A CMOS 0.8- µm transistor-only 1.63-MHz switched-current bandpass ΣΔ modulator for AM signal A/D conversion

This paper presents a CMOS 0.8-/spl mu/m switched-current (SI) fourth-order bandpass /spl Sigma//spl Delta/ modulator (BP-/spl Sigma//spl Delta/M) IC capable of handling signals up to 1.63 MHz with 105-bit resolution and 60-mW power consumption from a 5-V supply voltage. This modulator Is intended for direct A/D conversion of narrow-band signals within the commercial AM band, from 530 kHz to 1.6 MHz. Its architecture is obtained by applying a low-pass-to-bandpass transformation (z/sup -1//spl rarr/-z/sup -2/) to a 1-bit second-order low-pass /spl Sigma//spl Delta/ modulator (LP-/spl Sigma//spl Delta/M). The design of basic building blocks is based upon a detailed analysis of the influence of SI errors on the modulator performance, followed by design optimization. Memory-cell errors have been identified as the dominant ones. In order to attenuate these errors, fully differential regulated-folded cascode memory cells are employed. Measurements show a best SNR peak of 65 dB for signals of 10-kHz bandwidth and an intermediate frequency (IF) of 1.63 MHz. A correct noise-shaping filtering is achieved with a sampling frequency of up to 16 MHz.This work has been supported by the Spanish CICYT Project TIC 97-0580

Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4.

In addition to its well-known role as a crosslinker of actin filaments at focal-adhesion sites, actinin-4 is known to be localized to the nucleus. In this study, we reveal the molecular mechanism underlying nuclear localization of actinin-4 and its novel interactions with transcriptional regulators. We found that actinin-4 is imported into the nucleus through the nuclear pore complex in an importin-independent manner and is exported by the chromosome region maintenance-1 (CRM1)-dependent pathway. Nuclear actinin-4 levels were significantly increased in the late G2 phase of the cell cycle and were decreased in the G1 phase, suggesting that active release from the actin cytoskeleton was responsible for increased nuclear actinin-4 in late G2. Nuclear actinin-4 was found to interact with the INO80 chromatin-remodeling complex. It also directs the expression of a subset of cell-cycle-related genes and interacts with the upstream-binding factor (UBF)-dependent rRNA transcriptional machinery in the M phase. These findings provide molecular mechanisms for both nucleocytoplasmic shuttling of proteins that do not contain a nuclear-localization signal and cell-cycle-dependent gene regulation that reflects morphological changes in the cytoskeleton

Doublet-Triplet Splitting and Fermion Masses with Extra Dimensions

The pseudo-Goldstone boson mechanism for the ``doublet-triplet splitting'' problem of the grand unified theory can be naturally implemented in the scenario with extra dimensions and branes. The two SU(6) global symmetries of the Higgs sector are located on two separate branes while the SU(6) gauge symmetry is in the bulk. After including several vector-like fields in the bulk, and allowing the most general interactions with their natural strength (including the higher dimensional ones which may be generated by gravity) which are consistent with the geometry, a realistic pattern of the Standard Model fermion masses and mixings can be naturally obtained without any flavor symmetry. Neutrino masses and mixings required for the solar and atmospheric neutrino problems can also be accommodated. The geometry of extra dimensions and branes provides another way to realize the absence of certain interactions (as required in the pseudo-Goldstone boson mechanism) or the smallness of some couplings (e.g., the Yukawa couplings between the fermions and the Higgs bosons), in addition to the usual symmetry arguments.Comment: 16 pages, 4 figures, LaTeX, references and some clarifying remarks added, to be published in Phys. Rev.

Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics

Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively. Transcriptome data of cells treated with CKI or 5-Fluorouracil (5-FU) for 24 and 48 hours were subsequently acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.Zhipeng Qu, Jian Cui, Yuka Harata-Lee, Thazin Nwe Aung, Qianjin Feng, Joy M. Raison, Robert Daniel Kortschak, David L. Adelso

Engineering of Cyclodextrin Product Specificity and pH Optima of the Thermostable Cyclodextrin Glycosyltransferase from Thermoanaerobacterium thermosulfurigenes EM1

The product specificity and pH optimum of the thermostable cyclodextrin glycosyltransferase (CGTase) from Thermoanaerobacterium thermosulfurigenes EM1 was engineered using a combination of x-ray crystallography and site-directed mutagenesis. Previously, a crystal soaking experiment with the Bacillus circulans strain 251 β-CGTase had revealed a maltononaose inhibitor bound to the enzyme in an extended conformation. An identical experiment with the CGTase from T. thermosulfurigenes EM1 resulted in a 2.6-Å resolution x-ray structure of a complex with a maltohexaose inhibitor, bound in a different conformation. We hypothesize that the new maltohexaose conformation is related to the enhanced α-cyclodextrin production of the CGTase. The detailed structural information subsequently allowed engineering of the cyclodextrin product specificity of the CGTase from T. thermosulfurigenes EM1 by site-directed mutagenesis. Mutation D371R was aimed at hindering the maltohexaose conformation and resulted in enhanced production of larger size cyclodextrins (β- and γ-CD). Mutation D197H was aimed at stabilization of the new maltohexaose conformation and resulted in increased production of α-CD. Glu258 is involved in catalysis in CGTases as well as α-amylases, and is the proton donor in the first step of the cyclization reaction. Amino acids close to Glu258 in the CGTase from T. thermosulfurigenes EM1 were changed. Phe284 was replaced by Lys and Asn327 by Asp. The mutants showed changes in both the high and low pH slopes of the optimum curve for cyclization and hydrolysis when compared with the wild-type enzyme. This suggests that the pH optimum curve of CGTase is determined only by residue Glu258.

A Study on the Contract of Employment about Volunteers: Based on the Legal System and Interpretation of Volunteer Remuneration in France

departmental bulletin pape

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission