A non-contact optical technique for vehicle tracking along bounded trajectories

This paper presents a method for measuring the non-controlled trajectory of a cart along a bounded rectilinear path. The method uses non-contact measurement devices to identify the position of a movable laser scanner working in helical mode in order to reconstruct the 3D model of bridges. The main idea of the proposed method is to use vision systems in order to identify the coordinates of the laser scanner placed on the cart with respect to the global reference system. A fit-to-purpose vision system has been implemented: the system uses three CCD's cameras mounted on the cart to identify the relative rotations with respect to the environment. Two lasers pointers and a laser distance meter are fixed at the starting point of the trajectory and pointing in the direction of motion of the cart, creating three dots on a plane placed on the cart. One of the camera detects the cart displacements and rotations in the plane using a blob analysis procedure. The method described in this paper has a constant uncertainty and the measurement range only depends on the lasers power. The theoretical accuracy of the measurement system is close to 1 mm for the translation along the motion direction and around 0.5 mm along the other two directions. Orientations measurement have a theoretical accuracy of less than 0.1 °. The solution has been implemented for the 3D reconstruction of concrete bridge; preliminary experimental results are presented and discussed

Osteonecrosis of the jaw after adjuvant endocrine therapy plus alendronate in a breast cancer patient

Background. Bisphosphonates-associated osteonecrosis of the jaws (BRONJ) is a serious complication, which has been defined by Bedogni et al. (1) as an adverse drug reaction consisting of progressive destruction and death of bone that affects the mandible and/or maxilla of patients exposed to the treatment with nitrogen-containing bisphosphonates (NBPs) in absence of a previous radiation treatment. Generally, IV NBPs have a strong association with BRONJ than oral NBPs as evidenced by the higher incidence of BRONJ (0-10%) in patients treated with IV drugs than in patients in oral therapy (<1%). Objectives. The aim of this study was to report a clinical case of BRONJ in an oncologic patient who has been treated with anastrozole and oral NBPs for secondary osteoporosis. Case report. In February 2014 a 75-year-old woman was referred because of history of pain in the left posterior mandibular region and hypoesthesia/anesthesia of the homolateral inferior lip and chin. In the anamnesis, she had referred to be in therapy with alendronate since 2004, for a history of severe osteoporosis and, in multimodal chemotherapy and anastrazole since 2010 for a diagnosis of breast cancer. Furthermore, left lower molar extraction was performed on March 2013. Clinical examination revealed swelling of the extraoral soft tissue in the left emimandible; intraorally, the presence of a mucosal fistula on the left mandibular angle was identified. CT was performed and BRONJ diagnosis was defined with a stage 2A according to Bedogni et al. Conclusions. Administration of NBP is indicated to treat also osteoporosis anastrazole-induced in oncological patients, showing that patients with hormone receptor-positive early-stage breast cancer taking oral BP could represent a subset in which it would be useful to apply BRONJ prevention protocols

Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: a case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started

JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT

A large deletion in the GP9 gene in Cocker Spaniel dogs with Bernard-Soulier syndrome

Inherited bleeding disorders including abnormalities of platelet number and function rarely occur in a variety of dog breeds, but are probably underdiagnosed. Genetically characterized canine forms of platelet disorders provide valuable large animal models for understanding similar platelet disorders in people. Breed-specific disease associated genetic variants in only eight different genes are known to cause intrinsic platelet disorders in dogs. However, the causative genetic variant in many dog breeds has until now remained unknown. Four cases of a mild to severe bleeding disorder in Cocker Spaniel dogs are herein presented. The affected dogs showed a platelet adhesion defect characterized by macrothrombocytopenia with variable platelet counts resembling human Bernard-Soulier syndrome (BSS). Furthermore, the lack of functional GPIb-IX-V was demonstrated by immunocytochemistry. Whole genome sequencing of one affected dog and visual inspection of the candidate genes identified a deletion in the glycoprotein IX platelet (GP9) gene. The GP9 gene encodes a subunit of a platelet surface membrane glycoprotein complex; this functions as a receptor for von Willebrand factor, which initiates the maintenance of hemostasis after injury. Variants in human GP9 are associated with Bernard-Soulier syndrome, type C. The deletion spanned 2460 bp, and included a significant part of the single coding exon of the canine GP9 gene on dog chromosome 20. The variant results in a frameshift and premature stop codon which is predicted to truncate almost two-thirds of the encoded protein. PCR-based genotyping confirmed recessive inheritance. The homozygous variant genotype seen in affected dogs did not occur in 98 control Cocker Spaniels. Thus, it was concluded that the structural variant identified in the GP9 gene was most likely causative for the BSS-phenotype in the dogs examined. These findings provide the first large animal GP9 model for this group of inherited platelet disorders and greatly facilitate the diagnosis and identification of affected and/or normal carriers in Cocker Spaniels

Exploring the G-quadruplex binding and unwinding activity of the bacterial FeS helicase DinG

Despite numerous reports on the interactions of G-quadruplexes (G4s) with helicases, systematic analysis addressing the selectivity and specificity of each helicase towards a variety of G4 topologies are scarce. Among the helicases able to unwind G4s are those containing an iron-sulphur (FeS) cluster, including both the bacterial DinG (found in E. coli and several pathogenic bacteria) and the medically important eukaryotic homologues (XPD, FancJ, DDX11 and RTEL1). We carried out a detailed study of the interactions between the E. coli DinG and a variety of G4s, by employing physicochemical and biochemical methodologies. A series of G4-rich sequences from different genomic locations (promoter and telomeric regions), able to form unimolecular G4 structures with diverse topologies, were analyzed (c-KIT1, KRAS, c-MYC, BCL2, Tel23, T30695, Zic1). DinG binds to most of the investigated G4s with little discrimination, while it exhibits a clear degree of unwinding specificity towards different G4 topologies. Whereas previous reports suggested that DinG was active only on bimolecular G4s, here we show that it is also able to bind to and resolve the more physiologically relevant unimolecular G4s. In addition, when the G4 structures were stabilized by ligands (Pyridostatin, PhenDC3, BRACO-19 or Netropsin), the DinG unwinding activity decreased and in most cases was abolished, with a pattern that is not simply explained by a change in binding affinity. Overall, these results have important implications for the biochemistry of helicases, strongly suggesting that when analysing the G4 unwinding property of an enzyme, it is necessary to investigate a variety of G4 substrates

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs

Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolopyrimidinones Tethered with Hydrazide-Hydrazones.

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compound

Conservation-compatible retrofit solutions in historic buildings: An integrated approach

Historic, listed, or unlisted, buildings account for 30% of the European building stock. Since they are complex systems of cultural, architectural, and identity value, they need particular attention to ensure that they are preserved, used, and managed over time in a sustainable way. This implies a demand for retrofit solutions able to improve indoor thermal conditions while reducing the use of energy sources and preserving the heritage significance. Often, however, the choice and implementation of retrofit solutions in historic buildings is limited by socio-technical barriers (regulations, lack of knowledge on the hygrothermal behaviour of built heritage, economic viability, etc.). This paper presents the approach devised in the IEA-SHC Task 59 project (Renovating Historic Buildings Towards Zero Energy) to support decision makers in selecting retrofit solutions, in accordance with the provision of the EN 16883:2017 standard. In particular, the method followed by the project partners to gather and assess compatible solutions for historic buildings retrofitting is presented. It focuses on best practices for walls, windows, HVAC systems, and solar technologies. This work demonstrates that well-balanced retrofit solutions can exist and can be evaluated case-by-case through detailed assessment criteria. As a main result, the paper encourages decision makers to opt for tailored energy retrofit to solve the conflict between conservation and energy performance requirements