THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12–THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.     

Ultrasound initiated maleic anhydride grafted onto a novel polypropylene copolymer

The reaction of maleic anhydride (MAH) grafted onto propylene‐based copolymer (DP) without adding any initiator was conducted through ultrasound assisted extrusion in this article. The effects of ultrasound power, die temperature, and MAH content on the grafting degree and efficiency were studied. With increasing ultrasound power, the grafting degree and efficiency of DP‐g‐MAH increase. The presence of ultrasound with higher power and lower die temperature is beneficial to increase the grafting degree and efficiency. The increase of MAH content can increase the grafting degree but reduce the grafting efficiency. Based on the results of melt flow index, dynamical rheological, gel permeation chromatograph (GPC), and Fourier transform infrared spectroscopy (FTIR) tests, the mechanisms of the grafting reaction were proposed. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers     

Salmonella in uncooked retail meats in New Zealand

A national quantitative survey of Salmonella in five types of uncooked retail meats in New Zealand was undertaken from August 2003 to May 2005 to establish baseline proportionality data. The overall prevalence of Salmonella in 1,108 meat samples was 1.1% (95% confidence interval, 0.6 to 1.9). Low prevalences of Salmonella in each meat type were observed, with 3% (1.2 to 6.1) in chicken, 1.3% (0.3 to 3.8) in lamb and mutton, 0.5% (0 to 3.0) in unweaned veal, 0.4% (0 to 2.4) in beef, and 0% (0 to 1.6) in pork. The Salmonella serotypes isolated were Salmonella Infantis from beef; Salmonella Typhimurium PT1 from unweaned veal and chicken; Salmonella sp. 6,7:k:-, Salmonella Enteritidis PT9a, Salmonella sp. 4,5,12:-:-, Salmonella sp. 4,12:-:-, and Salmonella Typhimurium PT160 from chicken; and Salmonella sp. 4:-:2 and Salmonella Brandenburg from lamb. Four of the isolates from chicken, Salmonella sp. 4,5,12:-:- (two isolates), Salmonella sp. 4,12:-:-, and Salmonella Typhimurium PT1, were very similar phenotypically and serologically to the attenuated Salmonella vaccine strain used in MeganVacl for poultry. One lamb sample yielded a count of Salmonella Brandenburg of 4.24 most probable number (MPN)/g, while all other positive samples were <1.0 MPN/g. The results provide baseline proportionality data for Salmonella in retail uncooked meats that will contribute invaluably toward future risk assessment in light of other information, such as consumption data that can be used for risk characterization.     

Characterization of an antioxidant polylactic acid (PLA) film prepared with α-tocopherol,BHT and polyethylene glycol using film cast extruder

Polylactic acid (PLA) films were prepared with α-tocopherol, buthylated hydroxytoluene (BHT), and polyethylene glycol 400 (PEG 400) using a cast film extruder in an effort to create an antioxidant film. Film properties were characterized by radical scavenging activity and thermal, physical, and gas barrier properties. Final resin compounding and pelletization was achieved by a twin screw extruder and a pelletizator to permit the homogenization of all resin components prior to film casting. Three different PLA films were fabricated for this study: pure PLA film, PLA film with BHT and PEG 400 (BP-PLA film), PLA film with α-tocopherol, BHT, and PEG 400 (ABP-PLA film). The addition of PEG 400 into the pure PLA film decreased the glass transition temperature (T_g) of the film. The BP-PLA and ABP-PLA film had around 51 °C of T_g while pure PLA film had 66 °C. Due to the decreased T_g of both the BP-PLA and ABP-PLA film, both films had an increased elongation at break (%E). The addition of plasticizer into the pure PLA film also caused increased water vapor permeability (WVP) and decreased oxygen permeability (OP). The ABP-PLA film had highest DPPH radical scavenging activity, 90%, while pure PLA and BP-PLA film had only 0 and 14%, respectively.     

Novel polyamide nanocomposites based on silicate nanotubes of the mineral halloysite

In this study, the silicate nanotubes of the mineral halloysite will be used as reinforcement in polyamide-6 (PA 6). The nanocomposites based on PA-6 and as-received halloysite were prepared by melt extrusion and an adjacent injection moulding process. Mechanical and thermomechanical properties have been investigated by tensile testing and dynamic mechanical analysis. The results show an increased strength and stiffness as well as an enhanced elongation at break at low halloysite content. To evaluate the potential of halloysite as a new candidate in the class of nanofillers, the properties of the halloysite nanocomposites has been compared to those of conventional nanocomposites based on organically modified montmorillonite. From this comparison it can be seen, that both types of nanocomposites show enhanced tensile properties as well as an increased storage modulus, but the increase in tensile strength is more pronounced in the organoclay nanocomposites, whereas the raise of the storage modulus is more prominent in the halloysite nanocomposites.     

Tariff adjustment frameworks for privately financed infrastructure projects

Since privately financed infrastructure (PFI) projects are usually natural monopolies, their tariffs should be regulated to ensure socially desirable outcomes. In reality, the regulation is usually realized through tariff adjustment mechanisms. There are four basic tariff adjustment frameworks for PFI projects - adjustment based on sale price, revenue, operating income and profit after tax. They have different risk exposures and incentives. The adjustment based on the sale price provides the project company with the highest potential to increase profit but exposes it to the highest risk, while the adjustment based on the guaranteed ROR exposes the project company to the lowest risk but provides the least potential for increasing profit. Adjustments based on the revenue or the operating income are somewhere in between. In practice, a hybrid of two or more adjustment frameworks may be adopted to adapt to specific project environments. A well-designed tariff adjustment framework can create a ‘win-win’ solution for both the public and private sectors.     

LTPS circuit integration for system‐on‐glass LCDs

Abstract— A 3.5‐in. QVGA‐formatted driving‐circuit fully integrated LCD has been developed using low‐temperature poly‐Si (LTPS) technology. This display module, in which no external ICs are required, integrates all the driving circuits for a six‐bit RGB digital interface with an LTPS device called a “FASt LDD TFT” and achieves a high‐quality image, narrow frame width, and low power consumption. The LTPS process, device, and circuit technologies developed for system‐on‐glass LCD discussed. The development phase of LTPS circuit integration for system‐on‐glass LCDs is also reviewed.     

Effectiveness of Explicit Stations Grouping in Crowded Wireless LANs

In this letter, we evaluate the effectiveness of a multi-stage contention scheme for wireless local area networks (WLANs) medium access control (MAC). Multi-stage contention schemes basically divide the stations into smaller groups to resolve the contention more efficiently. Previous researchers have proposed virtual grouping schemes for WLANs MAC. Here we quantitatively analyze what can be achieved with a simple grouping scheme, i.e. through multi-stage contention. Our analysis shows that the multi-stage scheme is efficient in resolving contention, making it a good alternative to the commonly used exponential backoff mechanism.     

Highly Flexible Graphene Oxide Nanosuspension Liquid‐Based Microfluidic Tactile Sensor

A novel graphene oxide (GO) nanosuspension liquid‐based microfluidic tactile sensor is developed. It comprises a UV ozone‐bonded Ecoflex–polydimethylsiloxane microfluidic assembly filled with GO nanosuspension, which serves as the working fluid of the tactile sensor. This device is highly flexible and able to withstand numerous modes of deformation as well as distinguish various user‐applied mechanical forces it is subjected to, including pressing, stretching, and bending. This tactile sensor is also highly deformable and wearable, and capable of recognizing and differentiating distinct hand muscle‐induced motions, such as finger flexing and fist clenching. Moreover, subtle differences in the handgrip strength derived from the first clenching gesture can be identified based on the electrical response of our device. This work highlights the potential application of the GO nanosuspension liquid‐based flexible microfluidic tactile sensing platform as a wearable diagnostic and prognostic device for real‐time health monitoring. Also importantly, this work can further facilitate the exploration and potential realization of a functional liquid‐state device technology with superior mechanical flexibility and conformability.