The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.     

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

We previously showed that, according to the frequency and distribution of specific cell types, the rainbow trout (RT) intestinal mucosa can be divided in two regions that form a complex nonlinear three-dimensional (3D) pattern and have a different renewal rate. This work had two aims. First, we investigated whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well-defined enterocytes functional markers: peptide transporter 1 (PepT1), sodium–glucose/galactose transporter 1 (SGLT-1), and fatty-acid-binding protein 2 (Fabp2). Second, we characterized the structure of RT intestinal stem-cell (ISC) niche and determined whether the different proliferative is accompanied by a different organization and/or extension of the stem-cell population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1, and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT, but their localization is completely different, suggesting also substantial functional differences. Lastly, higher renewal rates are supported by a more abundant ISC population.     

Radar ECCM based on phase-aid distributed compressive sensing

This paper proposes an electronic counter countermeasure (ECCM) technique to suppress randomly distributed multiple false targets generated by digital radio frequency memory-based electronic warfare equipment. Firstly, we present the modulation behaviors of deceptive multiple false targets jamming. Afterward, we discuss the ECCM potential of distributed compressive sensing (DCS) which not only could eliminate random distributed jamming signals but also could preserve the target echo. Further, an approach is proposed relying on phase-aided DCS to improve the performance against a special case of jamming signals that fall in the same range cell but with random amplitudes and phases. Finally, the suppression performances are evaluated through simulations illustrating the feasibility and validity of proposed algorithm.     

Development and performance analysis of PCL/silica nanocomposites for bone regeneration

In the present article, several developments of biocomposites containing silica nanoparticles intended for bone regeneration are reported. Nanocomposites of poly(ε-caprolactone) (PCL) and silica, in which either the silica nanoparticles or the PCL have been modified in order to improve interfacial adhesion through chemical graft between the phases are hereafter described. The composites are characterized with respect to their chemical–physical and mechanical properties. Their biocompatibility and capacity to induce the osteoblastic phenotype in human bone marrow mesenchymal stem cells have been assessed.     

Analysis and design of a DPSK optical heterodyne receiver in the presence of laser phase noise and frequency detuning

This paper is concerned with the analysis and design of an improved differential heterodyne optical receiver for differentially-encoded binary PSK (briefly, DPSK) signals in a coherent lightwave communication system. In the first part of the paper, we discuss the relevant design criteria to be employed when dealing with asynchronous heterodyne receivers for ASK, FSK or DPSK optical signals. In particular, we introduce a convenient definition of the signal-to-noise ratio at the data detector input to be assumed as the system performance measure when the non-negligible linewidth of the transmit/receive laser sources are to be taken into account. Following this design approach, we show that by properly modifying the traditional delay-and-multiply DPSK receiver, i. e. by allowing the delay to be a fraction of the symbol interval, we can considerably reduce the performance degradation caused by laser phase noise. We show thus that the superior power-efficiency of DPSK can be traded in favour of a decreased sensitivity to phase noise through a proper choice of the differential detector delay. In this respect, our results reveal that DPSK may still be competitive with other modulation formats even with non-negligible linewidth sources. In the last part of the paper, the behaviour of the optimized DPSK, ASK and large-deviation FSK data demodulators in the presence of a quasistationary frequency detuning of the local laser is also discussed under the same set of conditions as in the previous analysis. The results can be employed to derive accurate design requirements for the AFC loop of the receiver.     

Using random set theory to propagate epistemic uncertainty through a mechanical system

The Epistemic Uncertainty Project of Sandia National Laboratories (NM, USA) proposed two challenge problems intended to assess the applicability and the relevant merits of modern mathematical theories of uncertainty in reliability engineering and risk analysis. This paper proposes a solution to Problem B: the response of a mechanical system with uncertain parameters. Random Set Theory is used to cope with both imprecision and dissonance affecting the available information. Imprecision results in an envelope of CDFs of the system response bounded by an upper CDF and a lower CDF. Different types of parameter discretizations are introduced. It is shown that: (i) when the system response presents extrema in the range of parameters considered, it is better to increase the fineness of the discretization than to invoke a global optimization tool; (ii) the response expectation differed by less than 0.5% when the number of function calls was increased 15.7 times; (iii) larger differences (4–5%) were obtained for the lower tails of the CDFs of the response. Further research is necessary to investigate (i) parameter discretizations aimed at increasing the accuracy of the CDFs (lower) tails; (ii) the role of correlation in combining information.     

Designing a videoconference system for active networks

Active networks are receiving increasing attention due to their promise of great flexibility in tailoring services to applications. This capability stems from the exploitation of network devices whose behaviour can be changed dynamically by applications, possibly using technologies and architectures originally conceived for mobile code systems. Notwithstanding the promise of active networks, real-world applications that clearly benefit by them are still missing. In this paper we describe the design of a videoconference system conceived expressly for operation over active networks. The goal of this activity is to pinpoint the benefits that mobile code and active networks bring to this application domain and to provide isnights for the exploitation of these concepts in other application domains.     

On the Metabolically Active Form of Metaglidasen: Improved Synthesis and Investigation of Its Peculiar Activity on Peroxisome Proliferator‐Activated Receptors and Skeletal Muscles

Metaglidasen is a fibrate‐like drug reported as a selective modulator of peroxisome proliferator‐activated receptor γ (PPARγ), able to lower plasma glucose levels in the absence of the side effects typically observed with thiazolidinedione antidiabetic agents in current use. Herein we report an improved synthesis of metaglidasen′s metabolically active form halofenic acid (R)‐ 2 and that of its enantiomer (S)‐ 2 . The activity of the two stereoisomers was carefully examined on PPARα and PPARγ subtypes. As expected, both showed partial agonist activity toward PPARγ; the investigation of PPARα activity, however, led to unexpected results. In particular, (S)‐ 2 was found to act as a partial agonist, whereas (R)‐ 2 behaved as an antagonist. X‐ray crystallographic studies with PPARγ were carried out to gain more insight on the molecular‐level interactions and to propose a binding mode. Given the adverse effects provoked by fibrate drugs on skeletal muscle function, we also investigated the capacity of (R)‐ 2 and (S)‐ 2 to block conductance of the skeletal muscle membrane chloride channel. The results showed a more beneficial profile for (R)‐ 2 , the activity of which on skeletal muscle function, however, should not be overlooked in the ongoing clinical trials studying its long‐term effects.     

Superior Osteo-Inductive and Osteo-Conductive Properties of Trabecular Titanium vs. PEEK Scaffolds on Human Mesenchymal Stem Cells: A Proof of Concept for the Use of Fusion Cages

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) scaffold on human mesenchymal stem cells (hMSCs), in both absence and presence of biochemical osteogenic stimuli. Same abilities were assessed on PEEK and standard 2D plastic surface, the latter meant as gold-standard for in vitro differentiation studies. hMSCs adhered and colonized both T-Ti and PEEK scaffolds. In absence of osteogenic factors, T-Ti triggered osteogenic induction of MSCs, as demonstrated by alkaline phosphatase activity and calcium deposition increments, while PEEK and standard 2D did not. Addition of osteogenic stimuli reinforced osteogenic differentiation of hMSCs cultured on T-Ti in a significantly higher manner with respect to standard 2D plastic culture surfaces, whereas PEEK almost completely abolished the process. T-Ti driven differentiation towards osteoblasts was confirmed by gene and marker expression analyses, even in absence of osteogenic stimuli. These results clearly indicate superior in vitro osteo-inductive and osteo-conductive capacity of T-Ti compared to PEEK, and make ground for further studies supporting the use of T-Ti cages to improve bone fusion.