Seismic behavior of posttensioned self-centering precast concrete dual-shell steel columns

This paper describes an innovative bridge column technology for application in seismic regions. The proposed technology combines a precast posttensioned composite steel-concrete hollow-core column, with supplemental energy dissipation, in a way to minimize postearthquake residual lateral displacements. The column consists of two steel cylindrical shells, with high-performance concrete cast in between. Both shells act as permanent formwork; the outer shell substitutes for the longitudinal and transverse reinforcement, because it works in composite action with the concrete, whereas the inner shell removes unnecessary concrete volume from the column, prevents concrete implosion, and prevents buckling of energy dissipating dowels when embedded in the concrete. Large inelastic rotations can be accommodated at the end joints with minimal structural damage, since gaps are allowed to open at these locations and to close upon load reversal. Longitudinal posttensioned high-strength steel threaded bars, designed to respond elastically, in combination with gravity forces ensure self-centering behavior. Internal or external steel devices provide energy dissipation by axial yielding. This paper describes the main requirements for the design of these columns and also discusses the experimental findings from two quasi-static tests

Fluorescence Resonance Energy Transfer (FRET) as a method to calculate the dimerization strength of basic Helix-Loop-Helix (bHLH) proteins

Post-translational modifications such as phosphorylation play a vital role in the regulation of protein function. In our study of the basic Helix-loop-Helix (bHLH) transcription factor HAND1, we show that HAND1 is phosphorylated during the trophoblast giant cell differentiation on residues residing in Helix I of the bHLH domain. Our hypothesis is that these modifications result in changes in HAND1 dimerization affinities with other bHLH factors. To test this idea, we employed FRET to measure the protein-protein interactions of HAND1 and HAND1 point mutants in HEK293 cells using YFP and CFP fusion proteins and laser scanning confocal microscopy

The MICADO first light imager for ELT: its astrometric performance

We report on our ongoing efforts to ensure that the MICADO NIR imager reaches differential absolute (often abbreviated: relative) astrometric performance limited by the SNR of typical observations. The exceptional 39m diameter collecting area in combination with a powerful multi-conjugate adaptive optics system (called MAORY) brings the nominal centroiding error, which scales as FWHM/SNR, down to a few 10 uas. Here we show that an exceptional effort is needed to provide a system which delivers adequate and calibrateable astrometric performance over the full field of view (up to 53 arcsec diameter).Comment: 5 pages, submitted to SPIE 2018 Astronomical Telescopes + Instrumentatio

Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer's Disease : The Paradigmatic Example of CSF

The use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer's disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal loss and amyloid deposition has led to the understanding that AD is characterized by a long preclinical phase. It is also supporting the transition towards a biology-grounded framework and definition of the disease. Nevertheless, though sufficient evidence exists about the analytical validity (i.e., accuracy, reliability, and reproducibility) of the candidate AD biomarkers, their clinical validity (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and clinical utility (i.e., if and how the test improves the patient's outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices) have not been fully proven. In the present review, some of the methodological issues and challenges that should be addressed in order to better appreciate the potential benefits and limitations of AD biomarkers are discussed. The ultimate goal is to stimulate a constructive discussion aimed at filling the existing gaps and more precisely defining the directions of future research. Specifically, four main aspects of the clinical validation process are addressed and applied to the most relevant CSF biomarkers: (1) the definition of reference values; (2) the identification of reference standards for the disease of interest (i.e., AD); (3) the inclusion within the diagnostic process; and (4) the statistical process supporting the whole framework

Antiparkinsonian efficacy of guanosine in rodent models of movement disorder

Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the neuroprotective effects of GUO have been corroborated in cellular models of Parkinson's disease (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD animal models. Accordingly, we evaluated the effectiveness of GUO in reversing motor impairments in several rodent movement disorder models, including catalepsy, tremor, and hemiparkinsonism. Our results showed that orally administered GUO antagonized reserpine-mediated catalepsy, reduced reserpine-induced tremulous jaw movements, and potentiated the number of contralateral rotations induced by L-3,4-dihydroxyphenylalanine in unilaterally 6-hydroxidopamine-lesioned rats. In addition, at 5 and 7.5 mg/kg, GUO inhibited L-DOPA-induced dyskinesia in rats chronically treated with a pro-dopaminergic agent. Overall, we describe the therapeutic potential of GUO, which may be effective not only for reversing parkinsonian motor impairments but also for reducing dyskinesia induced by treatment for PD

The valanginian weissert oceanic anoxic event recorded in central-Eastern Sardinia (Italy)

Investigations on the S\u2019Ozzastru section from the northern part of the Mt Albo area (central-eastern Sardinia, Italy) for integrated litho- bio- and chemostratigraphy allowed the identification of the Valanginian Weissert Oceanic Anoxic Event (OAE), testified by a positive carbon isotope excursion (CIE). The section, which represents the deepest-water succession of the Valanginian in Sardinia, is composed of the Schiridd\ue8 Limestone followed by the Siniscola Marl, both proposed as new lithostratigraphic units. The presence among the ammonites of Busnardoites campylotoxus allows the attribution of the Schiridd\ue8 Limestone to the upper Lower Valanginian Inostranzewi Zone of Reboulet et al. 2014. Further characterization of this unit was not possible since it is barren/almost barren of nannofossils. The Siniscola Marl can be ascribed to the lower Upper Valanginian on the basis of the ammonite fauna indicating the Verrucosum Zone, and of the nannofossil content suggesting the Zone NK3. The carbon isotope record in the Siniscola Marl is characterized by a positive excursion with values up to 2.98 \u2030. In the nannofossil assemblages, nannoconids are not particularly abundant and are found, among others, together with C. oblongata, D. lehmanii, and pentaliths. The scarcity of nannoconids is regarded as a biostratigraphic support for the identification of the Weissert OAE, as it possibly reflects the \u201cnannoconid decline\u201d interval which characterizes this event. The end of the Weissert OAE CIE is not recorded probably because of suppression of the upper part of the succession for tectonic causes

Fiber bragg gratings for medical applications and future challenges: A review

In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system

Adenosine A1-A2A receptor-receptor interaction: contribution to guanosine-mediated effects

Guanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine's exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role of adenosine receptors (ARs) in mediating guanosine effects. We investigated the neuroprotective effects of guanosine in hippocampal slices from A2AR-deficient mice (A2AR-/-) subjected to oxygen/glucose deprivation (OGD). Next, we assessed guanosine binding at ARs taking advantage of a fluorescent-selective A2AR antagonist (MRS7396) which could engage in a bioluminescence resonance energy transfer (BRET) process with NanoLuc-tagged A2AR. Next, we evaluated functional AR activation by determining cAMP and calcium accumulation. Finally, we assessed the impact of A1R and A2AR co-expression in guanosine-mediated impedance responses in living cells. Guanosine prevented the reduction of cellular viability and increased reactive oxygen species generation induced by OGD in hippocampal slices from wild-type, but not from A2AR-/- mice. Notably, while guanosine was not able to modify MRS7396 binding to A2AR-expressing cells, a partial blockade was observed in cells co-expressing A1R and A2AR. The relevance of the A1R and A2AR interaction in guanosine effects was further substantiated by means of functional assays (i.e., cAMP and calcium determinations), since guanosine only blocked A2AR agonist-mediated effects in doubly expressing A1R and A2AR cells. Interestingly, while guanosine did not affect A1R/A2AR heteromer formation, it reduced A2AR agonist-mediated cell impedance responses. Our results indicate that guanosine-induced effects may require both A1R and A2AR co-expression, thus identifying a molecular substrate that may allow fine tuning of guanosine-mediated responses