Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

Combined effect of enterprise risk management and diversification on property and casualty insurer performance, The

Includes bibliographical references (pages 24-27).Published as: Journal of Risk and Insurance, vol. 85, no. 2, June 2018, pp. 513–543. https://doi.org/10.1111/jori.12166.In a well‐designed enterprise risk management (ERM) program, the firm integrates risk management into the strategic planning process, addressing strategic, financial, operational, and hazard risks under a single overarching process. This is particularly important to large financial firms, such as property and casualty (P&C) insurers, which face a diverse set of risks. Using a sample of P&C insurers with S&P ERM quality ratings from 2006 to 2013, we find that the quality of a firm's ERM is a significant determinant of P&C insurer performance and that, for firms with high‐quality ERM programs, product line diversification has a significant positive effect on performance

Optimal enterprise risk management and decision making with shared and dependent risks

Includes bibliographical references (pages 27-29).Published as: Journal of Risk and Insurance, vol. 84, no. 4, December 2017, pp. 1127–1169. https://doi.org/10.1111/jori.12140.Dynamic enterprise risk management (ERM) entails holistic decision-making for critical corporate functions such as capital budgeting and risk management. The interplay across business divisions, however, is complicated due to their natural interactions through the shared and dependent risk exposures within an intricate corporate structure. This paper develops an integrated optimization framework via a copula-based decision tree interface to facilitate ERM decision making to meet the specified enterprise goal in a multi-period setting. We illustrate our model and provide managerial insights with a case study for a financial services company engaged in both banking and insurance businesses

Molecular subgroups of adult medulloblastoma: a long-term single-institution study

Background Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. Methods We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Results Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. Conclusions We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome

Utjecaj otopine u čvrstom stanju i starenja na mikrostrukturu i mehanička svojstva kompozita čestica SiCp/Al-Si-Cu-Mg

The SiC particles (SiCp, mass fraction 30 %) reinforced with the Al-Si-Cu-Mg matrix composite have been prepared using one-way press method, sintering, and hot extrusion. The composite was subjected to solid solution treatment at temperatures of 470 °C, 485 °C, 500 °C, 515 °C, and 530 °C for 4 h. The sample was then subjected to ageing treatment at temperatures of 160 °C and 180 °C during different times after solid solution treatment at 515 °C for 4 h. The microstructure and mechanical properties of the SiCp/Al-Si-Cu-Mg matrix composite under the different ageing and solid solution treatments were tested using SEM and TEM microhardness analysis. The results show that the white granulated metallic compounds of the SiCp/Al-Si-Cu-Mg composite materials, which are formed in the sintering process of composite materials, dissolve back after the solid solution treatment at different temperatures. The higher the solid solution temperature, the more metallic compounds dissolve back. The microhardness of the composites reached maximum after solution treatment at 515 °C for 4 h. Following the ageing treatment and with the prolongation of ageing time, the hardness of the composite material reached “double peak” phenomenon. With the increase in ageing temperature, the hardening speed of the composite material also increased, but at the same time, the hardening ability had reduced. After the ageing treatment, the second phases of the composite are discoid Al5Cu6Mg2. This work is licensed under a Creative Commons Attribution 4.0 International License.Pripravljen je kompozit čestica SiC (SiCp) u masenom udjelom 30 % u matrici Al-Si-Cu-Mg prešanjem, sinteriranjem i ekstrudiranjem. Kompozit je 4 sata bio izložen otapanju u čvrstom stanju pri 470 °C, 485 °C, 500 °C, 515 °C i 530 °C. Nakon toga na uzorak je 4 sata pri 515 °C djelovalo otapanje u čvrstom stanju, a zatim su uzorci starili različito vrijeme pri temperaturama 160 i 180 °C. Mikrostruktura i mehanička svojstva kompozita proučena su tehnikama pretražnom i transmisijskom mikroskopijom te analizom mikrotvrdoće. Pri sinteriranju kompozita SiCp/Al-Si-Cu-Mg nastaje bijeli zrnasti metalni spoj koji se otapa u čvrstu otopinu pri različitim temperaturama. Što je viša temperatura čvrste otopine, više se otopi metalnog spoja. Mikrotvrdoća doseže maksimum pri izlaganju reakcijama u čvrstom stanju pri 515 °C kroz četiri sata. Nakon starenja i s produljenjem starenja tvrdoća materijala pokazuje dvostruki vrh. S povišenjem temperature povećava se brzina očvršćivanja, no istodobno se smanjuje mogućnost očvršćenja. Druga faza kompozita nakon starenja je diskoidni Al5Cu6Mg2. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna

Case Report: Integrated echocardiographic assessment guided Liwen procedure for treating obstructive hypertrophic cardiomyopathy with ventricular aneurysm

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease, with an estimated incidence of 0.2%–6%, and is the main cause of sudden cardiac death (SCD) in young athletes. Left ventricular apical aneurysm (LVAA) is a rare subtype of HCM, accounting for about 5% of HCM patients, and has a higher incidence of cardiovascular adverse events. In cases of hypertrophic obstructive cardiomyopathy with LVAA (HOCM-LVAA) that do not respond adequately to optimized medical therapy, the echocardiography-guided percutaneous intra-myocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) emerges as a promising and effective novel therapeutic approach. In this case report, we present for the first time a comprehensive application of echocardiographic techniques, including TTE, 2-D STE, and contrast enhancement, in the diagnosis, treatment, surgical guidance, and assessment of therapeutic outcomes in a case of HOCM-LVAA

Throughput Maximization for Intelligent Refracting Surface Assisted mmWave High-Speed Train Communications

With the increasing demands from passengers for data-intensive services, millimeter-wave (mmWave) communication is considered as an effective technique to release the transmission pressure on high speed train (HST) networks. However, mmWave signals ncounter severe losses when passing through the carriage, which decreases the quality of services on board. In this paper, we investigate an intelligent refracting surface (IRS)-assisted HST communication system. Herein, an IRS is deployed on the train window to dynamically reconfigure the propagation environment, and a hybrid time division multiple access-nonorthogonal multiple access scheme is leveraged for interference mitigation. We aim to maximize the overall throughput while taking into account the constraints imposed by base station beamforming, IRS discrete phase shifts and transmit power. To obtain a practical solution, we employ an alternating optimization method and propose a two-stage algorithm. In the first stage, the successive convex approximation method and branch and bound algorithm are leveraged for IRS phase shift design. In the second stage, the Lagrangian multiplier method is utilized for power allocation. Simulation results demonstrate the benefits of IRS adoption and power allocation for throughput improvement in mmWave HST networks.Comment: 13 pages, 7 figures, IEEE Internet of Things Journa