Implications of Cellular Aging in Cardiac Reprogramming

Aging is characterized by a chronic functional decline of organ systems which leads to tissue dysfunction over time, representing a risk factor for diseases development, including cardiovascular. The aging process occurring in the cardiovascular system involves heart and vessels at molecular and cellular level, with subsequent structural modifications and functional impairment. Several modifications involved in the aging process can be ascribed to cellular senescence, a biological response that limits the proliferation of damaged cells. In physiological conditions, the mechanism of cellular senescence is involved in regulation of tissue homeostasis, remodeling, and repair. However, in some conditions senescence-driven tissue repair may fail, leading to the tissue accumulation of senescent cells which in turn may contribute to tumor promotion, aging, and age-related diseases. Cellular reprogramming processes can reverse several age-associated cell features, such as telomere length, DNA methylation, histone modifications and cell-cycle arrest. As such, induced Pluripotent Stem Cells (iPSCs) can provide models of progeroid and physiologically aged cells to gain insight into the pathogenesis of such conditions, to drive the development of new therapies for premature aging and to further explore the possibility of rejuvenating aged cells. An emerging picture is that the tissue remodeling role of cellular senescence could also be crucial for the outcomes of in vivo reprogramming processes. Experimental evidence has demonstrated that, on one hand, senescence represents a cell-autonomous barrier for a cell candidate to reprogramming, but, on the other hand, it may positively sustain the reprogramming capability of surrounding cells to generate fully proficient tissues. This review fits into this conceptual framework by highlighting the most prominent concepts that characterize aging and reprogramming and discusses how the aging tissue might provide a favorable microenvironment for in vivo cardiac reprogramming

preliminary investigation on impact resistance of additive manufactured ti 6al 4v

Abstract Understanding key failure mechanisms and material anomalies is one of the main challenges for an accelerated certification of additive manufactured parts. In this paper, the response to high velocity impact of Ti-6Al-4V printed by direct metal laser sintering was investigated and compared with wrought material. Taylor impact test at different impact velocities were performed with the scope to determine the velocity at onset damage development. Results show that such velocity is 57% lower than that of wrought material. Microscopy investigation on recovered samples reveals that the presence of initial voids in the microstructure, resulting from the printing process, reduces the shear resistance anticipating the formation of shear bands that is the main mechanism controlling fracture at high deformation rates

High sensitivity UV fluorescence spectroscopy based on an optofluidic jet waveguide: erratum.

A novel spectroscopic sensor based on an optofluidic liquid jet waveguide is presented. In this device, a liquid jet waveguide is generated with the solution under analysis. This stream, exploiting total internal reflection, acts as an optical waveguide confining the autofluorescence light produced by chemical or biological samples when opportunely excited. Using a self-aligned configuration, the liquid jet is directly coupled with a multimode optical fiber collecting the fluorescence towards the detection system. Experimental measurements have been performed using an UV excitation source on water solutions containing representative water pollutants as aromatic hydrocarbons or bacteria showing very low limit of detection

SFADI: the Speckle-Free Angular Differential Imaging method

We present a new processing technique aimed at significantly improving the angular differential imaging method (ADI) in the context of high-contrast imaging of faint objects nearby bright stars in observations obtained with extreme adaptive optics (EXAO) systems. This technique, named "SFADI" for "Speckle-Free ADI", allows to improve the achievable contrast by means of speckles identification and suppression. This is possible in very high cadence data, which freeze the atmospheric evolution. Here we present simulations in which synthetic planets are injected into a real millisecond frame rate sequence, acquired at the LBT telescope at visible wavelength, and show that this technique can deliver low and uniform background, allowing unambiguous detection of $10^{-5}$ contrast planets, from $100$ to $300$ mas separations, under poor and highly variable seeing conditions ($0.8$ to $1.5$ arcsec FWHM) and in only $20$ min of acquisition. A comparison with a standard ADI approach shows that the contrast limit is improved by a factor of $5$. We extensively discuss the SFADI dependence on the various parameters like speckle identification threshold, frame integration time, and number of frames, as well as its ability to provide high-contrast imaging for extended sources, and also to work with fast acquisitions.Comment: Accepted for publication in Ap

High-rate characterization of additively manufactured Ti-6Al-4V using Taylor cylinder impact test: Experiments

n/

Poly(Lactic-co-glycolic) Acid and Phospholipids Hybrid Nanoparticles for Regeneration of Biological Tissue

In tissue regeneration, biomaterials facilitate biological processes. However, a treatment with biomaterials will be successful only if supported by simple and inexpensive technologies which stimulate the regenerative processes. The present study focused on the possibility of creating formulations from which then to obtain suitable materials for the regeneration of heart tissue. The experimental procedure for precipitation of polymer- nanoparticles was modified ad hoc to obtain hybrid poly lactic-co-glycolic acid (PLGA)-phospholipid nanoparticles. The properties of the formulations produced by direct PLGA-phospholipid co-precipitation depend on the mass ratio R= polymer mass/phospholipid mass. The value of this parameter allows us to modulate the properties of the formulations. Formulations with R = 1.5, 2.3, 4, and 9 were prepared, and for each of them the particle-size distribution obtained by dynamic light scattering was studied. All samples showed that the hydrodynamic diameter decreases with increasing R value. This behavior is interpreted as polymer coil shrinkage due to contacts with the non-solvent. The spreadability and ease of obtaining thin sheets were evaluated for each formulation. The formulation with R=4 resulted in a homogeneous and easily workable material in thin sheets

Transverse cervical megapophysis as an uncommon cause of torticollis

Congenital abnormalities of the spine are not uncommon in the general population and can be asymptomatic. Transverse megapophysis is a congenital anomaly manifested as an enlargement of the transverse processes, typically common in the lumbar vertebrae. Here, we describe a 4-month-old infant female with episodes of shooting pain and torticollis. At the beginning of the third month, the parents noticed she held her neck inclined towards the left side in a changeable way, and movement caused discomfort and crying. Muscular tonus, laboratory investigations, ECG and heart and transfontanellar ultrasound were normal. A cervical CT and MRI displayed at the C7 level a megapophysis transverse involving both sides. Treatment with no steroidal anti-inflammatory drugs twice a day and, after a few days, symptoms solved. At 8 months follow-up, neck maintains its natural position and no unmotivated pain has been noticed. Transverse C7 megapophysis presenting with torticollis is an example of a cause of severe pain in infancy, and it should be considered in the differential diagnosis of infantile torticollis. Keywords: Transverse cervical megapophysis, Torticollis, Bertolotti syndrom

Numerical simulation of self-piercing riveting process (SRP) using continuum damage mechanics modelling

The extended Bonora damage model was used to investigate joinability of materials in self-piercing riveting process. This updated model formulation accounts for void nucleation and growth process and shear-controlled damage which is critical for shear fracture sensitive materials. Potential joint configurations with dissimilar materials have been investigated computationally. In particular the possible combination of DP600 steel, which is widely used in the automotive industry, with AL2024-T351, which is known to show shear fracture sensitivity, and oxygen-free pure copper, which is known to fail by void nucleation and growth, have been investigated. Preliminary numerical simulation results indicate that the damage modelling is capable to discriminate potential criticalities occurring in the SPR joining process opening the possibility for process parameters optimization and screening of candidate materials for optimum joint

Deformation and Failure of OFHC Copper under high strain rate shear compression

Hat-shaped specimen geometries were developed to generate high strain, high-strain-rates deformation under prescribed conditions. These geometries offer also the possibility to investigate the occurrence of ductile rupture under low or negative stress triaxiality, where most failure models fail. In this work, three tophat geometries were designed, by means of extensive numerical simulation, to obtain desired stress triaxiality values within the shear region that develops across the ligament. Material failure was simulated using the Continuum Damage Model (CDM) formulation with a unilateral condition for damage accumulation and validated by comparing with quasi-static and high strain rate compression tests results on OFHC copper. Preliminary results seem to indicate that ductile tearing initiates at the specimen corner location where positive stress triaxiality occurs because of local rotation and eventually propagates along the ligament