Aurones: Golden resource for active compounds

Deemed as poorly represented in nature, aurones have been often overlooked by researchers compared to other members of the flavonoid superfamily. However, over the past two decades, Abstract: Deemed as poorly represented in nature, aurones have been often overlooked by researchers compared to other members of the flavonoid superfamily. However, over the past two decades, they they have been reassessed by the scientific community, who are increasingly appreciating their ability to modulate several biological pathways. This review summarizes the recent literature on this have been reassessed by the scientific community, who are increasingly appreciating their ability to modulate several biological pathways. This review summarizes the recent literature on this class of class of compounds, which has been analyzed from both a chemical and a functional point of view. compounds, which has been analyzed from both a chemical and a functional point of view. Original Original articles, reviews and editorials featured in Pubmed and Scifinder over the last twenty years articles, reviews and editorials featured in Pubmed and Scifinder over the last twenty years have been have been taken into account to provide the readers with a view of the chemical strategies to obtain taken into account to provide the readers with a view of the chemical strategies to obtain them, their them, their functional properties, and their potential of technological use. The resulting comprehensive picture aims at raising the awareness of these natural derivatives as effective drug candidates, functional properties, and their potential of technological use. The resulting comprehensive picture aims at raising the awareness of these natural derivatives as effective drug candidates, fostering the fostering the development of novel synthetic analogues. development of novel synthetic analogues

Patient characteristics associated with the acceptability of teleconsultation: a retrospective study of osteoporotic patients post-COVID-19

Background: Due to the COVID-19 pandemic, teleconsultations (TCs) have become common practice for many chronic conditions, including osteoporosis. While satisfaction with TCs among patients increases in times of emergency, we have little knowledge of whether the acceptability of TCs persists once in-person visits return to being a feasible and safe option. In this study, we assess the acceptability of TCs across five dimensions for osteoporosis care among patients who started or continued with TCs after the COVID-19 pandemic had waned. We then explore the patient characteristics associated with these perceptions. Methods: Between January and April 2022, 80 osteoporotic patients treated at the Humanitas Hospital in Milan, Italy, were recruited to answer an online questionnaire about the acceptability of TCs for their care. The acceptability of TCs was measured using a modified version of the Service User Technology Acceptability Questionnaire (SUTAQ), which identifies five domains of acceptability: perceived benefits, satisfaction, substitution, privacy and discomfort, and care personnel concerns. Multivariable ordinary least squares (OLS) linear regression analysis was performed to assess which patient characteristics in terms of demographics, socio-economic conditions, digital skills, social support, clinical characteristics and pattern of TC use were correlated with the five domains of acceptability measured through the SUTAQ. Results: The degree of acceptability of TCs was overall good across the 80 respondents and the five domains. Some heterogeneity in perceptions emerged with respect to TCs substituting for in-person visits, negatively impacting continuity of care and reducing the length of consultations. For the most part, acceptability was not affected by patient characteristics with a few exceptions related to treatment time and familiarity with the TC service modality (i.e., length of osteoporosis treatment and number of TCs experienced by the patient). Conclusions: TCs appear to be an acceptable option for osteoporosis care in the aftermath of the COVID-19 pandemic. This study suggests that other characteristics besides age, digital skills and social support, which are traditionally relevant to TC acceptability, should be taken into account in order to better target this care delivery modality

The tensor hypercontracted parametric reduced density matrix algorithm: coupled-cluster accuracy with O(r^4) scaling

Tensor hypercontraction is a method that allows the representation of a high-rank tensor as a product of lower-rank tensors. In this paper, we show how tensor hypercontraction can be applied to both the electron repulsion integral (ERI) tensor and the two-particle excitation amplitudes used in the parametric reduced density matrix (pRDM) algorithm. Because only O(r) auxiliary functions are needed in both of these approximations, our overall algorithm can be shown to scale as O(r4), where r is the number of single-particle basis functions. We apply our algorithm to several small molecules, hydrogen chains, and alkanes to demonstrate its low formal scaling and practical utility. Provided we use enough auxiliary functions, we obtain accuracy similar to that of the traditional pRDM algorithm, somewhere between that of CCSD and CCSD(T).Comment: 11 pages, 1 figur

Will Technology-Aided Creativity Force Us to Rethink Copyright’s Fundamentals? Highlights from the Platform Economy and Artificial Intelligence

The platform economy, the move towards artificial intelligence (AI) and the growing importance of new creative and transformative technologies such as 3D printing raise questions as to whether copyright law suffices in its present form. Our article argues that copyright law is malleable enough to fulfil some of its traditional functions in this new technology-aided (and technology-dominated) environment. However, certain adjustments and complementary instruments seem to be necessary to revitalise these functions. For example, moral rights could be more effectively harmonised at international level, and made more easily enforceable, to reflect the global reach of social media and to protect their essential reputational value in a digital economy that prioritises online exposure over remuneration opportunities. We also consider that creators’ rights are difficult, if not impossible, to license and enforce in an environment where contractual practices such as social media terms and conditions impose standard agreements that either do not compensate creators at all or compensate them only marginally. In this context, restoring the bargaining power of creators through the right of access to the platforms’ data seems to have become as important as copyright itself. Finally, doubts remain as to whether requirements such as authorship and originality can continue to apply and trigger copyright protection. To this end, we believe that the distinction between fully generative machines and other technologies that merely assist human creators is essential for the proper identification of “authorless” works. For such works we advocate the adoption of a very short right that would support computational creativity without stifling human ingenuity

Running towards amblyopia recovery

Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life which is a major cause of impaired vision in infants and young children (prevalence around 3.5%). Current treatments such as eye patching are ineffective in a large number of patients, especially when applied after the juvenile critical period. Physical exercise has been recently shown to enhance adult visual cortical plasticity and to promote visual acuity recovery. With the aim to understand the potentialities for translational applications, we investigated the effects of voluntary physical activity on recovery of depth perception in adult amblyopic rats with unrestricted binocular vision; visual acuity recovery was also assessed. We report that three weeks of voluntary physical activity (free running) induced a marked and long-lasting recovery of both depth perception and visual acuity. In the primary visual cortex, ocular dominance recovered both for excitatory and inhibitory cells and was linked to activation of a specific intracortical GABAergic circuit

Significant Conditions on the Two-electron Reduced Density Matrix from the Constructive Solution of N-representability

We recently presented a constructive solution to the N-representability problem of the two-electron reduced density matrix (2-RDM)---a systematic approach to constructing complete conditions to ensure that the 2-RDM represents a realistic N-electron quantum system [D. A. Mazziotti, Phys. Rev. Lett. 108, 263002 (2012)]. In this paper we provide additional details and derive further N-representability conditions on the 2-RDM that follow from the constructive solution. The resulting conditions can be classified into a hierarchy of constraints, known as the (2,q)-positivity conditions where the q indicates their derivation from the nonnegativity of q-body operators. In addition to the known T1 and T2 conditions, we derive a new class of (2,3)-positivity conditions. We also derive 3 classes of (2,4)-positivity conditions, 6 classes of (2,5)-positivity conditions, and 24 classes of (2,6)-positivity conditions. The constraints obtained can be divided into two general types: (i) lifting conditions, that is conditions which arise from lifting lower (2,q)-positivity conditions to higher (2,q+1)-positivity conditions and (ii) pure conditions, that is conditions which cannot be derived from a simple lifting of the lower conditions. All of the lifting conditions and the pure (2,q)-positivity conditions for q>3 require tensor decompositions of the coefficients in the model Hamiltonians. Subsets of the new N-representability conditions can be employed with the previously known conditions to achieve polynomially scaling calculations of ground-state energies and 2-RDMs of many-electron quantum systems even in the presence of strong electron correlation

Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain

Background: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. Methods: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. Results: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-γ. Similarly, in situ the number of activated CD68+ macrophages was significantly reduced in areas with high levels of IL-9. Moreover, in the same conditions, IL-9 increased the secretion of the anti-inflammatory cytokine, transforming growth factor (TGF)-β. Conclusions: These results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS

Variational two-particle density matrix calculation for the Hubbard model below half filling using spin-adapted lifting conditions

The variational determination of the two-particle density matrix is an interesting, but not yet fully explored technique that allows to obtain ground-state properties of a quantum many-body system without reference to an $N$-particle wave function. The one-dimensional fermionic Hubbard model has been studied before with this method, using standard two- and three-index conditions on the density matrix [J. R. Hammond {\it et al.}, Phys. Rev. A 73, 062505 (2006)], while a more recent study explored so-called subsystem constraints [N. Shenvi {\it et al.}, Phys. Rev. Lett. 105, 213003 (2010)]. These studies reported good results even with only standard two-index conditions, but have always been limited to the half-filled lattice. In this Letter we establish the fact that the two-index approach fails for other fillings. In this case, a subset of three-index conditions is absolutely needed to describe the correct physics in the strong-repulsion limit. We show that applying lifting conditions [J.R. Hammond {\it et al.}, Phys. Rev. A 71, 062503 (2005)] is the most economical way to achieve this, while still avoiding the computationally much heavier three-index conditions. A further extension to spin-adapted lifting conditions leads to increased accuracy in the intermediate repulsion regime. At the same time we establish the feasibility of such studies to the more complicated phase diagram in two-dimensional Hubbard models.Comment: 10 pages, 2 figure