Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

AC Electric Field Activated Shape Memory Polymer Composite

Shape memory materials have drawn interest for applications like intelligent medical devices, deployable space structures and morphing structures. Compared to other shape memory materials like shape memory alloys (SMAs) or shape memory ceramics (SMCs), shape memory polymers (SMPs) have high elastic deformation that is amenable to tailored of mechanical properties, have lower density, and are easily processed. However, SMPs have low recovery stress and long response times. A new shape memory thermosetting polymer nanocomposite (LaRC-SMPC) was synthesized with conductive fillers to enhance its thermo-mechanical characteristics. A new composition of shape memory thermosetting polymer nanocomposite (LaRC-SMPC) was synthesized with conductive functionalized graphene sheets (FGS) to enhance its thermo-mechanical characteristics. The elastic modulus of LaRC-SMPC is approximately 2.7 GPa at room temperature and 4.3 MPa above its glass transition temperature. Conductive FGSs-doped LaRC-SMPC exhibited higher conductivity compared to pristine LaRC SMP. Applying an electric field at between 0.1 Hz and 1 kHz induced faster heating to activate the LaRC-SMPC s shape memory effect relative to applying DC electric field or AC electric field at frequencies exceeding1 kHz

Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling.

Smoothened (Smo) is a member of the Frizzled (FzD) class of G-protein-coupled receptors (GPCRs), and functions as the key transducer in the Hedgehog (Hh) signalling pathway. Smo has an extracellular cysteine-rich domain (CRD), indispensable for its function and downstream Hh signalling. Despite its essential role, the functional contribution of the CRD to Smo signalling has not been clearly elucidated. However, given that the FzD CRD binds to the endogenous Wnt ligand, it has been proposed that the Smo CRD may bind its own endogenous ligand. Here we present the NMR solution structure of the Drosophila Smo CRD, and describe interactions between the glucocorticoid budesonide (Bud) and the Smo CRDs from both Drosophila and human. Our results highlight a function of the Smo CRD, demonstrating its role in binding to small-molecule modulators

Anonymous Announcement System (AAS) for electric vehicle in VANETs

Vehicular Ad Hoc Network (VANET) allows vehicles to exchange information about road and traffic conditions through wireless communications. Nevertheless, providing reliable and authenticated information without violating the user\u27s privacy seems contradictory. In this paper, we propose an Anonymous Announcement System especially designed for Electric Vehicle (EV) in VANETs to achieve the aforementioned contradictory goals. We demonstrated the feasibility of the protocol with a prototype implementation on a suitable device and a network simulation with our protocol added on top of a normal VANET

Electric Field Activated Shape Memory Polymer Composite

Provided is an electrically activated shape memory polymer composite capable of thermal shape reformation using electric power to heat the composite through its matrix glass transition temperature. The composite includes an adaptable polymer matrix component using a diglycidyl ether resin, at least one substantially well-dispersed conductive or magnetic nano-filler component, and at least one elastic, laminated layer. Also provided are methods of preparing the composite and methods of activating the composite. A shape reformation of the composite is triggered by applying an electric field at DC and/or at a frequency above about 1.mu.Hz for a sufficient time

First and Second Sound Modes of a Bose-Einstein Condensate in a Harmonic Trap

We have calculated the first and second sound modes of a dilute interacting Bose gas in a spherical trap for temperatures ($0.6<T/T_{c}<1.2$) and for systems with $10^4$ to $10^8$ particles. The second sound modes (which exist only below $T_{c}$) generally have a stronger temperature dependence than the first sound modes. The puzzling temperature variations of the sound modes near $T_{c}$ recently observed at JILA in systems with $10^3$ particles match surprisingly well with those of the first and second sound modes of much larger systems.Comment: a shorten version, more discussions are given on the nature of the second sound. A long footnote on the recent work of Zaremba, Griffin, and Nikuni (cond-mat/9705134) is added, the spectrum of the (\ell=1, n_2=0) mode is included in fig.

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted

A Study of Shape Memory Polymer Based Slat-Cove Filler

Aircraft noise reduction is an application of current intense interest for which smart materials show significant potential. Specifically, the aeroacoustic noise produced by the unsteady aerodynamic flow about the leading-edge high-lift device, such as leading-edge slat, of typical transport-aircraft wings is of particular interest. Concepts with the most promise to mitigate this noise source, most notably the slat-cove filler concept, have focused on highly reconfigurable structures that change shape between different phases of the flight envelope. These shape changes often involve large deformation, which has stimulated the consideration of shape memory materials. In recent years, shape memory materials (SMMs) have drawn greater interest for applications such as smart fabrics, intelligent medical devices, self-deployable space structures, morphing structures and packaging. Compared to other shape memory materials, like shape memory alloys (SMAs) or shape memory ceramics (SMCs), shape memory polymers (SMPs) have desirable advantages such as high elastic deformation to enable large shape change, broad tailorability of mechanical properties, potential biocompatibility and biodegradability, ductility, light weight and ease of processing. However, SMPs still have some critical disadvantages such as insufficient mechanical and thermal characteristics for structural applications, low recovery stress, and long response time. The new LaRC shape memory thermosetting polymer composite (LaRC-SMPC) discussed herein was synthesized with nontoxic monomers and conductive/magnetic fillers to yield enhanced thermal/mechanical characteristics and faster response times. LaRC-SMPCs with a variety of fiber reinforcements [Kevlar, carbon fiber (standard and thin-ply), and carbon-nanotube (CNT) sheet] were fabricated to tailor the physical properties and test for suitability as a slat-cove filler (SCF). The performance of SCF prototypes fabricated with the developed LaRC-SMPCs was evaluated using a bench-top test apparatus. The SCFs made of Kevlar fiber fabric or carbon fiber fabric infused shape memory polymer composite (SMPC) exhibited kinking during simulated deployment and stowage, which can be problematic during operation. The SCF made of CNT sheet/SMP composite did not exhibit kinking, but the deployment was sluggish compared to carbon fiber fabric/SMP composite. This report documents the evolution of designing SMPCs as slat-cove fillers for aircraft noise reduction. In the course of the investigation, several 2 approaches were investigated to address shortcomings in material characteristics based on performance requirements of operational slat-cove fillers