A quantitative taxonomy of human hand grasps

Background: A proper modeling of human grasping and of hand movements is fundamental for robotics, prosthetics, physiology and rehabilitation. The taxonomies of hand grasps that have been proposed in scientific literature so far are based on qualitative analyses of the movements and thus they are usually not quantitatively justified. Methods: This paper presents to the best of our knowledge the first quantitative taxonomy of hand grasps based on biomedical data measurements. The taxonomy is based on electromyography and kinematic data recorded from 40 healthy subjects performing 20 unique hand grasps. For each subject, a set of hierarchical trees are computed for several signal features. Afterwards, the trees are combined, first into modality-specific (i.e. muscular and kinematic) taxonomies of hand grasps and then into a general quantitative taxonomy of hand movements. The modality-specific taxonomies provide similar results despite describing different parameters of hand movements, one being muscular and the other kinematic. Results: The general taxonomy merges the kinematic and muscular description into a comprehensive hierarchical structure. The obtained results clarify what has been proposed in the literature so far and they partially confirm the qualitative parameters used to create previous taxonomies of hand grasps. According to the results, hand movements can be divided into five movement categories defined based on the overall grasp shape, finger positioning and muscular activation. Part of the results appears qualitatively in accordance with previous results describing kinematic hand grasping synergies. Conclusions: The taxonomy of hand grasps proposed in this paper clarifies with quantitative measurements what has been proposed in the field on a qualitative basis, thus having a potential impact on several scientific fields

Glassiness and Heterogeneous Dynamics in Dense Solutions of Ring Polymers

Understanding how topological constraints affect the dynamics of polymers in solution is at the basis of any polymer theory and it is particularly needed for melts of rings. These polymers fold as crumpled and space-filling objects and, yet, they display a large number of topological constraints. To understand their role, here we systematically probe the response of solutions of rings at various densities to "random pinning" perturbations. We show that these perturbations trigger non-Gaussian and heterogeneous dynamics, eventually leading to non-ergodic and glassy behaviours. We then derive universal scaling relations for the values of solution density and polymer length marking the onset of vitrification in unperturbed solutions. Finally, we directly connect the heterogeneous dynamics of the rings with their spatial organisation and mutual interpenetration. Our results suggest that deviations from the typical behaviours observed in systems of linear polymers may originate from architecture-specific (threading) topological constraints

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Magnetic Polymer Models for Epigenetics-Driven Chromosome Folding

Epigenetics is a driving force of important and ubiquitous phenomena in nature such as cell differentiation or even metamorphosis. Opposite to its widespread role, understanding the biophysical principles that allow epigenetics to control and rewire gene regulatory networks remains an open challenge. In this work we study the effects of epigenetic modifications on the spatial folding of chromosomes\u2014and hence on the expression of the underlying genes\u2014by mapping the problem to a class of models known as magnetic polymers. In this work we show that a first order phase transition underlies the simultaneous spreading of certain epigenetic marks and the conformational collapse of a chromosome. Further, we describe Brownian dynamics simulations of the model in which the topology of the polymer and thermal fluctuations are fully taken into account and that confirm our mean field predictions. Extending our models to allow for nonequilibrium terms yields new stable phases which qualitatively agrees with observations in vivo. Our results show that statistical mechanics techniques applied to models of magnetic polymers can be successfully exploited to rationalize the outcomes of experiments designed to probe the interplay between a dynamic epigenetic landscape and chromatin organization

Donne immigrate e screening cervicale nel Veneto

According to the literature, women coming from countries with strong migratory pressure are at a greater risk of cancer of the cervix with respect to Italian women. This is connected with the fact that women born outside Italy are less likely to undergo a cervical smear. In the Veneto Region the official immigrant population is equivalent to approximately 10% of the total population. This article analyzes the utilization of cervical smear from immigrant women in the Veneto Region, taking into account the smears performed both inside and outside organized screening programmes. Data have been gathered both from the archives of the screening programmes of the Local Health Authorities and from PASSI, a national surveillance system based on a standardized questionnaire administered through telephone interviews. The screening crude participation rate among foreign women was 45.3%, only slightly lower than the one of Italian women. The participation is lower in women from Asia and in women above 50 years. The percentage of positive smear tests was 2.7% among Italian women and 4.0% among foreign women. Compliance to colposcopy has been 89.9% for Italian women and 88.1% for foreign women. The detection rate of cervical intraepithelial neoplasia grade II or worse (CIN II+ diagnoses) in foreign women has been twofold the one detected in Italian women. If we consider the number of smear tests carried out in the last three years and outside the context of screening programmes, the number of women who have undergone a pap smear is much higher among Italian women, women 39-45 years old and women with a high level of education and without particular economic difficulties. The opposite is true for the organized screening programmes, where the differences according to age, level of education, economic difficulties and citizenship are reduced. These data confirm that women coming from countries with strong migratory pressure are at a greater risk of cancer of the cervix with respect to Italian women. A decrease in inequalities (in terms of education level, socio-economical status and nationality) is shown when considering the access to the screening programs

Extrusion without a motor:a new take on the loop extrusion model of genome organization

Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo "Non-equilibrium chromosome looping via molecular slip-links", Physical Review Letters 119 138101 (2017)

Maximally Stiffening Composites Require Maximally Coupled Rather Than Maximally Entangled Polymer Species

Polymer composites are ideal candidates for next generation biomimetic soft materials because of their exquisite bottom-up designability. However, the richness of behaviours comes at a price: the need for precise and extensive characterisation of material properties over a highly-dimensional parameter space, as well as a quantitative understanding of the physical principles underlying desirable features. Here we couple large-scale Molecular Dynamics simulations with optical tweezers microrheology to characterise the viscoelastic response of DNA-actin composites. We discover that the previously observed non-monotonic stress-stiffening of these composites is robust, yet tunable, in a broad range of the parameter space that spans two orders of magnitude in DNA length. Importantly, we discover that the most pronounced stiffening is achieved when the species are maximally coupled, i.e. have similar number of entanglements, and not when the number of entanglements per DNA chain is largest. We further report novel dynamical oscillations of the microstructure of the composites, alternating between mixed and bundled phases, opening the door to future investigations. The generic nature of our system renders our results applicable to the behaviour of a broad class of polymer composites.Comment: Accepted in Soft Matte

Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure