Modeling of Immunosenescence and Risk of Death from Respiratory Infections: Evaluation of the Role of Antigenic Load and Population Heterogeneity

It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to describe and investigate the mechanism underlying the age pattern of the mortality rate caused by infectious diseases and to determine the cause-specific hazard rate as a function of immune system characteristics. For these purposes we develop a three-compartment model explaining observed risk-of-death. The model incorporates up-to-date knowledge about cellular mechanisms of aging, disease dynamics, population heterogeneity in resistance to infections, and intrinsic aging rate. The results of modeling show that the age-trajectory of mortality caused by respiratory infections may be explained by the value of antigenic load, frequency of infections and the rate of aging of the stem cell population (i.e. the population of T-lymphocyte progenitor cells). The deceleration of infection-induced mortality at advanced age can be explained by selection of individuals with a slower rate of stem cell aging. Parameter estimates derived from fitting mortality data indicate that infection burden was monotonically decreasing during the twentieth century, and changes in total antigenic load were gender-specific: it experienced periodic fluctuations in males and increased approximately two-fold in females

The therapeutic management of gut barrier leaking: the emerging role for mucosal barrier protectors

OBJECTIVE: Gut barrier is a functional unit organized as a multi-layer system and its multiple functions are crucial for maintaining gut homeostasis. Numerous scientific evidences showed a significant association between gut barrier leaking and gastro-intestinal/extra-intestinal diseases. MATERIALS AND METHODS: In this review we focus on the relationship between gut barrier leaking and human health. At the same time we speculate on the possible new role of gut barrier protectors in enhancing and restoring gut barrier physiology with the final goal of promoting gut health. RESULTS: The alteration of the equilibrium in gut barrier leads to the passage of the luminal contents to the underlying tissues and thus into the bloodstream, resulting in the activation of the immune response and in the induction of gut inflammation. This permeability alteration is the basis for the pathogenesis of many diseases, including infectious enterocolitis, inflammatory bowel diseases, irritable bowel syndrome, small intestinal bacterial overgrowth, celiac disease, hepatic fibrosis, food intolerances and also atopic manifestations. Many drugs or compounds used in the treatment of gastrointestinal disease are able to alter the permeability of the intestinal barrier. Recent data highlighted and introduced the possibility of using gelatin tannate, a mucosal barrier protector, for an innovative approach in the management of intestinal diseases, allowing an original therapeutic orientation with the aim of enhancing mucus barrier activity and restoring gut barrier. CONCLUSIONS: These results suggest how the mucus layer recovering, beside the gut microbiota modulation, exerted by gut barrier protectors could be a useful weapon to re-establish the physiological intestinal homeostasis after an acute and chronic injury

Single-electron tunneling in InP nanowires

We report on the fabrication and electrical characterization of field-effect devices based on wire-shaped InP crystals grown from Au catalyst particles by a vapor-liquid-solid process. Our InP wires are n-type doped with diameters in the 40-55 nm range and lengths of several microns. After being deposited on an oxidized Si substrate, wires are contacted individually via e-beam fabricated Ti/Al electrodes. We obtain contact resistances as low as ~10 kOhm, with minor temperature dependence. The distance between the electrodes varies between 0.2 and 2 micron. The electron density in the wires is changed with a back gate. Low-temperature transport measurements show Coulomb-blockade behavior with single-electron charging energies of ~1 meV. We also demonstrate energy quantization resulting from the confinement in the wire.Comment: 4 pages, 3 figure

Harmonization of design-based mapping for spatial populations

The mapping of a survey variable throughout a continuum or for finite populations of units is usually performed from a model-dependent perspective. Nevertheless, when a sample of locations/units is selected by a probabilistic sampling scheme, the complex task of modelling can be avoided by using the inverse distance weighting interpolator and deriving the properties of maps in a design-based perspective. Conditions ensuring consistency of maps can be derived mainly based on some obvious assumptions about the pattern of the survey variable throughout the study region as well from the feature of the sampling scheme adopted to select locations/units. Nevertheless, in a design-based setting the totals of the survey variable for a set of domains partitioning the study region are commonly estimated by traditional estimators such as the Horvitz–Thompson estimator in the case of finite populations or the Monte-Carlo estimator in the case of continuous populations or by related estimators exploiting the information of auxiliary variables. That necessarily gives rise to different total estimates with respect to those achieved from the resulting maps as the sum of the interpolated values within domains. To obtain non-discrepant results, a harmonization of maps is here suggested, in such a way that the resulting totals arising from maps coincide with those achieved by traditional estimation. The capacity of the harmonization procedure to maintain consistency is argued theoretically and checked by a simulation study performed on some real populations

Harmonization of design-based mapping for spatial populations

The mapping of a survey variable throughout a continuum or for finite populations of units is usually performed from a model-dependent perspective. Nevertheless, when a sample of locations/units is selected by a probabilistic sampling scheme, the complex task of modelling can be avoided by using the inverse distance weighting interpolator and deriving the properties of maps in a design-based perspective. Conditions ensuring consistency of maps can be derived mainly based on some obvious assumptions about the pattern of the survey variable throughout the study region as well from the feature of the sampling scheme adopted to select locations/units. Nevertheless, in a design-based setting the totals of the survey variable for a set of domains partitioning the study region are commonly estimated by traditional estimators such as the Horvitz–Thompson estimator in the case of finite populations or the Monte-Carlo estimator in the case of continuous populations or by related estimators exploiting the information of auxiliary variables. That necessarily gives rise to different total estimates with respect to those achieved from the resulting maps as the sum of the interpolated values within domains. To obtain non-discrepant results, a harmonization of maps is here suggested, in such a way that the resulting totals arising from maps coincide with those achieved by traditional estimation. The capacity of the harmonization procedure to maintain consistency is argued theoretically and checked by a simulation study performed on some real population

Pauli spin blockade in CMOS double quantum dot devices

Silicon quantum dots are attractive candidates for the development of scalable, spin-based qubits. Pauli spin blockade in double quantum dots provides an efficient, temperature independent mechanism for qubit readout. Here we report on transport experiments in double gate nanowire transistors issued from a CMOS process on 300 mm silicon-on-insulator wafers. At low temperature the devices behave as two few-electron quantum dots in series. We observe signatures of Pauli spin blockade with a singlet-triplet splitting ranging from 0.3 to 1.3 meV. Magneto-transport measurements show that transitions which conserve spin are shown to be magnetic-field independent up to B = 6 T.Comment: 5 pages , 4 figure

Oral contraceptive use and the risk of epithelial ovarian cancer.

The relation between the use of combination oral contraceptives (OCs) and the risk of epithelial ovarian cancer was investigated in a case-control study conducted in Milan on 209 women below the age of 60 with histologically confirmed epithelial ovarian cancer, and 418 age-matched controls with a spectrum of acute conditions apparently unrelated to OC use. Combination oral contraceptives were used by 18 (9%) cases, and 59 (14%) controls, giving a relative risk estimate of 0.6 (95% confidence interval = 0.3-1.0, P less than 0.05). The risk of ovarian cancer decreased with increasing duration of use and the point estimate remained below unity long after cessation of use. These results were not accounted for by parity, infertility, or other identified potential confounding factors. Thus, the findings of the present study add further support to the evidence emerging from American data of a reduction of approximately 40% in the risk of epithelial ovarian cancer among women who had used oral contraceptives

Nanomedicine and graphene-based materials: advanced technologies for potential treatments of diseases in the developing nervous system

Abstract: The interest in graphene-based nanomaterials (GBNs) application in nanomedicine, in particular in neurology, steadily increased in the last decades. GBNs peculiar physical–chemical properties allow the design of innovative therapeutic tools able to manipulate biological structures with subcellular resolution. In this review, we report GBNs applications to the central nervous system (CNS) when these nanomaterials are engineered as potential therapeutics to treat brain pathologies, with a focus on those of the pediatric age. We revise the state-of-the art studies addressing the impact of GBNs in the CNS, showing that the design of GBNs with different dimensions and chemical compositions or the use of specific administration routes and doses can limit unwanted side effects, exploiting GBNs efficacy in therapeutic approaches. These features favor the development of GBNs-based multifunctional devices that may find applications in the field of precision medicine for the treatment of disorders in the developing CNS. In this framework, we address the suitability of GBNs to become successful therapeutic tools, such as drug nano-delivery vectors when being chemically decorated with pharmaceutical agents and/or other molecules to obtain a high specific targeting of the diseased area and to achieve a controlled release of active molecules. Impact: The translational potential of graphene-based nanomaterials (GBNs) can be used for the design of novel therapeutic approaches to treat pathologies affecting the brain with a focus on the pediatric age.GBNs can be chemically decorated with pharmaceutical agents and molecules to obtain a highly specific targeting of the diseased site and a controlled drug release.The type of GBNs, the selected functionalization, the dose, and the way of administration are factors that should be considered to potentiate the therapeutic efficacy of GBNs, limiting possible side effects.GBNs-based multifunctional devices might find applications in the precision medicine and theranostics fields