Interplay of the volume and surface plasmons in the electron energy loss spectra of C60_{60}

The results of a joint experimental and theoretical investigation of the C60 collective excitations in the process of inelastic scattering of electrons are presented. The shape of the electron energy loss spectrum is observed to vary when the scattering angle increases. This variation arising due to the electron diffraction of the fullerene shell is described by a new theoretical model which treats the fullerene as a spherical shell of a finite width and accounts for the two modes of the surface plasmon and for the volume plasmon as well. It is shown that at small angles, the inelastic scattering cross section is determined mostly by the symmetric mode of the surface plasmon, while at larger angles, the contributions of the antisymmetric surface plasmon and the volume plasmon become prominent.Comment: 11 pages, 3 figure

Reliability in the identification of metaphors in (filmic) multimodal communication

Research on multimodal communication is complex because multimodal analyses require methods and procedures that offer the possibility of disentangling the layers of meaning conveyed through different channels. We hereby propose an empirical evaluation of the Filmic Metaphor Identification Procedure (FILMIP, Bort-Mir, L. (2019). Developing, applying and testing FILMIP: the filmic metaphor identification procedure, Ph.D. dissertation. Universitat Jaume I, Castellón.), a structural method for the identification of metaphorical elements in (filmic) multimodal materials. The paper comprises two studies: (i) A content analysis conducted by independent coders, in which the reliability of FILMIP is assessed. Here, two TV commercials were shown to 21 Spanish participants for later analysis with the use of FILMIP under two questionnaires. (ii) A qualitative analysis based on a percentage agreement index to check agreement among the 21 participants about the metaphorically marked filmic components identified on the basis of FILMIP’s seven steps. The results of the two studies show that FILMIP is a valid and reliable tool for the identification of metaphorical elements in (filmic) multimodal materials. The empirical findings are discussed in relation to multimodal communication open challenges

On the Possibility of a Trans-Planckian Duality

We investigate the possibility of a trans-Planckian duality, which exchanges a manifold of events (space-time), with a manifold of momenta (energy-momentum). Gravity has a dual counter-part, that is, a geometric theory defined on the manifold of momenta. We provide a mathematical framework that can possibly realize this idea, and analyze its classical behaviour.Comment: 21 pages, 4 figure

DNA damage induced by 7,12-dimethylbenz[a]anthracene in the liver and the mammary gland of rats exposed to polycyclic aromatic hydrocarbon enzyme inducers during perinatal life

The long-lasting modulating effect induced by the prenatal or neonatal exposure to phenobarbital (PB) and aroclor on the genotoxic activity of 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats was studied. The effect was measured as DNA damage evaluated in the liver and in the mammary gland of 55-day-old animals, 4 and 24 h after an i.g. injection of 80 mg/kg of DMBA. PB was given per os, i.g. or in drinking water to pregnant females and by i.g. only to neonates or in adult progeny. Aroclor was injected i.g. in prenatal and in neonatal life, and a second dose was given in adult life. Under these experimental conditions it was shown that DNA damage kinetics caused by DMBA are modulated by exposure to PB and, to a minor extent, by aroclor. The amount and persistence of DNA damage were highest when PB was administered to neonates. An average 2-fold increase in the elution constants (K) of DNA in the liver and the mammary gland was observed 4 h after DMBA treatment, as compared to uninduced animals. Repeated enzyme induction by PB seems to reduce DMBA genotoxicity, as shown by a decrease in DNA damage and persistence in the liver and mammary gland. The inducibility of the monooxygenase enzyme system in perinatal life favouring metabolic activation of inactivation of polycyclic aromatic hydrocarbons might be critical in determining individual susceptibility of adult progeny to chemical carcinogenesis by DMB

Chronic kidney disease: Which role for xanthine oxidoreductase activity and products?

The present review explores the role of xanthine oxidoreductase (XOR) in the development and progression of chronic kidney disease (CKD). Human XOR is a multi-level regulated enzyme, which has many physiological functions, but that is also implicated in several pathological processes. The main XOR activities are the purine catabolism, which generates uric acid, and the regulation of cell redox state and cell signaling, through the production of reactive oxygen species. XOR dysregulation may lead to hyperuricemia and oxidative stress, which could have a pathogenic role in the initial phases of CKD, by promoting cell injury, hypertension, chronic inflammation and metabolic derangements. Hypertension is common in CKD patients and many mechanisms inducing it (upregulation of renin-angiotensin-aldosterone system, endothelial dysfunction and atherosclerosis) may be influenced by XOR products. High XOR activity and hyperuricemia are also risk factors for obesity, insulin resistance, type 2 diabetes and metabolic syndrome that are frequent CKD causes. Moreover, CKD is common in patients with gout, which is characterized by hyperuricemia, and in patients with cardiovascular diseases, which are associated with hypertension, endothelial dysfunction and atherosclerosis. Although hyperuricemia is undoubtedly related to CKD, controversial findings have been hitherto reported in patients treated with urate-lowering therapies

Structure and Computation in Immunoreagent Design : From Diagnostics to Vaccines

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Immunodiagnostic-based serological tests offer rapid and high-throughput diagnosis of multiple pathogens and can ascertain disease progression.3D structures of protein antigens can be used to predict epitope location using computational biology methods.Computationally designed synthetic epitopes can provide new chemical tools with distinct applications, from diagnosis and patient profiling to therapeutic approaches based on new vaccines.Structure-based antigen design is predicted to deliver future vaccines targeting challenging diseases such as HIV and cancer.As an alternative to nanoparticle epitope presentation systems, structure-based in silico epitope grafting and design methods may be adopted to transplant epitopes onto protein scaffolds to generate antigens that stimulate more potent immune responses

Small-Molecule Theranostic Probes: A Promising Future in Neurodegenerative Diseases

Prion diseases are fatal neurodegenerative illnesses, which include Creutzfeldt-Jakob disease in humans and scrapie, chronic wasting disease, and bovine spongiform encephalopathy in animals. They are caused by unconventional infectious agents consisting primarily of misfolded, aggregated, \u3b2 -sheet-rich isoforms, denoted prions, of the physiological cellular prion protein (PrP(C)). Many lines of evidence suggest that prions (PrP(Sc)) act both as a template for this conversion and as a neurotoxic agent causing neuronal dysfunction and cell death. As such, PrP(Sc) may be considered as both a neuropathological hallmark of the disease and a therapeutic target. Several diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders (such as Alzheimer's disease, Parkinson's disease, and prion disease). Examples of these probes are Congo red, thioflavin T, and their derivatives. We synthesized a series of styryl derivatives, denoted theranostics, and studied their therapeutic and/or diagnostic potentials. Here we review the salient traits of these small molecules that are able to detect and modulate aggregated forms of several proteins involved in protein misfolding diseases. We then highlight the importance of further studies for their practical implications in therapy and diagnostics

Skeletal Divergence and Condylar Asymmetry in Patients with Temporomandibular Disorders (TMD): A Retrospective Study

Introduction. This study was aimed at evaluating the association between vertical skeletal patterns, condylar height symmetry, and temporomandibular disorders in adults. Methods. The study sample consisted of 200 patients (ages 18-30 years old) retrospectively recruited: 100 with temporomandibular disorders (TMD) and 100 without TMD (control), diagnosed by Diagnostic Criteria for the Temporomandibular Disorders (DC/TMD). For each subject, skeletal divergence was assessed on lateral cephalograms, and condylar height symmetry was evaluated by orthopantomography (Habets' method). Results. Subjects with temporomandibular disorders showed a strong association with condylar asymmetry (p0.29). Conclusions. Although it does not imply a direct cause-and-effect relationship, the present study suggests condylar asymmetry and hyperdivergent skeletal pattern are more likely to be associated with a higher risk of temporomandibular disorder joint diseases in adult patients

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

Immune checkpoint mechanisms are important molecular cell systems that maintain tolerance toward autoantigens in order to prevent immunity-mediated accidental damage. It is well known that cancer cells may exploit these molecular and cellular mechanisms to escape recognition and elimination by immune cells. Programmed cell death protein-1 (PD-1) and its natural ligand programmed cell death ligand-1 (PD-L1) form the PD-L1/PD-1 axis, a well-known immune checkpoint mechanism, which is considered an interesting target in cancer immunotherapy. In fact, the expression of PD-L1 was found in various solid malignancies and the overactivation of PD-L1/PD-1 axis results in a poor patient survival rate. Breaking PD-L1/PD-1 axis, by blocking either the cancer side or the immune side of the axis, is currently used as anti-cancer strategy to re-establish a tumor-specific immune response. For this purpose, several blocking antibodies are now available. To date, three anti-PD-L1 antibodies have been approved by the FDA, namely atezolizumab, durvalumab and avelumab. The main advantages of anti-PD-L1 antibodies arise from the overexpression of PD-L1 antigen by a high number of tumor cells, also deriving from different tissues; this makes anti-PD-L1 antibodies potential pan-specific anti-cancer molecules. Despite the good results reported in clinical trials with anti-PD-L1 antibodies, there is a significant number of patients that do not respond to the therapy. In fact, it should be considered that, in some neoplastic patients, reduced or absent infiltration of cytotoxic T cells and natural killer cells in the tumor microenvironment or presence of other immunosuppressive molecules make immunotherapy with anti-PD-L1 blocking antibodies less effective. A strategy to improve the efficacy of antibodies is to use them as carriers for toxic payloads (toxins, drugs, enzymes, radionuclides, etc.) to form immunoconjugates. Several immunoconjugates have been already approved by FDA for treatment of malignancies. In this review, we focused on PD-L1 targeting antibodies utilized as carrier to construct immunoconjugates for the potential elimination of neoplastic cells, expressing PD-L1. A complete examination of the literature regarding anti-PD-L1 immunoconjugates is here reported, describing the results obtained in vitro and in vivo. The real potential of anti-PD-L1 antibodies as carriers for toxic payload delivery is considered and extensively discussed