FORMULATION AND EVALUATION OF FLOATING DRUG DELIVERY OF CEFOTAXIME USING RAFT FORMING APPROACH

The cefotaxime is a broad-spectrum cephalosporin antibiotic. It is mainly used in the treatment of bacterial infections. Cefotaxime is a suitable candidate for controlled release administration due to its short elimination time 1 hour. The main aim of the present investigation is to increase the gastric residence time by preparing floating drug delivery by using raft forming approach thereby improving bioavailability. The prepared Cefotaxime floating drug delivery by using raft forming approach were evaluated for hardness, weight variation, thickness, friability, drug content uniformity, total floating time, In-vitro dissolution studies and buoyancy lag time. Floating tablets were formulated using direct compression technique. Various polymers are used in the formulation they Microcrystalline cellulose used as binder, HPMC K15M, Guargum used as hydrophilic polymers, Chitosan, Sodium bicarbonate was incorporated as an effervescent substance, Sodium alginate used as viscous gel forming agent, Magnesium streate used as lubrication, talc was used as diluent. The formulated Cefotaxime tablet to be evaluated the following parameters as follow Weight variation (mg), Hardness, Thickness, Friability, Drug content uniformity, Floating lag time, the in vitro cumulative amount of drug released was shown the F7 is 99.28% within 45 minutes the comparative studies with marketed formulations F7 show the better results. Keywords: Cefotaxime, Direct compression, Raft forming, floating drug delivery system

Interplay between NS3 protease and human La protein regulates translation-replication switch of Hepatitis C virus

HCV NS3 protein plays a central role in viral polyprotein processing and RNA replication. We demonstrate that the NS3 protease (NS3pro) domain alone can specifically bind to HCV-IRES RNA, predominantly in the SLIV region. The cleavage activity of the NS3 protease domain is reduced upon HCV-RNA binding. More importantly, NS3pro binding to the SLIV hinders the interaction of La protein, a cellular IRES-trans acting factor required for HCV IRES-mediated translation, resulting in inhibition of HCV-IRES activity. Although overexpression of both NS3pro as well as the full length NS3 protein decreased the level of HCV IRES mediated translation, replication of HCV replicon RNA was enhanced significantly. These observations suggest that the NS3pro binding to HCV IRES reduces translation in favor of RNA replication. The competition between the host factor (La) and the viral protein (NS3) for binding to HCV IRES might regulate the molecular switch from translation to replication of HCV

An instrument to determine the technological literacy levels of upper secondary school students

In this article, an instrument for assessing upper secondary school students’ levels of technological literacy is presented. The items making up the instrument emerged from a previous study that employed a phenomenographic research approach to explore students’ conceptions of technology in terms of their understanding of the nature of technology and their interaction with technological artefacts. The instrument was validated through administration to 1,245 students on completion of their 12 years of formal schooling. A factor analysis was conducted on the data and Cronbach alpha reliability coefficients determined. The results show that a five-dimension factor structure (namely, artefact, process, direction/instruction, tinkering, and engagement) strongly supported the dimensions as developed during the original phenomenographic study. The Cronbach alpha reliability co-efficient of each dimension was satisfactory. Based on these findings, the instrument has been shown to be valid and reliable and can be used with confidence

A La Autoantigen Homologue Is Required for the Internal Ribosome Entry Site Mediated Translation of Giardiavirus

Translation of Giardiavirus (GLV) mRNA is initiated at an internal ribosome entry site (IRES) in the viral transcript. The IRES localizes to a downstream portion of 5′ untranslated region (UTR) and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA), known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200–348aa) of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus

Refractoriness of hepatitis C virus internal ribosome entry site to processing by Dicer in vivo

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a positive-strand RNA virus harboring a highly structured internal ribosome entry site (IRES) in the 5' nontranslated region of its genome. Important for initiating translation of viral RNAs into proteins, the HCV IRES is composed of RNA structures reminiscent of microRNA precursors that may be targeted by the host RNA silencing machinery.</p> <p>Results</p> <p>We report that HCV IRES can be recognized and processed into small RNAs by the human ribonuclease Dicer in vitro. Furthermore, we identify domains II, III and VI of HCV IRES as potential substrates for Dicer in vitro. However, maintenance of the functional integrity of the HCV IRES in response to Dicer overexpression suggests that the structure of the HCV IRES abrogates its processing by Dicer in vivo.</p> <p>Conclusion</p> <p>Our results suggest that the HCV IRES may have evolved to adopt a structure or a cellular context that is refractory to Dicer processing, which may contribute to viral escape of the host RNA silencing machinery.</p

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

Design of arithmetic circuits in quantum dot cellular automata nanotechnology

This research monograph focuses on the design of arithmetic circuits in Quantum Dot Cellular Automata (QCA). Using the fact that the 3-input majority gate is a primitive in QCA, the book sets out to discover hitherto unknown properties of majority logic in the context of arithmetic circuit designs. The pursuit for efficient adders in QCA takes two forms. One involves application of the new results in majority logic to existing adders. The second involves development of a custom adder for QCA technology. A QCA adder named as hybrid adder is proposed and it is shown that it outperforms existing multi-bit adders with respect to area and delay. The work is extended to the design of a low-complexity multiplier for signed numbers in QCA. Furthermore the book explores two aspects unique to QCA technology, namely thermal robustness and the role of interconnects. In addition, the book introduces the reader to QCA layout design and simulation using QCADesigner. Features & Benefits: This research-based book: ·         Introduces the reader to Quantum Dot Cellular Automata, an emerging nanotechnology. ·         Explores properties of majority logic. ·         Demonstrates application of the properties to design efficient arithmetic circuits. ·         Guides the reader towards layout design and simulation in QCADesigner

CORDIC-Based Azimuth Calculation and Obstacle Tracing via Optimal Sensor Placement on a Mobile Robot

Autonomous robots are currently engaged in emergency informatics and participate in operations such as search and rescue. Real-time data collection is a key requirement while there are constraints on the space, height and weight of the hardware on-board with such robots. In this paper, we investigate the amount and sophistication of sensing and processing hardware needed by amobile robot for performing high-level tasks in real time. In particular, we consider two tasks, namely azimuth calculation and dynamic obstacle tracing and show that one ultrasonic sensor along with a coordinate rotation digital computer processor are adequate for azimuth calculation while one more ultrasonic sensor is required for dynamic obstacle tracing. For dynamic obstacle tracing, we also study a related problem of optimal placement of a pair of ultrasonic sensors. Experiments with a field programmable gate array-based robot equipped with ultrasonic sensors are presented to support the theory