VLSI design of the tiny RISC microprocessor

This report describes the Tiny RISC microprocessor designed at UC Irvine. Tiny RISC is a 16-bit microprocessor and has a RISC-style architecture. The chip was fabricated by MOSIS [1] in a 2μm n-well CMOS technology. The processor has a cycle time of 70 ns

A user configurable data acquisition and signal processing system for high-rate, high channel count applications

Real-time signal processing in plasma fusion experiments is required for control and for data reduction as plasma pulse times grow longer. The development time and cost for these high-rate, multichannel signal processing systems can be significant. This paper proposes a new digital signal processing (DSP) platform for the data acquisition system that will allow users to easily customize real-time signal processing systems to meet their individual requirements. The D-TACQ reconfigurable user in-line DSP (DRUID) system carries out the signal processing tasks in hardware co-processors (CPs) implemented in an FPGA, with an embedded microprocessor (μP) for control. In the fully developed platform, users will be able to choose co-processors from a library and configure programmable parameters through the μP to meet their requirements. The DRUID system is implemented on a Spartan 6 FPGA, on the new rear transition module (RTM-T), a field upgrade to existing D-TACQ digitizers. As proof of concept, a multiply-accumulate (MAC) co-processor has been developed, which can be configured as a digital chopper-integrator for long pulse magnetic fusion devices. The DRUID platform allows users to set options for the integrator, such as the number of masking samples. Results from the digital integrator are presented for a data acquisition system with 96 channels simultaneously acquiring data at 500 kSamples/s per channel

Synthesis and Isolation of Specific DNA Aptamer Against Ovarian CancerCell Line

  Introduction: Identification and targeting of cancer cell surface biomarkers is highly important for targeted drug delivery and reduction of chemotherapy side effect. Aptamer or chemical antibody is single-stranded DNA or RNA sequences that fold into secondary and tertiary structures making them bind to certain targets with extremely high specificity. Aptamer is a useful tool for biomarker discovery, drug targeted delivery or applied to make a biosensor. Methods and Results: In this study, the Cell-based Systematic Evolution of Liganeds by Exponential Enrichment (Cell-SELEX) was used to develop aptamer against ovarian cancer cell lines. Monitor Pool enrichment was done by flow cytometry. SSDNA of Round 12 was cloned in to pTZ57R\T vector and was sequenced. Specificity and affinity of isolated Aptamer were determined by flow cytometry... Aptamer selection was performed for 14 rounds. Round 12 selected as appropriate round for cloning. sixty aptamers were sequenced and alignment by DNAMAN software. homology of isolated aptamer was 34.1 percent. Eight aptamer were selected after phylogenic tree generated among these aptamers Mana88 sequences was specific against ovarian cancer cell line. Mana14 and Mana94 did not attached to normal cell line but they recognized other cancer cell line. Kd of isolated aptamer were 41, 250 and 2500 for Mana88, Mana14 and Mana94 respectively Conclusions: Chemotherapy is the main technique of cancer therapy; however, its side effects make it a toxic and invasive procedure. The goal of targeted chemotherapy is to overcome at least some of these nonspecific side effects. Aptamers are a class of molecule which rival antibodies in therapeutic and diagnostic applications. Mana 88 isolated in this study could use for targeted drug delivery and diagnostic ovarian cancer. Mana14 could use for targeted drug delivery ovarian and breast cancers. Isolation. Target of isolated aptamer on the cell surface will be recognized by proteomics approache

Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus

BACKGROUND: Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein in rat hippocampus. METHODS: Crocin (12.5, 25, and 50 mg/kg), imipramine (10 mg/kg; positive control) and saline (1 mL/kg; neutral control) were administered intraperitoneally (IP) to male Wistar rats for 21 days. The antidepressant effects were studied using the forced swimming test (FST) on day 21 after injection. Protein expression and transcript levels of genes in the rat hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. RESULTS: Crocin significantly reduced the immobility time in the FST. Western blot analysis showed that 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently. All doses of crocin increased the VGF levels in a dose-dependent manner. Levels of p-CREB increased significantly by 50 mg/kg dose of crocin. Only 12.5 mg/kg crocin could significantly increase the transcript levels of BDNF. No changes in CREB and VGF transcript levels were observed in all groups. CONCLUSIONS: These results suggest that crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus

Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer

Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA- mediated P-gp downregulation. Materials and Methods: NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamineTM (OFA) in vitro and in vivo. Results: Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. Conclusion: The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy

Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53–57.59 μM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50 = 0.80–14.81 μM) and HDAC1 inhibitory activity (IC50 = 0.47–0.87 μM and also, had no effect on Huvec (human normal cell line) viability (IC50 > 100 μM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47 ± 0.02 μM near equal to the reference drug Entinostat (IC50 = 0.41 ± 0.06 μM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzym

A colorimetric aptasensor for selective detection of oxytetracycline in milk, using gold nanoparticles and oxytetracline-short aptamer

Objective (s): In light of misuse of antibiotics in animal husbandry and their side effects on human health, there is an argent need to develop simple and rapid methods for determining the quantification of antibiotics in biological systems. Materials and Methods: In this work a facile and ultrasensitive colorimetric aptasensor was reported for detection of oxytetracycline (OTC) in water and milk samples employing OTC-short aptamer and gold nanoparticles (AuNPs). Results: In the presence of OTC, the interaction between OTC and its aptamer leads to the separation of OTC aptamer from the surface of AuNPs which is followed by the aggregation of AuNPs by salt, showing an evident color change from red to blue. On the contrary, in the absence of OTC, the attachment of aptamer on the surface of AuNPs can protect AuNPs against salt-induced aggregation with a wine-red color. The proposed aptasensor exhibits excellent sensitivity for detection of OTC with linear range between 20 to 2000 nM with limit of detection (LOD) as low as 10 nM. Furthermore, this strategy was applied to detect OTC in spiked milk samples and presented satisfying linear range from 25 to 1500 nM with the LOD of 20 nM. Conclusion: Owing to demonstrating appropriate sensitivity and selectivity, the designed biosensor can be considered as a promising tool to be applied in the field of biomedicine and food safety

The effects of crocin on spatial memory impairment induced by hyoscine: Role of NMDA, AMPA, ERK, and CaMKII proteins in rat hippocampus

Objective(s): Crocus sativus L. and its active constituent, crocin, have neuroprotective effects. The effects of crocin on memory impairment have been mentioned in studies but the signaling pathways  have not been evaluated. Therefore, the aim of this study was to evaluate the effects of crocin on the hyoscine-induced memory impairment in rat. Additionally, the level of NMDA (N-methyl-D-aspartate receptors), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicd acid), ERK (extracellular signal-regulated kinases), CaMKII (calcium (Ca2+)/calmodulin (CaM)-dependent kinaseII) mRNA and proteins were determined in rat hippocampus. Materials and Methods: Crocin (10, 20, and 40 mg/kg), hyoscine (1.5 mg/kg), normal saline and rivastigmine  were administered intraperitoneally to male Wistar rats for 5 days. The effects on memory improvement were studied using Morris water maze (MWM) test. Then, the protein levels of NMDA, AMPA, ERK, pERK, CaMKII and p.CaMKII  in hippocampus were analized using the Western blot test. Furthermore, the mRNA levels of NMDA, AMPA, ERK and pCaMKII genes were evaluated using real-time quantitative reverse transcription-polymerase chain reaction (qRT- PCR) method. Results: Aadminestration of crocin (20 mg/kg) and rivastigmine  significantly improved learning and memory impairment induced by hyoscine. Also, administration of hyoscine reduced  protein level of pERK,  while treatment with crocin (20 mg/kg) recovered the protein level.  No changes were observed in the protein levels and mRNA gene expression of NMDA, AMPA, ERK, CaMKII and pCaMKII following adminestration of hyoscine or crocin. Conclusion: Adminestration of crocin improved memory and learning. The effect of crocin in this model can be mediated by alteration in pERK protein level in rat hippocampus

Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats

Objective(s): Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats. Materials and Methods: Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (3 g/kg/day, gavage), thymoquinone (2.5, 5, 10 mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (10 mg/Kg/day, IP) groups. Treatments were carried out in four weeks. Results: Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-2 ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity. Conclusion: This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis