Temporal-logic query checking over finite data streams

International Journal on Software Tools for Technology Transfer - This paper describes a technique for solving temporal-logic queries over finite sets of finite-length data streams. Such data...     

In Search of Concerted Strategies for Competitive and Resilient Regions

The European space-economy represents a complex system with a great internal heterogeneity, intensive socioeconomic interactions and differential growth trajectories among countries and regions. The present study aims to investigate the connectivity between spatial competitiveness and resilience in Europe and seeks to design an operational framework for concerted strategies of competitive and resilient regions. To assess the linkage between resilience and competitiveness, we have developed a new measure, viz. the Resilience and Competitiveness Index (RACI) as a function of two constituent sub-indices: Resilience and Competitiveness. This approach is tested on the basis of detailed data on European regions. The empirical results from 268 EU NUTS2 regions offer a solid anchor point for the proposed operational framework for concerted development strategies of competitive and resilient regions. Our research distinguishes and proposes several systematic types of concerted regional strategies according to the performance of a region measured by Resilience and Competiveness sub-indices. A key result of the study is the design of an operational constellation for strategic regional policy evaluation, with a major added value for policy- and decision-making purposes. The use of official data from Eurostat and of standard indicators in our research assures continuity and consistency with the official Regional Competitiveness Index (RCI) classification and measurement, so that policy makers are able to compare the performance of their regions over time and to develop proper concerted strategies accordingly. The clear evidence of a connectivity between regional competitiveness and resilience may help to develop a governance approach that balances competitiveness (mainly represented by productive assets) with resilience (mainly represented by sustainability and ecological awareness) and thus to deal with the complexity in socioeconomic systems.

     

Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.     

Structural insights into peptide self-assembly using photo-induced crosslinking experiments and discontinuous molecular dynamics

Determining the structure of the (oligomeric) intermediates that form during the self-assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo-induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid-forming peptide, Aβ_16-22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*_16–22). Electrospray ionization ion-mobility spectrometry mass-spectrometry (ESI-IMS-MS) analysis of the PIC products confirmed that Aβ*_16–22 forms assemblies with the monomers arranged as anti-parallel, in-register β-strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ_16-22 assembles through a single-step nucleation into a β-sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ_16-22 self-assembly processes, paving the way to explore the self-assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.     

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2

Protein–protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor-suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl-1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl-1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl-1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α-helical domains of their partner proteins.     

A Holistic Approach on Junctionless Dual Material Double Gate (DMDG) MOSFET with High k Gate Stack for Low Power Digital Applications

Silicon - The 2D analytical models for electrostatic potential, threshold voltage, subthreshold swing, Drain Induced Barrier Lowering (DIBL) and drain current of the Dual Material Double Gate...     

Genome-wide effect of tetracycline,doxycycline and 4-epidoxycycline on gene expression in Saccharomyces cerevisiae

Tetracycline (Tet) and derivative chemicals (e.g., doxycycline or Dox) have gained widespread recognition for their antibiotic properties since their introduction in the late 1970s, but recent work with these chemicals in the lab has shifted to include multiple techniques in all genetic model systems for the precise control of gene expression. The most widely used Tet-modulated methodology is the Tet-On/Tet-Off gene expression system. Tet is generally considered to have effects specific to bacteria; therefore, it should have few off-target effects when used in eukaryotic systems, and a previous study in the yeast Saccharomyces cerevisiae found that Dox had no effect on genome-wide gene expression as measured by microarray. In contrast, another study found that the use of Dox in common cell lines and several model organisms led to mitonuclear protein imbalance, suggesting an inhibitory role of Dox in eukaryotic mitochondria. Recently, a new Dox derivative, 4-epidoxycycline (4-ED) was developed that was shown to have less off-target consequences on mitochondrial health. To determine the best tetracycline family chemical to use for gene expression control in S. cerevisiae, we performed RNA sequencing (RNA-seq) on yeast grown on standard medium compared with growth on media supplemented with Tet, Dox or 4-ED. We found each caused dozens of genes to change expression, with Dox eliciting the greatest expression responses, suggesting that the specific tetracycline used in experiments should be tailored to the specific gene(s) of interest when using the Tet-On/Tet-Off system to reduce the consequences of confounding off-target responses.     

Controlled Individual Skyrmion Nucleation at Artificial Defects Formed by Ion Irradiation

Magnetic skyrmions are particle‐like deformations in a magnetic texture. They have great potential as information carriers in spintronic devices because of their interesting topological properties and favorable motion under spin currents. A new method of nucleating skyrmions at nanoscale defect sites, created in a controlled manner with focused ion beam irradiation, in polycrystalline magnetic multilayer samples with an interfacial Dzyaloshinskii–Moriya interaction, is reported. This new method has three notable advantages: 1) localization of nucleation; 2) stability over a larger range of external field strengths, including stability at zero field; and 3) existence of skyrmions in material systems where, prior to defect fabrication, skyrmions were not previously obtained by field cycling. Additionally, it is observed that the size of defect nucleated skyrmions is uninfluenced by the defect itself—provided that the artificial defects are controlled to be smaller than the inherent skyrmion size. All of these characteristics are expected to be useful toward the goal of realizing a skyrmion‐based spintronic device. This phenomenon is studied with a range of transmission electron microscopy techniques to probe quantitatively the magnetic behavior at the defects with applied field and correlate this with the structural impact of the defects.