The experimental determination of the properties of the newly discovered boson at the Large Hadron Collider is currently the most crucial task in high-energy physics. We show how information about ...the spin, parity, and, more generally, the tensor structure of the boson couplings can be obtained by studying angular and mass distributions of events in which the resonance decays to pairs of gauge bosons, ZZ, WW, and gamma gamma . A complete Monte Carlo simulation of the process pp arrow right X arrow right VV arrow right 4functionof is performed and verified by comparing it to an analytic calculation of the decay amplitudes X arrow right VV arrow right 4functionof. Our studies account for all spin correlations and include general couplings of a spin J = 0, 1, 2 resonance to Standard Model particles. We also discuss how to use angular and mass distributions of the resonance decay products for optimal background rejection. It is shown that by the end of the 8 TeV run of the LHC, it might be possible to separate extreme hypotheses of the spin and parity of the new boson with a confidence level of 99% or better for a wide range of models. We briefly discuss the feasibility of testing scenarios where the resonance is not a parity eigenstate.
To date, the pharmacotherapy of Alzheimer's disease (AD) has relied on acetylcholinesterase (AChE) inhibitors (AChEIs) and, more recently, an N-methyl-D-aspartate receptor (NMDAR) antagonist. AD is a ...multifactorial syndrome with several target proteins contributing to its etiology. "Multi-target-directed ligands" (MTDLs) have great potential for treating complex diseases such as AD because they can interact with multiple targets. The design of compounds that can hit more than one specific AD target thus represents an innovative strategy for AD treatment. Tacrine was the first AChEI introduced in therapy. Recent studies have demonstrated its ability to interact with different AD targets. Furthermore, numerous tacrine homo- and heterodimers have been developed with the aim of improving and enlarging its biological profile beyond its ability to act as an AChEI. Several tacrine hybrid derivatives have been designed and synthesized with the same goal. This review will focus on and summarize the last two years of research into the development of tacrine derivatives able to hit AD targets beyond simple AChE inhibition.
Abstract Revision knee data from six joint arthroplasty centers were compiled for 2010 and 2011 to determine mechanism of failure and time to failure. Aseptic loosening was the predominant mechanism ...of failure (31.2%), followed by instability (18.7%), infection (16.2%), polyethylene wear (10.0%), arthrofibrosis (6.9%), and malalignment (6.6%). Mean time to failure was 5.9 years (range 10 days to 31 years). 35.3% of all revisions occurred less than 2 years after the index arthroplasty, 60.2% in the first 5 years. In contrast to previous reports, polyethylene wear is not a leading failure mechanism and rarely presents before 15 years. Implant performance is not a predominant factor of knee failure. Early failure mechanisms are primarily surgeon-dependent.
OPTIMIZATION OF VR APPLICATION IN TEXTURING CULTURAL HERITAGE Bolognesi, C. M.; Manfredi, V.
International archives of the photogrammetry, remote sensing and spatial information sciences.,
02/2024, Letnik:
XLVIII-2/W4-2024
Journal Article, Conference Proceeding
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Odprti dostop
The research question underlying this short essay refers to the possibility of realizing through a well-established workflow a high level of immersivity in the VR representation of Cultural Heritage ...to be used as a working tool by architects and renovators as well as heritage scholars. At present active or passive 3D scanning techniques are a known reality where the choice of data acquisition system depends both on the final purpose and characteristics of the object to be surveyed. With the maturity achieved in point cloud acquisition, post processing phases and the development of BIM-based systems, the model has given the possibility to become a repository of information related to the existing, to be used for maintenance or renovation processes. If the model can represent the existing with a certain level of detail, it can be assumed that a differentiated Level of Immersivity can be organized depending on the specific needs it intends to fulfil. In the context of renovation or preservation of Cultural Heritage, the potential offered by VR becomes more interesting when it can provide a realistic portrait not only of the geometry, but also of the materiality and state of preservation of the buildings. This research opens new possibilities to develop tools to aid designers and renovators in degradation analysis, intervention projects, and scheduled maintenance. The research question starts analyzing the possibility of creating photorealistic immersive environments that are easy to access, organized based on surveys of existing heritage buildings using specific datasets.
The multifunctional nature of Alzheimer's disease (AD) provides the logical foundation for the development of an innovative drug design strategy centered on multi-target-directed-ligands (MTDLs). In ...recent years, the MTDL concept has been exploited to design different ligands hitting different biological targets. Our first rationally designed MTDL was the polyamine caproctamine (1), which provided a synergistic cholinergic action against AD by antagonizing muscarinic M(2) autoreceptors and inhibiting acetylcholinesterase (AChE). Lipocrine (7) represented the next step in our research. Due to its ability to inhibit AChE catalytic and non-catalytic functions together with oxidative stress, 7 emerged as an interesting pharmacological tool for investigating the neurodegenerative mechanism underlying AD. Memoquin (9) is a quinone-bearing polyamine endowed with a unique multifunctional profile. With its development, we arrived at the proof of concept of the MTDL drug discovery approach. Experiments in vitro and in vivo confirmed its multimodal mechanisms of action and its interaction with different end-points of the neurotoxic cascade leading to AD. More recently, the MTDL approach led to carbacrine (12). In addition to the multiple activities displayed by 7, 12 displayed an interesting modulation of NMDA receptor activity. The pivotal role played by this target in AD pathogenesis suggests that 12 may be a promising new chemical entity in the MTDL gold rush.
To evaluate the anti-inflammatory effects of clinically relevant naproxen sodium (Nx) concentrations on human monocyte-derived macrophages in a controlled in vitro system and human primary synovial ...fluid (SF) cells.
Using phorbol 12-myristate 13-acetate, THP-1 human monocytic cells were differentiated into mature monocyte-derived macrophages in vitro then treated with Nx pre- or post-activating an inflammatory response with lipopolysaccharide (LPS) and hyaluronan (HA) fragments (n = 8/group). Cell culture supernatants were assessed for NF-κB activity and prostaglandin E2 (PGE2), indicating cyclooxygenase enzyme activity. Under Duke IRB approval, primary human SF cells were collected at the time of knee joint replacement (n = 19 individuals) for osteoarthritis (OA), and cultured with LPS, HA and Nx; SF cells were characterized by polychromatic flow cytometry for cell surface markers and intracellular cytokines.
Compared to placebo treatment of THP-1 cells, low dose Nx (corresponding 27.5–440 mg/L orally) added both pre- and post-activation with LPS/HA, significantly reduced NF-κB activity and PGE2: mean reduction to 73%, 61%, 17% and 10% of placebo, respectively. LPS/HA treatment of primary OA SF cells significantly increased the number of IL-1β producing primary monocytes and macrophages, and by 24 h the overall production of secreted cytokines (IL-1β, IL-6, IL8, and TNF-α). Low dose Nx reduced the percentage of IL-1β producing primary monocytes and macrophages.
LPS/HA induced inflammation of THP-1 monocytic and primary human SF cells. Low dose Nx both prevented and reduced inflammatory responses of a human monocytic cell line and reduced IL-1β production by primary human SF monocytes and macrophages.
Alzheimer’s disease (AD) is the most common cause of dementia, clinically characterized by loss of memory and progressive deficits in different cognitive domains. An emerging disease-modifying ...approach to face the multifactorial nature of AD may be represented by the development of Multi-Target Directed Ligands (MTDLs), i.e., single compounds which may simultaneously modulate different targets involved in the neurodegenerative AD cascade. The structure of tacrine, an acetylcholinesterase (AChE) inhibitor (AChEI), has been widely used as scaffold to provide new MTDLs. In particular, its homodimer bis(7)tacrine represents an interesting lead compound to design novel MTDLs. Thus, in the search of new rationally designed MTDLs against AD, we replaced the heptamethylene linker of bis(7)tacrine with the structure of cystamine, leading to cystamine-tacrine dimer. In this study we demonstrated that the cystamine-tacrine dimer is endowed with a lower toxicity in comparison to bis(7)tacrine, it is able to inhibit AChE, butyrylcholinesterase (BChE), self- and AChE-induced beta-amyloid aggregation in the same range of the reference compound and exerts a neuroprotective action on SH-SY5Y cell line against H
2O
2-induced oxidative injury. The investigation of the mechanism of neuroprotection showed that the cystamine-tacrine dimer acts by activating kinase 1 and 2 (ERK1/2) and Akt/protein kinase B (PKB) pathways.
This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.
► The linker of bis(7)tacrine was substituted with the structure of cystamine. ► This dimer showed the ability to inhibit cholinesterases and Aβ aggregation. ► Cystamine-tacrine dimer showed a lower toxicity in comparison with bis(7)tacrine. ► Cystamine-tacrine dimer exerted neuroprotective action against oxidative injury. ► Cystamine-tacrine dimer acts by activating prosurvival ERK1/2 and PKB pathways.
Understanding molecular femtosecond dynamics under intense X-ray exposure is critical to progress in biomolecular imaging and matter under extreme conditions. Imaging viruses and proteins at an ...atomic spatial scale and on the time scale of atomic motion requires rigorous, quantitative understanding of dynamical effects of intense X-ray exposure. Here we present an experimental and theoretical study of C60 molecules interacting with intense X-ray pulses from a free-electron laser, revealing the influence of processes not previously reported. Our work illustrates the successful use of classical mechanics to describe all moving particles in C60, an approach that scales well to larger systems, for example, biomolecules. Comparisons of the model with experimental data on C60 ion fragmentation show excellent agreement under a variety of laser conditions. The results indicate that this modelling is applicable for X-ray interactions with any extended system, even at higher X-ray dose rates expected with future light sources.
The coupling of two different pharmacophores, each endowed with different biological properties, afforded the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to ...those of prototypes tacrine and lipoic acid. Lipocrine is the first compound that inhibits the catalytic activity of AChE and AChE-induced amyloid-β aggregation and protects against reactive oxygen species. Thus, it emerged as a valuable pharmacological tool to investigate Alzheimer's disease and as a promising lead compound for new anti-Alzheimer drugs.
EXTRACTION OF PRIMITIVES AND OBJECTS FROM HSHAPES Bolognesi, C.; Caffi, V.
International archives of the photogrammetry, remote sensing and spatial information sciences.,
01/2019, Letnik:
XLII-2/W9
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
This paper deals with 3D morphological studies of architecture surveyed with TLS to allow the modelling of a Renaissance villa in a BIM environment; the aim is to create Renaissance objects to be ...shaped into a parametric software and made recognizable in a BIM environment balancing level of accuracy and shortness of workflow. The approach of this study lies in the comparison of different workflows, using different BIM software and apps, useful to extract transverse ridge or primitive ribs from the point cloud of walls as vaulted ceilings, shape accurate objects, considering their level of detail and their morphological and typological aspect. The first steps of Data Processing from 3D Survey started with an accurate cleaning and transformation in appropriate but different format to be analysed into different environment and treated for a modelling phase. The different results of the different workflow have been compared to measure grade of simplification, when existent, of the single objects compared. The case study deepens the entrance of a Renaissance Villa in Tuscany, Villa di Poggio a Caiano, in its main elevation considering the vaults of porches and entrances as barrel vaults or lunette-like with double-curved nails.
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