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Conversion of mechanical forces, vibrations and sound which have energy in the range of milli- to tens of watts (also referred to as "small kinetic energies" in this paper) into electricity has received global attention owing to the potential in powering electronic devices. However, most of the small kinetic energy generators can only generate electric power below 1 mu W/cm(3). As a result, an energy storage device is required to accumulate the energy generated until it reaches a sufficient level. Herein, we report the exceptionally-high acoustoelectric conversion ability of randomly-orientated electrospun poly(vinylidenefluoride-co-trifluoroethylene) nanofiber nonwoven webs. The optimized device under sound is able to generate peak voltage and current of 14.5 V and 28.5 mu A with a volume power density output of 306.5 mu W/cm(3) (5.9 mW/cm(3) based on nanofiber web thickness). Without accumulation in any energy storage unit, the electricity generated by the nanofiber device is sufficient to light up tens of commercial LEDs, run electrochemical reactions and protect metals from corrosion. Such a novel acoustoelectric generator may offer an effective solution to recycling noise pollution into usable electricity.

Intergeneric hybridization is an important strategy to introgress alien genes into common wheat for its improvement. But presence of cross ability barrier mechanism regulated by Kr1 gene played a major destructive role for hybridization than other reported genes. In order to know the underlying molecular mechanism and to dissect out this barrier, a new annealing system, ACP (anneling control primer) system was used in chromosome 5B (containing Kr1 gene) specific Recombinant Inbred Line (RIL) population. Two differentially expressed fragments for Kr1 gene was identified, cloned and sequenced. Further the expression was confirmed by northern blotting analysis. Sequence analysis of the resulted clones revealed classes of putative genes, including stress responsive and signal transduction.

Objective: To unravel the interplay between HIV-1 and its host cell, the effect of HIV-1 infection on cellular gene expression was investigated. Methods: HIV-1(SF33)-infected and uninfected H9 T cells were screened by differential display and RNase protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)-infected P4-CCR5 HeLa cells, which were also examined after PDS5A siRNA knockdown in regard to HIV-1 replication by quantitative RT-PCR, p24 ELISA and LTR-driven beta-galactosidase expression. The PDS5A knockdown effect on cellular gene expressions was studied by microarray analysis. PDS5A tissue expression was determined by Northern blotting. Results: Regulator of cohesion maintenance, homolog A (PDS5A) was found to be down-regulated by HIV-1. When PDS5A was suppressed by siRNA, HIV-1 replication was unaffected. PDS5A was found to be highly expressed in skeletal muscle tissue, and to lesser degrees in pancreas, heart, placenta, lung, kidney, liver and brain. Microarray analysis of PDS5A knockdown revealed 91 differential gene products over-representing cell cycle, transport and protein stability regulation, including 4 genes (PP2A, RANTES, PCAF, TCF7L2) previously reported to interact with HIV-1. Conclusion: The data show a downregulation of proliferation-associated host gene PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication. Copyright (C) 2011 S. Karger AG, Basel

Powder coatings have been receiving attention because they are environmentally friendly. They do not contain solvents in their composition, and their components have decorative and corrosion-protection functions, among many others. However, the presence of polymers in their composition increases the risk of combustion in adverse situations. In this context, this study aims to develop and characterize acrylic-based powder paints with the addition of 2 wt % and 4 wt % montmorillonite clays (MMT) as Cloisite 30B (MMT-30B) and Cloisite 15A (MTT-15A), employed as flame retardants. The characterization of the coatings was carried out by thermogravimetric analysis (TGA), X-ray diffraction, and scanning electron microscopy. After application of the coatings on carbon steel substrates, flammability tests were performed. The coatings with 2 wt % MMT-30B showed overall better results, especially in the flammability tests. Flames spread less on these coatings than on the other systems. However, when the surface and bottom temperatures were analyzed by the cone calorimeter test, the samples prepared with 4 wt % MMT-15A were considered safer to be applied in fire scenarios. (c) 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45031.

Purpose/Background: The aim of this study was to evaluate the effects of quetiapine XR and lithium on actigraphy-measured circadian parameters in patients with bipolar II depression. Methods/Procedures: This was an 8-week, open-label, prospective, randomized comparative study. The assessments included the 17-item Hamilton Depression Rating Scale score and actigraphic measures concerning the previous 7 days, collected at each visit (weeks 0 [baseline], 1, 2, 4, 6, and 8); the actigraphic data were analyzed with a cosinor analysis. Findings/Results: Medication, time, and the interaction between medication and time were significantly associated with acrophase for the entire group (Ps = 0.003, 0.020, and 0.042, respectively). More specifically, acrophase was significantly delayed at weeks 1 and 6 (Ps = 0.004 and 0.039, respectively) in the quetiapine XR group. The F statistics significantly increased over time for the entire group (P < 0.001), and there was a significant increase in F statistics on weeks 4 and 6 in the quetiapine XR group (Ps = 0.016 and 0.020, respectively) and on weeks 4 and 8 in the lithium group (Ps = 0.001 and 0.016, respectively). In addition, scores on the 17-item Hamilton Depression Rating Scale were significantly associated with the F statistics during 8 weeks for the entire group (P = 0.008). Implications/Conclusions: Both quetiapine XR and lithium affected several circadian parameters, including peak activity time and robustness of circadian rhythm, but exerted different effects on acrophase in patients with bipolar II depression. In particular, clinical depressive symptoms were associated with robustness of circadian rhythm during the course of the 8-week treatment.

Actinobacteria are Gram-positive bacteria commonly found in soil, freshwater and marine ecosystems. In this investigation, bias in codon usages of ninety actinobacterial genomes was analyzed by estimating different indices of codon bias such as Nc (effective number of codons), SCUO (synonymous codon usage order), RSCU (relative synonymous codon usage), as well as sequence patterns of codon contexts. The results revealed several characteristic features of codon usage in Actinobacteria, as follows: 1) C- or G-ending codons are used frequently in comparison with A- and U ending codons; 2) there is a direct relationship of GC content with use of specific amino acids such as alanine, proline and glycine; 3) there is an inverse relationship between GC content and Nc estimates, 4) there is low SCUO value (<0.5) for most genes; and 5) GCC-GCC, GCC-GGC, GCC-GAG and CUC-GAC are the frequent context sequences among codons. This study highlights the fact that: 1) in Actinobacteria, extreme GC content and codon bias are driven by mutation rather than natural selection; (2) traits like aerobicity are associated with effective natural selection and therefore low GC content and low codon bias, demonstrating the role of both mutational bias and translational selection in shaping the habitat and phenotype of actinobacterial species. (C) 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Mirror neurons (MNs) are a fascinating class of cells originally discovered in the ventral premotor cortex (PMv) and, subsequently, in the inferior parietal lobule (IPL) of the macaque, which become active during both the execution and observation of actions. In this review, I will first highlight the mounting evidence indicating that mirroring others' actions engages a broad system of reciprocally connected cortical areas, which extends well beyond the classical IPL-PMv circuit and might even include subcortical regions such as the basal ganglia. Then, I will present the most recent findings supporting the idea that the observation of one's own actions, which might play a role in the ontogenetic origin and tuning of MNs, retains a particular relevance within the adult MN system. Finally, I will propose that both cortical and subcortical mechanisms do exist to decouple MN activity from the motor output, in order to render it exploitable for high-order perceptual, cognitive, and even social functions. The findings reviewed here provide an original framework for envisaging the main challenges and experimental directions of future neurophysiological and neuroanatomical studies of the monkey MN system.

In this paper a new framework is introduced to develop a coupled active and reactive market in distribution networks. Distributed energy resources (DERs) such as synchronous machine-based distributed generations and wind turbines offer their active and reactive powers to the proposed market. For the considered DERs, multicomponent reactive power bidding structures are introduced based on their capability curves. Also, the hourly speed variations of wind turbines are considered in the proposed model. A distribution company buys active and reactive powers from a wholesale market and sells them via this market. The demand side is active, and responsive loads or aggregators can participate in the market using a demand bidding/buyback program. The objective function of the proposed market is to minimize the active and reactive power costs of DERs and distribution companies, the penalty cost of CO2 emission, and the cost of running a demand bidding/buyback program. The effectiveness of the proposed method is examined on a 22-bus 20-kV radial distribution test system.

A highly reconfigurable merged analog baseband (MABB) with not only tunable bandwidth (BW), gain, and order but also reconfigurable power, noise, and linearity is proposed for multistandard integrated wireless receivers in this brief. The MABB could arrange the total gain to different stages for noise and linearity tradeoffs by introducing the merged biquad topology. To save power, the operational amplifier (Opamp) for the proposed MABB can reduce the GBW, as long as it meets the GBW requirement for different BW, gain, and order. A flexible power-efficient high-GBW Opamp with an adaptive common-mode bias circuit is also proposed for the eighth-order active-RC MABB. The proposed MABB covers a cutoff frequency range from 200 kHz to 20 MHz, whereas the gain could be tuned between 0 and 72 dB. The proposed highly reconfigurable MABB is suitable for multistandard integrated wireless receivers.

With the development of integrated circuits, the fully integrated continuous time filter has been focused widely. A Nth-order universal filter based on Current Feedback Operational Amplifier (CFOA) is proposed. Compared with available circuits, the proposed circuit using less components (2n CFOAs, n capacitors, and 3n resistors) can realize the universal filter functions without changing circuit configuration, and the operating frequency of proposed filter circuit is at least 10 MHz. All of capacitors in proposed circuit are grounded, this is another benefit from integration point of view. PSPICE simulations have been carried out using 0.18 mu m CMOS technology, and sensitivity analysis of proposed Nth-order low-pass filter circuit is completed. (C) 2015 Elsevier GmbH. All rights reserved.

This paper presents different state feedback approaches of finite control set model predictive control (FCS-MPC) applied to a grid-connected voltage-source converter (VSC) with an LCL filter. Besides converter-side current feedback, two multivariable control approaches and line-side current control are introduced and compared based on theoretical and experimental evaluation. As the LCL filter introduces an additional resonance frequency to the system, the use of different active damping (AD) methods in combination with FCS-MPC is discussed. Furthermore, practical control implementation issues are discussed. The presented methods reveal the great potential, high dynamic performance, and flexibility of FCS-MPC, enabling multivariable control as well as both reduced switching losses and low harmonic current distortion at the same time. Eventually, the feasibility of the theoretical control concepts is shown in a laboratory environment.

Capacitor current feedback active damping is extensively used in grid-connected converters with an LCL filter. However, systems tends to become unstable when the digital control delay is taken into account, especially in low switching frequencies. This paper discusses this issue by deriving a discrete model with a digital control delay and by presenting the stable region of an active damping loop from high to low switching frequencies. In order to overcome the disadvantage of capacitor current feedback active damping, this paper proposes a modified approach using grid current and converter current for feedback. This can expand the stable region and provide sufficient active damping whether in high or low switching frequencies. By applying the modified approach, the active damping loop can be simplified from fourth-order into second-order, and the design of the grid current loop can be simplified. The modified approach can work well when the grid impedance varies. Both the active damping performance and the dynamic performance of the current loop are verified by simulations and experimental results.

The high-power grid-connected inverters with LCL filters have been widely used. Current control plays a key role in the grid-connected inverter control system. To cope with the inherent resonance of the LCL filter, active damping (AD) methods are usually employed. However, the AD performance is impaired by control delays which are introduced in the digital control implementation process. Besides, the lag phase due to control delays limits the system bandwidth and stability margin. The effects of control delays are more noteworthy in the high-power grid-connected inverter due to its low switching frequency. This paper investigates the current control strategy based on multisampling for the high-power grid-connected inverter with the LCL filter. First, the multisampled AD scheme is studied, which can reduce control delays effectively and improve AD performance. Besides, the multisampled control without additional damping whether passive or active is researched. Through the inverter-side current feedback, the system can realize single-current-loop control based on multisampling. Thus, the control system is simplified and it can be stable, and achieve better dynamic performance. Finally, experimental results show that the proposed control schemes are effective.

Resonant poles of LCL filters may challenge the entire system stability especially in digital-controlled pulse width modulation (PWM) inverters. In order to tackle the resonance issues, many active damping solutions have been reported. For instance, a notch filter can be employed to damp the resonance, where the notch frequency should be aligned exactly to the resonant frequency of the LCL filter. However, parameter variations of the LCL filter as well as the time delay appearing in digital control systems will induce resonance drifting, and thus break this alignment, possibly deteriorating the original damping. In this paper, the effectiveness of the notch filter-based active damping is first explored, considering the drifts of the resonant frequency. It is revealed that when the resonant frequency drifts away from its nominal value, the phase lead or lag introduced by the notch filter may make itself fail to damp the resonance. Specifically, the phase lag can make the current control stable despite of the resonant frequency drifting, when the grid current is fed back. In contrast, in the case of an inverter current feedback control, the influence of the phase lead or lag on the active damping is dependent on the actual resonant frequency. Accordingly, in this paper, the notch frequency is designed away from the nominal resonant frequency to tolerate the resonance drifting, being the proposed robust active damping. Simulations and experiments performed on a 2.2-kW three-phase grid-connected PWM inverter verify the effectiveness of the proposed design for robust active damping using digital notch filters.

Control of the LCL-type three-phase grid-connected converter is difficult due to high resonance peak of the LCL filter. Active damping is the state-of-the-art solution to this problem, but the damping performance will be affected by the inherent time delay of digital control, especially for high-power low switching frequency applications. Based on a discrete-time stability analysis of an LCL-type converter with capacitor-current-feedback active damping, a simple and effective time delay compensation method, which is based on area equalization concept, is proposed. The method can reduce the negative impact of the computation delay significantly. It has the potential to serve as a general solution to time delay compensation of a digitally controlled PWM converter. The validity of the proposed method is proved by experimental results.

The wind power generation techniques are continuing to develop and increasing numbers of doubly fed induction generator (DFIG)-based wind power systems are connecting to the on-shore and off-shore grids, local standalone weak networks, and microgrid applications. The impedances of the weak networks are too large to be neglected and require careful attention. Due to the impedance interaction between the weak network and the DFIG system, both subsynchronous resonance (SSR) and high-frequency resonance (HFR) may occur when the DFIG system is connected to the series or parallel compensated weak network. This paper will discuss the SSR and the HFR phenomena based on the impedance modeling of the DFIG system and the weak networks, and the cause of these two resonances will be explained in details. The following factors will be discussed in this paper: 1) transformer configuration; 2) different power scale of DFIG system with different parameters; 3) L or LCL filter adopted in the grid side converter (GSC); 4) rotor speed; 5) current closed-loop controller parameters; and 6) digital control delay. On the basis of the analysis, active damping strategies for HFR using virtual impedance concept will be proposed.

Energy storage systems (ESSs) are generally planned based on the active power. While, reactive power is another important aspect of the ESSs that has not been adequately addressed and discussed. Moreover, ESSs are often managed individually, but coordinated planning on the ESSs and distributed generators (DGs) may result in more suitable outcomes. In order to address these issues, a coordinated ESS and DG planning is presented in this paper. In the proposed planning, the place and capacity of the ESSs and DGs are determined at the same time. The active and reactive powers are included in the planning for both the ESSs and DGs. In other words, the optimal active and reactive capacities are denoted for both the ESSs and DGs on the network. The proposed coordinated ESS and DG planning is carried out on a radial distribution network under deregulated electricity market. Objective function of the proposed planning is to maximize the profit of distribution company (DISCO) subject to the secure operation of the network. The planning is expressed as a nonlinear, mixed integer optimization problem and solved by advanced PSO as a strong Meta-heuristic optimization technique. Simulation results demonstrate the great impacts of the proposed planning on the network. The results demonstrate the priority of the proposed coordinated DG and ESS planning compared to the individual ESS planning. Additionally, it is verified that considering reactive power of the DGs and ESSs changes the results of the planning and provides more realistic and reasonable outputs. The proposed planning significantly increases DISCO profit while guarantees the safe operation of the network through satisfying several security constraints.

In this paper we present an analysis of the voltage amplifier needed for double differential (DD) sEMG measurements and a novel, very simple circuit for implementing DD active electrodes. The three-input amplifier that standalone DD active electrodes require is inherently different from a differential amplifier, and general knowledge about its design is scarce in the literature. First, the figures of merit of the amplifier are defined through a decomposition of its input signal into three orthogonal modes. This analysis reveals a mode containing EMG crosstalk components that the DD electrode should reject. Then, the effect of finite input impedance is analyzed. Because there are three terminals, minimum bounds for interference rejection ratios due to electrode and input impedance unbalances with two degrees of freedom are obtained. Finally, a novel circuit design is presented, including only a quadruple operational amplifier and a few passive components. This design is nearly as simple as the branched electrode and much simpler than the three instrumentation amplifier design, while providing robust EMG crosstalk rejection and better input impedance using unity gain buffers for each electrode input. The interference rejection limits of this input stage are analyzed. An easily replicable implementation of the proposed circuit is described, together with a parameter design guideline to adjust it to specific needs. The electrode is compared with the established alternatives, and sample sEMG signals are obtained, acquired on different body locations with dry contacts, successfully rejecting interference sources.

The performance of some Fourier transform based fundamental current detection algorithms is evaluated and compared in this paper. Some difficult conditions are imposed by a load which draws a highly distorted current with a slight fluctuation, i. e. with non-equal semi-periods. The implemented algorithms are Recursive Discrete Fourier Transform (RDFT), Discrete Fourier Transform (DFT) implemented through a Finite Impulse Response (FIR) filter and respectively the Fast Fourier Transform (FFT) with Butterfly operation and radix-2 decimation in time (DIT). A digital signal processor (DSP) based solution is used for real-time implementation, namely a dSPACE 1103 controller development board. MATLAB/Simulink software is used for the design of the algorithms because it provides specialized tools and blocks. For the performance comparison one used criteria like total harmonic distortion (THD) and settling time of detected fundamental current and also the run time for the DSP. This study may be useful as a guide for engineers in selecting the suitable Fourier transform based control algorithm for active power filters or other grid-synchronized equipments which are operating in difficult load conditions.

A high-efficiency, high-power-density buffer architecture is proposed for power pulsation decoupling in power conversion between dc and single-phase ac. We present an active decoupling solution that yields improved efficiency and reduced circuit complexity compared to existing solutions. In the proposed architecture, the main energy storage capacitor is connected in series with an active buffer converter across the dc bus. The series-stacked capacitor blocks the majority of the dc bus voltage to reduce the voltage stress on the buffer converter, such that fast, low-voltage transistors can be employed for the buffer converter. Moreover, the series capacitor provides the majority of the power pulsation decoupling through a wide voltage swing, and the buffer converter only needs to process a small fraction of the total power of the entire architecture, allowing a very small active circuit volume and very high system efficiency. The circuit operation and design constraints are analyzed in detail. In the proposed buffer architecture, the series stacking of a nearly lossless capacitor and a lossy converter presents a challenge of capacitor voltage balancing and power loss compensation. We propose a control scheme exploiting the small ripple in the bus voltage and dc input current to compensate for the power loss in the buffer converter while maintaining the voltage balance. Light-load techniques are also introduced to ensure that the buffer architecture meets strict ripple requirements while providing sufficient loss compensation. A 2-kW hardware prototype based on low-voltage GaN switches has been built to demonstrate the performance of the proposed solution. A power density of 25W/cm(3) (410 W/in(3)) by rectangular box volume and an efficiency above 98.9% across a wide load range has been experimentally verified.

A power divider/combiner circuit, which simultaneously achieves wide bandwidth, flat gain characteristics, and bidirectional operation, is proposed for multichannel broadband system applications. The proposed circuit utilizes cascode-based bidirectional amplifier cores, which steer the operation modes between a divider and a combiner depending on the control input, and a two-stage distributed-amplifier topology with artificial transmission lines. Implemented in a 130-nm silicon-germanium BiCMOS technology platform, the proposed divider/combiner provides the advantage of seamless integration with digital control blocks. The power divider/combiner exhibits the flat in-band gain of 9 dB and the operational bandwidth of 2-22 GHz, which covers S-, C-, X-, and Ku-bands. In addition, it shows the amplitude imbalance of 0.8 dB, the phase imbalance of 3.5 degrees, the port-to-port isolation of 22 dB, the output 1-dB compression point of 3 dBm, and good impedance matching under 100-mW dc power consumption.

Equivalently implementing a generalized memristor by using common components and then making a nonlinear circuit with a reliable property, are conducive to experimentally exhibit the nonlinear phenomena of the memristive chaotic circuit and show practical applications in generating chaotic signals. Firstly, based on a memristive diode bridge circuit, a new first-order actively generalized memristor emulator is constructed with no grounded restriction and ease to realize. The mathematical model of the emulator is established and its fingerprints are analyzed by the pinched hysteresis loops with different sinusoidal voltage stimuli. The results verified by experimental measurements indicate that the emulator uses only one operational amplifier and nine elementary electronic circuit elements and is an active voltage-controlled generalized memristor. Secondly, by parallelly connecting the proposed emulator to a capacitor and then linearly coupling with an RC bridge oscillator, a memristor based chaotic circuit without any inductance element is constructed. The dynamical model of the inductorless memristive chaotic circuit is established and the phase portraits of the chaotic attractor with typical circuit parameters are obtained numerically. The dissipativity, equilibrium points, and stabilities are derived, which indicate that in the phase space of the inductorless memristive chaotic circuit there exists a dissipative area where are distributed two unstable nonzero saddle-foci and a non-dissipative area containing an unstable origin saddle point. Furthermore, by utilizing the bifurcation diagram, Lyapunov exponent spectra, and phase portraits, the dynamical behaviors of the inductorless memristive chaotic circuit are investigated. Results show that with the evolution of the parameter value of the coupling resistor, the complex nonlinear phenomena of the coexisting bifurcation modes and coexisting attractors under two different initial conditions of the state variables can be found in the inductorless memristive chaotic circuit. Finally, a prototype circuit with the same circuit parameters for numerical simulations is developed, from which it can be seen that the prototype circuit has a simple circuit structure and is inexpensive and easy to practically fabricate with common components. Results of both the experimental measurements and the numerical simulations are consistent, verifying the validity of the theoretical analyses.

Transformation of research in all biological fields necessitates the design, analysis and, interpretation of large data sets. Preparing students with the requisite skills in experimental design, statistical analysis, and interpretation, and mathematical reasoning will require both curricular reform and faculty who are willing and able to integrate mathematical and statistical concepts into their life science courses. A new Faculty Learning Community (FLC) was constituted each year for four years to assist in the transformation of the life sciences curriculum and faculty at a large, Midwestern research university. Participants were interviewed after participation and surveyed before and after participation to assess the impact of the FLC on their attitudes toward teaching, perceived pedagogical skills, and planned teaching practice. Overall, the FLC had a meaningful positive impact on participants' attitudes toward teaching, knowledge about teaching, and perceived pedagogical skills. Interestingly, confidence for viewing the classroom as a site for research about teaching declined. Implications for the creation and development of FLCs for science faculty are discussed. (C) 2016 by The International Union of Biochemistry and Molecular Biology

An active matrix organic light emitting diode (AMOLED) display driver IC, enabling real-time thin-film transistor (TFT) nonuniformity compensation, is presented with a hybrid driving method to satisfy fast driving speed, high TFT current accuracy, and a high aperture ratio. The proposed hybrid column-driver IC drives a mobile UHD (3840 x 2160) AMOLED panel, with one horizontal time of 7.7 mu s at a scan frequency of 60 Hz, simultaneously senses the TFT current for back-end TFT variation compensation. Due to external compensation, a simple 3T1C pixel circuit is employed in each pixel. Accurate current sensing and high panel noise immunity is guaranteed by a proposed current-sensing circuit. By reusing the hybrid column-driver circuitries, the driver embodies an 8 bit current-mode ADC to measure OLED V-I transfer characteristic for OLED luminance-degradation compensation. Measurement results show that the hybrid driving method reduces the maximum current error between two emulated TFTs with a 60 mV threshold voltage difference under 1 gray-level error of 0.94 gray level (37 nA) in 8 bit gray scales from 12.82 gray level (501 nA). The circuit-reused current-mode ADC achieves 0.56 LSB DNL and 0.75 LSB INL.

\There are many factors that affect the performance of active power filter, which is a key factor for command current tracking control. Aiming at the deficiency of traditional PR controller, this paper puts forward an improved PR controller-vector resonant controller. The controller has the advantages of stronger anti-interference ability and greater gain at the resonance point, and it can improve the accuracy of harmonic compensation in the current compensation control. In this paper, the digital controller in the digital control system has been given a detailed design. Finally, the experimental results show that the control strategy can further reduce the harmonic content and improve the compensation accuracy.

This paper presents a power electronic converter used to redistribute the power among the phases in unbalanced power systems, which is supposed to be designed based on the involved degree of unbalance. A bidirectional converter is chosen for this purpose, whose modeling is presented in the dq0 system. This solution can be considered as part of a unified control system, where conventional active power filters may be solely responsible for compensating harmonics and/or the tuning of passive filters becomes easier, with consequent reduction in involved costs in a decentralized approach. The adopted control strategy is implemented in digital signal processor TMS320F2812, while experimental results obtained from an experimental prototype rated at 17.86 kVA are properly discussed considering that the converter is placed at the secondary side of a transformer supplying three distinct single-phase loads. It is effectively shown that the converter is able to balance the currents in the transformer phases, thus leading to the suppression of the neutral current.

This paper reports a source follower-based active RC filter topology for RF front-ends in wideband systems. In the proposed active RC filter, the noise figure and bandwidth are improved through adopting the proposed sub-1 Omega Z(out) source follower, which replaces the conventional operational amplifier-based unity gain buffer and through simply changing its location in the filter. Applying the proposed scheme to the conventional Sallen-Key filter also improves the stopband rejection performance. Furthermore, the proposed filter topology ultimately suppresses the DC offset voltage and flicker noise of the unity gain buffer, which is the only active circuit in the filter. The proposed biquad filter is implemented in 0.18 mu m CMOS and the measurements exhibit >26 dBm IIP3, +12 dBm input P-1dB, and <15 dB noise figure over 50-450 MHz of a 6 bit tunable frequency range. The proposed biquad filter consumes 14 mA from a 1.8 V supply and the chip occupies 1000x500 mu m(2).

Recently, we have reported on a compact microcontroller-based unit developed to accurately synchronize excimer laser pulses (Mingesz et al. 2012 Fluct. Noise Lett. 11, 1240007 (doi:10.1142/S021947751240007X)). We have shown that dithering based on random jitter noise plus pseudorandom numbers can be used in the digital control system to radically reduce the long-term drift of the laser pulse from the trigger and to improve the accuracy of the synchronization. In this update paper, we present our new experimental results obtained by the use of the delay-controller unit to tune the timing of a KrF excimer laser as an addition to our previous numerical simulation results. The hardware was interfaced to the laser using optical signal paths in order to reduce sensitivity to electromagnetic interference and the control algorithm tested by simulations was applied in the experiments. We have found that the system is able to reduce the delay uncertainty very close to the theoretical limit and performs well in real applications. The simple, compact and flexible system is universal enough to also be used in various multidisciplinary applications.

The current-mode first-order allpass filter (APP) using only the active elements has been studied in the present paper. The proposed circuit comprises two operational transconductance amplifiers (OTAs) and one operational amplifier (OA) which is suitable to future development into an integrated circuit. The pole frequency and phase response can be electronically adjusted with changing the dc bias currents of OTAs. The APF has high output impedance, which is easy to cascade in high-order filter or drive load without using a buffering device. The current-mode quadrature oscillator is included to show the usability of the proposed filter. The results of PSPICE simulation are accordant with the theoretical analysis.

An 8th-order Cheybshev-II ladder active-RC BPF was fabricated in a 40 nm CMOS low-leakage digital process. A new technique to design for zero capacitance spread (ZCS) is reported to enable the application of integrator frequency compensation (IFC). Combined with wideband op-amps employing a current-reusing, split-path feed-forward compensation (FFC) technique, significant power savings is achieved in a standard 40 nm CMOS process. The BPF measures a center frequency (CF) of 85-225 MHz and four programmable bandwidth-to-center frequency (BW/CF) ratios of 5%-40%. Both the CF and BW/CF ratio are digitally programmable. It also measures a maximum in-band IIP3 of 31 dBm at 0 dB gain and a maximum in-band frequency-response deviation of 0.2 dB while consuming 33 mA from a 1.5 V supply.

Aims: Activin E is a newly identified member of the transforming growth factor-beta superfamily. To assess the role of activin E in glucose/energy metabolism, we investigated the transcriptional regulation of activin E in the liver. Main methods: Northern blotting, Western blotting, quantitative real-time polymerase chain reaction (PCR), reporter assays and chromatin immunoprecipitation assays were used in this study. Key findings: Insulin up-regulated activin E expression at the mRNA and protein level in HepG2 cells. Reporter assays revealed that the putative, functional, promoter sequence of human activin E gene was responsible for the effect of insulin. Mutational analysis of the promoter revealed that CCAAT/enhancer-binding proteins (C/EBPs) play a key role in regulating activin E expression and in the stimulatory effect of insulin on activin E transcription. Chromatin immunoprecipitation assays revealed that the C/EBPs can bind to the activin E promoter in HepG2 cells. The expression of activin E mRNA was up-regulated in the liver of diet-induced obese mice. Significance: These observations suggest that activin E plays a pathophysiological role in glucose metabolism. (C) 2009 Elsevier Inc. All rights reserved.

Background and purpose: Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. Methods: Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). Results: The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 2.4 years (UH, 2.8 +/- 3.0; LH, 1.5 +/- 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients (P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). Conclusions: We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia.

This paper presents the A-Diakoptics methodology (Diakoptics based on actors) for the high performance simulation of microgrids. Microgrids are clusters of loads and microsources that operate within a single controllable system, which provides electricity and heat to its local area even if they get separated from the distribution system. Several commercial solutions are addressing this topic using numerous methods; however, to keep the computing time required to solve the system when the size of the system grows represents a major challenge. In this paper, this challenge is addressed by separating the distribution grid in independent subnetworks. Then, for the computational implementation, each subnetwork is assigned to an independent solver using the actor model. As a result, the solution algorithm is composed of multiple parallel and concurrent solvers. These exchange information using high-speed communication interfaces for reducing the computational burden without losing accuracy. A-Diakoptics is an advanced algorithm that combines existing methods for simulating large distribution systems; these methods are upgraded to make them suitable for parallel processing and to cover the basic needs for the simulation of smart grid applications.

This paper presents a digital control technique to achieve valley switching in a bidirectional flyback converter used to drive a dielectric electroactive polymer-based capacitive incremental actuator. This paper also provides the design of a low input voltage (24 V) and variable high output voltage (0-2.5 kV) bidirectional dc-dc flyback converter for driving a capacitive incremental actuator. The incremental actuator consists of three electrically isolated-mechanically connected capacitive actuators. It requires three high-voltage (HV) (2-2.5 kV) bidirectional dc-dc converters to accomplish the incremental motion by charging and discharging the capacitive actuators. The bidirectional flyback converter employs a digital controller to improve the efficiency and charge/discharge speed using the valley switching technique during both charge and discharge processes, without the need to sense signals on the output HV side. Experimental results verifying the bidirectional operation of a HV flyback converter are presented using a 3-kV polypropylene-film capacitor as the load. The energy-loss distributions of the converter are presented when 4- and 4.5-kV HV MOSFETs are used on HV side. The flyback prototype with a 4 kV MOSFET demonstrated 89% charge energy efficiency to charge the capacitive load from 0 V to 2.5 kV, and 84% discharge energy efficiency to discharge it from 2.5 kV to 0 V.

The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.

Background: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation: A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 degrees C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm(3), 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient's four limbs. MRI acquired after 3 weeks showed that the previously reported alterations were no longer present. Conclusion: This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM.

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acutephase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapyunresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients.

Objective and design Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. Materials Acute kidney injury in mice was induced by cisplatin. Treatments Mice were administered with DEX 25 mu g/kg or atipamezole 250 mu g/kg (once a day, for 3 days) after cisplatin treatment. Methods The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80(+) macrophages, CD3(+) T cells, and NF-kappa B were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction. Results DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-kappa B activation and decreased expression of TNF-alpha, IL-1 beta, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to alpha(2) adrenoceptor-dependent pathway. Conclusion We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.

Background: Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf(+/+)). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1(+/-)). Methods: Three groups of 25 +/- 5-week-old healthy male mice (Wt Igf(+/+)) were included in the protocol: untreated controls (Wt). Controls that received CCl4 (Wt + CCl4) and Wt + CCl4 were treated subcutaneously with IGF-1 (2 mu g/100 g body weight/day) for 10 days (Wt + CCl4 + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1(+/-)) groups were studied: untreated Hz, Hz + CCl4, and Hz + CCl4 + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean +/- SEM. Results: An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl4 + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl4. Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. Conclusions: IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver damage, could be a feasible therapeutic option.

Adenoviruses cause a variety of diseases that range from mild to fatal in vulnerable patients. Its evolution occurs as a process of selection pressure; for example, genetic recombination generates intermediate strains that can be more infectious or pathogenic than parental strains. This study sought to determine the diversity of circulating adenoviruses in Paraguayan children less than 5 years of age hospitalized with acute lower respiratory infection, by using molecular biology and bioinformatics tools, though amplification of penton, hexon and fiber genes in 26 samples of nasopharyngeal aspirates. It was demonstrated the circulation of three species: B (4/26), C (21/26), and D (1/26), as well as recombination events corresponding to the HAdV-D isolate, with at least three different genotypes (D49, D9 y D15). The HAdV-D are associated with gastrointestinal or ocular diseases, and less commonly with respiratory infections. Recently, however, it has been reported changes in behavior of these viruses due to recombination, allowing them to expand their host cell repertoire. These data extend the knowledge about the genetic diversity of HAdV in Paraguay and strongly support the importance of genomic analysis using bioinformatics tools in epidemiological surveillance of emerging recombinant strains of HAdV.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. While survival rates for ALL have improved, central nervous system (CNS) relapse remains a significant cause of treatment failure and treatment-related morbidity. Accordingly, there is a need to identify more efficacious and less toxic CNS-directed leukemia therapies. Extensive research has demonstrated a critical role of the bone marrow (BM) microenvironment in leukemia development, maintenance, and chemoresistance. Moreover, therapies to disrupt mechanisms of BM microenvironment-mediated leukemia survival and chemoresistance represent new, promising approaches to cancer therapy. However, in direct contrast to the extensive knowledge of the BM microenvironment, the unique attributes of the CNS microenvironment that serve to make it a leukemia reservoir are not yet elucidated. Recent work has begun to define both the mechanisms by which leukemia cells migrate into the CNS and how components of the CNS influence leukemia biology to enhance survival, chemoresistance, and ultimately relapse. In addition to providing new insight into CNS relapse and leukemia biology, this area of investigation will potentially identify targetable mechanisms of leukemia chemoresistance and self-renewal unique to the CNS environment that will enhance both the durability and quality of the cure for ALL patients.

RNA-sequencing of the patient's bone marrow detected fusion transcripts in which the coding sequence of the FAM53B gene (from 10q26) was fused to a genomic sequence (from 19q13) that mapped upstream of the SLC7A10 locus. Reverse transcription-polymerase chain reaction together with Sanger sequencing verified the presence of this fusion transcript. The FAM53B fusion transcript is not expected to produce any chimeric protein. However, it may code for a truncated FAM53B protein consisting of the first 302 amino acids of FAM53B together with amino acids from the 19q13 sequence. Functionally, the truncated FAM53B would be similar to the protein encoded by the FAM53B sequence with accession no. BC031654.1 (FAM53B protein accession no. AAH31654.1). Furthermore, the truncated protein contains the entire conserved domain of the FAM53 protein family. The chromosome aberration t(10;19)(q26;q13) detected in this study was previously reported in a single case of ALL, in which it was also the sole karyotypic change. Both patients entered complete hematological and cytogenetic remission following treatment.

Purpose ETV6/RUNX1(+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. Materials and Methods Sixty-three patients were diagnosed with ETV6/RUNX1(+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETI/6/RUNX1(+) fusion, and the presence of additional cytogenetic abnormalities. Results The 5-year event-free survival was 84.1 +/- 4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9 4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5 +/- 6.9%. Conclusion ETV6/RUNX1(+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end of remission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

IntroductionThe translocation t(12;21)(p13;q22) resulting in the fusion gene ETV6-RUNX1, is the most frequent gene fusion in childhood B lymphoblastic leukemia. In the Nordic Society of Paediatric Haematology and Oncology ALL-2008 treatment protocol, treatment stratification in B-lineage ALL is based on results of minimal residual disease (MRD) analysis with fluorescence-activated cell sorting (FACS). In this study, we determined whether RT-qPCR of the ETV6-RUNX1 fusion transcript can be a reliable alternative for MRD analysis. MethodsSeventy-eight bone marrow samples from 29 children at diagnosis and day 15, 29, and 78 during treatment were analyzed for MRD with FACS and with quantitative reverse transcription polymerase chain reaction (RT-qPCR). Fusion transcript MRD was defined as the ETV6-RUNX1/GUSB ratio at the follow-up time point (day 15/29/78) divided with the ETV6-RUNX1/GUSB ratio at diagnosis (%). ResultsMRD analysis with FACS and with RT-qPCR of ETV6-RUNX1 fusion transcript showed strong correlation. All cases showed concordant results at the treatment stratifying time points day 29 and day 78, when comparing the two methods with a cutoff set to 0.1%. ConclusionRT-qPCR is a valuable addition and could also be an alternative to FACS in cases where FACS is not achievable for MRD analysis.

Glucocorticoids (GCs) induce apoptosis in lymphoid lineage cells and are therefore used in the therapy of acute lymphoblastic leukemia (ALL) and related malignancies. MicroRNAs (miRNAs) and the related mirtrons are similar to 22 nucleotide RNAs derived from polymerase-II transcripts and implicated in the control of essential biological functions, including apoptosis. Whether GCs regulate miRNA-encoding transcription units is unknown. We investigated miRNA/mirtron expression and GC regulation in 8 leukemia/lymphoma in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time reverse transcription (RT)-PCR and northern blotting to detect mature miRNAs and/or their precursors. We found that mature miRNA regulations can be inferred from expression data of their host genes. Although a simple miRNA-initiated canonical pathway to GC-induced apoptosis or cell cycle arrest did not emerge, we identified several miRNAs/mirtrons that were regulated by GC in patients and cell lines, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing miR15 similar to 16 clusters. In an in vitro model, overexpression of miR15b similar to 16 mimics increased and silencing by miR15b similar to 16 inhibitors decreased GC sensitivity. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context-dependent manner.

Treatment of acute myelogenous leukemia (AML) over the past four decades remains mostly unchanged and the prognosis for the majority of patients remains poor. Most of the significant advances that have been observed are in defining cytogenetic abnormalities, as well as the genetic and epigenetic profiles of AML patients. While new cytogenetic and genetic aberrations such as the FLT3-ITD and NPM1 mutations are able to guide prognosis for the majority of patients with AML, outcomes are still dismal and relapse rates remain high. It is thought that relapse in AML is in part driven by minimal residual disease (MRD) that remains in the patient following treatment. Thus, there is a need for sensitive and objective methodology for MRD detection. Methodologies such as multiparameter flow cytometry (MFC), quantitative real-time polymerase chain reaction (RQ-PCR), digital PCR (dPCR), or next-generation sequencing (NGS) are being employed to evaluate their utility in MRD assessment. In this review, we will provide an overview of AML and the clinical utility of MRD measurement. We will discuss optimal timing to MRD measurement, the different approaches that are available, and efforts in the standardization across laboratories.

The mammalian target of rapamycin (mTOR) has recently been implicated in leukaemic cell growth, tumour-associated angiogenesis and expression of vascular endothelial growth factor (VEGF). We examined whether mTOR plays a role as regulator of growth and VEGF-expression in acute myeloid leukaemia (AML). Three mTOR-targeting drugs, rapamycin, everolimus (RAD001) and CCI-779, were applied. The effects of these drugs on growth, survival, apoptosis and VEGF expression in primary AML cells and various AML cell lines were examined. Growth of AML cells and AML-derived cell lines was assessed by (3)H-thymidine incorporation, survival was examined by light- and electron microscopy, by Tunel assay and by AnnexinV-staining, and the expression of VEGF by Northern blotting, RT-PCR and ELISA. Rapamycin was found to counteract growth in the AML cell lines U937 and KG1a as well as in primary AML cells in 14/18 patients examined. The effects of rapamycin and its derivatives were dose-dependent (IC(50): 10 pM-100 nM). It was also found that exposure to mTOR-targeting drugs resulted in apoptosis and in decreased expression of VEGF in leukaemic cells. mTOR-targeting drugs exert antileukaemic effects on AML cells in vitro through multiple actions, including direct inhibition of proliferation, induction of apoptosis and suppression of VEGF. Based on this study and other studies, mTOR can be regarded as a potential drug target in AML.

Background/Purpose: Mutations in the tet oncogene family member 2 gene (TET2) are frequently found in adult patients with acute myeloid leukemia (AML). Reports of TET2 mutations in children are limited. We assessed the prevalence of TET2 mutations in Taiwanese children with AML and analyzed their prognosis. Methods: Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled at the National Taiwan University Hospital. The analysis for TET2 mutations was performed using direct sequencing. Clinical characteristics and overall survival (OS) were compared between patients with and without TET2 alterations. Results: Intronic and missense mutations were identified. No nonsense or frameshift mutations were observed. Two putative disease-causing missense mutations (S609C and A1865G) were identified in one patient. We estimated the prevalence of TET2 mutations in the current patient population to be 1.4%. The most common polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L (6%). Patients with polymorphism I1762V had an increased 10-year survival rate compared with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square test; OS was not different when examined using the Kaplan-Meier method (p = 0.104). Conclusion: The prevalence of TET2 mutations in children with AML compared with adults with AML was lower and less complex. Patient prognosis associated with TET2 mutations in children requires further investigation. Copyright (C) 2015, Formosan Medical Association. Published by Elsevier Taiwan LLC.

Several studies have reported previously that acute myeloid leukemia (AML) may express WT1 detected by RT-PCR and/or Northern blotting. The diagnostic utility of WT1 expression in AML using immunohistochemistry has not been reported previously. Paraffin-embedded tissue sections from 55 AML, 12 acute lymphoblastic leukemia (ALL), and 10 normal bone marrow specimens were immunostained for WT1 (anti-N terminus antibody). 22/55 AML cases (40%) demonstrated nuclear immunopositivity for WT1, including 20/47 bone marrow trephines and 2/4 granulocytic sarcomas. All the ALL and normal bone marrow specimens were negative. A significant proportion of AML expresses nuclear immunostaining for WT1, a finding that has only been described previously in Wilms' tumor and desmoplastic small round cell tumor. This finding is important for the correct interpretation of immunohistochemical findings in the diagnosis of "small round cell'' tumors of childhood, especially in cases of extramedullary deposits of AML, in which traditional myeloid markers may be negative.

The karyotype is critical for the evaluation of acute myeloid leukemia (AML) at diagnosis. Cytogenetic abnormalities detected in AML are one of the most powerful independent prognostic factors. It impacts on the choice of treatment in clinical trials. All chromosomes can be targeted, common chromosomal abnormalities are recurrent and may be associated with a cytological well-defined type. In 40% of the cases, the karyotype is normal and must be associated with molecular biology studies that can refine the prognosis. The usefulness of the karyotype is more limited during the follow-up of the patient due to its limited sensitivity, but it is still useful in the clinical management of relapse. Since 2001, the WHO (World Health Organization) classification of hematological malignancies integrates cytogenetic data in the classification of AML. Karyotype is therefore mandatory in the diagnosis of AML.

Purpose: To correlate visual acuity outcomes and clinical features with quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN). Methods: Retrospective, consecutive case series. Results: In total, 14 eyes of 13 patients were diagnosed with ARN, based on the American Uveitis Society criteria, and were followed for a mean of 324.5 days (median 250.5 days, SD +/- 214 days). Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of 14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%) and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 x 10(6)/mL (median 2.10 x 10(6)/mL, range: 0-5.60 x 10(7)/mL). Eyes with quantitative PCR DNA copy number of 5.0 x 10(6)/mL (n = 6 eyes) had worse baseline visual acuity (logMAR 1.48 +/- 0.71 vs 0.94 +/- 0.76, p = 0.196) and final visual acuity (logMAR 2.10 +/- 0.60 vs 0.82 +/- 0.81, p = 0.007) compared with patients with a DNA copy number <5.0 x 10(6)/mL (n = 8 eyes). Patients with a DNA copy number of 5.0 x 10(6)/mL were more likely to have at least 5 clock hours of retinitis on funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p = 0.08). Conclusions: Quantitative DNA copy number of 5.0 x 10(6)/mL is associated with more extensive retinitis, worse visual acuity, and development of retinal detachment in patients with acute retinal necrosis.

This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis on the Mendelian randomization design. The Mendelian randomization approach uses genetic variants associated with lifelong high plasma YKL-40 levels that are largely unconfounded and not prone to reverse causation. Thus, the approach mimics a controlled double-blind randomized trial, but it uses genetic variants rather than a drug and placebo, and like a blinded trial, it allows inference about causality. Moreover, the review also covers background on the molecular biology and functions of YKL-40, YKL-40 levels in healthy individuals and reference range, and the role of YKL-40 as a biomarker of cardiovascular and alcoholic liver disease. YKL-40 is a plasma protein named after its three N-terminal amino acids, Y (tyrosine), K (lysine) and L (leucine), and its molecular weight of 40kDa. It is produced by local inflammatory cells in inflamed tissues, such as lipid-laden macrophages inside the vessel wall and perhaps also hepatic stellate cells. Observational studies show that plasma YKL-40 levels are elevated in patients with cardiovascular and liver disease and are associated with disease severity and prognosis. Furthermore, elevated plasma YKL-40 levels in apparently healthy individuals are associated with a 2-fold increased risk of future ischemic stroke and venous thromboembolism, but not with myocardial infarction, suggesting that YKL-40 could play a role in the formation of embolisms rather than atherosclerosis per se. Further, elevated YKL-40 levels combined with excessive alcohol consumption are associated with 10-years risk of alcoholic liver cirrhosis of up to 7%, suggesting that YKL-40 can be used as a strong noninvasive marker of predicting alcoholic liver cirrhosis. Importantly, in Mendelian randomization studies, genetically elevated plasma YKL-40 levels were not associated with risk of cardiovascular and alcoholic liver disease, thus suggesting that plasma YKL-40 does not play a causal role in the development of these diseases. Despite this, plasma YKL-40 levels may play a role in disease progression after diagnosis, and inhibition of YKL-40 activity might be a novel therapy in some cardiovascular and liver diseases.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Introduction: The recent approval of adalimumab (trade name Humira, Abbvie inc.) by the FDA for the treatment of noninfectious intermediate, posterior and panuveitis marks the first on label' non-corticosteroid drug available to ophthalmologists. Immunomodulatory (IMT) and biologic agents have long been shown to be effective in inducing remission of chronic uveitis but have remained as orphan drugs due to lack of financial incentive and perceived need. Areas covered: Here we provide detail into the background and use of adalimumab for uveitic patients. Topics include pharmacology, therapeutic indications and usage, dosage, drug safety, physician monitoring, side effects and adverse events. Expert opinion: We see the approval of adalimumab for uveitis as an important milestone improving upon the accepted standards of care for patients with this severe, sight threatening disease. We implore medical professionals to consider the use of IMT and biologic treatments for patients with recurrent non-infectious uveitis, referring to ocular immunology and uveitis specialists when necessary.

Aims: Trophoblast fusion in the placenta is prerequisite to successful pregnancy and the pathological conditions related to it. The presence of syncytin-1, is not sufficient to explain the complete event and ADAM12 is a major co-player candidate. Via differential splicing, the ADAM12 gene produces a short and a long form, being the ADAM12-S and the ADAM12-L respectively. Methods and results: We investigated the localisation of both variants in the human placenta using whole mount in situ hybridisation, immunohistochemistry and Northern blotting in 1st (n = 8) and 3rd (n = 8) trimester placentae and in the case of NB in several cell lines. In Northern blotting, 1st and 3rd trimester placentae were positive for the ADAM12-S and Bewo, 293HEK, JAR, leucocytes, macrophages, 1st and 3rd trimester placentae were positive for ADAM12-L. In whole mount in situ hybridisation, the 1st and 3rd trimester placental syncytium was positive for both variants. In immunohistochemistry, ADAM12-L localised in the cytotrophoblast of both 1st and 3rd trimester placentae, while ADAM12-S localised in the complete syncytium, often including the cytotrophoblast. Conclusion: The different localisation of ADAM12-S and ADAM12-L indicates a possible different role making ADAM12-L a candidate for the fusion event, while the syncytial localisation of the ADAM12-S makes it a candidate for cell-cell and cell-matrix interactions between the placental syncytium and the maternal interface. (C) 2011 Elsevier GmbH. All rights reserved.

This paper proposes an adaptive controller with an improved high-frequency injection method for sensorless synchronous reluctance drive systems. A mathematical model is presented to show that the use of a high-frequency injection method that takes into account the effects of unequal mutual-inductances and the influence of speed reduces the rotor position estimation error. The adaptive speed control algorithm offers improved transient performance in comparison to typical proportional-integral (PI) controllers that are employed in sensorless drive systems. To demonstrate the viability, the proposed adaptive controller and the modified high-frequency injection method are implemented using a TMS-320F-28335A digital signal processor to control a 500 W prototype synchronous reluctance motor drive. Experimental results are presented to show that the transient, load disturbance, and tracking responses of the proposed drive system are superior in comparison to a drive that uses a PI controller. Both experimental and theoretical analyses clearly indicate that the proposed high-frequency injection method with an adaptive speed-loop controller offers improved performance in adjustable speed synchronous reluctance drive systems.

In this paper, a current sensorless adaptive secondary-side control is proposed for the series resonant converter (SRC), making it a good candidate for MHz 48 voltage regulators. By means of varying ac equivalent resistance, the output voltage regulation is achieved by controlling the duty cycle of the synchronous MOSFET. By taking advantage of the secondary-side control, SRCs can operate under zero-voltage switching at any input voltage and load conditions. A current sensorless adaptive digital control is proposed to control the current-type synchronous MOSFETs, which automatically compensates the delay caused by the current-sensor circuit and the gate driver, and also eliminates the current sensor in the power path. A hybrid control strategy is introduced to overcome the efficiency degradation caused by the secondary-side control.

A recursive smoothing filter employing a bank of fading-memory polynomial sub-filters is presented. Variance estimates are used to mix the outputs of the sub-filters, imparting variable gain and phase characteristics that permit it to automatically adapt to signal parameter changes. The proposed adaptive technique does not involve the estimation of plant parameters; therefore, it may be used in both open-loop and closed-loop configurations. In open-loop estimation problems, variable gain/bandwidth allows it to reduce the impact of random errors caused by sensor noise and the impact of bias errors caused by model mismatch during ` maneuvers'. In feedback control problems, variable phase/delay allows it to act as a lag filter for an improved steady-state response (i.e. greater noise attenuation) and act as a lead filter, or a proportionalderivative controller, for an improved transient response (i.e. increased closed-loop damping) for input discontinuities. Copyright (C) 2015 John Wiley & Sons, Ltd.

In this paper, a novel mixed iterative adaptive dynamic programming (ADP) algorithm is developed to solve the optimal battery energy management and control problem in smart residential microgrid systems. Based on the data of the load and electricity rate, two iterations are constructed, which are P-iteration and V-iteration, respectively. The V-iteration is implemented based on value iteration, which aims to obtain the iterative control law sequence in each period. The P-iteration is implemented based on policy iteration, which updates the iterative value function according to the iterative control law sequence. Properties of the developed mixed iterative ADP algorithm are analyzed. It is shown that the iterative value function is monotonically nonincreasing and converges to the solution of the Bellman equation. In each iteration, it is proven that the performance index function is finite under the iterative control law sequence. Finally, numerical results and comparisons are given to illustrate the performance of the developed algorithm.

This paper proposes a dimmable energy-efficient light-emitting diode (LED) driver for applications in interior lighting. High efficiency is achieved by an adaptive voltage regulation, which minimizes power losses in the linear current regulator. A digital control mechanism employing a resistive digital-to-analog converter for feeding the analog feedback input of a dc-dc converter is introduced. It is shown that the digital control methodology gives maximum design flexibility and enhances control over regulation speed and stability. In an experimental setup, the proposed concept is verified and evaluated. Operating at an input voltage of 24 V, the LED driver provides a relatively wide output voltage range of 3.5-38 V. Output current is regulated to 700 mA with a steady-state precision of more than 98.8%, whereas pulsewidth modulation dimming with a frequency of 1 kHz and shortest on-time of 4 mu s is employed. A peak efficiency of the complete system of 93.9% is achieved.

Environmental governance systems are under greater pressure to adapt and to cope with increased social and ecological uncertainty from stressors like climate change. We review principles of social cognition and decision making that shape and constrain how environmental governance systems adapt. We focus primarily on the interplay between key decision makers in society and legal systems. We argue that adaptive governance must overcome three cooperative dilemmas to facilitate adaptation: (1) encouraging collaborative problem solving, (2) garnering social acceptance and commitment, and (3) cultivating a culture of trust and tolerance for change and uncertainty. However, to do so governance systems must cope with biases in people's decision making that cloud their judgment and create conflict. These systems must also satisfy people's fundamental needs for self-determination, fairness, and security, ensuring that changes to environmental governance are perceived as legitimate, trustworthy, and acceptable. We discuss the implications of these principles for common governance solutions (e.g., public participation, enforcement) and conclude with methodological recommendations. We outline how scholars can investigate the social cognitive principles involved in cases of adaptive governance.

Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.

In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels.

CRISPR-Cas are self-/nonself-discriminating systems found in prokaryotic cells. They represent a remarkable example of molecular memory that is hereditarily transmitted. Their discovery can be considered as one of the first fruits of the systematic exploration of prokaryotic genomes. Although this genomic feature was serendipitously discovered in molecular biology studies, it was the availability of multiple complete genomes that shed light about their role as a genetic immune system. Here we tell the story of how this discovery originated and was slowly and painstakingly advanced to the point of understating the biological role of what initially was just an odd genomic feature.

In this chapter has been proposed a robust sensorless cascade control scheme for a Permanent Magnet Synchronous Motor (PMSM) drive. A Discrete Time Variable Structure Control (DTVSC) is considered and the rotor position and speed are obtained through an Adaptive Extended Kalman Filter (AEKF). The performance of the filter is improved by an on line adjustment of the input and measurement noise covariances obtained by a suitably defined estimation algorithm. The proposed solution is experimentally tested on a commercial PMSM drive equipped with a control system based on a floating point Digital Signal Processor (DSP).

This paper presents a power system harmonic elimination using the mixed adaptive linear neural network and variable step-size leaky least mean square (ADALINE-VSSLLMS) control algorithm based active power filter (APF). The weight vector of ADALINE along with the variable step-size parameter and leakage coefficient of the VSSLLMS algorithm are automatically adjusted to eliminate harmonics from the distorted load current. For all iteration, the VSSLLMS algorithm selects a new rate of convergence for searching and runs the computations. The adopted shunt-hybrid APF (SHAPF) consists of an APF and a series of 7th tuned passive filter connected to each phase. The performance of the proposed ADALINE-VSSLLMS control algorithm employed for SHAPF is analyzed through a simulation in a MATLAB/Simulink environment. Experimental results of a real-time prototype validate the efficacy of the proposed control algorithm.

The proposed frequency-locked loop (FLL) utilizes the flat frequency response characteristics of the moving window filter (MWF) in closed-loop and adaptive sampling pulse adjustment for capacitance measurement. An operational amplifier (op-amp) based relaxation oscillator generates a square wave whose fundamental sine wave is extracted by MWF. Then, the fundamental sine wave is tracked by the FLL to estimate its frequency which is inversely proportional to the unknown capacitance. The FLL employs another MWF to track the center frequency and its variation due to capacitance. The MWF offers an almost flat frequency response around the center frequency in closed-loop. However, the small magnitude and phase errors observed in the flat frequency response had been corrected by adjusting the sampling pulses adaptively. Experimental investigation demonstrates the capabilities of the scheme for wider and accurate capacitance measurement.

The proof of principle of an acquisition system of +/-50ppm repeatability, 10 V range, real-time delay less than 1.2 its is presented. The system will be integrated into the digital control loop of a high -voltage modulator under design at ETH Zurich and University of Laval for the new particle accelerator under study at CERN, the Compact LInear Collider (CLIC). Initial specifications are presented and translated into system requirements. Main design choices are discussed and Pspice simulation results are reported to prove that the proposed system meets the demanding requirements.

In comparison with conventional operational amplifier, ring amplifier can achieve better power efficiency for switched capacitor circuits. However, the cascade-inverter architecture of ring amplifier may suffer from undesirable oscillation which has a great impact on transient stability. This paper presents a latched-based ring amplifier which is capable of decreasing the probability of oscillation. Besides, two auto-zero schemes are employed in different pipelined stages to reduce the common-mode voltage offset and to increase the stability. The prototype ADC was fabricated in a 90-nm CMOS technology. The measured SNDR and SFDR are 52.06 dB and 63.15 dB, respectively, for a Nyquist frequency input sampled at 35 MS/s, and the ADC consumes 3.65 mW.

Background/Aims: The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods: Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1-/-). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1-/-mice. However, albumin overload resulted in severe albuminuria in Adcy1-/-mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. Copyright (C) 2010 S. Karger AG, Basel

The endogenous oxytocin system plays a vital role in facilitating parturition, lactation and social interaction in humans and other mammals. It also impacts on a number of important endocrine, immune and neurotransmitter systems. A well-regulated oxytocin system has been proposed to increase resilience, and therefore reduce the likelihood of an individual developing mental illness or substance dependence. This review discusses the adverse external influences that can modulate oxytocin receptor and protein levels and impact on substance use and mental health. The paper highlights the impact of adversity such as poor maternal care, parental substance use and child abuse or neglect. We review clinical and preclinical data on the impact of adversity on the basis of the time of exposure from infancy and early childhood, to adolescence, adulthood to older age. Previous research suggests that dysregulation of the endogenous oxytocin system may be implicated in determining susceptibility to stress, anxiety, addiction and mental health conditions. The impact of external influence seems to be strongest in specific time periods where the system shows experience-based development or natural fluctuations in oxytocin levels. Interventions that target the oxytocin system during or soon after exposure to adversity may prove protective. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

Background and aims Deficits in social cognitive abilities including emotion recognition and theory of mind (ToM) can play a significant role in interpersonal difficulties observed in alcohol use disorder (AUD). This meta-analysis aims to estimate mean effect sizes of deficits in social cognition inAUD and examines the effects of demographic and clinical confounding factors on the variability of effect sizes across studies. Methods A literature review was conducted on research reports published from January 1990 to January 2016. Twenty-five studies investigating ToM and facial emotion recognition performances of 756 individuals with AUD and 681 healthy controls were selected after applying inclusion and exclusion criteria. Weighted effect sizes (d) were calculated for ToM, decoding and reasoning aspects of ToM, total facial emotion recognition and recognition of each of six basic emotions. Results Facial emotion recognition was significantly impaired [d=0.65,95% confidence interval (CI)=0.42-0.89], particularly for disgust and anger. AUDwas also associated with deficits in ToM (d=0.58, 95% CI=0.36-0.81). These deficits were evident in tasks measuring both decoding (d=0.46, 95% CI=0.19-0.73) and reasoning (d=0.72, 95% CI=0.37-1.06) aspects of ToM. The longer duration of alcohol misuse and more depressive symptoms were associated with more severe deficits in recognition of facial emotions. Conclusions Alcohol use disorder appears to be associated with significant impairment in facial emotion recognition and theory of mind.

Aims To investigate whether: (1) childmaltreatment is associated with life-time cannabis use, early-onset cannabis use, daily cannabis use and DSM-IV cannabis abuse in young adulthood; and (2) behaviour problems, tobacco use and alcohol use at age 14 are associated with cannabis use. Design Birth cohort using linked government agency child protection data to define exposure to child maltreatment. Setting The Mater-University of Queensland Study of Pregnancy in Brisbane, Australia. Participants Of the original cohort of 7223 mother and child pairs, obtained from consecutive presentations for prenatal care at a hospital serving a cross-section of the community, 3778 (52.3%) of the young people participated at age 21 years. Measurements Exposure to child maltreatment was established by substantiated government agency reports. Cannabis outcomes were by self-report questionnaire and Composite International Diagnostic Interview (CIDI)-Auto at age 21. Associations were adjusted for a range of potential confounders. Additional adjustment was carried out for variables measured at age 14-youth behaviour problems [Achenbach Child Behavior Checklist (CBCL)], tobacco use and alcohol use. Findings After adjustment, substantiated child maltreatment was associated with any life-time cannabis use [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.08-2.39], cannabis use prior to age 17 (OR = 2.47, 95 % CI = 1.67-3.65), daily cannabis use (OR = 2.68, 95% CI = 1.49-4.81) and DSM-IV cannabis abuse/dependence (OR = 1.72, 95% CI = 1.07-2.77). Externalizing behaviour and tobacco and alcohol use at age 14 were associated significantly with almost all cannabis outcomes (P < 0.05), with internalizing behaviour associated inversely (P < 0.05). Conclusions Children in Australia who are documented as having been maltreated are more likely to go on to use cannabis before the age of 17, use cannabis as an adult, use cannabis daily and meet DSM-IV criteria for cannabis dependence. Externalizing behaviour in adolescence appears partly to mediate the association with adult cannabis use.

The purpose of this project was to examine the emotional health and wellbeing of Canadian caregivers of persons with significant mental health or addictions problems. We assessed the emotional health of caregivers by care-receiver condition type (i.e. mental health or addictions vs. physical or other health problems), levels of caregiver stress and methods particularly for reducing stress among caregivers of persons with mental health or addictions disorders. Weighted cross-sectional data from the 2012 General Social Survey (Caregiving and Care Receiving) were modelled using weighted descriptive and logistic regression analyses to examine levels of stress and the emotional health and well-being of caregivers by care-receiver condition type. Caregivers of persons with mental health or addictions problems were more likely to report that caregiving was very stressful and that they felt depressed, tired, worried or anxious, overwhelmed; lonely or isolated; short-tempered or irritable; and resentful because of their caregiving responsibilities. The results of this study suggest that mental health and addictions caregivers may experience disparate stressors and require varying services and supports relative to caregivers of persons with physical or other health conditions.

Defined as sexually explicit material that elicits erotic thoughts, feelings, and behaviours, internet pornography is a prevalent form of media that may facilitate problematic use and craving for engagement. Research suggests that superordinate cognitions and information processing, such as desire thinking and metacognition, are central to the activation and escalation of craving in addictive behaviours. The current study aimed to contribute to the literature by testing the proposed metacognitive model of desire thinking and craving in a sample of problematic pornography users, while revising the model by incorporating negative affect. From a theoretical perspective, environmental cues trigger positive metacognitions about desire thinking that directly influence desire thinking, resulting in the escalation of craving, negative metacognitions, and negative affect. Participants were recruited via an online survey and screened for problematic internet pornography use. Path analyses were used to investigate relationships among the aforementioned constructs in a final sample of 191 participants. Consistent with previous research, results of this study validated the existence of metacognitive processes in the activation of desire thinking and escalation of craving, while indicating that desire thinking has the potential to influence negative affect. Additionally, results supported the role of significant indirect relationships between constructs within the revised model of metacognition, desire thinking, and psychopathology. Collectively, the findings demonstrate the clinical value of a metacognitive conceptualisation of problematic pornography use. Exploring the metacognitive mechanisms that underpin problematic internet pornography use may give rise to the development of new treatment and relapse prevention strategies. (C) 2017 Elsevier Ltd. All rights reserved.

In many low-to-mid power applications, critical mode boost power factor corrector converters are widely used because of its low switching loss and simple control. However, near the zero crossing of the input line voltage, an input current distortion and a low power factor are caused by delayed switching period and negative input currents. Generally, an additional on-time method according to the input voltage is used to compensate the input current distortion. However, a detailed quantitative analysis for the exact additional on time has not been studied till now. In this paper, the explicit form of the optimized additional on time has been obtained using a quantitative analysis and the advantage of the digital control. From a state trajectory and "net input charge" analysis, it is shown that the optimized on time should be related to not only the input voltage, but also the output power. Also, in order to improve the efficiency in a high input and light load condition, circulating currents are reduced in the inevitable dead angle with a gate turning-off technique. By using digital control, the optimized additional on time and the gate turn-off technique have been implemented with the 90-230 V-rms input and 380 V/200 W output prototype.

For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively. A total of 1325 lymph nodes were collected from 49 patients, grouped into 3 groups: lower mediastinal, paracardial, and abdominal. The former 2 groups were examined by monoclonal antibodies against Ber-Ep4 and CD44v6. The incidence of LNMM in mediastinal group was 37% (18/49) for Ber-Ep4 and 33% (16/49) for CD44v6. While in routine histological diagnosis, the number of patients with the positive lymph nodes was 7 (14%). When combining IHC with histopathology (HE) staining, the incidence of positive mediastinal lymph nodes was increased to 24%, with a total number of 37 lymph nodes from 28 patients (57%). Micrometastases indicated by Ber-Ep4 and CD44v6 were associated with the depth of tumor invasion (P=0.020 and 0.037, respectively), histopathological nodal status (P=0.024 and 0.01, respectively), and Lauren classification (P=0.038 and, respectively). Expression of CD44v6 and Ber-Ep4 was positively correlated (r=0.643, P<0.001). The 3- and 5-year survival rates for all patients were 66% and 50%, respectively. The patients with LNMM had a lower 3-year survival rate of 51%, compared to 80% from no LNMM group; 5-year survival rate was also lower in LNMM group, which is 29% versus 68% (P=0.006) in the no LNMM group. Patients with positive Ber-Ep4 cells had a lower survival, but not statistically significant (P=0.058). CD44v6-positive group had a significantly reduced survival (P<0.001). In patients group with negative lower mediastinal lymph nodes, patients without LNMM obtained a significant survival benefit (P=0.021). Our study demonstrated that routine test for LNMM is necessary for patients with negative lymph nodes. As a positive prognostic factor, thorough lower mediastinal lymphadenectomy in an invasive approach should be considered when necessary. Ber-Ep4 and CD44v6 were shown to be great markers for detecting LNMM.

Aims: Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV-related ACC-like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in-situ hybridization, and clinicopathological information for all cases is presented. Methods and results: Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease. Conclusion: We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable.

The aim of the present study was to investigate the role of chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor, chemokine (C-X-C motif) receptor 4 (CXCR4) in the pathogenesis of adenomyosis (AD). Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction analysis were used to measure the protein and mRNA expression of CXCL12 and CXCR4 in eutopic endometrial and ectopic foci tissue samples. Samples from a total of 36 patients with AD (study group) were compared with endometrial tissue samples from 33 patients who underwent uterine fibroids surgery (control group) during the same period. All data are presented as the mean +/- standard deviation and were analyzed with SPSS software (version 16.0). Analysis of variance was used for between group analysis and pairwise comparison was performed using Fisher's least significant difference post hoc test. The results of the present study revealed that CXCL12 and CXCR4 protein expression was significantly increased in ectopic foci tissue compared with eutopic endometrial tissue samples from patients with AD. CXCL12 and CXCR4 protein expression in ectopic foci and eutopic endometrial tissue samples were significantly increased compared with the control group (P< 0.05 for between group comparisons). No significant differences were identified in CXCL12 and CXCR4 protein expression between the proliferative and secretory phases within each group. Furthermore, CXCL12 and CXCR4 mRNA expression was significantly increased in ectopic foci tissue and eutopic endometrial tissue compared with the control group (P< 0.05 for between group comparisons). CXCL12 mRNA expression was markedly increased in ectopic foci tissue compared with eutopic endometrial tissue of patients with AD. The expression of CXCR4 mRNA was significantly increased in eutopic endometrial tissue compared with ectopic foci tissue and the control group (P< 0.05 for between group comparisons). No significant differences were identified in CXCL12 and CXCR4 mRNA expression between proliferative and secretory phase within each group. In conclusion, CXCL12 and CXCR4 may induce the ectopia, and promote the spread and localized growth of endometrial cells in the development of AD.

Objective: We investigated the expression and potential roles of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, IL-37, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF) in patients with adenomyosis. Materials and methods: This prospective study examined 16 women with histologically proven adenomyosis and 52 women without adenomyosis, all of whom were undergoing a hysterectomy for non-endometrial pathology at the Department of Gynaecology, the First Hospital of Jilin University, Changchun, China, from December 2011 to September 2012. Serum samples were collected from the patients, and the concentrations of serum IL-2, IL-4, IL-6, IL-10, IL-17A, IL-37, IFN-gamma, and TNF were measured by Enzyme-Linked Immunosorbent Assay (ELISA). We then calculated specificity and sensitivity of cytokines, taking Cancer Antigen (CA) 125 as a reference, distinguishing cases from controls by receiver operating characteristic (ROC) curve. The correlation between individual cytokines and CA 125 was also analysed. Results: IL-37 was detectable in 69.2% and the other cytokines in 30.8% of sera samples from the 52 controls. All the eight cytokines were detectable in the sera samples from 16 patients with adenomyosis. Significantly higher levels of serum IL-37 and IL-10 and significantly lower levels of serum IL-17A and TNF were detected in adenomyosis patients when compared with controls (p< 0.05). Conclusions: Serum levels of IL-10, IL-17A, IL-37, and TNF varied significantly between cases and controls, and could be involved in the pathogenesis of adenomyosis.

Objectives: Inflammatory response and cytokine activation are markedly stimulated in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine, released by all cell types, binds to a class of G protein-coupled receptors to induce various skeletal muscle effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly adenosine A2B receptors, could stimulate IL-6 gene expression in rat L6 skeletal muscle cells. Materials and Methods: The rat L6 skeletal muscle cells were cultured in 25 cm2 flasks. These differentiated cells were treated and then quantitative reverse transcription-polymerase chain reaction (Probe-based) was used to analyze IL-6 gene expression level among different treatment conditions. Results: Adenosine-5'-N-ethyluronamide (NECA), a stable adenosine analogue, concentration-and time-dependently stimulates IL-6 gene expression in skeletal muscle cells. The effect of NECA is inhibited by a selective adenosine A2B receptor antagonist, PSB 603. By using cyclic adenosine monophosphate (cAMP)-arising reagent forskolin, cAMP is found to be involved in the up-regulation of IL-6 induction. Conclusion: Here, a novel relationship between adenosine and IL-6 up-regulation has been demonstrated for the first time; IL-6 up-regulation induced by NECA is mediated by adenosine A2B receptor activation in skeletal muscle and is dependent on mainly a cAMP pathway. Adenosine A2B receptors are, thus, potentially important pharmacological targets in treating inflammation and related diseases in skeletal muscle tissues.

Adenosine triphosphate- binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate- binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate- binding cassette gene expression profiles ( signatures), based on the expression of all 49 human adenosine triphosphate- binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate- binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate- binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients- breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real- time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate- binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate- binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 ( official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers.

Background:To perform a molecular epidemiological analysis of viral conjunctivitis among excess conjunctivitis cases recorded at the University Hospital of Patras, Greece, for the period March to June 2012. Methods: A structured questionnaire containing demographic and clinical data was developed in order to collect retrospective data on the cases. Eye swab specimens were collected and molecular detection of adenoviruses was performed by nested PCR. Positive results were confirmed by sequencing. To determine the relatedness between the isolated sequences, a phylogenetic analysis was conducted. Results: The epidemiological analysis (including retrospective data) included 231 conjunctivitis cases (47.1% male, and 52.8% female). Based on clinical features 205 of the cases were diagnosed of viral origin (46.3% male and 53.7% female), 4 of bacterial origin (50% male and 50% female) while 22 were undefined conjunctivitis. The outbreak excess cases (included 156 cases) affected all age groups regardless gender predilection. For the positive samples indicated that 29 samples (72.5%) were AdV17, and 5 (12.5%) as AdV54. Conclusions: Molecular analysis could define the cause of viral conjunctivitis, while epidemiological data contributed to the assessment of the risk factors and underlined possible preventive measures. This study is one of the very few on viral conjunctivitis in Greece. This outbreak underscores the need for a national surveillance system for acute infectious conjunctivitis outbreaks. The epidemiological as well as molecular investigation on HAdV ocular infections is rather absent in Greece, which has no surveillance system for viral conjunctivitis.

The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai. Variable number tandem repeats of DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by PCR-AGE. Several allele repeats of the genes were observed in the screened subjects. Statistical significance was observed for the 10R/10R genotype of the DAT1 3'UTR VNTR between cases and controls.

Objective-Endothelial activation is implicated in atherogenesis and diabetes. The role of peroxisome proliferator-activated receptor-delta (PPAR-delta) in endothelial activation remains poorly understood. In this study, we investigated the anti-inflammatory effect of PPAR-delta and the mechanism involved. Methods and Results-In human umbilical vein endothelial cells (HUVECs), the synthetic PPAR-delta ligands GW0742 and GW501516 significantly inhibited tumor necrosis factor (TNF)-alpha-induced expression of vascular cell adhesion molecule-1 and E-selectin (assayed by real-time RT-PCR and Northern blotting), as well as the ensuing endothelial-leukocyte adhesion. Activation of PPAR-delta upregulated the expression of antioxidant genes superoxide dismutase 1, catalase, and thioredoxin and decreased reactive oxygen species production in ECs. Chromatin immunoprecipitation assays showed that GW0742 switched the association of BCL-6, a transcription repressor, from PPAR-delta to the vascular cell adhesion molecule ( VCAM)-1 promoter. Small interfering RNA reduced endogenous PPAR-delta expression but potentiated the suppressive effect of GW0742 on EC activation, which suggests that the nonliganded PPAR-delta may have an opposite effect. Conclusions-We have demonstrated that ligand activation of PPAR-delta in ECs has a potent antiinflammatory effect, probably via a binary mechanism involving the induction of antioxidative genes and the release of nuclear corepressors. PPAR-delta agonists may have a potential for treating inflammatory diseases such as atherosclerosis and diabetes.

Aims/hypothesis The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. Methods Male Sprague-Dawley rats received N-omega-nitro-Larginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. Results Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. Conclusions/interpretation Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.

Leptin is an adipocytokine that regulates body weight, and maintains energy homeostasis by promoting reduced food intake and increasing energy expenditure. Leptin expression and secretion is regulated by various factors including hormones and fatty acids. Butyrate is a short-chain fatty acid that acts as source of energy in humans. We determined whether this fatty acid can play a role in leptin expression in fully differentiated human adipocytes. Mature differentiated adipocytes were incubated with or without increasing concentrations of butyrate. RNA was extracted and leptin mRNA expression was examined by Northern blot analysis. Moreover, the cells were incubated with regulators that may affect signals which may alter leptin expression and analyzed with Northern blotting. Butyrate stimulated leptin expression, and stimulated mitogen activated protein kinase (MAPK) and phospho-CREB signaling in a time-dependent manner. Prior treatment of the cells with signal transduction inhibitors as pertusis toxin, G(i) protein antagonist, PD98059 (a MAPK inhibitor), and wortmannin (a PI3K inhibitor) abolished leptin mRNA expression. These results suggest that butyrate can regulate leptin expression in humans at the transcriptional level. This is accomplished by: 1) G(i) protein-coupled receptors specific for short-chain fatty acids, and 2) MAPK and phosphatidylinositol-3-kinase (P13K) signaling pathways.

Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases - 109 and - 100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.

Background: Autologous fat grafting is a prevalent technique used for softtissue augmentation; however, the poor survival rate of the grafted tissue remains a drawback of this method. Although adipose-derived stem cells (ASCs) are an attractive candidate for enhancing graft retention, the poor posttransplantation viability of these cells limits their application. Here we investigated whether overexpression of the antiapoptotic protein heat-shock protein 70 (Hsp70) could enhance ASCs' therapeutic potential for fat transplant survival. Methods: Recombinant adenoviral vectors were used to overexpress Hsp70 in ASCs isolated from a healthy woman. The Hsp70 expression was assessed by quantitative real- time polymerase chain reaction and Western blot analyses. The adipose tissue granules aspirated from anotherwomanweremixed with ASCs expressing green fluorescent protein (GFP)-tagged Hsp70 (group A) or GFP alone (group B), untreated ASCs (group C), and phosphate-buffered saline (group D). Fat mixtures were then injected subcutaneously into the backs of nude mice, and graft survival was compared after 3 months. Results: Adipose-derived stem cells transduced with recombinant adenoviral vectors exhibited significantly increased Hsp70 expression in vitro. Meanwhile, weight retention analyses demonstrated that fat grafts using the group A cell population exhibited significantly higher survival rates than the other treatment groups in vivo. Moreover, histological analyses revealed that fat grafts containing GFP-Hsp70-expressing ASCs yielded significantly lower levels of tissue fibrosis and fat cysts/vacuoles, higher capillary densities, and increased numbers of viable adipocytes than the control groups. Conclusions: Our data indicate that Hsp70 overexpression enhances the efficacy of ASC therapy by improving the survival and quality of the transplanted fat tissues.

Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1 alpha-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1 alpha transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1 alpha gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH >IH >RA; P>>SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1 alpha activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1 alpha transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.

Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31(-)/CD45(-)/CD34(+)/CD146(-) cells (adventitial stromal/stem cells [ASCs]) and CD31(-)/CD45(-)/CD34(-)/CD146(+) cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n=67) and PCs (n=73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n=429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH(br)ASC (most primitive); (b) ALDH(dim)ASC; (c) ALDH(br)PC; (d) ALDH(dim)PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and coexpression networks. Stem Cells2017;35:1273-1289

Extensive research has been performed to determine the effect of freezing protocol and cryopreservation agents on the viability of adipose tissue-derived stromal/stem cells (ASCs) as well as other cells. Unfortunately, the conclusion one may draw after decades of research utilizing fundamentally similar cryopreservation techniques is that a barrier exists, which precludes full recovery. We hypothesize that agents capable of inducing a subset of heat shock proteins (HSPs) and chaperones will reduce the intrinsic barriers to the post-thaw recovery of ASCs. ASCs were exposed to 43 degrees C for 1 h to upregulate HSPs, and the temporal HSP expression profile postheat shock was determined by performing quantitative polymerase chain reaction (PCR) and western blotting assays. The expression levels of HSP70 and HSP32 were found to be maximum at 3 h after the heat shock, whereas HSP90 and HSP27 remain unchanged. The heat shocked ASCs cryopreserved during maximal HSPs expression exhibited increased post-thaw viability than the nonheat shocked samples. Histochemical staining and quantitative reverse transcription-PCR indicated that the ASC differentiation potential was retained. Thus, suggesting that the upregulation of HSPs before a freezing insult is beneficial to ASCs and a potential alternative to the use of harmful cryoprotective agents.

The long-term effect of feeding the catecholamine analog ractopamine (RAC; ractopamine hydrochloride, Elanco Animal Health, Indianapolis, IN) on the expression of genes involved in energy and lipid metabolism in subcutaneous adipose tissue was studied. Large White pigs (84 kg) were fed corn- and soybean meal-based diets supplemented with 0, 20, or 60 mg/kg of RAC for 14, 28, or 42 d. Expression (mRNA abundance) in adipose tissue of sterol regulatory binding protein-1 (SREBP-1), PPAR alpha, PPAR gamma 2, fatty acid synthase (FAS), glucose transporter 4 (GLUT4), and stearoyl-CoA desaturase was determined by Northern blotting. Feed intakes did not differ, and RAC (20 and 60 mg/kg) improved BW gain at d 14, 28, and 42 (P < 0.05) and increased loin eye area (measured on d 42 only; P < 0.05). Expression of SREBP-1 and PPAR gamma 2 declined (P < 0.05) with RAC by d 28 and 42, whereas expression of PPAR alpha was increased (P < 0.05) on d 14, 28, and 42. After 14 d, expression of FAS and GLUT4 was decreased (P < 0.05) with 60 mg/kg of RAC, whereas both RAC concentrations attenuated FAS expression on d 28 and 42. Overall, adipose tissue stearoyl-CoA desaturase expression was not affected by RAC but showed somewhat less expression (P < 0.15) on d 28 at 60 mg/kg of RAC. Although prolonged, chronic RAC feeding most likely downregulates adipose tissue membrane beta-adrenergic receptors, mRNA abundances of anabolic lipid metabolism transcription factors, glucose transporters, and enzymes (SREBP-1, PPAR gamma 2, FAS, GLUT4) were still attenuated up to d 42. Conversely, a transcription factor related to oxidative metabolism expression (PPAR alpha) was enhanced. We conclude that even after 42 d, RAC still decreased expression of lipogenic genes in adipose tissue by yet undefined cyclic adenosine monophosphate-directed mechanisms, but in contemporary lean pigs, this effect is likely of limited practical significance.

Conveyor systems allow quick and efficient transportation for a wide variety of materials, which make them very popular in the material handling and packaging industries. Many kinds of conveying systems are available and used according to the various needs of different industries. Adjustable speed drives are used for the operation of the conveyors used in a number of industries. We can use adjustable electric drives in a number of industrial applications. A typical adjustable speed drive consists of an induction motor and a power electronic converter. In most cases, motor speed is commanded so that the control system requires an actual speed signal for closing the speed loop. In industrial applications, speed sensors, as well as sensorless solutions, are used. Due to the possibility of current speed sensor noises and for maintenance and economic aspects, the trend is to substitute speed sensors by computational solutions. Comprehensive reviews of the sensorless drives show that there are still some persistent problems associated with the sensorless control, that needs new solutions. In ASDs, the advanced control approach of IM is the FOC method, used in modern industrial drives. The current stator controller is the integral part of various FOC systems. In the classical FOC solution, PI or hysteresis controllers are generally used. However, PCCs are reported to have better properties. System sensitivity to inaccuracy and changes of motor equivalent circuit parameters are another problem in electrical drives. Almost all of the FOC systems are very sensitive to such inaccuracies; therefore, some parameters should be estimated online, and a robust structure of the control is required. The real-time implementation of the system is an important task even for electric drives or power converters.

Four groupA streptococcal glycolipopeptide vaccine candidates with different lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of the compounds was evaluated by macrophage and dendritic cell uptake studies and by in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates showed significant induction of the IgG response.

Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques. Advances in particle engineering now allow highly tunable physicochemical properties of particle-based vaccines, including composition, size, shape, surface characteristics, and degradability. Enhanced collaborative efforts between researchers in immunology and materials science are expected to rise to next-generation vaccines. This process will be significantly aided by a greater understanding of the immunological principles guiding vaccine antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted adjuvants and particle physicochemical properties, this review aims to provide an overview of the current literature to guide and focus rational particle-based vaccine design efforts.

Critical issues about scientific reproducibility have been raised about biomedical research, including the reliability of data and analyses within a given study. The case example in this article examined a reproducibility issue pertaining to the use of administrative data systems for evaluation of child maltreatment (CM) prevention, making use of a prevention study conducted over a decade ago that provided a unique opportunity. The place-randomization study, which randomized counties to condition, found that community-wide implementation of a parenting and family support intervention produced positive impact on county-wide rates for substantiated CM cases and out-of-home placements, documented through a state information system. The key consideration is whether and to what extent the administrative record data re-examined retroactively a decade later for the original study's time period would yield comparable results to those based on data acquired at the time of the study. The results indicated that despite small changes over time, the same data patterns and statistical effects were reproducible for the two archival outcome variables. For substantiated CM, the reproduced analyses reflected higher effect sizes and a clear pattern of reduction as a function of intervention. For out-of-home placements, effect sizes were quite comparable to the original ones, reflecting preventive impact. Overall, this case study illustrated the verifiability of data reproducibility in the context of a population outcome evaluation, which underscores the importance of reliable population-prevalence measurement as an essential part of a comprehensive public health strategy aimed at the prevention of CM. (C) 2016 Elsevier Ltd. All rights reserved.

Aims: Ancient DNA (aDNA) extracted from historical bones is damaged and fragmented into short segments, present in low quantity, and usually copurified with microbial DNA. A wide range of DNA quantification methods are available. The aim of this study was to compare the five most common DNA quantification methods for aDNA. Materials and Methods: Quantification methods were tested on DNA extracted from skeletal material originating from an early medieval burial site. The tested methods included ultraviolet (UV) absorbance, real-time quantitative polymerase chain reaction (qPCR) based on SYBR (R) green detection, real-time qPCR based on a forensic kit, quantification via fluorescent dyes bonded to DNA, and fragmentary analysis. Differences between groups were tested using a paired t-test. Results: Methods that measure total DNA present in the sample (NanoDrop (TM) UV spectrophotometer and Qubit (R) fluorometer) showed the highest concentrations. Methods based on real-time qPCR underestimated the quantity of aDNA. The most accurate method of aDNA quantification was fragmentary analysis, which also allows DNA quantification of the desired length and is not affected by PCR inhibitors. Conclusions: Methods based on the quantification of the total amount of DNA in samples are unsuitable for ancient samples as they overestimate the amount of DNA presumably due to the presence of microbial DNA. Real-time qPCR methods give undervalued results due to DNA damage and the presence of PCR inhibitors. DNA quantification methods based on fragment analysis show not only the quantity of DNA but also fragment length.

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-termeffects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. Furthermore, we observed profound alterations in several prefrontal cortical molecular pathways consistent with sub-cortical DAergic dysregulation. Our findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to THC in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.