Modal identification of storage racks for cheese wheels

During the Emilia-Romagna earthquake (2012), a great number of steel racks used to store cheese wheels collapsed, causing a non-negligible damage to the Italian economy. Therefore, for similar structures that survived and are in service, a deep investigation towards the assessment of their effective safety is required. In the seismic analysis of these frames, the mechanical constraint acting onto the racks due to the reinforced concrete sidewalls, possible nonlinearities exhibited by the base-plate joints and the in-plane restraint provided by wooden boards that connects adjacent columns should be carefully modelled to ensure realistic design results. In the paper, an experimental activity, based on suitable modal identification techniques, is presented to capture the dynamic behaviour of these peculiar structures. The scope is to collect data useful to calibrate numerical finite element models in order to accurately define the aforementioned unknown parameters. Furthermore, a few numerical models based on ideal restraints are herein discussed stressing out non-negligible differences in terms of expected seismic and static response

Characterizing receptive field selectivity in area V2

The computations performed by neurons in area V1 are reasonably well understood, but computation in subsequent areas such as V2 have been more difficult to characterize. When stimulated with visual stimuli traditionally used to investigate V1, such as sinusoidal gratings, V2 neurons exhibit similar selectivity (but with larger receptive fields, and weaker responses) relative to V1 neurons. However, we find that V2 responses to synthetic stimuli designed to produce naturalistic patterns of joint activity in a model V1 population are more vigorous than responses to control stimuli that lacked this naturalistic structure (Freeman, et. al. 2013). Armed with this signature of V2 computation, we have been investigating how it might arise from canonical computational elements commonly used to explain V1 responses. The invariance of V1 complex cell responses to spatial phase has been previously captured by summing over multiple “subunits” (rectified responses of simple cell-like filters with the same orientation and spatial frequency selectivity, but differing in their receptive field locations). We modeled V2 responses using a similar architecture: V2 subunits were formed from the rectified responses of filters computing the derivatives of the V1 response map over frequencies, orientations, and spatial positions. A V2 complex cell” sums the output of such subunits across frequency, orientation, and position. This model can qualitatively account for much of the behavior of our sample of recorded V2 neurons, including their V1-like spectral tuning in response to sinusoidal gratings as well as the pattern of increased sensitivity to naturalistic images

A point process framework for modeling electrical stimulation of the auditory nerve

Model-based studies of auditory nerve responses to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe auditory nerve spiking while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of the auditory nerve that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semi-analytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data and explain differences in auditory nerve responses to high and low pulse rate stimulation. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds.Comment: 1 title page, 27 manuscript pages, 14 figures, 1 table, 1 appendi

Combining geometric edge detectors for feature detection

We propose a novel framework for the analysis and modeling of discrete edge filters, based on the notion of signed rays. This framework will allow us to easily deduce the geometric and localization properties of a family of first-order filters, and use this information to design custom filter banks for specific applications. As an example, a set of angle-selective corner detectors is constructed for the detection of buildings in video sequences. This clearly illustrates the merit of the theory for solving practical recognition problems

Quantitative single molecule analysis of podoplanin clustering in fibroblastic reticular cells uncovers CD44 function

Upon initial immune challenge, dendritic cells (DCs) migrate to lymph nodes and interact with fibroblastic reticular cells (FRCs) via C-type lectin-like receptor 2 (CLEC-2). CLEC-2 binds to the membrane glycoprotein podoplanin (PDPN) on FRCs, inhibiting actomyosin contractility through the FRC network and permitting lymph node expansion. The hyaluronic acid receptor CD44 is known to be required for FRCs to respond to DCs but the mechanism of action is not fully elucidated. Here, we use DNA-PAINT, a quantitative single molecule super-resolution technique, to visualize and quantify how PDPN clustering is regulated in the plasma membrane of FRCs. Our results indicate that CLEC-2 interaction leads to the formation of large PDPN clusters (i.e. more than 12 proteins per cluster) in a CD44-dependent manner. These results suggest that CD44 expression is required to stabilize large pools of PDPN at the membrane of FRCs upon CLEC-2 interaction, revealing the molecular mechanism through which CD44 facilitates cellular crosstalk between FRCs and DCs

Carfilzomib plus dexamethasone in patients with relapsed and refractory multiple myeloma: A retro-prospective observational study

Objective: We investigate safety and efficacy in common clinical practice of the combination of carfilzomib and dexamethasone (Kd56) approved for the ENDEAVOR trial for the treatment of relapsed or refractory multiple myeloma. Methods: We retro-prospective analyzed 75 patients in three centers in Tuscany, 48 of whom had a clinically relevant comorbidity and 50 of whom were older than 65 years, treated with a median use in the fourth line of therapy. We assessed the efficacy based on the International Myeloma Working Group criteria. Results: The overall response rate was 60%. Median PFS was 10 months in the general cohort; in patients treated for more than 1 cycle of therapy PFS was 12 months. Quality of response to Kd56 treatment was found to positively impact PFS. Refractory status to previous line of therapy or to lenalidomide or an history of exposure to pomalidomide, seemed to have no impact on survival. We also showed a low adverse events rate, with no neuropathy events, and a relatively small number of cardiovascular events above grade 3 (10%). Conclusion: Kd56 is an effective and well tolerated regimen in highly pretreated and elderly patients with a good safety profile

Mediterranean Sea large-scale low-frequency ocean variability and water mass formation rates from 1987 to 2007: A retrospective analysis

We describe a synthesis of the Mediterranean Sea circulation structure and dynamics from a 23-year- long reanalysis of the ocean circulation carried out by Adani et al. (2011). This mesoscale permitting dynamical reconstruction of past ocean variability in the Mediterranean Sea allows the study of the time-mean circulation and its low frequency, decadal, components. It is found that the time-mean circu- lation is composed of boundary and open ocean intensified jets at the border of cyclonic and anticyclonic gyres. The large scale basin circulation is generally characterized in the northern regions by cyclonic gyres and in its southern parts by anticyclonic gyres and eddy-dominated flow fields, with the exception of the Tyrrhenian and the northern Ionian Sea. The time-mean Tyrrhenian Sea circulation is dominated by cyclonic gyres of different intensity and intermittency. The northern Ionian Sea circulation, however, reverses in sign in two ten-year periods, the first in 1987–1996 and the second in 1997–2006, which is here called the Northern Ionian reversal phenomenon. This reversal is provoked by the excursion of the Atlantic-Ionian Stream from the middle to the northern parts of the basin. The decadal variability of other parts of the basin is characterized by changes in strength of the basin scale structures. The water mass formation rates and variability are dominated by event-like periods where the intermediate and deep waters are formed for 2–3 years at higher rates. The largest deep water formation events of the past 23 years occurred separately in the western and eastern Mediterranean basin: the first coincided with the Eastern Mediterranean Transient (Roether et al., 1996) and the second with the western Mediterranean deep water formation event in 2005–2006 (Smith et al., 2008). A new schematic of the basin-scale circu- lation is formulated and commented.Published318-3324A. Oceanografia e climaJCR Journa

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2 (BioNTech) and mRNA-1273 (Moderna) vaccines. Plasma and peripheral blood mononuclear cells samples were collected before vaccination, post the second and the third doses and tested for spike-specific antibodies, ACE2/RBD antibody inhibition binding activity and spike-specific B cells. The third vaccine dose significantly increased the spike-specific IgG titers in both ruxolitinib-treated and untreated patients, and strongly enhanced the percentage of subjects with antibodies capable of in vitro blocking ACE2/RBD interaction, from 50% up to 80%. While a very low frequency of spike-specific B cells was measured in blood 7 days after the second vaccination dose, a strong and significant increase was elicited by the third dose administration, generating a B cell response similar to the one detected in healthy controls. Despite the overall positive impact of the third dose in MF patients, two patients that were under active concomitant immunosuppressive treatment at the time of vaccination, and a patient that received lymphodepleting therapies in the past, remained low responders. The third mRNA vaccine dose strongly increases the SARS-CoV-2 specific humoral and B cell responses in MF patients, promoting a reactivation of the immune response similar to the one observed in healthy controls

Efficient Coding of Local 2D Shape

Efficient coding provides a concise account of key early visual properties, but can it explain higher-level visual function such as shape perception? If curvature is a key primitive of local shape representation, efficient shape coding predicts that sensitivity of visual neurons should be determined by naturally-occurring curvature statistics, which follow a scale-invariant power-law distribution. To assess visual sensitivity to these power-law statistics, we developed a novel family of synthetic maximum-entropy shape stimuli that progressively match the local curvature statistics of natural shapes, but lack global structure. We find that humans can reliably identify natural shapes based on 4th and higher-order moments of the curvature distribution, demonstrating fine sensitivity to these naturally-occurring statistics. What is the physiological basis for this sensitivity? Many V4 neurons are selective for curvature and analysis of population response suggests that neural population sensitivity is optimized to maximize information rate for natural shapes. Further, we find that average neural response in the foveal confluence of early visual cortex increases as object curvature converges to the naturally-occurring distribution, reflecting an increased upper bound on information rate. Reducing the variance of the curvature distribution of synthetic shapes to match the variance of the naturally-occurring distribution impairs the linear decoding of individual shapes, presumably due to the reduction in stimulus entropy. However, matching higher-order moments improves decoding performance, despite further reducing stimulus entropy. Collectively, these results suggest that efficient coding can account for many aspects of curvature perception

Plasma-activated medium as an innovative anticancer strategy: Insight into its cellular and molecular impact on in vitro leukemia cells

Cold atmospheric plasma (CAP) has received attention as a potential anticancer strategy. In this study, culture medium was exposed to a microsecond-pulsed dielectric barrier discharge jet to produce plasma-activated medium (PAM). On the T-lymphoblastic cell line, PAM induced apoptosis through the activation of the intrinsic pathway and inhibited the cell-cycle progression. The use of the scavengers N-acetylcysteine or O-phenantroline significantly decreased the PAM proapoptotic activity. The genetic impact of PAM on TK6 cells was assessed, resulting in an increased micronuclei frequency. PAM exhibited cytotoxic effects even on leukemia cells cultivated in hypoxia, which plays a critical role in promoting chemoresistance. PAM was also tested on normal lymphocytes, showing its partial selectivity. Taken together, these results contribute to understand the pharmacotoxicological profile of CAP