bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of common parallel architectures for the execution of the island model and the global parallelization of evolutionary algorithms
Authors: Limmer Steffen , Fey Dietmar
Published: February 2016

Evolutionary algorithms are one of the most popular forms of optimization algorithms. They are comparatively easy to use and were successfully employed for a wide variety of practical applications. However, frequently, it is necessary to execute them in parallel in order to reduce the runtime. There are a number of different approaches for the parallelization of evolutionary algorithms, and various hardware platforms can be used for the parallel execution. However, not every platform is equally suitable for any kind of parallelization of evolutionary algorithms. In addition, it also depends on properties of the concrete optimization problem to be solved and on the used evolutionary algorithm, which platform is best suited for the execution. The present work observes this in detail for two common forms of parallelization of evolutionary algorithms – the island model and the global parallelization – and for four widely used parallel computing platforms – multi‐core CPUs, clusters, graphics cards, and grids. Based on empirical and analytical investigations, it is determined, under which circumstances an architecture is better suited for the execution of a parallel evolutionary algorithm than another (and vice versa). Guidelines are derived that support users of parallel evolutionary algorithms with the choice of an appropriate platform. Copyright © 2016 John Wiley & Sons, Ltd.
Game theoretic modeling of security and trust relationship in cyberspace
Authors: Njilla Laurent Yamen , Pissinou Niki , Makki Kia
Published: February 2016

Today, online network services have evolved as the highest‐emergent medium, enabling various online activities to be lucrative. However, these lucrative activities also bring new forms of privacy threats to the community. In a reliable e‐business service, users should be able to trust the providers of the service to protect their customers' privacy. The service providers should not risk the personal and private information about their customers in cyberspace. There is an economic gain for a business provider when users trust the service provider. Despite those benefits, cyber security concern is the main reason some large organization may go bankrupted. Unfortunately, attackers may attempt to breach a provider's database and expose customers' private information. Therefore, in this paper, we propose a game theoretic framework for security and trust relationship in cyberspace for users, service providers, and attackers. Mathematical proofs and evaluations support our model. Service providers may use the model to see how important and dissuasive against attackers is when investing in cybersecurity. Copyright © 2016 John Wiley & Sons, Ltd.
Cost‐effectiveness of a risk‐based secondary screening programme of type 2 diabetes
Authors: Nagy Balázs , Zsólyom Adriána , Nagyjánosi László , Merész Gergő , Steiner Tamás , Papp Eszter , Dessewffy Zoltán , Jermendy György , Winkler Gábor , Kaló Zoltán , Vokó Zoltán
Published: February 2016

Objective

The objective of this study was to develop a long‐term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk‐based screening programme in a country specific setting.

Methods

The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units.

Results

The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three‐yearly screening gained 0.0229 quality adjusted life years for an additional €83 per person compared with no screening and resulted an incremental cost‐effectiveness ratio of €3630/quality adjusted life years.

Conclusion

From the economic perspective introduction of the 3‐yearly screening programme is justifiable and it provides a good value for money. Copyright © 2016 John Wiley & Sons, Ltd.
Two‐dimensional correlation infrared spectroscopy applied to the identification of ephedrine and pseudoephedrine in illegally adulterated slimming herbal products
Authors: Miao Li , Liu Yan , Li Hao , Qi Yunpeng , Lu Feng
Published: February 2016

Two‐dimensional correlation spectroscopy (2DCOS) was employed for the identification of ephedrine (Ep) and pseudoephedrine (Ps) present in illegally adulterated slimming herbal products (SHPs). Second derivative (SD) spectral pretreatment was used prior to 2DCOS analysis to highlight specific features not readily observable by Fourier transform infrared spectroscopy (FTIR), SD‐FTIR, or original 2DCOS, leading to enhanced resolution and a reduced lower limit of detection (<1% in this study). After examining the power spectra of suspicious SHPs, bands containing characteristic peaks for Ep (701, 747, 1042, 1363, 1375, 1451, 1478 cm‐1etc) and/or Ps (703, 767, 1037, 1375, 1428, 1455, 1590 cm‐1, etc.) were selected to construct synchronous and asynchronous maps for further analysis, while the latter was applied to discriminate positive SHPs adulterated simultaneously with Ep and Ps. The proposed method is simple and economical and has the potential to identify other chemicals in illegally adulterated herbal products. Copyright © 2016 John Wiley & Sons, Ltd.
Fundamental Research on Control Method for Power Conversion Circuit of Wireless In‐Wheel Motor Using Magnetic Resonance Coupling
Authors: GUNJI DAISUKE , IMURA TAKEHIRO , FUJIMOTO HIROSHI
Published: February 2016

The in‐wheel motor (IWM) is the most preferred driving mechanism of electric vehicles for its advantages of vehicle motion control, energy efficiency, and vehicle design flexibility. One of the technical problems of the IWM is the reliability of power and the signal wires. Wireless power transfer technology is the best solution to this problem. In this paper, a bidirectional wireless power transfer circuit using a primary inverter and a secondary converter is proposed. We propose a control method for both the inverter and the converter to stabilize the secondary dc‐link voltage. The proposed method is verified by simulation and experiment using simulated test equipment.
Development of Semicircular Tubular Coreless Linear Motor and Its Motion Control
Authors: OMURA MOTOTSUGU , SHIMONO TOMOYUKI , FUJIMOTO YASUTAKA
Published: February 2016

This paper proposes a semicircular tubular linear synchronous motor called a “circular shaft motor” (CSM). A CSM can realize direct‐drive motion along the circumference of a circle. The design of the CSM is described. A magnetic field analysis was performed for the CSM model. The thrust characteristics of the prototype CSM system were measured in experiments. Angle control and force control were performed to demonstrate the utility of the developed CSM.
Near Infrared Light Triggered Reactive Oxygen Species Responsive Upconversion Nanoplatform for Drug Delivery and Photodynamic Therapy
Authors: Zhang Ting , Lin Huiming , Cui Liru , An Na , Tong Ruihan , Chen Yuhua , Yang Chunyu , Li Xin , Liu Jiuyu , Qu Fengyu
Published: February 2016

Near‐infrared (NIR) light‐sensitive nanocomposites are increasingly receiving attention for their convenient manipulation to obtain on‐demand drug‐release patterns and enhanced therapeutic efficacy. Here, we present a novel strategy based on preparing NaYF4:Yb,Er@NaYF4 upconverting nanoparticles (UCNP) and coating them with a photosensitizer (chlorin e6; Ce6)‐doped mesoporous silica shell (named UCNP@mSiO2/Ce6). The thioketal group, a visible light cleavable linker, was chosen as the “gate” to encapsulate the drug (doxorubicin, DOX) in the mesopore by a simple silane coupling reaction. Upon NIR (980 nm) irradiation, the emitted visible light can excite Ce6 to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). In addition, the ROS generation can also break down the thioketal link to induce the “gate” opening and drug release. The in vitro NIR‐triggered release kinetics were investigated by varying the amount of thioketal graft and irradiation intensity. HeLa cells were used as model cancer cells, and detailed cell experiments further illuminate the fast uptake and NIR‐induced cytotoxicity. More importantly, the synergistic action of chemotherapy and PDT led to enhanced cytotoxicity, which means these nanocomposites have potential applications in cancer therapy.
Multichannel Reaction of α‐Bromo­enones with 1,2‐Diamines: Synthesis of 1,4‐Diazabicyclo[4.1.0]hept‐4‐enes by Reaction with N‐Unsubstituted 1,2‐Diamines
Authors: Muzalevskiy Vasily M. , Rulev Alexander Yu. , Kondrashov Evgeniy V. , Romanov Alexey R. , Ushakov Igor A. , Chertkov Vyacheslav A. , Nenajdenko Valentine G.
Published: February 2016

The reaction of 2‐bromoenones with N‐unsubstituted 1,2‐diamines was studied. An easy access to 1,4‐diazabicyclo[4.1.0]hept‐4‐enes was developed. The multistep mechanism of the reaction is discussed. Final conclusions on the influence of the structure of the starting 2‐bromoenones and 1,2‐diamines on the direction of the reaction are established.
Optimizing a rotor‐stator filter matrix for high‐gradient magnetic separation of functionalized magnetic particles
Authors: Shaikh Yonas S. , Seibert Christian , Schumann Christiane , Ferner Marvin J. , Raddatz Heike , Kampeis Percy
Published: February 2016

The processing of wines with enzymes is a process chain in which losses of biocatalyst are unavoidable. A promising technique for the minimization of these losses and for the reduction of processing time is the high‐gradient magnetic separation in combination with enzymes, which are immobilized onto functionalized magnetic particles. When magnetizable particles are used and magnetic separation is applied to separate these particles from nonmagnetizable particles and solutes, the enzymes can be recycled and used for several production batches. The magnetic filter used in this study had a filter matrix with concentrically stacked circular rotor and stator plates which are arranged in an alternating order. Different geometries of the filter plate notches were examined to optimize the reproducibility of particle retention. In computational fluid dynamic studies, the influence of the notch geometries on the shear rate generation was analyzed for the rinsing procedure. Separation experiments with an optimized geometry of the filter plates were carried out in water and white wine suspensions.
Planar Perovskite Solar Cells using CH3NH3PbI3 Films: A Simple Process Suitable for Large‐Scale Production
Authors: Wang Yangyang , Luo Jiaming , Nie Riming , Deng Xianyu
Published: February 2016

Despite the rapid progress of the power conversion efficiency (PCE) of perovskite solar cells, the reproducibility, stability, and large‐scale production are major challenges. Here, we present a simple and quick solution‐depositing process to achieve high‐quality perovskite films by adding an insulating polymer of polyacrylonitrile (PAN) as a film‐forming additive into the CH3NH3PbI3 solution. With the CH3NH3PbI3:PAN films serving as an active layer, planar heterojunction perovskite solar cells show a PCE of 13.08 % at an area of 0.12 cm2 and 7.32 % at a large area of 1.0 cm2. The PCE loss is only about 40 % from the small‐area to larger‐area devices fabricated by using a solution‐based deposition process. The measurements were performed in air without any device encapsulation. We also used the conjugated polymer poly(3‐hexylthiophene) (P3HT) as the alternative for PAN. The device performance indicates that the conjugated polymer is unsuitable as the additive, which we attribute to the photo‐induced charge transfer between CH3NH3PbI3 and P3HT.
Near‐fault effects on residual displacements of RC structures
Authors: Liossatou Eftychia , Fardis Michael N.
Published: February 2016

Residual displacements of single‐degree‐of‐freedom systems due to ground motions with velocity pulses or fling step displacements are presented as a function of period T and of its ratio to the pulse period Tp. Four hysteretic behaviors are considered: bilinear elastoplastic, stiffness‐degrading with cycling, stiffness‐cum‐strength degrading, with or without pinching. When expressed in terms of T/Tp, peak inelastic and residual displacements due to motions with a pulse or fling appear similar to those due to far‐fault motions, if the response to far‐field records are expressed in terms of the ratio of T to the record's characteristic period. However, as the latter is usually much shorter than the pulse period of motions with fling, the range of periods of interest for common structures becomes a short‐period range under fling motions and exhibits very large amplification of residual and peak inelastic displacements. Similar, but less acute, are the effects of motions with a velocity pulse. Wavelets of different complexity are studied as approximations to near‐fault records. Simple two‐parameter wavelets for fling motions overestimate peak inelastic displacements; those for pulse‐type motions overestimate residual displacements. A more complex four‐parameter wavelet for motions with a velocity pulse predicts overall well residual and peak displacements due to either pulse‐ or fling‐type motions; a hard‐to‐identify parameter of the wavelet impacts little computed residual displacements; another significantly affects them and should be carefully estimated from the record. Even this most successful of wavelets overpredicts residual displacements for the periods of engineering interest. Copyright © 2016 John Wiley & Sons, Ltd.
Local and interannual variations in mercury and cadmium in eggs of eight seabird species of the Sinaloa coast, México
Authors: Ceyca Juan P. , Castillo-Guerrero J. Alfredo , García-Hernández Jaqueline , Fernández Guillermo , Betancourt-Lozano Miguel
Published: February 2016

Mercury (Hg) and cadmium (Cd) concentrations in eggs of 8 seabird species inhabiting 5 coastal ecosystems in Sinaloa, México were determined during 2 breeding seasons (2012 and 2013): blue-footed booby (Sula nebouxii), brown booby (Sula leucogaster), double-crested cormorant (Phalacrocorax auritus), magnificent frigatebird (Fregata magnificens), brown pelican (Pelecanus occidentalis), royal tern (Thalasseus maximus), laughing gull (Leucophaeus atricilla), and Heermann's gull (Larus heermanni). The interspecific differences found in the concentrations of both metals were attributed to the diet and foraging ecology of the species. The highest Hg concentrations were detected in piscivorous species (brown pelican, 0.42 µg/g; brown booby, 0.31 µg/g; blue-footed booby, 0.26 µg/g; and double-crested cormorant, 0.23 µg/g); whereas species with more varied diets presented the highest Cd concentrations (Heermann's gull, 0.31 µg/g; laughing gull, 0.27 µg/g; and magnificent frigatebird, 0.27 µg/g). Cadmium concentrations were significantly greater in 2013 than 2012 for most species, and brown pelican and laughing gull also had higher Hg concentrations in 2013 in Santa María Bay, suggesting a relationship as a result of the changes either in oceanographic conditions or in continental runoff. Mercury concentrations in brown pelican and Cd concentrations in Heermann's gull and laughing gull were above threshold levels for adverse effects on reproduction and survival. Environ Toxicol Chem 2016;35:2330–2338. © 2016 SETAC
Bubble‐based stabilized finite element methods for time‐dependent convection–diffusion–reaction problems
Authors: Sendur A. , Nesliturk A.
Published: February 2016

In this paper, we propose a numerical algorithm for time‐dependent convection–diffusion–reaction problems and compare its performance with the well‐known numerical methods in the literature. Time discretization is performed by using fractional‐step θ‐scheme, while an economical form of the residual‐free bubble method is used for the space discretization. We compare the proposed algorithm with the classical stabilized finite element methods over several benchmark problems for a wide range of problem configurations. The effect of the order in the sequence of discretization (in time and in space) to the quality of the approximation is also investigated. Numerical experiments show the improvement through the proposed algorithm over the classical methods in either cases. Copyright © 2016 John Wiley & Sons, Ltd.
Antidiabetic effects of Mangifera indica Kernel Flour‐supplemented diet in streptozotocin‐induced type 2 diabetes in rats
Authors: Irondi Emmanuel A. , Oboh Ganiyu , Akindahunsi Afolabi A.
Published: February 2016

Our previous report showed that Mangifera indica kernel flour (MIKF) is a rich source of pharmacologically important flavonoids and phenolic acids; and that its methanolic extract inhibits some key enzymes linked to the pathology and complications of type 2 diabetes (T2D) in vitro. Hence, this study evaluated the antidiabetic effects of 10% and 20% MIKF‐supplemented diets in T2D in rats. T2D was induced in rats using a high‐fat diet (HFD), low‐dose streptozotocin (HFD/STZ) model, by feeding the rats with HFD for 2 weeks followed by single dose administration of STZ (40 mg/kg body weight, intraperitoneally). The diabetic rats were later fed the MIKF‐supplemented diets, or administered with metformin (25 mg/kg b.w.) for 21 days; the control rats were fed basal diet during this period. Intake of the MIKF‐supplemented diets resulted in significant (P < 0.05) improvement in the fasting blood glucose, hepatic glycogen, glycosylated hemoglobin, lipid profile, plasma electrolytes, hepatic and pancreatic malonaldehyde, and the liver function markers of the diabetic rats, compared with the diabetic control rats. The ameliorative effect of 20% MIKF‐supplemented was comparable (P > 0.05) with that of metformin administration in the diabetic rats. It is concluded that M. indica kernel flour has antidiabetic effects in T2D rats, and could therefore be a promising nutraceutical therapy for the management of T2D and its associated complications.
Gas and Electric Harmonization Through Technology
Authors: Munson Sylvia
Published: February 2016

Technology is constantly changing the way business is conducted in the energy industry. One of the gauges that must be considered is when to use the latest and greatest technology and when to stick with the tried and true. But even with the tried and true, sometimes something new must be done when other peripheral advances force a forward movement.
Community Solar Is Potential Resolution for Distributed‐Generation Challenges
Authors: Campbell Becky , Mahrer Eran
Published: February 2016

Utilities around the country are experiencing booming interest from customers in distributed solar generation. With this increased interest, utilities are facing unprecedented challenges with distributed‐generation integration and rate reform pressures. In 2015, nearly 1.5 gigawatts of new residential photovoltaic (PV) were installed during the first three‐quarters of the year,1 and Pacific Gas and Electric surpassed 175,000 distributed solar interconnections on its grid.2
Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood
Authors: Yang TienYu Owen , Cairns Benjamin J. , Kroll Mary E. , Reeves Gillian K. , Green Jane , Beral Valerie ,   on behalf of the Million Women Study Collaborators
Published: February 2016

Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17‐1.51, for BMI 35+ vs <22.5 kg/m2), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10–1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.
Change in CD3ζ‐chain expression is an independent predictor of disease status in head and neck cancer patients
Authors: Upreti Deepak , Zhang Man‐li , Bykova Elena , Kung Sam K. P. , Pathak K. A.
Published: February 2016

CD3ζ has emerged as a clinically important immunological marker in head and neck squamous cell carcinoma (HNSCC) with reduced level of expression reported in both tumor infiltrating lymphocytes and peripheral blood lymphocytes. In this prospective study (power = 0.99, α = 0.05), CD3ζ expression was compared in 47 HNSCC patients and 53 controls using standardized flow cytometric method. There was no statistical difference in the percentages of the CD3 ε+ T‐cell subset present in the peripheral blood mononuclear cells of the HNSCC patients and the healthy controls; however, T cells from the HNSCC patients produced a significantly weaker IFN‐γ response in comparison to the healthy controls, when they were stimulated by the recall viral CEF peptide antigen. All patients were followed up for at least 3 years with a median follow‐up of 45 months. Levels of CD3ζ‐chain expression were measured at 117 follow‐up visits at six‐month intervals. Receiver operating characteristic curve identified the optimal cut off as a 12% increase in post treatment CD3ζ‐chain expression from the baseline levels to confirm absence of HNSCC with the area under curve of 0.81 (95% CI = 0.68–0.94) for predicting absence of HNSCC. The specificity, sensitivity and positive predictive value were 81.25% 79.21% and 97.56%, respectively. Three‐year disease specific survival (DSS) was significantly lower (p = 0.007) at 63.2% for patients who showed <12% increase in CD3ζ‐chain level as compared to 96.2% for patients who had ≥12% increase. Our results indicate that the change in CD3ζ‐chain expression from the baseline is an independent predictor of residual and recurrent HNSCC.
NSCLC harboring EGFR exon‐20 insertions after the regulatory C‐helix of kinase domain responds poorly to known EGFR inhibitors
Authors: Yang Mengmeng , Xu Xiaoxi , Cai Jie , Ning Jinying , Wery Jean Pierre , Li Qi‐Xiang
Published: February 2016

Anecdote clinical observations hint that non‐small cell lung cancer (NSCLC) with exon‐20 insertions might respond poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), contrasting to those with classic mutations. Lack of patient‐derived experimental models has been a major hurdle for the discovery of new treatment for the diseases. We established two NSCLC‐PDXs harboring two different exon‐20 insertions, LU0387‐adenocarcinoma (ADC) with a nine‐base insertion at 2319 (H773‐V774insNPH) and LU3075‐squamous cell carcinoma (SCC) with a nine‐base insertion at 2316 (P772‐H773insDNP). Both insertions immediately follow the regulatory C‐helix of the kinase domain. Contrary to the generally good responses to EGFR inhibitors observed in PDXs with classic mutations, both exon‐20 insertions are largely resistant to cetuximab and TKIs in vivo, suggesting fundamental difference from the classic EGFR mutations, consistent with the poor response rate to TKI seen in anecdotal clinic reports. It is worth noting that although responses are generally poor, they differ between the two exon‐20 mutants depending on the type of TKI. In vitro drug sensitivity assays using established primary cell lines from our two PDXs largely confirmed the in vivo data. Our data from patient‐derived experimental models confirmed that exon‐20 insertions in domain immediately following the C‐helix confer poor response to all known EGFR inhibitors, and suggested that these models can be utilized to facilitate the discovery of new therapies targeting NSCLC harboring exon‐20 insertions.
Catalytic Conversion of Furans and Pyrroles to Natural Products and Analogues Utilizing Donor‐Acceptor Substituted Cyclopropanes as Key Intermediates
Authors: Reiser Oliver
Published: February 2016

This review is an account of our work on developing stereoselective cyclopropanations of furans and pyrroles as a facile entry into donor‐acceptor substituted cyclopropanes. The application of these building blocks for the synthesis of paraconic acids, sesquiterpene lactones, pyrrolidinones, and conformationally restricted β‐amino acids is discussed.
Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow‐Derived Mesenchymal Stem Cells
Authors: Kalomoiris Stefanos , Cicchetto Andrew C. , Lakatos Kinga , Nolta Jan A. , Fierro Fernando A.
Published: February 2016

Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over‐expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self‐renewal of MSCs in culture. HMGA2 is a DNA‐binding protein that regulates self‐renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow‐derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let‐7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF‐2, a growth factor commonly used to promote self‐renewal in MSCs, rapidly induces HMGA2 expression in a time‐ and concentration‐dependent manner. The signaling pathway involves FGF‐2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let‐7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over‐expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF‐2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF‐2, and is involved in both proliferation and adipogenesis of MSCs. J. Cell. Biochem. 117: 2128–2137, 2016. © 2016 Wiley Periodicals, Inc.
Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF‐κB‐Regulated Anti‐Apoptosis and p53/PCNA‐ and ATM/ATR‐Chk1/2‐Controlled DNA‐Damage Response Pathways
Authors: Zhao Tuo , Tang Xin , Umeshappa Channakeshava Sokke , Ma Hong , Gao Haijun , Deng Yulin , Freywald Andrew , Xiang Jim
Published: February 2016

Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6‐10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up‐ and down‐regulation of pro‐apoptotic and anti‐apoptotic genes, respectively. Moreover, up‐ and down‐regulation of pro‐apoptotic (Caspases 3, 7, 8) and anti‐apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF‐κB‐p65, which is complemented by the predominant localization of NF‐κB‐p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF‐κB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down‐regulated in cells exposed to SMG, among which down‐regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. In addition, we demonstrate a significant inhibition of molecules involved in the DNA‐damage response, such as p53, PCNA, ATM/ATR, and Chk1/2. Taken together, our work reveals that SMG promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF‐κB‐regulated apoptosis and the p53/PCNA‐ and ATM/ATR‐Chk1/2‐controlled DNA‐damage response pathways. Thus, our investigation provides novel information, which may help us to determine the cause of negative alterations in human physiology occurring at spaceflight environment. J. Cell. Biochem. 117: 2138–2148, 2016. © 2016 Wiley Periodicals, Inc.
Improving B3LYP heats of formation with three‐dimensional molecular descriptors
Authors: Zhou Yuwei , Wu Jianming , Xu Xin
Published: February 2016

In the present work, we propose the X3D method that extends the B3LYP method by correcting its errors on heats of formation of hydrocarbons (HCs) with three‐dimensional (3D) molecular descriptors. Inspired by the widely used Wiener index, these 3D descriptors are developed to improve over the original B3LYP method for a better description of atom‐atom, atom‐bond and bond‐bond interactions. On top of a training set of only 45 species, the X3D method is validated against various sets of different chemistry, displaying an overall near chemical accuracy. In particular, X3D improves over B3LYP, reducing its mean absolute errors from 28.4 to 0.3 kcal/mol for (Set 1) 21 n‐alkanes up to n‐C32H66, from 19.3 to 0.6 kcal/mol for (Set 2) n‐C7H16 and its branched isomers, from 29.5 to 1.6 kcal/mol for (Set 3) 36 polycyclic saturated HCs, from 8.6 to 1.1 kcal/mol for (Set 4) 41 C6H8 isomers of rings, alkenes, alkynes, and cumulenes, from 20.3 to 0.6 kcal/mol for (Set 5) 41 benzene‐based compounds, and 8.1 to 1.3 kcal/mol for (Set 6) 66 radicals, etc. Comparisons with the G4 results are also presented. © 2016 Wiley Periodicals, Inc.
Differential Response of Human Hepatocyte Chromatin to HDAC Inhibitors as a Function of Microenvironmental Glucose Level
Authors: Felisbino Marina Barreto , Alves da Costa Thiago , Gatti Maria Silvia Viccari , Mello Maria Luiza Silveira
Published: February 2016

Diabetes is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion. Recent observations suggest that the complexity of the disease cannot be entirely accounted for genetic predisposition and a compelling argument for an epigenetic component is rapidly emerging. The use of histone deacetylase inhibitor (HDACi) in clinical setting is an emerging area of investigation. In this study, we have aimed to understand and compare the response of hepatocyte chromatin to valproic acid (VPA) and trichostatin A (TSA) treatments under normoglycemic or hyperglycemic conditions to expand our knowledge about the consequences of HDACi treatment in a diabetes cell model. Under normoglycemic conditions, these treatments promoted chromatin remodeling, as assessed by image analysis and H3K9ac and H3K9me2 abundance. Simultaneously, H3K9ac marks shifted to the nuclear periphery accompanied by HP1 dissociation from the heterochromatin and a G1 cell cycle arrest. More striking changes in the cell cycle progression and mitotic ratios required drastic treatment. Under hyperglycemic conditions, high glucose per se promoted chromatin changes similar to those promoted by VPA and TSA. Nonetheless, these results were not intensified in cells treated with HDACis under hyperglycemic conditions. Despite the absence of morphological changes being promoted, HDACi treatment seems to confer a physiological meaning, ameliorating the cellular hyperglycemic state through reduction of glucose production. These observations allow us to conclude that the glucose level to which the hepatocytes are subjected affects how chromatin responds to HDACi and their action under high‐glucose environment might not reflect on chromatin remodeling. J. Cell. Physiol. 231: 2257–2265, 2016. © 2016 Wiley Periodicals, Inc.
Alteration in Phospholipidome Profile of Myoblast H9c2 Cell Line in a Model of Myocardium Starvation and Ischemia
Authors: Sousa Bebiana , Melo Tânia , Campos Ana , Moreira Ana S.P. , Maciel Elisabete , Domingues Pedro , Carvalho Rita Pereira , Rodrigues Teresa Ribeiro , Girão Henrique , Domingues Maria Rosario M.
Published: February 2016

Myocardium infarction is one of the most deathly cardiovascular diseases. It is characterized by myocardium ischemia as a result of nutrients depletion and hypoxia. The cell can respond to this injury by autophagy or apoptosis, which determines the evolution and possible recovery of the myocardium infarction. Lipids play an important role in cardiovascular disease. However reports stating lipidome variations in cardiovascular disease are scarce and the role that lipids play in this pathological condition is not completely understood. The aim of this work was to identify changes in lipid profile of a myoblast H9c2 cell line under starvation and ischemia, to better understand and recognize new biomarkers for myocardial infarction. Lipidomic profile was evaluated by HILIC‐LC‐MS and GC‐MS. Cardiac cells showed alterations in phosphatidylcholines PC (34:1) and PC (36:2), lysophosphatidylcholines lyso PC(16:0), lysoPC(18:1) and lysoPC(18:0), phosphatidylethanolamine PE (34:1), phosphatidylserine PS (36:1), phosphatidylinositol PI (36:2), PI (38:3) and PI (38:5), sphingomyelin SM (34:1) and cardiolipins CL(68:4), CL(72:5) and CL(74:7) in ischemia and/or starvation, in comparison with control. Specific differences observed only in starvation were decrease of SM (34:1) and FA (20:4), and increase of PS (36:1). Differences observed only in ischemia were decrease of PC (36:2), lyso PC (16:0) and FA (18:1) and simultaneous increase of FA (16:0), and FA (18:0). Interestingly, PC (34:1) increased in ischemia and decreased in starvation. In conclusion, our work suggests that lipids are potential markers for evaluation of cell fate, either cell death or recovery, which will be useful to improve diagnosis and prognostic of cardiovascular diseases. J. Cell. Physiol. 231: 2266–2274, 2016. © 2016 Wiley Periodicals, Inc.
Renal sonography in bipolar patients on long‐term lithium treatment
Authors: Jończyk‐Potoczna Katarzyna , Abramowicz Maria , Chłopocka‐Woźniak Maria , Strzelczuk‐Judka Lidia , Michalak Michał , Czekalski Stanisław , Rybakowski Janusz K.
Published: February 2016

Purpose

The aim of the study was to analyze sonographic (US) renal findings in lithium‐treated bipolar patients and to correlate them with renal function.

Methods

Renal US and renal function tests were performed on 120 patients with bipolar disorder. Ninety patients (30 males, 60 females), aged 36–82 years, had received lithium therapy for an average of 16 years, whereas 30 patients (10 males, 20 females), aged 35–85 years, who had never been exposed to lithium, served as controls.

Results

In the lithium‐treated group, patients with macrocysts (22%) had poorer renal function with higher creatinine serum concentrations, lower estimated glomerular filtration rates, and lower urine specific gravity, compared with the patients without macrocysts. The US changes characteristic for lithium nephropathy (punctate hyperechoic foci, microcysts < 2 mm, and increased echogenicity) were seen in three patients. These patients had been treated with lithium for more than 20 years and had impaired renal function. Sixteen percent of patients in the control group had macrocysts; however, no correlation between their presence and impaired renal function was found.

Conclusions

The presence of macrocysts in the kidneys of lithium‐treated bipolar patients is associated with impaired renal function. The US changes characteristic for lithium nephropathy are rare, and in our study, were only found in patients treated with lithium for 20 years or more. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:354–359, 2016
Sonographically detected free appendicolith as a sign of retrocecal perforated appendicitis in a 2‐year‐old child
Authors: Lovrenski Jovan , Jokić Radoica , Varga Ivan
Published: February 2016

Prompt and accurate diagnosis of perforated appendicitis is crucial for proper and timely treatment. The appendix, however, cannot always be identified with sonography (US). We report the case of a 2‐year‐old child with atypical clinical presentation, and US detection of a free appendicolith as a sign of perforated appendicitis, without visualization of the appendix itself. Laparoscopy revealed a retrocecal, gangrenous, perforated appendix with autoamputation, fibrinopurulent peritonitis, and a free appendicolith within the abdominal fluid. US detection of a free appendicolith in a child is a very rare, but unequivocal sign of perforated appendicitis, which should be sought. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:395–398, 2016
Thyroid calcifications: a pictorial essay
Authors: Lacout Alexis , Chevenet Carole , Thariat Juliette , Marcy Pierre Yves
Published: February 2016

Incidental diagnosis of thyroid nodules is very common on adult neck ultrasonography examination. Thyroid calcifications are encountered in benign thyroid nodules and goiters as well as in thyroid malignancy. Depiction and characterization of such calcifications within a thyroid nodule may be a key element in the thyroid nodule diagnosis algorithm. The goal of this paper is to display typical radio‐pathological correlations of various thyroid pathologies of benign and malignant conditions in which the calcification type diagnosis can play a key role in the final diagnosis of the thyroid nodule. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:245–251, 2016
Cardiac troponin in patients hospitalized with acute decompensated heart failure: A systematic review and meta‐analysis
Authors: Yousufuddin Mohammed , Abdalrhim Ahmed D. , Wang Zhen , Murad M. Hassan
Published: February 2016

BACKGROUND

Elevated cardiac troponin (cTn) is often observed in patients with acute decompensated heart failure (ADHF). We assessed the magnitude of association and quality of supporting evidence between cTn and clinically important outcomes in persons hospitalized for ADHF.

METHODS

We searched MEDLINE In‐Process & Other Non‐Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through February 28, 2015. The outcomes analyzed included hospital length of stay (LOS), readmissions, and mortality. Random effects meta‐analysis was used to combine outcomes across studies.

RESULTS

We included 26 clinical studies. A detectable or elevated cTn was associated with increased LOS (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01‐1.10), increased in‐hospital mortality (OR: 2.57; 95% CI: 2.27‐2.91), and a composite of mortality and major adverse events (OR: 1.33; 95% CI: 1.03‐1.71) during hospitalization. ADHF patients with a detectable or elevated cTn were at increased risk for mortality and composite of mortality and readmission over the short term (mortality OR: 2.11; 95% CI: 1.43‐3.12; composite OR: 2.81; 95% CI: 1.60‐4.92), intermediate term (mortality OR: 2.21; 95% CI: 1.46‐3.35; composite OR: 2.30; 95% CI: 1.78‐2.99), and long term (mortality OR: 3.69; 95% CI: 2.64‐5.18; composite OR: 3.49; 95% CI: 2.08‐5.84). The overall confidence in estimates was moderate.

CONCLUSIONS

Among ADHF patients, a detectable or elevated cTn identifies subjects at increased risk for adverse clinical outcomes during acute hospitalization and those at higher risk for postdischarge mortality and composite of readmission and mortality. Journal of Hospital Medicine 2016;11:446–454. 2016 Society of Hospital Medicine
Differential association of STAT3 and HK‐II expression in hepatitis B virus‐ and hepatitis C virus‐related hepatocellular carcinoma
Authors: Li Man , Wang Weihua , Jin Rui , Zhang Tieying , Li Na , Han Qunying , Wei Ping , Liu Zhengwen
Published: February 2016

STAT3 and hexokinase II (HK‐II) are involved in viral infection and carcinogenesis of various cancers including hepatocellular carcinoma (HCC). The roles of STAT3 and HK‐II in hepatitis B virus (HBV)‐ and hepatitis C virus (HCV)‐related HCC remain largely unclear. This study examined STAT3 and HK‐II expression in HBV‐ and HCV‐related HCC, HBV‐related liver fibrosis, and normal control liver by using tissue microarray and immunohistochemical method. Results showed that STAT3 expression in HBV‐related HCC, HCV‐related HCC, and HBV‐related liver fibrosis was significantly higher than in control liver (P < 0.001, P = 0.016, and P = 0.005, respectively) and had no significant differences between these three diseased liver tissues. The HK‐II expression in HBV‐related HCC was significantly higher than that in HCV‐related HCC, HBV‐related liver fibrosis, and control liver (P = 0.007, P = 0.029, and P = 0.008, respectively) but had no significant elevation in and no significant differences between HCV‐related HCC, HBV‐related liver fibrosis, and control liver. The HK‐II expression was significantly correlated to STAT3 expression in HBV‐related HCC (P = 0.022), but no correlation was observed in HCV‐related HCC, HBV‐related liver fibrosis, and control liver. In conclusion, STAT3 expression is upregulated in both HBV‐ and HCV‐related HCC, while HK‐II is predominantly upregulated and correlated to STAT3 in HBV‐related HCC. These differential expression and association may suggest the distinct roles of STAT3 and HK‐II in hepatocarcinogenesis of HBV and HCV infection. Studies are needed to confirm the relationship of STAT3 and HK‐II and to examine the underlying mechanisms. J. Med. Virol. 88:1552–1559, 2016. © 2016 Wiley Periodicals, Inc.
TNF‐α and IL‐10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals
Authors: Aroucha Dayse Celia , Carmo Rodrigo Feliciano , Vasconcelos Luydson Richardson Silva , Lima Raul Emidio , Mendonça Taciana Furtado , Arnez Lucia Elena , Cavalcanti Maria do Socorro Mendonça , Muniz Maria Tereza Cartaxo , Aroucha Marcilio Lins , Siqueira Erika Rabelo , Pereira Luciano Beltrão , Moura Patrícia , Pereira Leila Maria Moreira Beltrão , Coêlho Maria Rosangela
Published: February 2016

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro‐ and anti‐inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin‐10 (IL‐10) and the tumor necrosis factor alpha (TNF‐α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF‐α ‐308 G>A (rs1800629), IL‐10 ‐1082 G>A (rs1800896) and ‐819/‐592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real‐time PCR. Diplotypes associated with low IL‐10 production and the TNF‐α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL‐10 ‐819 (‐592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL‐10 and the TNF‐α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587–1595, 2016. © 2016 Wiley Periodicals, Inc.
A topological approach unveils system invariances and broken symmetries in the brain
Authors: Tozzi Arturo , Peters James F.
Published: February 2016

Symmetries are widespread invariances underscoring countless systems, including the brain. A symmetry break occurs when the symmetry is present at one level of observation but is hidden at another level. In such a general framework, a concept from algebraic topology, namely, the Borsuk‐Ulam theorem (BUT), comes into play and sheds new light on the general mechanisms of nervous symmetries. The BUT tells us that we can find, on ann‐dimensional sphere, a pair of opposite points that have the same encoding on ann– 1 sphere. This mapping makes it possible to describe both antipodal points with a single real‐valued vector on a lower dimensional sphere. Here we argue that this topological approach is useful for the evaluation of hidden nervous symmetries. This means that symmetries can be found when evaluating the brain in a proper dimension, although they disappear (are hidden or broken) when we evaluate the same brain only one dimension lower. In conclusion, we provide a topological methodology for the evaluation of the most general features of brain activity, i.e., the symmetries, cast in a physical/biological fashion that has the potential to be operationalized. © 2016 Wiley Periodicals, Inc.
Molecular mechanisms of biological aging in intervertebral discs
Authors: Vo Nam V. , Hartman Robert A. , Patil Prashanti R. , Risbud Makarand V. , Kletsas Dimitris , Iatridis James C. , Hoyland Judith A. , Le Maitre Christine L. , Sowa Gwendolyn A. , Kang James D.
Published: February 2016

Advanced age is the greatest risk factor for the majority of human ailments, including spine‐related chronic disability and back pain, which stem from age‐associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair‐deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress‐induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age‐related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age‐associated IDD. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1289–1306, 2016.