Development of n-DoF Preloaded structures for impact mitigation in cobots

A core issue in collaborative robotics is that of impact mitigation, especially when collisions happen with operators. Passively compliant structures can be used as the frame of the cobot, although, usually, they are implemented by means of a single-degree-offreedom (DoF). However, n-DoF preloaded structures offer a number of advantages in terms of flexibility in designing their behavior. In this work, we propose a comprehensive framework for classifying n-DoF preloaded structures, including one-, two-, and threedimensional arrays. Furthermore, we investigate the implications of the peculiar behavior of these structures-which present sharp stiff-to-compliant transitions at designdetermined load thresholds-on impact mitigation. To this regard, an analytical n-DoF dynamic model was developed and numerically implemented. A prototype of a 10DoF structure was tested under static and impact loads, showing a very good agreement with the model. Future developments will see the application of n-DoF preloaded structures to impact-mitigation on cobots and in the field of mobile robots, as well as to the field of novel architected materials

A New Mechanism for the Deployment of Modular Solar Arrays: Kinematic and Static Analysis

This paper presents a new solar arrays deployment mechanism for space applications. It consists of a modular kinematic structure, which is operated by a single cable (1 DoF). Compared to traditional methods, this mechanism has the advantage of being reversible in the movement. Kinematic analysis of the mechanism is carried out in this work, as well as static analysis. They allow to define the main actuation parameters such as cable pull tension and spring stiffness. Moreover, suitable values for the mechanism parameters are computed by means of a dedicated algorithm

The Freehand Technique: The Ability of the Human Eye to Identify Implant Sites on the Patient

In implantology, among the key choices, to obtain predictable results, it is essential to establish, using cone beam computed tomography (CBCT), the bone site and where to insert the implants; during the surgical phase, these sites must be identified on the oral mucosa. Surgical templates are a valid aid, especially in complex cases which require the insertion of more than three or four implants. In cases of a single implant, on the other hand, surgical guides are rarely used, and the implant is often inserted freehand; therefore, the identification of the implant site on the oral mucosa (after choosing the location on the CBCT) is more difficult. For this reason, the clinician uses the teeth in the arch as a reference. This study evaluates the ability of the human eye to identify, on the oral mucosa, where the implant collars will be positioned, the position of which has previously been chosen on the CBCT, in cases where the hands-free surgical technique (without surgical guides) is used. The verification of this precision is carried out using particular thermo-printed templates which contain radiopaque metal spheres. The results show that, in the freehand technique, it is difficult to precisely identify the implant sites (chosen via X-ray) on the mucosa, especially when they are far from natural teeth adjacent to the edentulous area. In case of monoedentulism, the freehand implant technique seems to be applicable by expert implantologists with a reduced risk of error; in fact, clinical experience helps to find the correct correspondence between the implant site chosen on the CBCT and its identification on the mucosa. The level of experience is fundamental in the clinician’s decision about whether or not to use surgical guides; in fact, doctors with little experience should use surgical guides even in the simplest cases to reduce the risk of error

Oxidative stress neuroinflammation and cellular stress response in sensorineural hearing loss: novel nutritional therapeutical approaches

This study is intended to validate the hypothesis that changes in the redox state of glutathione, the major endogenous antioxidant, associated with the abnormal expression and activity of cytoprotective vitagenes, which in normal conditions are expressed only at low level may represent a critical factor, involved in the physiopathological changes associated to degenerative damage occurring in cochlear diseases. Moreover modulation of stress responsive vitagenes by nutritional antioxidants can be an effective therapeutic strategy to minimize consequences of oxidative stress associated to the pathogenesis and course of sensorineural hearing loss. One therapeutic approach can be antioxidant substances, as cisteina and superoxide dismutase supplementation to burst vitagenes and confer neuroprotection. The damage caused in the inner ear by oxidative stress can induce apoptosis and necrosis of both the hair cells as neurons of the spiral ganglion. Reactive oxygen species (ROS) and free radicals are formed not only as by-products of various metabolic pathways but also for exposure to ototoxic substances such as aminoglycosides and cisplatin, for hypoxia/ischemia and to exposure to noise. Although the mechanism of production of ROS within the cochlea has not yet been precisely identified, it is conceivable that mitochondrial dysfunction and consequent burst in oxidative stress are major causative factors. Consistent with this notion, it is known that the base of the cochlea is more vulnerable to oxidative damage resulted from exposure to ototoxic substances than the apical portions. The difference in survival between the basal outer hair cells and the apical ones appear to be due to a significantly lower level of glutathione in the basal outer hair cells than the apical, a phenomenon that makes it easier basal cells vulnerable to damage from free radicals. © Mattioli 188

Application of a low-cost camera on a UAV to estimate maize nitrogen-related variables

The development of small unmanned aerial vehicles and advances in sensor technology have made consumer digital cameras suitable for the remote sensing of vegetation. In this context, monitoring the in-field variability of maize (Zea mays L.), characterized by high nitrogen fertilization rates, with a low-cost color-infrared airborne system could be the basis for a site-specific nitrogen (N) fertilization support system. An experimental field with different N treatments applied to silage maize was monitored during the years 2014 and 2015. Images of the field and reference destructive measurements of above ground biomass, its N concentration and N uptake were taken at V6 and V9 development stages. Classical normalized difference vegetation indices (NDVI) and the indices adjusted by crop ground cover were calculated and regressed against the measured variables. Finally, image colorgrams were used to explore the potential of band-related information in variable estimation. A colorgram is a linear signal that summarizes the color content of each digital image. It is composed of a sequence of the frequency distribution curves of the camera bands, of their related parameters and of results of the principal components analysis applied to each image. The best predictors were found to be the ground cover and the adjusted green-based NDVI: regression equation at V9 resulted in R2 of 0.7 and RRMSE < 25% in external validation. Colorgrams did not improve prediction performance due to the spectral limitations of the camera. Therefore, the feasibility of the method should be tested in future research. In spite of limitations of sensor setup, the modified camera was able to estimate maize biomass due to the very high spatial resolution. Since the above ground biomass is a robust proxy of N status, the modified camera could be a promising tool for a low-cost N fertilization support system

Unraveling the effect of proliferative stress in vivo in hematopoietic stem cell gene therapy mouse study

The hematopoietic system of patients enrolled in hematopoietic stem cells (HSC) gene therapy (GT) treatments is fully reconstituted upon autologous transplantation of engineered stem cells. HSCs highly proliferate up to full restoration of homeostasis and compete for niche homing and engraftment. The impact of the proliferation stress in HSC on genetic instability remains an open question that cured patients advocate for characterizing long-term safety and efficacy. The accumulation of somatic mutations has been widely used as a sensor of proliferative stress. Vector integration site (IS) can be used as a molecular tool for clonal identity, inherited by all HSC progeny, to uncover lineage dynamics in vivo at single-cell level. Here we characterized at single-clone granularity the proliferative stress of HSCs and their progeny over time by measuring the accumulation of mutations from the DNA of each IS. To test the feasibility of the approach, we set-up an experimental framework that combines tumor-prone Cdkn2a-/- and wild type (WT) mouse models of HSC-GT and molecular analyses on different hematopoietic cell lineages after transplantation of HSCs transduced with genotoxic LV (LV.SF.LTR) or GT-like non-genotoxic LV (SIN.LV.PGK). The Cdkn2a-/- mouse model provided the experimental conditions to detect the accumulation of somatic mutations, since the absence of p16INK4A and p19ARF enhances the proliferative potential of cells that have acquired oncogenic mutations. As expected, mice transplanted with Cdkn2a-/- Lin- cells marked with LV.SF.LTR (N=24) developed tumors significantly earlier compared to mock (N=20, p<0.0001), while mice treated with SIN. LV.PGK (N=23) did not. On the other side, mice that received WT Lin- cells treated with LV.SF.LTR (N=25) or SIN.LV.PGK (N=24) vector have not developed tumors. Given this scenario, we expect that Cdkn2a-/- Lin- cells transduced with LV.SF.LTR are associated with higher mutation rates compared to the SIN.LV.PGK group and wild type control mice. The composition of peripheral blood, lymphoid (B and T) and myeloid compartments was assessed by FACS on samples collected every 4 weeks and IS identification. More than 200,000 IS have been recovered. To identify the presence of somatic mutations, the genomic portions of sequencing reads flanking each different IS were analyzed with VarScan2. The accumulation rates of mutations have been evaluated by our new Mutation Index (MI) which normalizes the number of mutations by clones and coverage. Considering that a large portion of IS has been discarded since not covered by a minimum number of 5 unique reads (genomes), the remaining number of IS contained >90% of reads in each group. The MI increased over time in both LV.SF.LTR groups, with higher values for the Cdkn2a-/-. On the other hand, treatment with SIN.LV.PGK resulted in lower MI in both groups compared to LV.SF.LTR groups, reflecting the higher clonal composition of the cells treated with the SIN.LV.PGK and the phenomenon of insertional mutagenesis in the LV.SF.LTR. Moreover, the higher MI values of the SIN.LV.PGK Cdkn2a-/- group compared with the WT group proved the induction of DNA fragility. Our results showed that the analysis of the accumulation of somatic mutations at single clone unraveled HSC proliferation stress in vivo, combining for the first time the analysis of acquired mutations with IS. We are now applying our model to different clinical trials, and studying HSCs sub- clonal trees by symmetric divisions, previously indistinguishable by IS only. Our study will open the doors to in vivo long-term non-invasive studies of HSC stability in patients

Acquisition of somatic mutations after hematopoietic stem cell gene therapy varies among cell lineages and is modulated by vector genotoxicity and the activity of key cellular senescence gene

The hematopoietic system of patients undergoing Hematopoietic Stem and Progenitor Cell (HSPC) Gene Therapy (GT) is fully restored when autologous engineered HSPCs are reinfused into the patient. During this process, HSPCs go through a high level of proliferation until the hematopoietic reconstitution is complete. The impact of proliferation in HSPCs on cellular fitness and safety remains an open question. Moreover, the accumulation of somatic mutations in vivo could show differences in different hematopoietic lineages depending on their susceptibility to the negative effects elicited by the DNA damage response. Furthermore, oncogene activation in human HSPCs has been shown to trigger a chronic inflammatory response leading to hematopoietic decay. Here we studied the clonality and the accumulation of somatic mutations in different hematopoietic lineages and during hematopoietic reconstitution in mice subjected to HSPC-GT. Indeed, wild type C57 mice were transplanted with bone marrow-derived lineage negative (Lin-) cells from WT mice or tumor-prone Cdkn2a-/- mice which lack p16INK4A and p19ARF proteins and thus have no barriers against proto-oncogene activation. Moreover, to evaluate if genotoxic integrations may increase the probability of acquiring somatic mutation upon oncogene activation, Lin- cells were transduced with a genotoxic LV harboring the strong retroviral enhancer/promoter Spleen Focus Forming Virus in the LTR (LV.SF.LTR) or the safer GTlike non-genotoxic LV (SIN.LV.PGK). Mice receiving WT Lin- cells treatedwith LV.SF.LTR (N= 25) or SIN.LV.PGK (N= 24) did not develop tumors, while mice transplanted with Cdkn2a/LV.SF.LTR-marked cells (N = 24) developed tumors significantly earlier compared to mock (N = 20, p < 0.0001) and mice receiving Cdkn2a/SIN.LV.PGK-treated cells (N = 23, p < 0.0001). To evaluate the clonal dynamics of hematopoietic reconstitution, vector integration sites (IS)were identified by by Sonication Mediated Integration Site (SLiM) PCR from peripheral blood, lymphoid (B and T) and myeloid cells collected every 4 weeks post transplantation. Somatic mutations were identified by analyzing the mouse genomic portion flanking each IS using VarScan2. Overall, we detected >200,000 IS, corresponding to more than 135 Mb of genomic sequence information. We introduced a new Mutation Index (MI), which normalizes the number of mutations by clones and coverage to assess mutation accumulation rates. By this approach, we found that the MI increased over time in LV.SF.LTR-treated mice and was significantly higher when compared to SIN.LV.PGK-treated mice (p < 0.001). Notably, myeloid clones exhibited a higher frequency of mutation accumulation compared to T and B cell lineages. This phenomenon was further exacerbated in Cdkn2a/LV.SF.LTR-marked cells, indicating that the absence of barriers to proto-oncogene activation and the presence of genotoxic insertions result in progressive somatic mutation accumulation and insertional mutagenesis. These results demonstrate for the first time that by combining the assessment of acquired mutations with IS analysis at the single clone level we can identify differential accumulations of somatic mutations in different hematopoietic lineages in vivo which depend on the genotoxic potential of the vector used and the ability of the genetically modified cells to sense and react to genotoxic lesions

Agronomic and Environmental Benefits of Cover Crops in Northern Italy

Cover crops have a number of benefits (reduction of nitrate leaching and of soil erosion, control of weed seed bank, increase of soil organic matter and increase of cash crop yield), but these were seldom quantified in cropping systems of Northern Italy. This experiment aimed to quantify some of these effects, by comparing cover crop species and their management techniques