Extracellular Vesicles in Myeloid Neoplasms

Myeloid neoplasms arise from malignant primitive cells, which exhibit growth advantage within the bone marrow microenvironment (BMM). The interaction between these malignant cells and BMM cells is critical for the progression of these diseases. Extracellular vesicles (EVs) are lipid bound vesicles secreted into the extracellular space and involved in intercellular communication. Recent studies have described RNA and protein alterations in EVs isolated from myeloid neoplasm patients compared to healthy controls. The altered expression of various micro-RNAs is the best-described feature of EVs of these patients. Some of these micro-RNAs induce growth-related pathways such as AKT/mTOR and promote the acquisition of stem cell-like features by malignant cells. Another well-described characteristic of EVs in myeloid neoplasms is their ability to suppress healthy hematopoiesis either via direct effect on healthy CD34+ cells or via alteration of the differentiation of BMM cells. These results support a role of EVs in the pathogenesis of myeloid neoplasms. mainly through mediating the interaction between malignant and BMM cells, and warrant further study to better understand their biology. In this review, we describe the reported alterations of EV composition in myeloid neoplasms and the recent discoveries supporting their involvement in the development and progression of these diseases.     

Zero-Forcing Successive Decoding Under Nakagami-<Emphasis Type="Italic">m</Emphasis> Fading Channels

In this paper, the performance of a multiuser distributed spatial multiplexing system is analytically investigated. The system operates under a Nakagami-m fading environment. All the users, equipped with single antennas, are simultaneously transmitting their streams to a multi-antenna receiver. Zero-forcing is applied along with successive interference cancellation as a means for efficient detection of the received streams. New exact closed-form expressions with regards to some important performance metrics, namely, outage probability and ergodic capacity of each stream are presented. Both the analytical expressions and the simulation results show the impact of channel severity and scale of antenna array to the overall system performance. A particular emphasis on the scenario of the emerging massive multiple input-multiple output systems is provided.     

Fractal self-transform functions

The concept of fractal (self-similar) self-transform functions is examined. A general method to prove existence of these functions is introduced, and necessary conditions for this existence are derived. The results are general and apply to all transforms with product-type kernels.     

f-Value: measuring an article’s scientific impact

The f-value is a new indicator that measures the importance of a research article by taking into account all citations received, directly and indirectly, up to depth n. The f-value considers all information present in a Citation Graph in order to produce a ranking of the articles. Apart from the mathematical equation that calculates the f-value, we also present the corresponding algorithm with its implementation, plus an experimental comparison of f-value with two known indicators of an article’s scientific importance, namely, the number of citations and the Page Rank for citation analysis. Finally, we discuss the similarities and differences among the indicators.     

Exploring the relationship between energy use and economic growth with bivariate models: New evidence from G-7 countries

There is a rapidly growing literature on the interaction between energy use and economic development, with many analysts drawing policy conclusions on the basis of Granger causality tests that involve only an energy and an economic variable. This paper attempts to demonstrate empirically that such studies, although useful for certain applications, may be of limited use for policy purposes. After outlining theoretical and methodological issues associated with such approaches, I apply bivariate energy–economy causality tests for Canada, France, Germany, Italy, Japan, the United Kingdom and the United States, using aggregate and sectoral data and three different modern econometric methods. The results, which are often contradictory or economically implausible, illustrate explicitly that one should be cautious when drawing policy implications with the aid of bivariate causality tests on small samples. I therefore underline the importance of utilizing as large sample sizes as possible and using multivariate models, which are closer to economic theory, accommodate several mechanisms and causality channels and provide a better representation of real-world interactions between energy use and economic growth.     

Particulate matter mass measurements for low emitting diesel powered vehicles: what''s next?

Legislation word-wide imposes stringent emission standards for particulate matter emitted by diesel engines, as an outcome of evidence associating emitted particulate with a series of adverse health effects. Such emission standards call for significant reductions in the particulate matter emission levels for small and large on-road diesel vehicles. In fact, emission levels adopted for the near future are so low that the existing, regulated procedures might not be sensitive enough to accurately determine the absolute level of emissions. In this regard, extensive research is conducted in the direction of both improving existing procedures and developing alternative methods for more sensitive particulate matter measurements. This review paper summarizes the developments in the area and provides an outlook to the future. At first, the character of diesel particulate matter (DPM) is shortly discussed, mainly to show that the complex nature of emitted particulate is responsible for a series of implications when its quantitative determination is considered. Secondly, the regulated procedure for sampling and measurement of DPM is reviewed and its main qualities and shortcomings are presented. The recent technical advances aimed at improving the characteristics of the reference procedure in the measurement of ultra-low emission levels are then presented. Next the presentation of alternative methods follows which are gradually incorporated in regulations for particulate matter sampling. The strength of these techniques is that only a small fraction of exhaust is sampled and conditioned before measurement, hence significantly reducing the cost compared to the reference procedure. In addition to sampling, the determination of the actual particulate mass emitted is an area which has attracted significant developments. The most relevant instrumentation for DPM determination is also described and their potential for application in emissions certification is examined based on published evidence. Finally, the cost of the different sampling and instrumentation techniques is compared to demonstrate the cost-effectiveness of each option.     

Seismic response analysis of nonlinear structures

A solution method for the response of a class of nonlinear viscoelastic shear building structures subjected to stochastic excitation has been developed by means of a stochastic equivalent linearlization technique. The nonlinear viscoelastic properties of the structures are modelled in terms of an equation of motion which linearly involves the auxiliary variables as part of the restoring force and in terms of the auxiliary equation which describes a nonlinear relationship among the story displacements and auxiliary variables and their time derivatives. This auxiliary equation is linearized using a stochastic linearization technique. The integration of the equation of motion together with the linearized auxiliary equation is carried out numerically using the state-vector formulation. In doing so, an iterative upgrading of the values of the linearization coefficients is performed simultaneously for all the stories in the first time interval until a convergence criterion is satisfied. The iterative process is then repeated in the time intervals that follow, until the entire time interval for which the dynamic analysis is performed is covered. The analysis is based on the modal method which, however, requires the use of complex eigenvalues and eigenvectors. The proposed analysis produces covariance functions of the story displacements and velocities among other response quantities. These covariance functions play an important role in estimating structural reliability. The covariance function thus developed agrees very well with that obtained by the Monte Carlo technique.     

Application of Failure Mode and Effect Analysis (FMEA), cause and effect analysis, and Pareto diagram in conjunction with HACCP to a corn curl manufacturing plant

The Failure Mode and Effect Analysis (FMEA) model has been applied for the risk assessment of corn curl manufacturing. A tentative approach of FMEA application to the snacks industry was attempted in an effort to exclude the presence of GMOs in the final product. This is of crucial importance both from the ethics and the legislation (Regulations EC 1829/2003; EC 1830/2003; Directive EC 18/2001) point of view. The Preliminary Hazard Analysis and the Fault Tree Analysis were used to analyze and predict the occurring failure modes in a food chain system (corn curls processing plant), based on the functions, characteristics, and/or interactions of the ingredients or the processes, upon which the system depends. Critical Control points have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram, and the fishbone diagram). Finally, Pareto diagrams were employed towards the optimization of GMOs detection potential of FMEA.     

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity**

Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4^CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4^CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4^CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4^CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.     

Effect of Initial Microstructure on the Performance of 6XXX Al-alloy Laser Welds: A Computational Study

Laser welding (LW) offers an attractive joining technique for Al-alloys. The performance of laser welds usually suffers from mechanical strength degradation in the heat-affected zone (HAZ). In the present study, the effect of the initial-aged microstructure on the post-welded state of 6XXX Al-alloys laser welds was examined via computational modeling techniques. A well-established and detailed precipitation model was used, coupled with a strength model. The influence of the main process variables for aging heat treatment (time and temperature) and LW (power and speed) on the mechanical integrity of weld joints and specifically in the yield strength profile in the HAZ was analyzed. Also, a simple method for the prediction of the width of HAZ is provided. It is concluded that more coarsened microstructures show better performance (compared with the aged state) due to lower degradation of mechanical strength and narrower width of HAZ on the post-welded state. This study provides a method for the selection of the appropriate process parameters for aging and LW of 6XXX Al-alloys.