Linear Convergence for Natural Policy Gradient with Log-linear Policy Parametrization

We analyze the convergence rate of the unregularized natural policy gradient algorithm with log-linear policy parametrizations in infinite-horizon discounted Markov decision processes. In the deterministic case, when the Q-value is known and can be approximated by a linear combination of a known feature function up to a bias error, we show that a geometrically-increasing step size yields a linear convergence rate towards an optimal policy. We then consider the sample-based case, when the best representation of the Q- value function among linear combinations of a known feature function is known up to an estimation error. In this setting, we show that the algorithm enjoys the same linear guarantees as in the deterministic case up to an error term that depends on the estimation error, the bias error, and the condition number of the feature covariance matrix. Our results build upon the general framework of policy mirror descent and extend previous findings for the softmax tabular parametrization to the log-linear policy class

Dark energy-matter equivalence by the evolution of cosmic equation of state

We consider a model-independent approach to constrain the equivalence redshift, $z_{eq}$, at which dark energy and the total matter (cold dark matter and baryonic) equate their magnitudes. To this aim, in the context of a homogeneous and isotropic universe, we first consider a generic model where the dark energy contribution is provided by an unknown function of barotropic fluids. Afterwards, we compute the deceleration and jerk parameters, evaluating at our epoch, namely $z=0$, and at $z=z_{eq}$. Thus, by Taylor expanding around current time the Hubble rate, luminosity and angular distances, we substitute the theoretical expressions obtained from the aforementioned generic dark energy model, defining a correspondence between quantities evaluated at $z=0$ and $z=z_{eq}$. In so doing, we directly fit these quantities by means of current data sets, involving the most recent Pantheon type Ia supernovae, baryonic acoustic oscillation and Hubble rate points. We consider two hierarchies in our fitting procedures and compare our findings in the spatially-flat universe first and including spatial curvature, later. We assess constraints on the overall equation of state of the universe and its first derivative. We compare our results with those predicted by the standard $\Lambda$CDM paradigm. Specifically, our findings are in agreement at the 2$\sigma$ confidence level, assuming a constant dark energy term. However, our analysis does not rule out the possibility of a slight evolution of dark energy, indicating a small deviation from the scenario of a pure cosmological constant. In particular, the possible departures appear consistent with a phenomenological $\omega$CDM model, rather than more complicated dark energy parameterizations.Comment: 28 pages, 8 figures, 3 table

Seismic reliability-based design of hardening structures equipped with double sliding devices

This study deals with seismic reliability-based design (SRBD) relationships in terms of beha-vior factors and displacement demands for hardening structures equipped with double fric-tion pendulum system (DFPS) bearings. An equivalent 3dof system having a hardening post-yield slope is adopted to describe the superstructure behavior, whereas velocity-dependent laws are assumed to model the responses of the two surfaces of the DFPS. The yielding cha-racteristics of the superstructures are defined for increasing behavior factors in compliance with the seismic hazard of L’Aquila site (Italy) and with NTC18 assuming a lifetime of 50 years. Considering several natural seismic records and building properties under the hypo-thesis of modelling the friction coefficients of the two surfaces of the DFPS as random variables, incremental dynamic analyses are performed to evaluate the seismic fragility and the seismic reliability of these systems. Finally, seismic reliability is evaluated and seismic relia-bility-based design (SRBD) curves for the two surfaces of the double sliding devices are de-scribed

The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity

Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA-induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p, miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de-repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic expression in the aggressive Group 3 MB cells attenuates their proliferation, migration and invasion. This study unveils the first lncRNA-based ceRNA network in central nervous system tumours and provides a novel molecular circuit underlying the enigmatic Group 4 medulloblastoma

Exploitation of wasted bread as substrate for polyhydroxyalkanoates production through the use of Haloferax mediterranei and seawater

The use of the halophile microorganism Haloferax mediterranei, able to synthesize poly(hydroxybutyrate-hydroxyvalerate) (PHBV), is considered as a promising tool for the industrial production of bioplastic through bioprocessing. A consistent supplementation of the growth substrate in carbohydrates and minerals is overall necessary to allow its PHBV production. In this work, wasted bread was used as substrate for bioplastic production by microbial fermentation. Instead of the consistent and expensive minerals supplement required for Hfx. mediterranei DSM1411 growth, microfiltered seawater was added to the wasted bread-derived substrate. The suitable ratio of wasted bread homogenate and seawater, corresponding to 40:60, was selected. The addition of proteases and amylase to the bread homogenate promoted the microbial growth but it did not correspond to the increase of bioplastic production by the microorganism, that reach, under the experimental conditions, 1.53 g/L. An extraction procedure of the PHBV from cells, based on repeated washing with water, followed or not by a purification through ethanol precipitation, was applied instead of the conventional extraction with chloroform. Yield of PHBV obtained using the different extraction methods were 21.6 ± 3.6 (standard extraction/purification procedure with CHCl3:H2O mixture), 24.8 ± 3.0 (water-based extraction), and 19.8 ± 3.3 mg PHAs/g of wasted bread (water-based extraction followed by ethanol purification). Slightly higher hydroxyvalerate content (12.95 vs 10.78%, w/w) was found in PHBV obtained through the water-based extraction compared to the conventional one, moreover, the former was characterized by purity of 100% (w/w). Results demonstrated the suitability of wasted bread, supplemented with seawater, to be used as substrate for bioplastic production through fermentation. Results moreover demonstrated that a solvent-free extraction, exclusively based on osmotic shock, could be used to recover the bioplastic from cells

A Case Study of Malignant Edema in Postpartum Mediterranean Buffaloes (Bubalus bubalis)

The paper describes for the first time four cases of postparturient malignant edema in water buffaloes due to Clostridium septicum (Cl. septicum). The study was carried out on four primiparous buffaloes that showed swelling of perineal and perivulvar areas, fever and agalactia a few hours after calving. Two of them died within 20 hours after calving. The other two developed edema in the skeletal muscles of one leg and were treated with sulfadiazine-trimethoprim for 10 days. The clinical signs completely resolved. Culture and molecular investigations identified the pathogen isolated from exudate taken from the vulva as Cl. septicum. The isolate showed multi-drug resistance. In the management of infection due to Cl. septicum, timely diagnosis and the chirurgic curettage, associated with a broad-spectrum antibiotic therapy, were found to be sufficient for the survival and recovery of the infected animals

Cardiac Hypertrophy: from Pathophysiological Mechanisms to Heart Failure Development

Cardiac hypertrophy develops in response to increased workload to reduce ventricular wall stress and maintain function and efficiency. Pathological hypertrophy can be adaptive at the beginning. However, if the stimulus persists, it may progress to ventricular chamber dilatation, contractile dysfunction, and heart failure, resulting in poorer outcome and increased social burden. The main pathophysiological mechanisms of pathological hypertrophy are cell death, fibrosis, mitochondrial dysfunction, dysregulation of Ca2+-handling proteins, metabolic changes, fetal gene expression reactivation, impaired protein and mitochondrial quality control, altered sarcomere structure, and inadequate angiogenesis. Diabetic cardiomyopathy is a condition in which cardiac pathological hypertrophy mainly develop due to insulin resistance and subsequent hyperglycaemia, associated with altered fatty acid metabolism, altered calcium homeostasis and inflammation. In this review, we summarize the underlying molecular mechanisms of pathological hypertrophy development and progression, which can be applied in the development of future novel therapeutic strategies in both reversal and prevention

Micro-Raman Spectroscopy and Univariate Analysis for Monitoring Disease Follow-Up

Micro-Raman spectroscopy is a very promising tool for medical applications, thanks to its sensitivity to subtle changes in the chemical and structural characteristics of biological specimens. To fully exploit these promises, building a method of data analysis properly suited for the case under study is crucial. Here, a linear or univariate approach using a R2 determination coefficient is proposed for discriminating Raman spectra even with small differences. The validity of the proposed approach has been tested using Raman spectra of high purity glucose solutions collected in the 600 to 1,600 cm−1 region and also from solutions with two known solutes at different concentrations. After this validation step, the proposed analysis has been applied to Raman spectra from oral human tissues affected by Pemphigus Vulgaris (PV), a rare life-threatening autoimmune disease, for monitoring disease follow-up. Raman spectra have been obtained in the wavenumber regions from 1,050 to 1,700 cm−1 and 2,700 to 3,200 cm−1 from tissues of patients at different stages of pathology (active PV, under therapy and PV in remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage have been detected at 1,150–1,250 cm−1 (amide III) and 1,420–1,450 cm−1 (CH3 deformation) regions and around 1,650 cm−1 (amide I) and 2,930 cm−1 (CH3 symmetric stretch). The analysis of tissue Raman spectra by the proposed univariate method has allowed us to effectively differentiate tissues at different stages of pathology

Urokinase Plasminogen Activator Inhibits HIV Virion Release from Macrophage-Differentiated Chronically Infected Cells via Activation of RhoA and PKCε

HIV replication in mononuclear phagocytes is a multi-step process regulated by viral and cellular proteins with the peculiar feature of virion budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase-type plasminogen activator (uPA) with its cell surface receptor (uPAR) has been shown to favor virion accumulation in such sub-cellular compartment in primary monocyte-derived macrophages and chronically infected promonocytic U1 cells differentiated into macrophage-like cells by stimulation with phorbol myristate acetate (PMA). By adopting this latter model system, we have here investigated which intracellular signaling pathways were triggered by uPA/uPAR interaction leading the redirection of virion accumulation in intra-cytoplasmic vesicles.uPA induced activation of RhoA, PKCδ and PKCε in PMA-differentiated U1 cells. In the same conditions, RhoA, PKCδ and PKCε modulated uPA-induced cell adhesion and polarization, whereas only RhoA and PKCε were also responsible for the redirection of virions in intracellular vesicles. Distribution of G and F actin revealed that uPA reorganized the cytoskeleton in both adherent and polarized cells. The role of G and F actin isoforms was unveiled by the use of cytochalasin D, a cell-permeable fungal toxin that prevents F actin polymerization. Receptor-independent cytoskeleton remodeling by Cytochalasin D resulted in cell adhesion, polarization and intracellular accumulation of HIV virions similar to the effects gained with uPA.These findings illustrate the potential contribution of the uPA/uPAR system in the generation and/or maintenance of intra-cytoplasmic vesicles that actively accumulate virions, thus sustaining the presence of HIV reservoirs of macrophage origin. In addition, our observations also provide evidences that pathways controlling cytoskeleton remodeling and activation of PKCε bear relevance for the design of new antiviral strategies aimed at interfering with the partitioning of virion budding between intra-cytoplasmic vesicles and plasma membrane in infected human macrophages