INTERACTIONS AND EFFECTS OF BIOMOLECULES ON AU NANOMATERIAL SURFACES

Au nanoparticles are increasingly being used in biological applications. Their use is of interest based upon their unique properties that are achieved at the nanoscale, which includes strong optical absorbances that are size and aggregation state dependent. Such absorbances can be used in sensitive chemical/biological detection schemes where bioligands can be directly attached to the nanoparticle surface using facile methods. Unfortunately, a number of complications persist that prevent their wide-scale use. These limitations include minimal nanoparticle stability in biological-based media of high ionic strength, unknown surface functionalization effects using simple biomolecules, and determining the binding motifs of the ligands to the nanoparticle surface. This situation can be further complicated when employing shaped materials where crystallographic facets can alter the binding potential of the bioligands. We have attempted to address these issues using traditional nanoparticle functionalization techniques that are able to be characterized using readily available analytical methods. By exploiting the optical properties of Au nanomaterials, we have been able to determine the solution stability of Au nanorods in a buffered medium and site-specifically functionalized Au nanomaterials of two different shapes: spheres and rods. Such abilities are hypothesized to be intrinsic to the bioligand once bound to the surface of the materials. Our studies have focused mainly on simple amino acids that have demonstrated unique assembly abilities for the materials in solution, resulting in the formation of specific patterns. The applications for such capabilities can range from the use of the materials as sensitive biochemical sensors to their directed assembly for use as device components

Cone Beam Computed Tomography Evaluation and Surgical Treatment of an Open Apex Case with Biodentine

Trauma to the facial region is a common event with injury of teeth. The treatment is aimed at the functional restoration of tooth along with complete biologic healing. Biodentine (Septodont, St Maurdes Fossés, France) introduced in the year 2011. It is a calcium silicate based material and is claimed by the manufacturers as repair of crown and root dentin repair treatment, perforations, resorptions, apexification, and root end fillings. This article presents a case report of conebeam computed tomography (CBCT) diagnosis and surgical management of an open apex case using biodentine as retrograde filling material

Differential cell responses to nanoparticle docetaxel and small molecule docetaxel at a sub-therapeutic dose range

Current preclinical evaluations of nanoparticle taxanes have focused on the effect of nanoparticle size and shape on the efficacy and toxicity. It is generally assumed that nanoparticle therapeutics have the same cellular response on tumor and normal cells as their small molecule counterparts. Here, we show that nanoparticle taxanes can mediate cellular effects distinct from that of small molecule taxanes at the sub-therapeutic dose range. Cells that are exposed to two polymeric nanoparticle formulations of docetaxel were found to undergo a different cell cycle and cell fate than that of cells that were exposed to small molecule docetaxel. Our results suggest that nanoparticle formulation of therapeutics can affect the therapeutic effect of its cargo

Indium-doped ZnOas efficient photosensitive material for sunlight driven hydrogen generation and DSSC applications: integrated experimental and computational approach

Electricity generation using simple and cheap dye-sensitized solar cells and photocatalytic water splitting to produce future fuel, hydrogen, directly under natural sunlight fascinated the researchers worldwide. Herein, synthesis of indium-doped wurtzite ZnO nanostructures with varying molar percentage of indium from 0.25 to 3.0% with concomitant characterization indicating wurtzite structure is reported. The shift of (002) reflection plane to higher 2θ degree with increase in indium-doping thus is a clear evidence of doping of indium in zinc oxide nanoparticles. Surface morphological as well as microstructural studies of In@ZnO exhibited generation of ZnO nanoparticles and nanoplates of diameter 10–30 nm. The structures have been correlated well using computational density functional (DFT) studies. Diffuse reflectance spectroscopy depicted the extended absorbance of these materials in the visible region. Hence, the photocatalytic activity towards hydrogen generation from water under natural sunlight as well as efficient DSSC fabrication of these newly synthesized materials has been demonstrated. In-doped ZnO exhibited enhanced photocatalytic activity towards hydrogen evolution (2465 μmol/h/g) via water splitting under natural sunlight. DSSC fabricated using 2% In-doped ZnO exhibited an efficiency of 3.46% which is higher than other reported In-doped ZnO based DSSCs

Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel Radiosensitizer for the Treatment of Non-Small Cell Lung Cancer

A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease

A Framework for Resilient, Transparent, High-throughput, Privacy-Enabled Central Bank Digital Currencies

Central Bank Digital Currencies refer to the digitization of lifecycle\u27s of central bank money in a way that meets first of a kind requirements for transparency in transaction processing, interoperability with legacy or new world, and resilience that goes beyond the traditional crash fault tolerant model. This comes in addition to legacy system requirements for privacy and regulation compliance, that may differ from central bank to central bank. This paper introduces a novel framework for Central Bank Digital Currency settlement that outputs a system of record---acting a a trusted source of truth serving interoperation, and dispute resolution/fraud detection needs---, and brings together resilience in the event of parts of the system being compromised, with throughput comparable to crash-fault tolerant systems. Our system further exhibits agnosticity of the exact cryptographic protocol adopted for meeting privacy, compliance and transparency objectives, while ensuring compatibility with the existing protocols in the literature. For the latter, performance is architecturally guaranteed to scale horizontally. We evaluated our system\u27s performance using an enhanced version of Hyperledger Fabric, showing how a throughput of >100K TPS can be supported even with computation-heavy privacy-preserving protocols are in place

Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity

Nanoparticles’ drug release kinetics can directly affect their therapeutic efficacy and toxicity

Hyperledger Fabric: A Distributed Operating System for Permissioned Blockchains

Fabric is a modular and extensible open-source system for deploying and operating permissioned blockchains and one of the Hyperledger projects hosted by the Linux Foundation (www.hyperledger.org). Fabric is the first truly extensible blockchain system for running distributed applications. It supports modular consensus protocols, which allows the system to be tailored to particular use cases and trust models. Fabric is also the first blockchain system that runs distributed applications written in standard, general-purpose programming languages, without systemic dependency on a native cryptocurrency. This stands in sharp contrast to existing blockchain platforms that require "smart-contracts" to be written in domain-specific languages or rely on a cryptocurrency. Fabric realizes the permissioned model using a portable notion of membership, which may be integrated with industry-standard identity management. To support such flexibility, Fabric introduces an entirely novel blockchain design and revamps the way blockchains cope with non-determinism, resource exhaustion, and performance attacks. This paper describes Fabric, its architecture, the rationale behind various design decisions, its most prominent implementation aspects, as well as its distributed application programming model. We further evaluate Fabric by implementing and benchmarking a Bitcoin-inspired digital currency. We show that Fabric achieves end-to-end throughput of more than 3500 transactions per second in certain popular deployment configurations, with sub-second latency, scaling well to over 100 peers.Comment: Appears in proceedings of EuroSys 2018 conferenc

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment