1 and p27 were involved in SCs proliferation and the following differentiation in the sciatic nerve after crush by transporting p27 from nucleus to cytoplasm. J. Cell. Biochem. 115: 130–140, 2014. © 2013 Wiley Periodicals, Inc.
The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu‐opioid receptor antagonist GSK1521498 in healthy subjects
Authors: Ziauddeen Hisham , Nathan Pradeep J. , Dodds Chris , Maltby Kay , Miller Sam R. , Waterworth Dawn , Song Kijoung , Warren Liling , Hosking Louise , Zucchetto Mauro , Bush Mark , Johnson Lakshmi Vasist , Sarai Bhopinder , Mogg Karin , Bradley Brendan P. , Richards Duncan B. , Fletcher Paul C. , Bullmore Edward T.
Published: August 2013

The mu‐opioid system has a key role in hedonic and motivational processes critical to substance addiction. However, existing mu‐opioid antagonists have had limited success as anti‐addiction treatments. GSK1521498 is a selective and potent mu‐opioid antagonist being developed for the treatment of overeating and substance addictions. In this study, 28 healthy participants were administered single doses of GSK1521498 20 mg, ethanol 0.5 g/kg body weight, or both in combination, in a double blind placebo controlled four‐way crossover design. The primary objective was to determine the risk of significant adverse pharmacodynamic and pharmacokinetic (PK) interactions. The effects of GSK1521498 on hedonic and consummatory responses to alcohol and the attentional processing of alcohol‐related stimuli, and their modulation by the OPRM1 A118G polymorphism were also explored. GSK1521498 20 mg was well tolerated alone and in combination with ethanol. There were mild transient effects of GSK1521498 on alertness and mood that were greater when it was combined with ethanol. These effects were not of clinical significance. There were no effects of GSK1521498 on reaction time, hedonic or consummatory responses. These findings provide encouraging safety and PK data to support continued development of GSK1521498 for the treatment of alcohol addiction.
Stem cell bioprocessing for regenerative medicine
Authors: Fernandes Tiago G. , Rodrigues Carlos A.V. , Diogo Maria Margarida , Cabral Joaquim M.S.
Published: August 2013

Stem cell‐derived products have the potential to represent promising therapeutic approaches for the treatment of a wide range of conditions. Neurodegenerative diseases, like Parkinson's disease or Huntington's disease, neurological disorders, cardiac failure, and blood disorders, among others, may one day be treated using cellular therapies and regenerative medicine approaches based on stem cells. Furthermore, owing to the potential positive impact in healthcare systems, translation of stem cell technologies into clinical applications will bring a broad social and economic advantage worldwide. However, to fully realize this potential, advanced bioprocessing systems are needed to deliver sufficient numbers of cells in compliance with stringent regulatory landscapes and that can be used in a safe and effective manner. This review presents and summarizes recent advancements in the field of stem cell engineering, in particular novel technologies for the interrogation of stem cell fate and systems for the robust manufacturing of cells under standardized, reproducible and strictly controlled conditions. © 2013 Society of Chemical Industry
PhiC31 integrase‐mediated genomic integration and stable gene expression in the mouse mammary gland after gene electrotransfer
Authors: Luo Yan , Liu Jun , Wang Yongsheng , Su Jianmin , Wu Yongyan , Hu Guangdong , Gao Mingqing , Quan Fusheng , Zhang Yong
Published: August 2013

Background

PhiC31 integrase is capable of conferring long‐term transgene expression in various transfected tissues in vivo. In the present study, we investigated the activity of phiC31 integrase in mouse mammary glands.

Methods

The normal mouse mammary epithelial cell line HC11 was transfected with FuGENE® HD Transfection Reagent (Roche Diagnostics, Shanghai, China). Transfection of the mouse mammary gland in vivo was performed by electrotransfer. Transgene expression was detected by western blotting and an enzyme‐linked immunosorbent assay. Genomic integration and integration at mpsL1 was confirmed by a nested polymerase chain reaction.

Results

An optimal electrotransfer protocol for the lactating mouse mammary gland was attained through investigation of different voltages and pulse durations. PhiC31 integrase mediated site‐specific transgene integration in HC11 cells and the mouse mammary gland. In addition, the site‐specific integration occurred efficiently at the ‘hot spot’ mpsL1. Co‐delivery of PhiC31 integrase enhanced and prolonged transgene expression in the mouse mammary gland.

Conclusions

The results obtained in the present study show that the use of phiC31 integrase is a feasible and efficient method for high and stable transgene expression in the mouse mammary gland. Copyright © 2013 John Wiley & Sons, Ltd.
Occurrence rate of extreme magnetic storms
Authors: Yermolaev Y. I. , Lodkina I. G. , Nikolaeva N. S. , Yermolaev M. Y.
Published: August 2013

We investigate the occurrence rate of magnetic storms at the Earth. During the first part of our study, the standard and integral distribution functions of magnetic storm value (minimal Dst index) for the period 1963–2012 are analyzed and results show that the standard and integral distribution functions have power law tails with indexes γ=−4.4 and −3.4, respectively. During the second part, statistical analysis of occurrence rate of magnetic storms induced by different types of interplanetary drivers is made using OMNI data for the period 1976–2000. Using our catalog of large‐scale types of solar wind streams, we study storms induced by interplanetary coronal mass ejections (ICMEs) (separately magnetic clouds (MCs) and Ejecta) and both types of compressed regions: corotating interaction regions (CIRs) and Sheaths. For these types of drivers, we calculate the integral probabilities of storms with minimum Dst ≤−50, −70, −100, −150, and −200 nT. The highest probability in this interval of Dst is observed for MCs, with the probabilities for other drivers being 3–10 times lower. Extrapolation of these results to extreme storms shows that a magnetic storm as large as the Carrington storm in 1859 with Dst=−1760 nT is observed on the Earth with frequency not higher than one event during ∼500 years.
Global seismic tomography with sparsity constraints: Comparison with smoothing and damping regularization
Authors: Charléty Jean , Voronin Sergey , Nolet Guust , Loris Ignace , Simons Frederik J. , Sigloch Karin , Daubechies Ingrid C.
Published: August 2013

We present a realistic application of an inversion scheme for global seismic tomography that uses as prior information the sparsity of a solution, defined as having few nonzero coefficients under the action of a linear transformation. In this paper, the sparsifying transform is a wavelet transform. We use an accelerated iterative soft‐thresholding algorithm for a regularization strategy, which produces sparse models in the wavelet domain. The approach and scheme we present may be of use for preserving sharp edges in a tomographic reconstruction and minimizing the number of features in the solution warranted by the data. The method is tested on a data set of time delays for finite‐frequency tomography using the USArray network, the first application in global seismic tomography to real data. The approach presented should also be suitable for other imaging problems. From a comparison with a more traditional inversion using damping and smoothing constraints, we show that (1) we generally retrieve similar features, (2) fewer nonzero coefficients under a properly chosen representation (such as wavelets) are needed to explain the data at the same level of root‐mean‐square misfit, (3) the model is sparse or compressible in the wavelet domain, and (4) we do not need to construct a heterogeneous mesh to capture the available resolution.
Estimation of extreme sea levels along the Bangladesh coast due to storm surge and sea level rise using EEMD and EVA
Authors: Lee Han Soo
Published: August 2013

Extreme sea levels due to storm surge and future sea level rise (SLR) in the year 2050 are estimated using ensemble empirical mode decomposition (EEMD) and extreme value analysis (EVA) based on long‐term sea level records from Hiron Point (HP) on the coast of western Bangladesh. EEMD is an adaptive method that can detrend the nonlinear trend and separate the tidal motions from the original sea level records to reconstruct storm surge levels at HP. The reconstructed storm surge levels are then applied to EVA to obtain the extreme storm surges in the target return periods at a 95% confidence interval (CI). The 30, 50, and 100 year return levels at HP obtained by EVA are 1.59, 1.66, and 1.75 m. The SLR trend obtained from EEMD is 4.46 mm/yr over April 1990 to March 2009, which is larger than the recent altimetry‐based global rate of 3.3 ± 0.4 mm/yr over the period from 1993 to 2007. The resulting SLR in 2050 is estimated as 0.34 m. Therefore, the extreme sea level in 2050 due to SLR and the storm surge at a 100 year return level would be 2.09 m (95% CI from 1.91 to 2.48 m). The SLR depends not only on changes in the mass and volume of sea water but also on other factors, such as local subsidence, river discharge, sediment and the effects of vegetation. The residual nonlinear trend of SLR obtained from EEMD can be regarded as an adaptive sea level after considering those factors and their nonlinearity.
Stepped‐to‐dart leaders preceding lightning return strokes
Authors: Stolzenburg Maribeth , Marshall Thomas C. , Karunarathne Sumedhe , Karunarathna Nadeeka , Warner Tom A. , Orville Richard E.
Published: August 2013

Using time‐correlated high‐speed video and electric field change data, three cases are described in which dart leaders toward ground are immediately preceded by stepped leaders that find and use previously used channels. These “stepped‐to‐dart leaders” occur in three natural negative ground flashes. Prior to the stepped‐to‐dart connection, the leaders have characteristics of stepped leaders, including average two‐dimensional speeds of 1.6–2.7 × 105 m s−1 (visible from 5.5, 3.4, and 0.9 km altitude). After the connection, they behave as dart (or dart‐stepped) leaders, with larger amplitude E‐change pulses and faster average speeds of 3.4–7.8 × 106 m s−1. Connection altitudes are 3.32, 1.57, and 0.75 km. Immediately after the connection, there is a brief lighting in a short part of the prior return stroke channel. Luminosity travels up the stepped leader path after the connection, while the dart leader proceeds toward ground. In two cases, all the strokes subsequent to the stepped‐to‐dart stroke follow the visible portion of its channel. The other case has two subsequent strokes which do not reuse any portion of the stepped‐to‐dart channel. For the other 12 strokes in these flashes, stepped leader average speeds range from 1.7 to 3.0 × 105 m s−1, and dart leader average speeds are 0.82 to 16.67 × 106 m s−1. Overall, the return stroke waveforms give reasonable indication of the type of leader that preceded the stroke. Stepped‐to‐dart leaders are apparently rare in optical data, occurring in about 1% of subsequent strokes and 2.5% of flashes.
Satellite‐derived estimates of ultrafine particle concentrations over eastern North America
Authors: Crippa Paola , Spracklen Dominick , Pryor S. C.
Published: August 2013

High concentrations of ultrafine particles (UFP, i.e., particles with diameter < 100 nm) impact both human health and Earth's climate. Recent innovations in remote sensing technologies and data retrievals offer the potential for predicting UFP concentrations based on data from satellite‐borne instrumentation. Herein we present a physically based statistical algorithm to estimate UFP concentrations across eastern North America using remotely sensed aerosol optical depth, Ångstrom exponent, ultraviolet solar radiation flux, and ammonia and sulfur dioxide concentrations. The proposed algorithm is built and independently evaluated using an array of in situ observations. The algorithm is able to capture up to 60% of the variability in daily measured UFP number concentrations at a regionally representative reference site and is thus applied to generate seasonal UFP concentration estimates across eastern North America. The resulting UFP concentrations are cross‐evaluated with simulations from a global aerosol microphysics model. There is a negative bias in the model output relative to the satellite‐driven proxy, which is largest (up to 76%) in summer and may be due to overestimation of UFP from the satellite‐based algorithm derived herein, due to the higher availability of remote sensing data in clear‐sky conditions or uncertainty in the model simulation of new particle formation. Nevertheless, the model and algorithm indicate similar spatial and seasonal variability (spatial correlation coefficients of 0.10 to 0.56), indicating the value of the satellite‐based UFP proxy in global and regional model evaluation exercises and in efforts to identify regions where future in situ data collection should be prioritized.
Enhanced Deep Blue aerosol retrieval algorithm: The second generation
Authors: Hsu N. C. , Jeong M.‐J. , Bettenhausen C. , Sayer A. M. , Hansell R. , Seftor C. S. , Huang J. , Tsay S.‐C.
Published: August 2013

The aerosol products retrieved using the Moderate Resolution Imaging Spectroradiometer (MODIS) collection 5.1 Deep Blue algorithm have provided useful information about aerosol properties over bright‐reflecting land surfaces, such as desert, semiarid, and urban regions. However, many components of the C5.1 retrieval algorithm needed to be improved; for example, the use of a static surface database to estimate surface reflectances. This is particularly important over regions of mixed vegetated and nonvegetated surfaces, which may undergo strong seasonal changes in land cover. In order to address this issue, we develop a hybrid approach, which takes advantage of the combination of precalculated surface reflectance database and normalized difference vegetation index in determining the surface reflectance for aerosol retrievals. As a result, the spatial coverage of aerosol data generated by the enhanced Deep Blue algorithm has been extended from the arid and semiarid regions to the entire land areas. In this paper, the changes made in the enhanced Deep Blue algorithm regarding the surface reflectance estimation, aerosol model selection, and cloud screening schemes for producing the MODIS collection 6 aerosol products are discussed. A similar approach has also been applied to the algorithm that generates the Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) Deep Blue products. Based upon our preliminary results of comparing the enhanced Deep Blue aerosol products with the Aerosol Robotic Network (AERONET) measurements, the expected error of the Deep Blue aerosol optical thickness (AOT) is estimated to be better than 0.05 + 20%. Using 10 AERONET sites with long‐term time series, 79% of the best quality Deep Blue AOT values are found to fall within this expected error.
Multiplatform analysis of the radiative effects and heating rates for an intense dust storm on 21 June 2007
Authors: Naeger Aaron R. , Christopher Sundar A. , Johnson Ben T.
Published: August 2013

Dust radiative effects and atmospheric heating rates are investigated for a Saharan dust storm on 21 June 2007 using a combination of multiple satellite data sets and ground and aircraft observations as input into a delta‐four stream radiative transfer model (RTM). This combines the strengths of the Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observations and CloudSat satellites and in situ aircraft data to characterize the vertical structure of the dust layers (5 km in height with optical depths between 1.5 and 2.0) and underlying low‐level water clouds. These observations were used, along with Aerosol Robotic Network retrievals of aerosol optical properties, as input to the RTM to assess the surface, atmosphere, and top of atmosphere (TOA) shortwave aerosol radiative effects (SWAREs). Our results show that the dust TOA SWARE per unit aerosol optical depth was −56 W m−2 in cloud‐free conditions over ocean and +74 W m−2 where the dust overlay low‐level clouds, and show heating rates greater than 10 K/d. Additional case studies also confirm the results of the 21 June case. This study shows the importance of identifying clouds beneath dust as they can have a significant impact on the radiative effects of dust, and hence assessments of the role of dust aerosol on the energy budget and climate.