On the characterization of materials and masonry walls of historical buildings: Use of optical system to obtain displacement maps in double-flat jack tests

Among the testing techniques aiming at the mechanical characterization of masonry, the double flat-jack testing method is widely adopted to identify the local value of significant parameters needed to perform structural analyses, such as elastic modulus, Poisson’s ratio and compressive strength. The experience gained from many applications has allowed not only to collect experimental data concerning different types of masonry, but also to highlight the difficulty in the interpretation of the results and the limitations of both single and double flat-jack tests. Although the accuracy of the flat-jack technique in detecting strength and deformability behavior of masonry is still debated in the technical literature and practical activities, changes in the testing procedure aiming at ascertaining the validity of the test results have not been formally defined yet. After a brief description of the standard test procedure and its uncertainties, the present paper proposes an upgrade of the test procedure for improving the level of reliability of the test results. In particular, an experimental case study related to a historical brick masonry building located in Italy is presented to point out the additional information necessary to validate the results of the testing process

Profiles of SUMO and ubiquitin conjugation in an Alzheimer's disease model

► Global levels of ubiquitinated proteins increased in the hippocampus of Tg2576 mice. ► No global changes in either SUMO-1 or SUMO-2/3 conjugation in any brain regions analysed. ► SUMO conjugating and deconjugating enzymes, UBC9 and SENP-1, unaltered in Tg2576 mice. ► Total levels of AMPA and kainate receptors were also unaffected in Tg2576 mice. ► Posttranslational modification by ubiquitin may play a role in Alzheimer's disease

Subducted organic matter buffered by marine carbonate rules the carbon isotopic signature of arc emissions

Ocean sediments consist mainly of calcium carbonate and organic matter (phytoplankton debris). Once subducted, some carbon is removed from the slab and returns to the atmo- sphere as CO2 in arc magmas. Its isotopic signature is thought to reflect the bulk fraction of inorganic (carbonate) and organic (graphitic) carbon in the sedimentary source. Here we challenge this assumption by experimentally investigating model sediments composed of 13C-CaCO3 + 12C-graphite interacting with water at pressure, temperature and redox con- ditions of an average slab–mantle interface beneath arcs. We show that oxidative dissolution of graphite is the main process controlling the production of CO2, and its isotopic compo- sition reflects the CO2/CaCO3 rather than the bulk graphite/CaCO3 (i.e., organic/inorganic carbon) fraction. We provide a mathematical model to relate the arc CO2 isotopic signature with the fluid–rock ratios and the redox state in force in its subarc source

A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma

Environmental consequences of Ontong Java Plateau and Kerguelen Plateau Volcanism

The mid-Cretaceous was marked by emplacement of large igneous provinces (LIPs) that formed gigantic oceanic plateaus, affecting ecosystems on a global scale, with biota forced to face excess CO2 resulting in climate and ocean perturbations. Volcanic phases of the Ontong Java Plateau (OJP) and the southern Kerguelen Plateau (SKP) are radiometrically dated and correlate with paleoenvironmental changes, suggesting causal links between LIPs and ecosystem responses. Aptian biocalcifi cation crises and recoveries are broadly coeval with C, Pb, and Os isotopic anomalies, trace metal infl uxes, global anoxia, and climate changes. Early Aptian greenhouse or supergreenhouse conditions were followed by prolonged cooling during the late Aptian, when OJP and SKP developed, respectively. Massive volcanism occurring at equatorial versus high paleolatitudes and submarine versus subaerial settings triggered very different climate responses but similar disruptions in the marine carbonate system. Excess CO2 arguably induced episodic ocean acidifi cation that was detrimental to marine calcifi ers, regardless of hot or cool conditions. Global anoxia was reached only under extreme warming, whereas cold conditions kept the oceans well oxygenated even at times of intensifi ed fertility. The environmental disruptions attributed to the OJP did not trigger a mass extinction: rock-forming nannoconids and benthic communities underwent a signifi cant decline during Oceanic Anoxic Event (OAE) 1a, but recovered when paroxysmal volcanism fi nished. Extinction of many planktonic foraminiferal and nannoplankton taxa, including most nannoconids, and most aragonitic rudists in latest Aptian time was likely triggered by severe ocean acidifi cation. Upgraded dating of paleoceanographic events, improved radiometric ages of the OJP and SKP, and time-scale revision are needed to substantiate the links between magmatism and paleoenvironmental perturbations

No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62)

A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (IQR) total and unbound DTG in CSF were 7.3(5.9-8.4) ng/mL and 1.7(1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years

[Abstract] OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability