Er doped waveguide amplifiers written with femtosecond laser in germanate glasses

The authors report the fabrication and characterization of active waveguides in GeO₂–PbO–Ga₂O₃ glass samples doped with Er³⁺, written with a femtosecond laser delivering pulses of 150 fs duration at 1 kHz repetition rate. Permanent refractive index change was obtained and waveguides were formed under different laser pulse energies and scan velocities. The passive and active optical properties of the waveguides were investigated. The minimum value of propagation loss was of 4.8 dB/cm. Optical amplification at 1.5 μm under 980 nm excitation was observed showing a maximal internal gain of 2.7 dB/cm.     

FC2Q: exploiting fuzzy control in server consolidation for cloud applications with SLA constraints

Modern cloud data centers rely on server consolidation (the allocation of several virtual machines on the same physical host) to minimize their costs. Choosing the right consolidation level (how many and which virtual machines are assigned to a physical server) is a challenging problem, because contemporary multitier cloud applications must meet service level agreements in face of highly dynamic, nonstationary, and bursty workloads. In this paper, we deal with the problem of achieving the best consolidation level that can be attained without violating application service level agreements. We tackle this problem by devising fuzzy controller for consolidation and QoS (FC2Q), a resource management framework exploiting feedback fuzzy logic control, that is able to dynamically adapt the physical CPU capacity allocated to the tiers of an application in order to precisely match the needs induced by the intensity of its current workload. We implement FC2Q on a real testbed and use this implementation to demonstrate its ability of meeting the aforementioned goals by means of a thorough experimental evaluation, carried out with real‐world cloud applications and workloads. Furthermore, we compare the performance achieved by FC2Q against those attained by existing state‐of‐the‐art alternative solutions, and we show that FC2Q works better than them in all the considered experimental scenarios. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of Drought and Methyl Jasmonate Treatment on Primary and Secondary Isoprenoid Metabolites Derived from the MEP Pathway in the White Spruce Picea glauca

White spruce (Picea glauca) emits monoterpenes that function as defensive signals and weapons after herbivore attack. We assessed the effects of drought and methyl jasmonate (MeJA) treatment, used as a proxy for herbivory, on monoterpenes and other isoprenoids in P. glauca. The emission of monoterpenes was significantly increased after MeJA treatment compared to the control, but drought suppressed the MeJA-induced increase. The composition of the emitted blend was altered strongly by stress, with drought increasing the proportion of oxygenated compounds and MeJA increasing the proportion of induced compounds such as linalool and (E)-β-ocimene. In contrast, no treatment had any significant effect on the levels of stored monoterpenes and diterpenes. Among other MEP pathway-derived isoprenoids, MeJA treatment decreased chlorophyll levels by 40%, but had no effect on carotenoids, while drought stress had no impact on either of these pigment classes. Of the three described spruce genes encoding 1-deoxy-D-xylulose-5-phosphate synthase (DXS) catalyzing the first step of the MEP pathway, the expression of only one, DXS2B, was affected by our treatments, being increased by MeJA and decreased by drought. These findings show the sensitivity of monoterpene emission to biotic and abiotic stress regimes, and the mediation of the response by DXS genes.     

Drug-Free Nasal Spray as a Barrier against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia

The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after infection, viral titer was reduced by about 12-folds and 3-folds on Day 4. The results suggest that AM-301 is safe and significantly decelerates SARS-CoV-2 replication in cell culture inhibition assays of prophylaxis (pre-viral load application) and mitigation (post-viral load application). Its physical (non-pharmaceutical) mechanism of action, safety and efficacy warrant additional investigations both in vitro and in vivo for safety and efficacy against a broad spectrum of airborne viruses and allergens.     

Active/passive control of sound radiation and power flow in fluid-loaded shells

The vibration and noise radiation from fluid-loaded cylindrical shells are controlled by using multiple stiffeners and passive constrained layer damping treatment. Dynamic and fluid finite elements are developed to study the fundamental phenomena governing the coupling between the stiffened shell, with and without damping, and the fluid domain surrounding it. The models are used to predict the response of the shell and to evaluate the effect of stiffening rings and damping treatment on both the structural vibration and noise radiation in the fluid domain. The geometry of the shell and fluid domain allows the formulation of a harmonic-based model, which uncouples the fluid–structural response of modes corresponding to different numbers of circumferential nodes.In this study, it is shown that stiffening of the shell reduces the amplitude of the vibration and noise radiation, particularly for high-order lobar modes. The attenuation of the shell response and sound radiation can be increased significantly through the application of passive constrained layer damping treatments on the inner surface of the stiffening rings.     

A global approach to the physics validation of simulation codes for future nuclear systems

This paper presents a global approach to the validation of the parameters that enter into the neutronics simulation tools for advanced fast reactors with the objective to reduce the uncertainties associated to crucial design parameters. This global approach makes use of sensitivity/uncertainty methods; statistical data adjustments; integral experiment selection, analysis and “representativity” quantification with respect to a reference system; scientifically based cross-section covariance data and appropriate methods for their use in multigroup calculations. This global approach has been applied to the uncertainty reduction on the criticality of the Advanced Burner Reactor (both metal and oxide core versions) presently investigated in the frame of the GNEP initiative. The results obtained are very encouraging and allow to indicate some possible improvements of the ENDF/B-VII data file.     

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.