Compact in-plane dual-axis spring-steel accelerometer

Presented in this paper is an improvement over a spring-steel dual-axis accelerometer that we had reported earlier.The fabrication process (which entails wire-cut electro discharge machining of easily accessible and inexpensive spring-steelfoil) and the sensing of the displacement (which is done using off-the-shelf Hall-effect sensors) remain the same. Theimprovements reported here are twofold: (i) the footprint of the packaged accelerometer is reduced from 80 mm square to 40mm square, and (ii) almost perfect de-coupling and symmetry are achieved between the two in-plane axes of the packageddevice as opposed to the previous embodiment where this was not the case. Good linearity with about 40 mV/g was measuredalong both the in-plane axes over a range of 0.1 to 1 g. The first two natural frequencies of the devices are at 30 Hz and 100Hz, respectively, as per the experiment. The highlights of this work are cost-effective processing, easy integration of the Hall-effect sensing capability on a customised printed circuit board, and inexpensive packaging without overly compromising eitherthe overall size or the sensitivity of the accelerometer. Through this work, we have reaffirmed the practicability of spring-steelaccelerometers towards the eventual goal of making it compete with micro machined silicon accelerometers in terms of sizeand performance. The cost is likely to be much lower for the spring-steel accelerometers than that of silicon accelerometers, especially when the volume of production is low and the sensor is to be used as a single packaged unit.

The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA

Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Delta 40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Delta 40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Delta 40p53 protein levels and the subsequent transcriptional activation of the 14-3-3 sigma gene, a known target of Delta 40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

HCV-like IRESs sequester eIF3: advantage virus

In a recent Nature paper, Hashem et al. attempted to probe deeper into the elusive role of eIF3 in translation initiation of viruses with hepatitis C virus-like internal ribosome entry sites (IRESs), but instead uncovered a surprising role of these IRESs in displacing eIF3 from the 40S subunit, favoring viral translation.

Carbohydrate-Appended Tumor Targeting Iron(III) Complexes Showing Photocytotoxicity in Red Light

Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand Fe(bpyag) (L)] (NO3) (1-3), where bpyag is N,N-bis(2- pyridylmethyl)-2-aminoethyl-beta-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H(2)phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H(2)anap) 2, and 3- (2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H(2)pyap) in 3, were synthesized and characterized. The complex Fe(dpma)(anapn(NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of similar to 5.9 mu(B) showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of similar to 20 mu M in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.

Modulation of glyceraldehyde-3-phosphate dehydrogenase activity by surface functionalized quantum dots

Enzymatic regulation is a fast and reliable diagnosis tool via identification and design of inhibitors for modulation of enzyme function. Previous reports on quantum dots (QDs)-enzyme interactions reveal a protein-surface recognition ability leading to promising applications in protein stabilization, protein delivery, bio-sensing and detection. However, the direct use of QDs to control enzyme inhibition has never been revealed to date. Here we show that a series of biocompatible surface-functionalized metal-chalcogenide QDs can be used as potent inhibitors for malignant cells through the modulation of enzyme activity, while normal cells remain unaffected. The in vitro activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme involved critically in the glycolysis of cancer cells, is inactivated selectively in a controlled way by the QDs at a significantly low concentration (nM). Cumulative kinetic studies delineate that the QDs undergo both reversible and irreversible inhibition mechanisms owing to the site-specific interactions, enabling control over the inhibition kinetics. These complementary loss-of-function probes may offer a novel route for rapid clinical diagnosis of malignant cells and biomedical applications.

Designing one dimensional Co-Ni/Co3O4-NiO core/shell nano-heterostructure electrodes for high-performance pseudocapacitor

A high-performance supercapacitor electrode based on unique 1D Co-Ni/Co3O4-NiO core/shell nano-heterostructures is designed and fabricated. The nano-heterostructures exhibit high specific capacitance (2013 F g(-1) at 2.5 A g(-1)), high energy and power density (23Wh kg(-1) and 5.5kW kg(-1), at the discharge current density of 20.8 A g(-1)), good capacitance retention and long cyclicality. The remarkable electrochemical property of the large surface area nano-heterostructures is demonstrated based on the effective nano-architectural design of the electrode with the coexistence of the two highly redox active materials at the surface supported by highly conducting metal alloy channel at the core for faster charge transport. (C) 2014 AIP Publishing LLC.

Iron(III) benzhydroxamates of dipicolylamines for photocytotoxicity in red light and cellular imaging

Benzhydroxamate (BHA) iron(III) complexes Fe(BHA)(L)ClICI (I, 2)], where L is (phenyl)dipicolylamine (phdpa in I) and (pyrenyl)dipicolylamine (pydpa in 2), were prepared and their photocytotoxicity in visible (400-700 nm) and red (600-720 nm) light was studied. Complex 1 was structurally characterized by X-ray crystallography. The complexes have high-spin iron(III) centers. Complex 2, with a pyrenyl fluorophore, was used for cellular imaging, showing both mitochondrial and nuclear localization in the fluorescence microscopic study. The complex exhibited photocytotoxicity in red light in HeLa cancer cells, giving IC50 value of 24.4(+/- 0.4) pM, but remained essentially non-toxic in the dark. The involvement of reactive oxygen species and an apoptotic nature of cell death were observed from the cellular studies. (C) 2014 Elsevier Ltd. All rights reserved.

Mitochondria-Targeted Photoinduced Anticancer Activity of Oxidovanadium( IV) Complexes of Curcumin in Visible Light

Oxidovanadium(IV) complexes VO(py-aebmz)(B)]Cl (1, 2) and VO(napth-py-aebmz)(cur)]Cl 3; py-aebmz = 2-(1H-benzimidazol-2-yl)-N-(pyridin-2-ylmethylene)ethanamine, HB = acetylacetone (Hacac, 1) and curcumin (Hcur, 2), napth-py-aebmz = naphthalimide conjugated to py-aebmz ] have been prepared, characterized and their photoinduced DNA cleavage activities and photocytotoxicities studied. Complexes 1-3 each exhibited an irreversible cyclic voltammetric response of the V-IV/V-III redox couple at around -0.85 V versus SCE in dmf/0.1 M tbap. The complexes showed DNA photocleavage activity in visible light of 454, 530 and 647 nm through hydroxyl radical and singlet oxygen pathways. Fluorescence microscopy data suggest mitochondrial localization of complex 3 bearing a naphthalimide with a two-fold increase in photocytotoxicity in HaCaT cells with an IC50 value of 6.3 M and a three-fold increase in MCF-7 cells with an IC50 of 5.4 M compared with complex 2. Both 2 and 3 were non-toxic in the dark.

Mitochondria targeting Photocytotoxic Oxidovanadium( IV) Complexes of Curcumin and ( Acridinyl) dipyridophenazine in Visible Light

Oxidovanadium(IV) complexes, VO(acac)(L)Cl] (1), VO(cur)(L)Cl] (2), and VO(scur)(L)Cl] (3) {acac = acetylacetonate, cur = curcumin monoanion, scur = diglucosylcurcumin monoanion, L = 11-(9-acridinyl)dipyrido3, 2-a:2',3'-c]phenazine (acdppz)}, were prepared and characterized. The complexes are non-electrolytic in DMF and 1:1 electrolytic in aqueous DMF. The one-electron paramagnetic complexes showed a d-d band near 725 nm in aqueous DMF and green emission near 520 nm in aqueous DMSO. The complexes exhibited an irreversible V-IV/V-III redox response near -0.85 V versus SCE in aqueous DMF. The complexes showed good binding strengths to calf thymus DNA (K-b: 3.1x10(5)-9.6x10(5) M-1) and efficient pUC19 DNA photocleavage activity in red light of 705 and 785 nm by singlet oxygen (O-1(2)) pathway. Complexes 1 and 2 exhibited significant photocytotoxicity (IC50: 0.1-1.0 M) in visible light (400-700 nm) with low dark toxicity (IC50: >20 M) in HeLa and HaCaT cells. Complex 3 was cytotoxic in both light and dark. DNA ladder formation experiments indicated cell death via apoptotic pathway. Confocal microscopy done with 1 and 2 revealed primarily cytosolic localization of the complexes with significant presence of the complex in the mitochondria as evidenced from the imaging data using mitotracker red.

A MICROMACHINED WIDE-BAND IN-PLANE SINGLE-AXIS CAPACITIVE ACCELEROMETER WITH A DISPLACEMENT-AMPLIFYING COMPLIANT MECHANISM

With the premise that electronic noise dominates mechanical noise in micromachined accelerometers, we present here a method to enhance the sensitivity and resolution at kHz bandwidth using mechanical amplification. This is achieved by means of a Displacement-amplifying Compliant Mechanism (DaCM) that is appended to the usual sensing element comprising a proof-mass and a suspension. Differential comb-drive arrangement is used for capacitive-sensing. The DaCM is designed to match the stiffness of the suspension so that there is substantial net amplification without compromising the bandwidth. A spring-mass-lever model is used to estimate the lumped parameters of the system. A DaCM-aided accelerometer and another without a DaCM-both occupying the same footprint-are compared to show that the former gives enhanced sensitivity: 8.7 nm/g vs. 1.4 nm/g displacement at the sensing-combs under static conditions. A prototype of the DaCM-aided micromachined acclerometer was fabricated using bulk-micromachining. It was tested at the die-level and then packaged on a printed circuit board with an off-the-shelf integrated chip for measuring change in capacitance. Under dynamic conditions, the measured amplification factor at the output of the DaCM was observed to be about 11 times larger than the displacement of the proof-mass and thus validating the concept of enhancing the sensitivity of accelerometers using mechanical amplifiers. The measured first in-plane natural frequency of the fabricated accelerometer was 6.25 kHz. The packaged accelerometer with the DaCM was measured to have 26.7 mV/g sensitivity at 40 Hz.

The Glycosylated Rv1860 Protein of Mycobacterium tuberculosis Inhibits Dendritic Cell Mediated TH1 and TH17 Polarization of T Cells and Abrogates Protective Immunity Conferred by BCG

We previously reported interferon gamma secretion by human CD4(+) and CD8(+) T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB) as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-alpha, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-beta unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-gamma and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-gamma and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-alpha compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH17-dominated adaptive immune response that is vital for protection against tuberculosis.

Improving the Sensitivity and Bandwidth of In-Plane Capacitive Microaccelerometers Using Compliant Mechanical Amplifiers

This paper presents a method to enhance both the sensitivity and bandwidth of in-plane capacitive micromachined accelerometers by using compliant mechanical amplifiers, and thus obviating the compromise between the sensitivity and bandwidth. Here, we compare one of the most sensitive single-axis capacitive accelerometers and another with large resonant frequency reported in the literature with the modified designs that include displacement-amplifying compliant mechanisms (DaCMs) occupying the same footprint and under identical conditions. We show that 62% improvement in sensitivity and 34% improvement in bandwidth in the former, and 27% and 25% in the latter can be achieved. Also presented here is a dual-axis accelerometer that uses a suspension that decouples and amplifies the displacements along the two in-plane orthogonal axes. The new design was microfabricated, packaged, and tested. The device is 25-mu m thick with the interfinger gap as large as 4 m. Despite the simplicity of the microfabrication process, the measured axial sensitivity (static) of about 0.58 V/g for both the axes was achieved with a cross-axis sensitivity of less than +/- 2%. The measured natural frequency along the two in-plane axes was 920 Hz. Displacement amplification of 6.2 was obtained using the DaCMs in the dual-axis accelerometer. 2013-0083]

Iron(III) Catecholates for Cellular Imaging and Photocytotoxicity in Red Light

Iron(III) complexes Fe(L)(L') (NO3)]-in which L is phenyl-N, N-bis(pyridin-2-yl) methyl]methanamine (1), (anthracen-9-yl)N, N-bis(pyridin-2-yl) methyl] methanamine (2), (pyreny-1-yl)-N, N-bis(pyridin- 2-yl) methyl] methanamine (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)benzene- 1,2-diolate (5)-were synthesized and their photocytotoxic proper-ties examined. The five electron-paramagnetic complexes displayed a FeIII/ Fe-II redox couple near similar to 0.4 V versus a saturated calomel electrode (SCE) in DMF/0.1m tetrabutylammonium perchlorate (TBAP). They showed unpre-cedented photocytotoxicity in red light (600-720 nm) to give IC50-15 mm in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785 nm to form hydroxyl radicals.