A Tutte polynomial for toric arrangements

We introduce a multiplicity Tutte polynomial M(x,y), with applications to zonotopes and toric arrangements. We prove that M(x,y) satisfies a deletion-restriction recurrence and has positive coefficients. The characteristic polynomial and the Poincare' polynomial of a toric arrangement are shown to be specializations of the associated polynomial M(x,y), likewise the corresponding polynomials for a hyperplane arrangement are specializations of the ordinary Tutte polynomial. Furthermore, M(1,y) is the Hilbert series of the related discrete Dahmen-Micchelli space, while M(x,1) computes the volume and the number of integral points of the associated zonotope.Comment: Final version, to appear on Transactions AMS. 28 pages, 4 picture

Extracellular vesicles: Small bricks for tissue repair/regeneration

Extracellular vesicles (EVs) are nano-sized membrane vesicles involved in intercellular communication. EVs have pleiotropic actions in physiological and pathological conditions. The ability of EVs to transports proteins, drugs and nucleic acid, to target specific cells and to increase the stability of therapeutic cargo, make EVs interesting as new devices for the treatment of human disease. In a recently published issue of European journal of pharmaceutical sciences, Silva and colleagues reviewed the ability of EVs to modulate tissue repair and regeneration, focusing on their roles and therapeutic potential as immunomodulatory messengers. In this perspective, we discussed the open questions regarding the dual role of EVs in immune system, as well as the technical limitation of the procedure for EVs isolation and administration in clinical practices. EV-based therapies require further studies to consider EVs as promising candidate for a novel cell-free therapy in the context of regeneration medicine

Efficient Geometric Linearization of Moving-Base Rigid Robot Dynamics

The linearization of the equations of motion of a robotics system about a given state-input trajectory, including a controlled equilibrium state, is a valuable tool for model-based planning, closed-loop control, gain tuning, and state estimation. Contrary to the case of fixed based manipulators with prismatic or rotary joints, the state space of moving-base robotic systems such as humanoids, quadruped robots, or aerial manipulators cannot be globally parametrized by a finite number of independent coordinates. This impossibility is a direct consequence of the fact that the state of these systems includes the system's global orientation, formally described as an element of the special orthogonal group SO(3). As a consequence, obtaining the linearization of the equations of motion for these systems is typically resolved, from a practical perspective, by locally parameterizing the system's attitude by means of, e.g., Euler or Cardan angles. This has the drawback, however, of introducing artificial parameterization singularities and extra derivative computations. In this contribution, we show that it is actually possible to define a notion of linearization that does not require the use of a local parameterization for the system's orientation, obtaining a mathematically elegant, recursive, and singularity-free linearization for moving-based robot systems. Recursiveness, in particular, is obtained by proposing a nontrivial modification of existing recursive algorithms to allow for computations of the geometric derivatives of the inverse dynamics and the inverse of the mass matrix of the robotic system. The correctness of the proposed algorithm is validated by means of a numerical comparison with the result obtained via geometric finite difference

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion

Fragility of bridge decks exposed to hydraulic and driftwood actions

A resilient bridge network is vital to a community recovery after natural disasters. Floods are the main cause of bridge collapses, but there is little research on the combined fragility of single-span bridge decks to hydrodynamic forces and driftwood clogging. Moreover, most studies concentrate on multi-span bridges and piers. By using HEC-RAS software and in-house developed Python scripts, this work proposes a method to obtain fragility curves for single-span bridges accounting for hydrodynamic actions and driftwoods. Due to the lack of indications from standards concerning uplift and overturning of bridge decks, these limit states are included in the formulation together with slippage. Results revealed that all three limit states must be taken into account and showed that driftwood clogging can have a severe impact on the failure probability of the bridge, with even a minor decrease in clearance causing a significant safety reduction. Additionally, this work discusses the influence of hydrologic model recalibration on the failure probability of a structure.The first, second and fourth authors acknowledge that, this work was partly financed by FCT/MCTES through national funds (PIDDAC) under the R&D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020, and under the Associate Laboratory Advanced Production and Intelligent Systems ARISE under reference LA/P/0112/2020. This work was sup-ported by the FCT Foundation for Science and Technology under Grant SFRH/BD/145478/2019

Detour-impact index method and traffic gathering algorithm for assessing alternative paths of disrupted roads

Infrastructure plays a key role in society. Recent collapses of bridges have underlined their importance for road functionality, causing disruptions to commuters and emergency vehicles. Major issues arise on rural roads, where the lack of redundancy leads to the isolation of entire communities. Actual approaches to assess the resilience of countryside roads rely on the availability of specific datasets, limiting their practical application; this issue is typically related to traffic data. This research aims to propose innovative algorithms to assess the road network’s vulnerability in rural areas, including a novel traffic data collection process and its calibration. The aggregate metric is called Detour-Impact Index (DII) and compares user costs before and after a disruptive event. The method uses traditional network-impact metrics in combination with a new algorithm that allows us to gather quantitative traffic data starting from qualitative information. User travel time showed good agreement between the proposed procedure and traditional web-based methods. Furthermore, the paper provides user delay costs functions accounting for traffic composition, trip purposes, vehicle operative costs, nonlinear volume–capacity relation, and average daily traffic. A significant aspect is the adaptability of this framework, as it is designed to be coupled with existing approaches. The method is demonstrated on a case study in Tuscany (Italy).The first, third and sixth authors acknowledge that, this work was partly financed by FEDER funds through the Competitivity Factors Operational Programme - COMPETE and by national funds through FCT Foundation for Science and Technology within the scope of the project POCI-01-0145- FEDER-007633. This work was supported by the FCT Foundation for Science and Technology under Grant SFRH/ BD/145478/2019

Risk management for bridges: a case study of unforeseen failure mode

Risk management plays a crucial role in the stakeholders’ decision making because it is directly related to safety, serviceability and economy. There is now a growing concern about how to relocate known risks into an acceptance threshold: this implies the evaluation of several options obtained from hazard scenarios considering the related consequences. In parallel, practitioners usually rely on standard tools for risk assessment, and on structural codes to compute performances. Although this approach is currently widely implemented, this research shows that hazardous situations can arise in properly designed infrastructures, due to errors in management. This paper deals with such issue, also highlighting a gap in current codes that could contribute to losses caused by unforeseen failure modes. In this study, a preliminary FMEA assessment was performed to identify the failure modes that required a deeper quantitative analysis. In a second step, a quantitative analysis was implemented, using a modular methodology that combines reliability theory with a risk-based approach. The results evidenced that a wider analysis focused on the identification of vulnerable areas shall be considered in every stage of the asset management. Furthermore, the dynamic of this process is regulated by the established safety level concerning possible damages to people, production sites and commercial activities.This work was partly financed by FEDER funds through the Competitivity Factors Operational Programme - COMPETE and by national funds through FCT Foundation for Science and Technology within the scope of the project POCI01-0145-FEDER-007633. This work was supported by the FCT Foundation for Science and Technology under Grant SFRH/BD/145478/2019. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 769255

Femoral artery ultrasound examination: a new role in predicting cardiovascular risk

We compared intima-media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesis

Background: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with osteolytic bone disease. Recently, the role of MM-derived exosomes in the osteoclastogenesis has been demonstrated although the underlying mechanism is still unknown. Since exosomes-derived epidermal growth factor receptor ligands (EGFR) are involved in tumor-associated osteolysis, we hypothesize that the EGFR ligand amphiregulin (AREG) can be delivered by MM-derived exosomes and participate in MM-induced osteoclastogenesis. Methods: Exosomes were isolated from the conditioned medium of MM1.S cell line and from bone marrow (BM) plasma samples of MM patients. The murine cell line RAW264.7 and primary human CD14 + cells were used as osteoclast (OC) sources. Results: We found that AREG was specifically enriched in exosomes from MM samples and that exosomes-derived AREG led to the activation of EGFR in pre-OC, as showed by the increase of mRNA expression of its downstream SNAIL in both RAW264.7 and CD14 + cells. The presence of neutralizing anti-AREG monoclonal antibody (mAb) reverted this effect. Consequently, we showed that the effect of MM-derived exosomes on osteoclast differentiation was inhibited by the pre-treatment of exosomes with anti-AREG mAb. In addition, we demonstrated the ability of MM-derived AREG-enriched exosomes to be internalized into human mesenchymal stromal cells (MSCs) blocking osteoblast (OB) differentiation, increasing MM cell adhesion and the release of the pro-osteoclastogenic cytokine interleukin-8 (IL8). Accordingly, anti-AREG mAb inhibited the release of IL8 by MSCs suggesting that both direct and indirect effects are responsible for AREG-enriched exosomes involvement on MM-induced osteoclastogenesis. Conclusions: In conclusion, our data indicate that AREG is packed into MM-derived exosomes and implicated in OC differentiation through an indirect mechanism mediated by OBs