Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer’s disease: study protocol for a randomized controlled trial

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Experimental study of regenerative EM -TMD system for building vibration control

Author name used in this publication: S. ZhuRefereed conference paper2011-2012 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Continuous multiparametric monitoring of cell metabolism in response to transient overexpression of the sirtuin deacetylase SIRT3

The analysis and visualisation of research data in an environment which is most similar to living conditions belong to the most challenging claims of present scientific research endeavours. To date, the effect of protein function on cell metabolism is most commonly assessed from a series of end point analyses, which finally allows an approximate estimation on how a specific effect takes its course. In the study presented herein, we demonstrate how the combination of transient transfection and a biosensor chip system gives the opportunity to analyse the effect of a specific protein on cell metabolism in living cells through real-time monitoring of metabolically relevant parameters, such as oxygen consumption, acidification rate and cell adhesion. In addition, this method allows online monitoring of the time course of metabolic changes due to changes in expression levels of metabolic regulative proteins from the time of transfection to maximum overexpression. The methodology presented herein was assessed for the transient overexpression of the sirtuin deacetylase SIRT3, a mitochondrial key element in the regulation of energy metabolism, metabolic disease, cancer and ageing

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Glycomics Analysis of Mammalian Heparan Sulfates Modified by the Human Extracellular Sulfatase HSulf2

The Sulfs are a family of endosulfatases that selectively modify the 6O-sulfation state of cell-surface heparan sulfate (HS) molecules. Sulfs serve as modulators of cell-signaling events because the changes they induce alter the cell surface co-receptor functions of HS chains. A variety of studies have been aimed at understanding how Sulfs modify HS structure, and many of these studies utilize Sulf knockout cell lines as the source for the HS used in the experiments. However, genetic manipulation of Sulfs has been shown to alter the expression levels of HS biosynthetic enzymes, and in these cases an assessment of the fine structural changes induced solely by Sulf enzymatic activity is not possible. Therefore, the present work aims to extend the understanding of substrate specificities of HSulf2 using in vitro experiments to compare HSulf2 activities on HS from different organ tissues.To further the understanding of Sulf enzymatic activity, we conducted in vitro experiments where a variety of mammalian HS substrates were modified by recombinant human Sulf2 (HSulf2). Subsequent to treatment with HSulf2, the HS samples were exhaustively depolymerized and analyzed using size-exclusion liquid chromatography-mass spectrometry (SEC-LC/MS). We found that HSulf2 activity was highly dependent on the structural features of the HS substrate. Additionally, we characterized, for the first time, the activity of HSulf2 on the non-reducing end (NRE) of HS chains. The results indicate that the action pattern of HSulf2 at the NRE is different compared to internally within the HS chain.The results of the present study indicate that the activity of Sulfs is dependent on the unique structural features of the HS populations that they edit. The activity of HSulf2 at HS NREs implicates the Sulfs as key regulators of this region of the chains, and concomitantly, the protein-binding events that occur there

Identification of Serum MicroRNAs as Novel Non-Invasive Biomarkers for Early Detection of Gastric Cancer

BACKGROUND: To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. METHODOLOGY/PRINCIPAL FINDINGS: All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. CONCLUSIONS/SIGNIFICANCE: These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC

The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo

The CACCC-box binding protein erythroid Kruppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Kruppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis

Mixing of Active and Sterile Neutrinos

We investigate mixing of neutrinos in the $\nu$MSM (neutrino Minimal Standard Model), which is the MSM extended by three right-handed neutrinos. Especially, we study elements of the mixing matrix $\Theta_{\alpha I}$ between three left-handed neutrinos $\nu_\alpha$ ($\alpha = e,\mu,\tau$) and two sterile neutrinos $N_I$ ($I=2,3$) which are responsible to the seesaw mechanism generating the suppressed masses of active neutrinos as well as the generation of the baryon asymmetry of the universe (BAU). It is shown that $\Theta_{eI}$ can be suppressed by many orders of magnitude compared with $\Theta_{\mu I}$ and $\Theta_{\tau I}$, when the Chooz angle $\theta_{13}$ is large in the normal hierarchy of active neutrino masses. We then discuss the neutrinoless double beta decay in this framework by taking into account the contributions not only from active neutrinos but also from all the three sterile neutrinos. It is shown that $N_2$ and $N_3$ give substantial, destructive contributions when their masses are smaller than a few 100 MeV, and as a results $\Theta_{e I}$ receive no stringent constraint from the current bounds on such decay. Finally, we discuss the impacts of the obtained results on the direct searches of $N_{2,3}$ in meson decays for the case when $N_{2,3}$ are lighter than pion mass. We show that there exists the allowed region for $N_{2,3}$ with such small masses in the normal hierarchy case even if the current bound on the lifetimes of $N_{2,3}$ from the big bang nucleosynthesis is imposed. It is also pointed out that the direct search by using $\pi^+ \to e^+ + N_{2,3}$ and $K^+ \to e^+ + N_{2,3}$ might miss such $N_{2,3}$ since the branching ratios can be extremely small due to the cancellation in $\Theta_{eI}$, but the search by $K^+ \to \mu^+ + N_{2,3}$ can cover the whole allowed region by improving the measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure

An improved ant colony optimization-based approach with mobile sink for wireless sensor networks

Traditional wireless sensor networks (WSNs) with one static sink node suffer from the well-known hot spot problem, that of sensor nodes near the static sink bear more traffic load than outlying nodes. Thus, the overall network lifetime is reduced due to the fact some nodes deplete their energy reserves much faster compared to the rest. Recently, adopting sink mobility has been considered as a good strategy to overcome the hot spot problem. Mobile sink(s) physically move within the network and communicate with selected nodes, such as cluster heads (CHs), to perform direct data collection through short-range communications that requires no routing. Finding an optimal mobility trajectory for the mobile sink is critical in order to achieve energy efficiency. Taking hints from nature, the ant colony optimization (ACO) algorithm has been seen as a good solution to finding an optimal traversal path. Whereas the traditional ACO algorithm will guide ants to take a small step to the next node using current information, over time they will deviate from the target. Likewise, a mobile sink may communicate with selected node for a relatively long time making the traditional ACO algorithm delays not suitable for high real-time WSNs applications. In this paper, we propose an improved ACO algorithm approach for WSNs that use mobile sinks by considering CH distances. In this research, the network is divided into several clusters and each cluster has one CH. While the distance between CHs is considered under the traditional ACO algorithm, the mobile sink node finds an optimal mobility trajectory to communicate with CHs under our improved ACO algorithm. Simulation results show that the proposed algorithm can significantly improve wireless sensor network performance compared to other routing algorithms

Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates

In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe–Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G) linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate