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

Incidental PET/CT Findings of Suspected COVID-19 in a Region of High Prevalence.

We describe a case of suspected COVID-19 pneumonia in a 61-year-old male with known primary central nervous system diffuse large B-cell lymphoma (DLBCL) who underwent restaging PET/CT during the initial peak of infection of COVID-19 pneumonia within the New York region. At the time of his routine PET-CT to assess for disease progression, typical CT imaging features of COVID-19 pneumonia were identified. Upon further investigation, the patient was asymptomatic, and his infection status remained unknown. He was subsequently lost to follow-up with his COVID-19 status pending

Oxidation and erythropoiesis

Purpose of review Erythropoiesis is a complex multistep process going from committed erythroid progenitors to mature red cells. Although recent advances allow the characterization of some components of erythropoiesis, much still remains to be investigated particularly on stress erythropoiesis. This review summarizes recent progresses made to understand the impact of oxidative stress on normal and pathologic erythropoiesis. Recent findings During erythroid maturation, reactive oxygen species might function as second messenger through either transient oxidation of cysteine residues on signaling targets or modulation of intracellular signaling pathways. Thus, in erythropoiesis, efficient cytoprotective systems are required to limit possible reactive oxygen species-related toxic effects especially in stress erythropoiesis characterized by severe oxidation such as b-thalassemia. In addition, prolonged or severe oxidative stress impairs autophagy, which might contribute to the block of erythroid maturation in stress erythropoiesis. Understanding the functional role of cytoprotective systems such as peroxiredoxin-2 or classical molecular chaperones such as the heat shock proteins will contribute to develop innovative therapeutic strategies for ineffective erythropoiesis. Summary We provide an update on cytoprotective mechanisms against oxidation in normal and stress erythropoiesis. We discuss the role of oxidative sensors involved in modulation of intracellular signaling during erythroid maturation process in normal and stress erythropoiesis

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

Andreev reflection in Si-engineered Al/InGaAs hybrid junctions

Andreev-reflection dominated transport is demonstrated in Al/n-In0.38Ga0.62As superconductor-semiconductor junctions grown by molecular beam epitaxy on GaAs(001). High junction transparency was achieved in low-doped devices by exploiting Si interface bilayers to suppress the native Schottky barrier. It is argued that this technique is ideally suited for the fabrication of ballistic transport hybrid microstructures.Comment: 9 REVTEX pages + 3 postscript figures, to be published in APL 73, (28dec98

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