An exactly solvable inflationary model

We discuss a model of gravity coupled to a scalar field that admits exact cosmological solutions displaying an inflationary behavior at early times and a power-law expansion at late times.Comment: 7 pages; several typos correcte

MicroRNAs in Cardiac Hypertrophy

Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy. - 2019 by the authors. Licensee MDPI, Basel, Switzerland

A Sub-Picojoule per Bit Integrated Magneto-Optic Modulator on Silicon: Modeling and Experimental Demonstration

Integrated magneto-optic (MO) modulators are an attractive but not fully explored alternative to electro-optic (EO) modulators. They are current driven, structurally simple, and could potentially achieve high efficiency in cryogenic and room temperature environments where fJ bit−1 optical interfaces are needed. In this paper, the performance and energy efficiency of a novel MO modulator at room temperature are for the first time assessed. First, a model of the micro-ring-based modulator is implemented to investigate the design parameters and their influence on the performance. Then, a fabricated device is experimentally characterized to assess its performance in terms of bit rate and energy efficiency. The model shows efficient operation at 1.2 Gbps using a 16 mA drive current, consuming only 155 fJ bit−1. The experimental results show that the MO effect is suitable for modulation, achieving error-free operation above 16 mA with a power consumption of 258 fJ bit−1 at a transient limited data rate of 1.2 Gbps

Structural Evaluation of Typical Historical Masonry Vaults of Cagliari: Sensitivity to Bricks Arrangements

Masonry vaults have a great diffusion in the historical architectural heritage: in this work, their structural behavior is investigated. Attention is focused on lowered sail vaults composed by several brick arrangements, a typical nineteenth-century masonry vault which have great diffusion in Cagliari (Sardinia). The target is evaluating the role played by bricks arrangement in their mechanical behavior. A series of rigorous laser scanner surveys have been performed in order to obtain the effective geometry both at macro-level – the vault shape – and at micro-level – brick patterns. A NURBS (Non-Uniform Rational B Spline) representation of the geometry is adopted and adaptive upper bound limit analyses are performed. NURBS entities, which are common in commercial CAD packages, have the great advantage to describe complex geometries such as curved elements, with very few elements. An upper bound limit analysis formulation is adopted, in which the NURBS elements forming the mesh are idealized as rigid bodies with dissipation allowed only along interfaces. The mesh constituted by few NURBS elements is progressively adjusted through a genetic algorithm in order to minimize the live load multiplier. Limit analysis is performed initially to determine the collapse multiplier of vertical loads, to assess the load bearing capacity of the vault, then attention is focused on differential settlements, that may be a serious hazard for this structural typology

Nano-Derived Therapeutic Formulations with Curcumin in Inflammation-Related Diseases

Due to its vast therapeutic potential, the plant-derived polyphenol curcumin is utilized in an ever-growing number of health-related applications. Here, we report the extraction methodologies, therapeutic properties, advantages and disadvantages linked to curcumin employment, and the new strategies addressed to improve its effectiveness by employing advanced nanocarriers. The emerging nanotechnology applications used to enhance CUR bioavailability and its targeted delivery in specific pathological conditions are collected and discussed. In particular, new aspects concerning the main strategic nanocarriers employed for treating inflammation and oxidative stress-related diseases are reported and discussed, with specific emphasis on those topically employed in conditions such as wounds, arthritis, or psoriasis and others used in pathologies such as bowel (colitis), neurodegenerative (Alzheimer's or dementia), cardiovascular (atherosclerosis), and lung (asthma and chronic obstructive pulmonary disease) diseases. A brief overview of the relevant clinical trials is also included. We believe the review can provide the readers with an overview of the nanostrategies currently employed to improve CUR therapeutic applications in the highlighted pathological conditions.N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017). This work was supported by the CONICYT PIA/APOYO CCTE AFB170007, Seed #2001050151 and Collaborative #2101050160—University of Sharjah and Fondo di Ateneo per la Ricerca 2020, University of Sassari

Strong frequency conversion in heterogeneously integrated GaAs resonators

n this contribution, we demonstrate the first integrated gallium arsenide (GaAs) ring resonator for second harmonic generation (SHG) on a GaAs-on-insulator platform. Such resonators exhibit high nonlinear optical coefficients, a strong optical confinement, and intrinsic quality factors exceeding 2.6 × 105, which makes them very attractive for nonlinear optical applications. The fabricated resonators exhibit a great potential for frequency conversion: when 61 μW of pump power at 2 μm wavelength is coupled into the cavity, the absolute internal conversion efficiency is 4%. We predict an external SHG efficiency beyond 1 000 000%/W based on the GaAs resonance devices. Such nonlinear resonant devices of GaAs and its aluminum GaAs alloy can be directly integrated with active components in nonlinear photonic integrated circuits (PICs). This work paves a way for ultra-high efficient and compact frequency conversion elements in PICs

Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis

Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response

Epac as a tractable therapeutic target

In 1957, cyclic adenosine monophosphate (cAMP) was identified as the first secondary messenger, and the first signaling cascade discovered was the cAMP-protein kinase A (PKA) pathway. Since then, cAMP has received increasing attention given its multitude of actions. Not long ago, a new cAMP effector named exchange protein directly activated by cAMP (Epac) emerged as a critical mediator of cAMP's actions. Epac mediates a plethora of pathophysiologic processes and contributes to the pathogenesis of several diseases such as cancer, cardiovascular disease, diabetes, lung fibrosis, neurological disorders, and others. These findings strongly underscore the potential of Epac as a tractable therapeutic target. In this context, Epac modulators seem to possess unique characteristics and advantages and hold the promise of providing more efficacious treatments for a wide array of diseases. This paper provides an in-depth dissection and analysis of Epac structure, distribution, subcellular compartmentalization, and signaling mechanisms. We elaborate on how these characteristics can be utilized to design specific, efficient, and safe Epac agonists and antagonists that can be incorporated into future pharmacotherapeutics. In addition, we provide a detailed portfolio for specific Epac modulators highlighting their discovery, advantages, potential concerns, and utilization in the context of clinical disease entities

Bidirectional Transmission in an Optical Network on Chip With Bus and Ring Topologies

n/