Manipulating Plasma Excitations with Terahertz Light Pulses in Superconducting Cuprates

Layered cuprates offer a preferential playground for optical non-linearity thanks to the emergence, below Tc, of soft out-of-plane Josephson plasmons. The hallmark of such a non-linearity is the observation of Third Harmonic Generation, that has been theoretically understood as a sum-frequency process involving a two-plasmon excitation. However, recent experiments in cuprates with two planes per unit cell challenge this interpretation, due to the lack of resonant response at the temperature where the driving frequency matches the plasma energy scale, as observed instead in single-layer cuprates. Here we show that such an apparent discrepancy in bilayer systems can be resolved by taking into account the combined effect of light polarization and Josephson-coupling anisotropy on setting the energy range where three-dimensional layered plasma modes can be resonantly excited. Our results offer a novel perspective on the possibility to tune on demand high-harmonic generation by artificially designing Josephson heterostructures

Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

According to the World Health Organization, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neurological disease characterized by widespread inflammation and multi-systemic neuropathology. Aetiology and pathogenesis are unknown, and several agents have been proposed as causative agents or as factors perpetuating the syndrome. Exposure to heavy metals, with particular reference to mercury and gold in dental amalgams, has been considered among the triggers of ME/CFS. Here we hypothesize that cadmium, a widespread occupational and environmental heavy metal pollutant, might be associated with some of the neurological findings described in ME/CFS. In fact, ME/CFS patients show a decrease of the volume of the gray matter in turn associated with objective reduction of physical activity. Cadmium induces neuronal death in cortical neurons through a combined mechanism of apoptosis and necrosis and it could then be hypothesized that cadmium-induced neuronal cell death is responsible for some of the effects of cadmium on the central nervous system, i.e. a decrease in attention level and memory in exposed humans as well as to a diminished ability for training and learning in rats, that are symptoms typical of ME/CFS. This hypothesis can be tested by measuring cadmium exposure in a cohort of ME/CFS patients compared with matched healthy controls, and by measuring gray matter volume in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients. In addition, we hypothesize that cadmium exposure could be associated with reduced cerebral blood flow in ME/CFS patients because of the disruptive effects of cadmium on angiogenesis. In fact, cadmium inhibits angiogenesis and low global cerebral flow is associated with abnormal brain neuroimaging results and brain dysfunction in the form of reduced cognitive testing scores in ME/CFS patients. This hypothesis can be tested by measuring cerebral cortex blood flow in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients. If our hypothesis is demonstrated correct, the consequences could affect prevention, early diagnosis, and treatment of ME/CFS. Implications in early diagnosis could entail the evaluation of symptoms typical of ME/CFS in cadmium-exposed subjects as well as the search for signs of exposure to cadmium in subjects diagnosed with ME/CFS. Nutritional supplementation of magnesium and zinc could then be considered, since these elements have been proposed in the prophylaxis and therapy of cadmium exposure, and magnesium was demonstrated effective on ME/CFS patients' symptom profiles

Metabolic Changes Associated with Different Levels of Energy Deficits in Mediterranean Buffaloes during the Early Lactation Stage: Type and Role of the Main Lipid Fractions Involved

Cell function and energy redistribution are influenced by lipid classes (phospholipids (PLs), free fatty acids (FFAs), triglycerides (TGs), and cholesterol esters (CEs)). The aim of this study was to investigate metabolic alterations that are related to changes in lipid classes according to different levels of energy deficits in early lactating Mediterranean buffaloes (MBs). Sixty-three MBs were enrolled at the beginning of lactation using an observational study with a cross-sectional experimental design. Serum β-hydroxybutyrate (BHB) levels were used to group the animals into a healthy group (Group H; n = 38; BHB < 0.70 mmol/L) and hyperketonemia risk group (Group K; n = 25; BHB ≥ 0.70 mmol/L). Statistical analysis was performed using a linear model that included the effect of the group and body condition score to assess differences in fatty acid (FA) concentrations. A total of 40 plasma FAs were assessed in each lipid class. Among the FAs, eight PLs, seven FFAs, four TGs, and four CEs increased according to BHB levels, while three FFAs, three TGs, and one CE decreased. The changes among lipid class profiles suggested the influence of inflammatory response, liver metabolism, and the state of body lipid reserves. In addition, the possible similarities of buffaloes at risk of hyperketonemia with ketotic cows suggest the necessity of further investigations in these ruminants

Revealing novel aspects of light-matter coupling in terahertz two-dimensional coherent spectroscopy: the case of the amplitude mode in superconductors

Recently developed terahertz (THz) two-dimensional coherent spectroscopy (2DCS) is a powerful technique to obtain materials information in a fashion qualitatively different from other spectroscopies. Here, we utilized THz 2DCS to investigate the THz nonlinear response of conventional superconductor NbN. Using broad-band THz pulses as light sources, we observed a third-order nonlinear signal whose spectral components are peaked at twice the superconducting gap energy $2\Delta$. With narrow-band THz pulses, a THz nonlinear signal was identified at the driving frequency $\Omega$ and exhibited a resonant enhancement at temperature when $\Omega = 2\Delta$. General theoretical considerations show that such a resonance can only arise from a disorder-activated paramagnetic coupling between the light and the electronic current. This proves that the nonlinear THz response can access processes distinct from the diamagnetic Raman-like density fluctuations, which are believed to dominate the nonlinear response at optical frequencies in metals. Our numerical simulations reveal that even for a small amount of disorder, the $\Omega=2\Delta$ resonance is dominated by the superconducting amplitude mode over the entire investigated disorder range. This is in contrast to other resonances, whose amplitude-mode contribution depends on disorder. Our findings demonstrate the unique ability of THz 2DCS to explore collective excitations inaccessible in other spectroscopies

A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages.

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects

Durability of Basalt/Hemp Hybrid Thermoplastic Composites

The Achilles heel of thermoplastic natural fibre composites is their limited durability. The environmental degradation of the mechanical properties of hemp and hemp/basalt hybrid-reinforced high-density polyethylene (HDPE) composites has been investigated with a special focus on the effects of water ageing and accelerated ageing, including hygrothermal and UV radiation. Modification of the matrix was carried out using a maleic anhydride high-density polyethylene copolymer (MAPE) as a compatibilizer. Hybridization of hemp fibres with basalt fibres and the incorporation of MAPE were found to significantly decrease the water uptake (up to 75%) and increase the retention of mechanical properties after accelerated ageing. Secondary crystallization phenomena occurring in the composites, as confirmed by differential scanning calorimetry (DSC) analysis, were able to counteract the severe combined effects of hygrothermal stress and UV radiation, with the exception of hemp-fibre composites where permanent damage to the fibres occurred, with 2% and 20% reduction in tensile strength and modulus, respectively, for a 30 wt % hemp fibre-reinforced HDPE

Prognostic factors in merkel cell carcinoma: A retrospective single-center study in 90 patients

Abstract Merkel Cell Carcinoma (MCC) is a rare but highly aggressive neuroendocrine neoplasm of the skin. This study aimed at describing characteristics, treatment, and prognosis of a series of consecutive cases of MCC patients, in order to contribute to the investigation of this rare malignancy and provide better patient care. This is a retrospective cohort study including all 90 patients diagnosed and/or treated for MCC between 1991 and 2018 at the Veneto Institute of Oncology in Padua (Italy). Patient and tumor characteristics, treatment, and immunohistochemical data were extracted from a prospectively collected local database. There were 68 primary (76%) and 22 non-primary (15 occult primary, three metastatic, four recurrence) tumors (24%). CK20 expression was associated with reduced overall (HR 2.92, 95% CI 1.04-8.16) and disease-specific (HR 4.62, 95% CI 1.31-16.28) survival. Immunomodulatory regimens for treatment of other comorbidities were associated with reduced disease-specific ((HR 2.15, 95% CI 1.06-4.36) and recurrence-free (HR 3.08, 95% CI 1.44-6.57) survival. latrogenic immunomodulation resulted as the main factor associated with impaired prognosis. Lack of CK20 expression was associated with better survival

A molecular model of the interaction between vitamin D binding protein-derived macrophage activating factor and vitamin D receptor

We previously demonstrated that the response of human monocytes to vitamin D binding protein-derived macrophage activating factor (DBP-MAF) is dependent on vitamin D receptor (VDR) polymorphisms [1]. Therefore, in order to verify the type of molecular interaction between DBP-MAF and VDR, we compared the amino acid sequences at their respective vitamin D binding sites. There are 23 hydrophobic amino acids (aa) near the amino terminus of DBP-MAF, and 23 aa near the carboxyl terminus of VDR. When these two sequence are aligned, it is possible to observe not only that in both proteins there is a long stretch (13-14) of hydrophobic aa, but that 4 hydrophobic aa are identical and 11 aa have similar functional valence. According to this model, the last 23 hydrophobic aa of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic aa of the DBP-MAF located at the external part of the plasma membrane, with vitamin D sandwiched in between the two vitamin D-binding proteins. Oleic acid, taken as an example of an unsaturated fatty acid bound to DBP-MAF, could stabilize the complex at the level of the plasma membrane. Therefore, it can be hypothesized that DBP-MAF and VDR have multiple sites of interaction at the level of the plasma membrane. Further studies will elucidate whether this interaction occurs only in the presence of vitamin D or whether the hydrophobic profile of the two proteins allows direct interaction without the need for vitamin D

Vitamin D binding protein-derived macrophage activating factor stimulates proliferation and signalling in a human neuronal cell line

Vitamin D (vitD), vitD binding protein-derived macrophage activating factor (DBP-MAF), and vitD receptor (VDR) are essential for adult neurogenesis [1], and this effect could be responsible for the recently reported effects of DBP-MAF on autism spectrum disorders (ASD) [2]. In order to test this hypothesis, we challenged a human neuronal cell line (SH-SY5Y, IZSLER) with DBP-MAF (Immuno Biotech), and we studied cAMP formation (cAMP EIA kit, Abnova), cell proliferation (MTT assay, Sigma Aldrich), apoptosis (human caspase 3 act, Invitrogen) and cell morphology. SH-SY5Y cells represent a validated in vitro model of human neurons in neurodegenerative diseases [3]. DBP-MAF induced rapid (15 min) formation of cAMP in a dose-dependent manner (0.4-40 ng/ml) as well as increase in cell proliferation at 24-48 and 72 h. Cell morphology was consistent with neurogenesis and an increase in the number of cells with high synthetic activity was observed. No apoptosis following DBP-MAF treatment was observed. Our results open the way to exploit these newly described effects to treat neurodegenerative disorders from Parkinson’s and Alzheimer’s diseases to Myalgic Encephalomyelitis and ASD

The earliest evidence for mechanically delivered projectile weapons in Europe

Microscopic analysis of backed lithic pieces from the Uluzzian technocomplex (45\u201340 thousand yr ago) at Grotta del Cavallo (southern Italy) reveals their use as mechanically delivered projectile weapons, attributed to anatomically modern humans. Use-wear and residue analyses indicate that the lithics were hunting armatures hafted with complex adhesives, while experimental and ethnographic comparisons support their use as projectiles. The use of projectiles conferred a hunting strategy with a higher impact energy and a potential subsistence advantage over other populations and specie