Interface Synthesis for Embedded Applications in a Codesign Environment

In embedded systems, programmable peripherals are often coupled with the main programmable processor to achieve desired functionality. Interfacing such peripherals with the processor qualifies as an important task of hardware software codesign. In this paper, three important aspects of such interfacing, namely the allocation of addresses to the devices, allocation of device drivers, and approaches to handle events and transitions have been discussed. The proposed approaches have been incorporated in a codesign system MICKEY. The paper includes a number of examples, taken from the results synthesized by MICKEY, to illustrate the ideas

Histamine and cis-urocanic acid augment tumor necrosis factor-alpha mediated induction of keratinocyte intercellular adhesion molecule-1 expression

Early cellular and molecular events in inflamed skin include the active participation of epidermal keratinocytes (KCs) and dermal mast cells which can produce diffusible mediators such as tumor necrosis factor-alpha (TNF-Α), histamine, and urocanic acid (UCA). Rapid induction of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by KCs is observed following a highly diverse array of stimuli which can provoke both irritant, inflammatory, as well as allergic and immune reactions. To determine if the aforementioned mediators could interact in either an additive or synergistic fashion with each other, cultured KCs were exposed to these mediators alone and in combination, and the degree of ICAM-1 mRNA and protein quantitated. Whereas histamine or cis-UCA alone only weakly induced KC ICAM-1, when they were combined with TNF-Α, significant augmentation was observed by Northern blot hybridization studies, immunostaining, and FACS analysis. Other histamine derivatives such as L-histidine, 1-methylhistidine, 3-methylhistidine, or all-trans-UCA had no effect. Histamine pretreatment did not affect cell surface high affinity TNF-Α receptors, as determined by ligand binding and immunodetection, and did not induce KC TNF-Α production. The KC histamine receptor was also characterized and found not to be influenced by TNF-Α, cis-UCA, all-trans-UCA, or diphenyhydramine (an H 1 antagonist), but it was inhibited by cimetidine (an H 2 antagonist). These results demonstrate that 1) KCs can be induced to express ICAM-1 by exposure to histamine and cis-UCA, 2) histamine and cis-UCA can also augment TNF-Α inducible ICAM-1 mRNA and cell surface protein expression, 3) this augmentation does not directly involve changes in KC TNF-Α receptor number, affinity, or TNF-Α production and, 4) KCs possess a type 2 histamine receptor which is not the photoreceptor for UCA. These findings highlight the potential for cross-talk between molecules produced by resident cutaneous cell types above (i.e., KCs) and below (i.e., mast cells) the epidermal basement membrane zone. These cells and their mediators can cooperate to respond to either exogenous or endogenous stimuli leading to rapid and strong KC ICAM-1 expression. Such induction of this important adhesion molecule by KCs ensures the retention of T lymphocytes necessary to participate in the maintenance of cutaneous immunohomeostasis. © 1993 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49885/1/1041560218_ftp.pd

Cationic Lipid Is Not Required for Uptake and Selective Inhibitory Activity of ICAM-1 Phosphorothioate Antisense Oligonucleotides in Keratinocytes

Keratinocyte intercellular adhesion molecule-1 (ICAM-1) is important in mediating retention of T cells within the epidermal compartment. To determine if antisense oligonucleotides designed to hybridize to various ICAM-1 mRNA regions could selectively influence cultured keratinocyte ICAM-1 expression following gamma interferon (IFN-γ), cells were exposed to several antisense compounds, in the absence and presence of cationic lipid (lipofectin). Keratinocytes rapidly internalized sense and antisense compounds (within 30-60 min), even in the absence of lipofectin with approximately 30% of the cell possessing positive nuclei. Such nuclear accumulation was not observed in the absence of lipofectin in cultured fibroblasts, smooth muscle cells, or endothelial cells, even though total cellular uptake within the cytoplasm was significantly increased in all these cell types. Using flow cytometry, IFN-γ-inducible ICAM-1 expression was reduced 50% by antisense compounds with lipofectin, and by 30% without lipofectin. This inhibition was specific as no change was observed for HLA-DR or tumor necrosis factor-α receptor expression. Northern blot hybridization studies confirmed that ICAM-1 antisense oligonucleotides selectively and significantly inhibited ICAM-1 expression. These results suggest that such antisense compounds interact with keratinocytes differently than other cell types, and provide the in vitro basis for clinical trials in which reduction (or elimination) of ICAM-1 expression by epidermal keratinocytes could be selectively accomplished without necessarily influencing dermal cell types such as fibroblasts, endothelial cells, or smooth muscle cells

Killing of endothelial cells and release of arachidonic acid

51 hromium-labeled rat pulmonary artery endothelial cells (EC) cultivated in MEM medium were killed, in a synergistic manner, by mixtures of subtoxic amounts of glucose oxidase-generated H 2 O 2 and subtoxic amounts of the following agents: the cationic substances, nuclear histone, defensins, lysozyme, poly- l -arginine, spermine, pancreatic ribonuclease, polymyxin B, chlorhexidine, cetyltrimethyl ammonium bromide, as well as by the membrane-damaging agents phospholipases A 2 (PLA 2 ) and C (PLC), lysolecithin (LL), and by streptolysin S (SLS) of group A streptococci. Cytotoxicity induced by such mixtures was further enhanced by subtoxic amounts either of trypsin or of elastase. Glucose-oxidase cationized by complexing to poly- l -histidine proved an excellent deliverer of membrane-directed H 2 O 2 capable of enhancing EC killing by other agonists. EC treated with rabbit anti-streptococcal IgG were also killed, in a synergistic manner, by H 2 O 2 , suggesting the presence in the IgG preparation of cross-reactive antibodies. Killing of EC by the various mixtures of agonists was strongly inhibited by scavengers of hydrogen peroxide (catalase, dimethylthiourea, MnCl 2 ), by soybean trypsin inhibitor, by polyanions, as well as by putative inhibitors of phospholipases. Strong inhibition of cell killing was also observed with tannic acid and by extracts of tea, but less so by serum. On the other hand, neither deferoxamine, HClO, TNF, nor GTP-γS had any modulating effects on the synergistic cell killing. EC exposed either to 6-deoxyglucose, puromycin, or triflupromazin became highly susceptible to killing by mixtures of hydrogen peroxide with several of the membrane-damaging agents. While maximal synergistic EC killing was achieved by mixtures of H 2 O 2 with either PLA 2 , PLC, LL, or with SLS, a very substantial release of [ 3 H]arachidonic acid (AA), PGE 3 , and 6-keto-PGF occurred only if a proteinase was also added to the mixture of agonists. The release of AA from EC was markedly inhibited either by scavengers of H 2 O 2 , by proteinase inhibitors, by cationic agents,by HClO, by tannic acid, and by quinacrin. We suggest that cellular injury induced in inflammatory and infectious sites might be the result of synergistic effects among leukocyte-derived oxidants, lysosomal hydrolases, cytotoxic cationic polypeptides, proteinases, and microbial toxins, which might be present in exudates. These “cocktails” not only kill cells, but also solubilize AA and several of its metabolites. However, AA release by the various agonists can be also achieved following attack by leukocyte-derived agonists on dead cells. It is proposed that treatment by “cocktails” of adequate antagonists might be beneficial to protect against cellular injury in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44512/1/10753_2004_Article_BF00918992.pd

Covalent organic framework based microspheres as an anode material for rechargeable sodium batteries

Covalent organic frameworks (COFs) promise several benefits as materials in terms of gas adsorption, for use in optoelectronic devices, etc. However, the energy storage ability of COFs has not been well studied, especially in sodium batteries. In this report, for the first time, a covalent organic framework (COF), TFPB-TAPT COF, is used as an anode with high capacity in sodium batteries. The TFPB-TAPT COF exhibits an initial reversible capacity of 246 mA h g−1 and a capacity of 125 mA h g−1 is retained after 500 cycles. The TFPB-TAPT COF further exhibits Na+ ion storage capability at different current rates. The Na+ ion storage viability of the TFPB-TAPT COF arises mainly because of its open ordered nanoporous framework, which provides reversible accommodation for ions. This work opens up a promising new approach for further utilization of COFs as electrode materials in rechargeable sodium batteries

Mitochondrial Variability as a Source of Extrinsic Cellular Noise

We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription, translation, stem cell differentiation and response to medication, but the specific random influences that affect these processes have yet to be clearly elucidated. Here we present a mechanism by which variability in mitochondrial volume and functionality, along with cell cycle dynamics, is linked to variability in transcription rate and hence has a profound effect on downstream cellular processes. Our model mechanism is supported by an appreciable volume of recent experimental evidence, and we present the results of several new experiments with which our model is also consistent. We find that noise due to mitochondrial variability can sometimes dominate over other extrinsic noise sources (such as cell cycle asynchronicity) and can significantly affect large-scale observable properties such as cell cycle length and gene expression levels. We also explore two recent regulatory network-based models for stem cell differentiation, and find that extrinsic noise in transcription rate causes appreciable variability in the behaviour of these model systems. These results suggest that mitochondrial and transcriptional variability may be an important mechanism influencing a large variety of cellular processes and properties

Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer

Recent studies have linked expression of lectin-like ox-LDL receptor 1 (OLR1) to tumorigenesis. We analyzed microarray data from Olr1 knockout (KO) and wild type (WT) mice for genes involved in cellular transformation and evaluated effects of OLR1 over-expression in normal mammary epithelial cells (MCF10A) and breast cancer cells (HCC1143) in terms of gene expression, migration, adhesion and transendothelial migration. Twenty-six out of 238 genes were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive genes contained NF-κB binding sites in their promoters. Further studies revealed broad inhibition of NF-kB target genes outside of the transformation-associated gene pool, with enrichment themes of defense response, immune response, apoptosis, proliferation, and wound healing. Transcriptome of Olr1 KO mice also revealed inhibition of de novo lipogenesis, rate-limiting enzymes fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd1) and ELOVL family member 6 (Elovl6), as well as lipolytic phospholipase A2 group IVB (Pla2g4b). In studies comparing MCF10A and HCC1143, the latter displayed 60% higher OLR1 expression. Forced over-expression of OLR1 resulted in upregulation of NF-κB (p65) and its target pro-oncogenes involved in inhibition of apoptosis (BCL2, BCL2A1, TNFAIP3) and regulation of cell cycle (CCND2) in both cell lines. Basal expression of FASN, SCD1 and PLA2G4B, as well as lipogenesis transcription factors PPARA, SREBF2 and CREM, was higher in HCC1143 cells. Over-expression of OLR1 in HCC1143 cells also enhanced cell migration, without affecting their adherence to TNFα-activated endothelium or transendothelial migration. On the other hand, OLR1 neutralizing antibody inhibited both adhesion and transmigration of untreated HCC1143 cells. We conclude that OLR1 may act as an oncogene by activation of NF-kB target genes responsible for proliferation, migration and inhibition of apoptosis and de novo lipogenesis genes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Levels, Trends and Disparities in Public-Health-Related Indicators among Reproductive-Age Women in Bangladesh by Urban-Rural and Richest-Poorest Groups, 1993-2011

Khan MH, Zanuzdana A, Krämer A. Levels, Trends and Disparities in Public-Health-Related Indicators among Reproductive-Age Women in Bangladesh by Urban-Rural and Richest-Poorest Groups, 1993-2011. PLoS ONE. 2013;8(9): e75261.BACKGROUND AND OBJECTIVES: Although Bangladesh has already achieved noticeable progress in the field of development and health, disparities in public health indicators for several markers are still reported. To assess public health development in Bangladesh during the last two decades, firstly, we analysed levels, trends and disparities in public-health-related indicators by rural versus urban as well as by the richest versus poorest group of women who have ever been married. Secondly, using the most recent data set we performed multiple analyses to check whether urban-rural and richest-poorest disparities were still significant. METHODS: The analysis was based on six nationally representative data sets from the Bangladesh Demographic and Health Surveys (BDHS) conducted in 1993-94 (n=9,640), 1996-1997 (n=9,127), 1999-2000 (n=10,544), 2004 (n=11,440), 2007 (n=10,996) and 2011 (n=17,749). The outcome variables were six selected public-health-related indicators. We performed various types of analyses, including multiple logistic regressions. RESULTS: The trend of all indicators except being overweight (1993-2011) displayed gradual improvements for both markers. However, the urban and richest groups revealed a better situation than their counterparts in both simple and multiple analyses. Disparities between richest-poorest groups were more pronounced than urban-rural disparities. For instance, the prevalence of delivery at any healthcare facility in 2011 was 20.4% in rural areas and 46.5% in urban areas, whereas it was 9.1% in the poorest group and 57.6% in the richest group. CONCLUSION: The public health sector in Bangladesh has achieved some successes over the last two decades. However, urban-rural and richest-poorest disparities are still considerable and therefore more public health strategies and efforts are clearly needed for the rural and poorest groups of women in order to reduce these gaps further