PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis,Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.     

Polymorphic Phase Transitions in Nanocrystalline Binary Metal Oxides

Binary metal oxides occur in different polymorphic states under applied pressure and temperature. Structural changes occur due to polymorphic transitions in binary metal oxides. It is essential to theoretically predict the conditions of polymorphic transitions so that materials can be effectively used in engineering applications. Temperature and pressure are the two main factors affecting the bulk state phase transformation of materials. For nanomaterials, it has been observed that particle size and temperature are the main factors affecting the phase transformation, e.g., γ‐Fe₂O₃ to α‐Fe₂O₃, monoclinic to orthorhombic transformation in MoO₃, anatase to rutile transformation in Titania, γ to α Alumina transformation. We compile from literature the main factors which affect the phase stability of a nanocrystalline binary metal oxide. A heuristic approach to formulate particle size is put forth. Factors like surface energy, surface tension, and particle shape are considered, and a value for critical particle size is formulated. The model fits well with the experimental results for nanocrystalline alumina, titania, zirconia, and Fe₂O₃. Such an approach can be applied to predict the particle size‐dependent stability of a phase at known temperature range.     

The Analysis and Performance of Multi-Rate Service in Distributed Video-on-Demand Systems

In this paper, we develop an end-to-end analysis of a distributed Video-on-Demand (VoD) system that includes an integrated model of the server and the network subsystems with analysis of its impact on client operations. The VoD system provides service to a heterogeneous client base at multiple playback rates. A class-based service model is developed where an incoming video request can specify a playback rate at which the data is consumed on the client. Using an analytical model, admission control conditions at the server and the network are derived for multi-rate service. We also develop client buffer requirements in presence of network delay bounds and delay jitter bounds using the same integrated framework of server and network subsystems. Results from an extensive simulation show that request handling policies based on limited redirection of blocked requests to other resources perform better than load sharing policies. The results also show that downgrading the service for blocked requests to a lower bitrate improves VoD system performance considerably. Combining the downgrade option with restrictions on access to high bitrate request classes is a powerful tool for manipulating an incoming request mix into a workload that the VoD system can handle.     

Formation of reconstituted casein micelles with human beta-caseins and bovine kappa-casein

Human beta-casein (CN) is the major protein of the human milk casein fraction (approximately 80%) and exists in six calcium-sensitive forms, having zero to five organic phosphates per molecule. The major forms are the doubly-phosphorylated (beta-CN-2P; approximately 30%) and the quadruply phosphorylated (beta-CN-4P; approximately 35%) forms. Although calcium-insensitive, kappa-CN is known for its role in preventing the precipitation of beta-CN in the presence of Ca+2, but it is not known how the different levels of phosphorylation may affect this. In the present investigation, turbidity, measured at 400 nm, was determined at increasing temperatures (4 up to 37 degrees C) for solutions of beta-CN-2P and beta-CN-4P (3 mg/ml in 0.02 M NaCl, 0.01 M imidazole, pH 7) individually and also mixed with bovine kappa-CN in 6/1 and 3/1 weight ratios of beta/kappa and containing 0, 5, and 10 mM Ca+2. The results indicate that the first step of micelle formation probably leads to polymers of limited size, the only complexes available to beta-CN-2P under most conditions. With beta-CN-4P, these polymers aggregate further to give reconstituted micelles, probably because of the ability to form crosslinks at this phosphorylation level. The formation of reconstituted micelles under various conditions of pH, Ca+2 concentration and kappa-CN content indicates that both hydrophobic interactions and Ca+2 bridges or crosslinks may contribute to protein aggregation and micelle building.     

Stochastic Optimization for Content Sharing in P2P Systems

Available resources in peer-to-peer (P2P) systems depend strongly on resource contributions made by individual peers. Empirical data shows that in the absence of incentives, a majority of the participating peers do not contribute resources. Modeling interactions between individual peers is often difficult as the number of peers in the system can be very large, and the relationships among them can be very complex. In this paper, we propose a new solution for P2P systems, where peers upload and download content to and from the contributing peers based on agreed-upon/determined sharing rates. We propose a P2P solution that deters free-riders by imposing constraints on participating peers; specifically, a peer is allowed access to new content only as long as its own content contribution exceeds an adaptively set threshold. The constraints are enforced either by a central authority (e.g., a tracker) or by a decentralized coalition of peers in a swarm, social network, etc. We derive optimal upload policies for the peers given their estimated future download requirements and their previous contribution (credit) to the other peers. Our results show considerable improvement in the cost-benefit tradeoff for peers that deploy such an optimal policy as compared to heuristic upload policies. We also propose mechanisms based on which the coalition of peers can provide incentives or penalties to participating peers to adjust their policies such that the availability of content and/or number of peers contributing content is maximized.     

Fatigue during prolonged intermittent overhead work: reliability of measures and effects of working height

Shoulder pain is prevalent among industrial workers and existing evidence supports that overhead work is an important specific risk factor. Existing guidelines are limited, with overhead work typically recommended to be avoided, and research on overhead work has been mixed in terms of the effects of increasing arm reach. A laboratory-based simulation of overhead work was conducted, at three working heights, in order to facilitate improved guidelines and to identify potential non-linear effects of overhead work height. Several indicators of shoulder fatigue served as outcome measures and a preliminary study was performed to assess the reliability of several of these measures. Fatigue measures based on electromyography (EMG) generally had low reliability, whereas excellent reliability was exhibited for ratings of perceived discomfort (RPD). Consistent with this, no effects of overhead work height were found on EMG-based measures, yet clear non-linear effects were found on RPD and task performance. The source of the effects of work height appeared to be related to a combination of muscle activation levels and demands on precision/control at the highest location. These results support the utility of subjective measures for relatively low-level intermittent exertions and demonstrate increasingly detrimental fatigue and performance effects at extremes in reach during overhead work.     

Metastable Pb1−xCdxS epitaxial films I. Growth and physical properties

The method of preparing (100)-oriented epitaxial layers of Pb_1?xCd_xS on (100) NaCl substrates is described. It is found that, by a careful control of substrate temperature and deposition rate, single-crystal films can be grown over the composition range 0?x?0.40, well in excess of the bulk phase diagram limits. Vegard's law is observed, and the lattice constant a₀ varies as

$\text{a}{}_0\text{= 5.938?0.375x}$

Some precipitation is observed as x approaches 0.40, together with a rejection of excess cadmium-rich material to the surface. It is concluded that metastable films can be readily prepared from these materials.     

End-to-end analysis of distributed video-on-demand systems

The focus of the research presented in this paper is the end-to-end analysis of a distributed Video-on-Demand (VoD) system. We analyze the distributed architecture of a VoD system to design global request handling and admission control strategies and evaluate them using global metrics. The performance evaluation methodology developed in this paper helps in determining efficient ways of using all resources in the VoD architecture within the constraints of providing guaranteed high quality service to each request. For instance, our simulation results show that request handling policies based on limited redirection of blocked requests to other resources perform better than load sharing policies. We also show that request handling policies based on redirection have simpler connection establishment semantics than load sharing policies and, therefore, are easily incorporated into reservation or signaling protocols.     

Carbohydrate Make Up of Huskey Barley

The chemical composition of two and six‐row huskey barley grown under Haryana agroclimatic conditions is reported. Two‐row varieties had slightly higher percentage of reducing sugars, sucrose and lignin, whereas protein, proanthocyanidins, starch, neutral detergent fibre (NDF), acid detergent fibre (ADF) and hemicellulose were higher in six‐row barleys. Malting significantly decreased the starch, sucrose and protein contents, while total soluble sugars, reducing sugars and maltose increased. The concommitant decrease in proanthocyanidins level is also desirable when barley is used for malting and brewing purposes. The variety RD2560 emerged to be superior for malting and brewing. The conduction of feeding trials and investigation of physico‐chemical properties of barley starch are suggested.