Synthesis and characterization of novel 2, 2'-bipyrimidine fluorescent derivative for protein binding

<p>Abstract</p> <p>Background</p> <p>Fluorescent dyes with biocompatible functional group and good fluorescence behavior are used as biosensor for monitoring different biological processes as well as detection of protein assay. All reported fluorophore used as sensors are having high selectivity and sensitivity but till there is more demand to synthesized new fluorophore which have improved fluorescence properties and good biocompatibility.</p> <p>Results</p> <p>Novel 4, 4'-(1, 1'-(5-(2-methoxyphenoxy)-[2, 2'-bipyrimidine]-4, 6-diyl)bis(1<it>H</it>-pyrazol-3, 1-diyl)) dianiline fluorescent dye was synthesized by multistep synthesis from 2-phenylacetonitrile, 2-chloropyrimidine and 2-methoxyphenol. This dye has absorption at 379 nm with intense single emission at 497 nm having fairly good quantum yield (0.375) and Stokes shift. The intermediates and dye were characterized by FT-IR, ¹H NMR, ¹³C NMR and Mass spectral analysis. The pyrazole bipyrimidine based fluorescent dye possessing two amino groups suitable for binding with protein is reported. Its utility as a biocompatible conjugate was explained by conjugation with bovine serum albumin. The method is based on direct fluorescence detection of fluorophore-labelled protein before and after conjugation. Purified fluorescent conjugate was subsequently analyzed by fluorimetry. The analysis showed that the tested conjugation reaction yielded fluorescent conjugates of the dye through carbodiimide chemistry.</p> <p>Conclusion</p> <p>In summery synthesized fluorophore pyrazole-bipyrimidine has very good interaction towards protein bovine serum albumin and it acts as good candidate for protein assay.</p

Modified SPLICE and its Extension to Non-Stereo Data for Noise Robust Speech Recognition

In this paper, a modification to the training process of the popular SPLICE algorithm has been proposed for noise robust speech recognition. The modification is based on feature correlations, and enables this stereo-based algorithm to improve the performance in all noise conditions, especially in unseen cases. Further, the modified framework is extended to work for non-stereo datasets where clean and noisy training utterances, but not stereo counterparts, are required. Finally, an MLLR-based computationally efficient run-time noise adaptation method in SPLICE framework has been proposed. The modified SPLICE shows 8.6% absolute improvement over SPLICE in Test C of Aurora-2 database, and 2.93% overall. Non-stereo method shows 10.37% and 6.93% absolute improvements over Aurora-2 and Aurora-4 baseline models respectively. Run-time adaptation shows 9.89% absolute improvement in modified framework as compared to SPLICE for Test C, and 4.96% overall w.r.t. standard MLLR adaptation on HMMs.Comment: Submitted to Automatic Speech Recognition and Understanding (ASRU) 2013 Worksho

An emerging protagonist: Sodium Glucose Co-transporters (SGLTs) as a burgeoning target for the treatment of diabetes mellitus

Contemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. The kidney emerges out as a novel and potential target to trim down the T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which is present at the luminal surface cells that cover the first segment of proximal tubules. Competitive inhibition of SGLT2 therefore represents an innovative therapeutic strategy for the treatment of hyperglycaemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. SGLT2 inhibitors are coupled with osmotic dieresis and loss of weight which aid in reducing blood pressure. The observation that individuals with familial renal glycosuria maintain normal long-term kidney function provides some encouragement that this mode of action will not adversely affect renal function. This novel mechanism of targeting the kidney for the treatment of T2DM is reasonably valuable and is independent of insulin and clutch with the low risk of hypoglycemia

Doctor of Philosophy

dissertationAsynchronous design has a very promising potential even though it has largely received a cold reception from industry. Part of this reluctance has been due to the necessity of custom design languages and computer aided design (CAD) flows to design, optimize, and validate asynchronous modules and systems. Next generation asynchronous flows should support modern programming languages (e.g., Verilog) and application specific integrated circuits (ASIC) CAD tools. They also have to support multifrequency designs with mixed synchronous (clocked) and asynchronous (unclocked) designs. This work presents a novel relative timing (RT) based methodology for generating multifrequency designs using synchronous CAD tools and flows. Synchronous CAD tools must be constrained for them to work with asynchronous circuits. Identification of these constraints and characterization flow to automatically derive the constraints is presented. The effect of the constraints on the designs and the way they are handled by the synchronous CAD tools are analyzed and reported in this work. The automation of the generation of asynchronous design templates and also the constraint generation is an important problem. Algorithms for automation of reset addition to asynchronous circuits and power and/or performance optimizations applied to the circuits using logical effort are explored thus filling an important hole in the automation flow. Constraints representing cyclic asynchronous circuits as directed acyclic graphs (DAGs) to the CAD tools is necessary for applying synchronous CAD optimizations like sizing, path delay optimizations and also using static timing analysis (STA) on these circuits. A thorough investigation for the requirements of cycle cutting while preserving timing paths is presented with an algorithm to automate the process of generating them. A large set of designs for 4 phase handshake protocol circuit implementations with early and late data validity are characterized for area, power and performance. Benchmark circuits with automated scripts to generate various configurations for better understanding of the designs are proposed and analyzed. Extension to the methodology like addition of scan insertion using automatic test pattern generation (ATPG) tools to add testability of datapath in bundled data asynchronous circuit implementations and timing closure approaches are also described. Energy, area, and performance of purely asynchronous circuits and circuits with mixed synchronous and asynchronous blocks are explored. Results indicate the benefits that can be derived by generating circuits with asynchronous components using this methodology

Automatic addition of reset in asynchronous sequential control circuits

pre-printAsynchronous finite state machines (AFSMs) usually require initialization to place them in a desired starting state. This normally occurs by toggling a reset signal upon power-up. This paper presents an algorithm to automatically generate power-up reset circuitry thus adding reset to an AFSM after technology mapping. This approach is independent of design methodology since it is applied to a gate netlist. The algorithm ensures all combinational cycles and primary outputs in the circuit are initialized. Options exist in reset generation to minimize the power or performance impact on the AFSM. Results are reported for applying this algorithm to designs of varying size and complexity

Advancements in Otology: Hearing Restoration and Cochlear Implant Innovations

Otology has made significant strides in recent years, most notably in the development of cochlear implants and the restoration of hearing. This thorough analysis looks at the most recent advancements in cochlear implant technology, treatment modalities, regenerative medicine, auditory rehabilitation techniques, and future prospects in otology. A variety of therapies are included in the field of audiology rehabilitation, such as digital signal processing in sophisticated hearing aids, assistive listening devices, and transformational cochlear implants. Cochlear implant innovations include improved electrode arrays, signal processing algorithms, and brain interface technologies that greatly increase patients' ability to perceive speech and enjoy music. Stem cell therapy, tissue engineering, and gene editing techniques are promising avenues for rebuilding damaged auditory components in regenerative medicine, which may lead to eventual restoration of hearing. Therapeutic options include gene-based medicines, pharmaceutical interventions that target certain biological pathways, and personalised medication plans that are customised to each patient's unique auditory profile. Emerging technology, multidisciplinary cooperation, a better comprehension of auditory difficulties, and the creation of biocompatible materials for implant technologies are critical to the future of otology. On the other hand, obstacles include the need to translate research into clinical practice, accessibility inequities, and regulatory issues. This review emphasises the need to solve enduring issues in the area of otology while also highlighting the possibility for revolutionary advances in the field

Interfacing synchronous and asynchronous domains for open core protocol

pre-printIntellectual property (IP) blocks are connected in a system on chip using a bus or network-on-chip (NoC). IP reuse is facilitated by the modularity that results when using common interfaces between the IP cores and the bus or NoC. This paper investigates and implements several versions of one of the common interfaces, the open core protocol (OCP). The paper addresses two new aspects of interface design. First, an approach is developed to partition the common protocol portion of the interface from the interface back-end which is specific to the particular IP. This is achieved with a component we call a domain interface at this boundary. Second, the domain interface is enhanced to synchronize between IP blocks and busses that use different clock frequencies or asynchronous (unclocked) logic. As a result IP operating at unrelated frequency and fully asynchronous (unclocked) blocks can more easily be integrated into a system. Results are reported for power, performance and area for these clocked and asynchronous implementations