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An explicit compatibility condition formula is presented for the Eulerian left Cauchy–Green deformation tensor field. It is shown to be the appropriate finite‐strain counterpart of Saint‐Venant's compatibility condition. The difference between the Eulerian problem and the Lagrangian one is highlighted. [ABSTRACT FROM AUTHOR]

It is well-known that the behaviour of supercritical fluids near the critical point changes considerably in the region around the Widom lines. We have found, for pure fluids, that the relationship between the thermal expansion coefficient and the isothermal compressibility is not only highly nonlinear in this region but in a certain temperature range can also be approximated well at constant pressure by a quadratic relationship, i.e., an ellipse. In this paper, we show this analytically, and demonstrate it for the van der Waals, Berthelot and IAPWS-95 water models numerically. Furthermore, the parameters of the ellipse are discovered to obey power and linear laws. The parameters of these laws are determined for the three aforementioned models. [Display omitted] • Leading elliptic relationship between thermal expansion coefficient and isothermal compressibility in the Widom region. • Power and linear laws for the parameters of the ellipse. • Model-independent analytical explanation. [ABSTRACT FROM AUTHOR]

Symplectic numerical schemes for reversible dynamical systems predict the solution reliably over large times as well, and are a good starting point for extension to schemes for simulating irreversible situations like viscoelastic wave propagation and heat conduction coupled via thermal expansion occuring in rocks, plastics, biological samples etc. Dissipation error (artificial nonpreservation of energies and amplitudes) of the numerical solution should be as small as possible since it should not be confused with the real dissipation occurring in the irreversible system. In addition, the other well-known numerical artefact, dispersion error (artificial oscillations emerging at sharp changes), should also be minimal to avoid confusion with the true wavy behavior. The continuum thermodynamical aspects (respect for balances with fluxes, systematic constitutive relationships between intensive quantities and fluxes, the second law of thermodynamics with positive definite entropy production, and the spacetime-based kinematic viewpoint) prove valuable for obtaining such extended schemes and for monitoring the solutions. Generalizing earlier works in this direction, here, we establish and investigate such a numerical scheme for one-dimensional viscoelastic wave propagation in the presence of heat conduction coupled via thermal expansion, demonstrating long-term reliability and the applicability of thermodynamics-based quantities in supervising the quality of the solution. [ABSTRACT FROM AUTHOR]

Rocks exhibit beyond-Hookean, delayed and damped elastic, behaviour (creep, relaxation etc.). In many cases, the Poynting-Thomson-Zener (PTZ) rheological model proves to describe these phenomena successfully. A forecast of the PTZ model is that the dynamic elasticity coefficients are larger than the static (slow-limit) counterparts. This prediction has recently been confirmed on a large variety of rock types. Correspondingly, according to the model, the speed of wave propagation depends on frequency, the high-frequency limit being larger than the low-frequency limit. This frequency dependence can have a considerable influence on the evaluation of various wave-based measurement methods of rock mechanics. As experience shows, commercial finite element softwares are not able to properly describe wave propagation, even for the Hooke model and simple specimen geometries, the seminal numerical artefacts being instability, dissipation error and dispersion error, respectively. This has motivated research on developing reliable numerical methods, which amalgamate beneficial properties of symplectic schemes, their thermodynamically consistent generalization (including contact geometry), and spacetime aspects. The present work reports on new results obtained by such a numerical scheme, on wave propagation according to the PTZ model, in one space dimension. The simulation outcomes coincide nicely with the theoretically obtained phase velocity prediction. [ABSTRACT FROM AUTHOR]

Intravenous administration of liposomal drugs can entail infusion reactions, also known as hypersensitivity reactions (HSRs), that can be severe and sometimes life-threatening in a small portion of patients. One empirical approach to prevent these reactions consists of lowering the infusion speed and extending the infusion time of the drug. However, different liposomal drugs have different levels of reactogenicity, which means that the optimal protocol for each liposomal drug may differ and should be identified and evaluated to make the treatment as safe and convenient as possible. The goal of the present study was to explore the use of pigs for the above purpose, using PEGylated liposomal prednisolone (PLP) as a model drug. We compared the reactogenicities of bolus versus infusion protocols involving 2-, 3- and 4-step dose escalations for a clinically relevant total dose, also varying the duration of infusions. The strength of HSRs was measured via continuous recording of hemodynamic parameters and blood thromboxane B2 levels. We showed that bolus administration or rapid infusion of PLP caused transient changes in systemic and pulmonary blood pressure and heart rate, most notably pulmonary hypertension with paralleling rises in plasma thromboxane B2. These adverse responses could be significantly reduced or eliminated by slow infusion of PLP, with the 3-h 3-step dose escalation protocol being the least reactogenic. These data suggest that the pig model enables the development of safe infusion protocols for reactogenic nanomedicines. Unlabelled Image [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-related fatigue is a prevalent symptom, with a significant impact on the daily lives of those affected. While physical exercise has demonstrated effectiveness in reducing the intensity and duration of fatigue, the literature still lacks sufficient evidence on the physiological mechanisms explaining this impact. This conceptual review aimed to provide an overview of the evidence regarding the effect of acute exercise on peripheral and neuronal inflammation, immune function, and the neuroendocrine system in the context of cancer. We aim to integrate these pathways into a conceptual model that can serve as a starting point for further research into the physiological mechanisms linking exercise and cancer-related fatigue. Cancer-related fatigue (CRF) is a prevalent and persistent issue affecting cancer patients, with a broad impact on their quality of life even years after treatment completion. The precise mechanisms underlying CRF remain elusive, yet its multifaceted nature involves emotional, physical, and cognitive dimensions. The absence of effective medical treatments has prompted researchers to explore integrative models for potential insights. Notably, physical exercise emerges as a promising strategy for managing CRF and related symptoms, as studies showed a reduction in CRF ranging from 19% to 40%. Current recommendations highlight aerobic training at moderate intensity as beneficial, although questions about a dose–response relationship and the importance of exercise intensity persist. Despite the positive impact of exercise on CRF, the underlying mechanisms remain elusive. This review aims to provide a theoretical model explaining how aerobic exercise may alleviate CRF. Focusing on acute exercise effects, this review delves into the potential influence on peripheral and neural inflammation, immune function dysregulation, and neuroendocrine system disruptions. The objective is to enhance our understanding of the intricate relationship between exercise and CRF, ultimately paving the way for tailored interventions and potential pharmacological treatments for individuals unable to engage in physical exercise. [ABSTRACT FROM AUTHOR]

The internal variable methodology of non-equilibrium thermodynamics, with a symmetric tensorial internal variable, provides an important rheological model family for solids, the so-called Kluitenberg–Verhás model family [Cs. Asszonyi et al., Contin. Mech. Thermodyn. 27, 2015]. This model family is distinguished not only by theoretical aspects but also on experimental grounds (see [Cs. Asszonyi et al., Period. Polytech., Civ. Eng. 60, 2016] for plastics and [W. Lin et al., Rock Engineering in Difficult Ground Conditions (Soft Rock and Karst), Proceedings of Eurock'09, 2009; K. Matsuki, K. Takeuchi, Int. J. Rock Mech. Min. Sci. Geomech. Abstr. 30, 1993; K. Matsuki, Int. J. Rock Mech. Min. Sci. 45, 2008] for rocks). In this article, we present and discuss how the internal variable formulation of the Kluitenberg–Verhás model family can be presented in the non-equilibrium thermodynamical framework GENERIC (General Equation for the Non-Equilibrium Reversible–Irreversible Coupling) [H. C. Öttinger, Beyond Equilibrium Thermodynamics, 2005; M. Grmela, J. Non-Newton. Fluid Mech. 165, 2010; M. Grmela, H. C. Öttinger, Phys. Rev. E 56, 1997; H. C. Öttinger, M. Grmela, Phys. Rev. E 56, 1997], for the benefit of both thermodynamical methodologies and promising practical applications. [ABSTRACT FROM AUTHOR]

Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as "nanomedicines", can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then focus on the reactions caused by mAb therapy. Because the alternative pathway of complement activation may amplify such adverse reactions, we highlight the potential use of complement factor H as an inhibitor of CARPA. [ABSTRACT FROM AUTHOR]

The unique magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) have led to their increasing use in drug delivery and imaging applications. Some polymer-coated SPIONs, however, share with many other nanoparticles the potential of causing hypersensitivity reactions (HSRs) known as complement (C) activation-related pseudoallergy (CARPA). In order to explore the roles of iron core composition and particle surface coating in SPION-induced CARPA, we measured C activation by 6 different SPIONs in a human serum that is known to react to nanoparticles (NPs) with strong C activation. Remarkably, only the carboxymethyldextran-coated (ferucarbotran, Resosvist®) and dextran-coated (ferumoxtran-10, Sinerem®) SPIONs caused significant C activation, while the citric acid, phosphatidylcholine, starch and chitosan-coated SPIONs had no such effect. Focusing on Resovist and Sinerem, we found Sinerem to be a stronger activator of C than Resovist, although the individual variation in 15 different human sera was substantial. Further analysis of C activation by Sinerem indicated biphasic dose dependence and significant production of C split product Bb but not C4d, attesting to alternative pathway C activation only at low doses. Consistent with the strong C activation by Sinerem and previous reports of HSRs in man, injection of Sinerem in a pig led to dose-dependent CARPA, while Resovist was reaction-free. Using nanoparticle tracking analysis, it was further determined that Sinerem, more than Resovist, displayed multimodal size distribution and significant fraction of aggregates – factors which are known to promote C activation and CARPA. Taken together, our findings offer physicochemical insight into how key compositional factors and nanoparticle size distribution affect SPION-induced CARPA, a knowledge that could lead to the development of SPIONs with improved safety profiles. [ABSTRACT FROM AUTHOR]

Because of their biological origins, therapeutic biologics can trigger an unwanted deleterious immune response with some patients. The immunogenicity of therapeutic biologics can affect drug efficacy and patient safety by the production of circulating anti-drug antibodies (ADA). In this study, quartz crystal microbalance (QCM) was developed as an assay to detect ADA. Etanercept (Enbrel®) was covalently grafted to dextran-modified QCM surfaces. Rabbits were immunized with etanercept to generate ADA. Results showed the QCM assay could detect purified ADA from rabbits at concentrations as low as 50 ng/mL, within the sensitivity range of ELISA. The QCM assay could also assess the ADA isotype. It was shown that the ADA were composed of the IgG isotype, but not IgM, as expected. Furthermore, it was shown that QCM surfaces that had been used to detect ADA could be regenerated in glycine-HCl solution and reused. The QCM assay was also demonstrated to detect ADA in crude serum samples. Serum was collected from the rabbits and analyzed before and after etanercept immunization. ADA were clearly detected in serum from rabbits after immunization, but not in serum before immunization. Serum from patients administered with etanercept for rheumatoid arthritis (RA) treatment was also analyzed and compared to serum from healthy donors. Sera from 10 RA patients were analyzed. Results showed one of the RA patient serum samples may have ADA present. In conclusion, QCM appears to be a viable assay to detect ADA for the immunogenicity assessment of therapeutic biologics. [ABSTRACT FROM AUTHOR]

Complement activation-related pseudoallergy (CARPA) is a hypersensitivity reaction occurring upon intravenous administration of numerous liposomal therapeutics, other nonbiological complex drugs and biologicals. It has a complex molecular and cellular mechanism that involves the production, actions and interactions of numerous vasoactive mediators in blood, including thromboxane A2 (TXA2). This short review focuses on the latter eicosanoid: its role in CARPA, effects underlying some of the symptoms and experimental evidence for its ratelimiting role in pulmonary hypertension in pigs. Animal experiments and recent clinical observations suggest that the cyclooxygenase blocker indomethacin may represent an effective new approach to prevent liposome-induced CARPA, lending clinical relevance to better understand the involvement of TXA2 and other eicosanoids in this adverse immune effect. [ABSTRACT FROM AUTHOR]

We present and analyse a thermodynamical theory of rheology with single internal variable. The universality of the model is ensured as long as the mesoscopic and/or microscopic background processes satisfy the applied thermodynamical principles, which are the second law, the basic balances and the existence of an additional-tensorial-state variable. The resulting model, which we suggest to call the Kluitenberg-Verhás body, is the Poynting-Thomson-Zener body with an additional inertial element or, in other words, is the extension of Jeffreys model to solids. We argue that this Kluitenberg-Verhás body is the natural thermodynamical building block of rheology. An important feature of the presented methodology is that nontrivial inequality-type restrictions arise for the four parameters of the model. We compare these conditions and other aspects to those of other known thermodynamical approaches, like Extended Irreversible Thermodynamics or the original theory of Kluitenberg. [ABSTRACT FROM AUTHOR]

Pigs are known to provide a sensitive model for studying complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction to liposomal and many other nanomedicines that limits their clinical use. The utility of rats as a CARPA model has, however, not been analyzed to date in detail. The present study compared the two models by inducing CARPA with i.v. bolus injections of two reactogenic liposomes that differed from each other in surface properties: one was AmBisome, a strong anionic, free-surface small unilamellar liposome (SUV), while the other was neutral, polyethylene glycol (PEG)-grafted SUV wherein the 2 kDa-PEG was anchored to the membrane via cholesterol (Chol-PEG). Both in pigs and rats AmBisome caused significant consumption of C3, indicating C activation, along with paralleling massive changes in blood pressure, white blood cell, platelet counts and in plasma thromboxane B2 levels, indicating CARPA. These processes were similar in the two species in terms of kinetics, but significantly differed in the doses that caused major hemodynamic changes (~ 0.01 and ~ 22 mg phospholipid (PL)/kg in pigs and rats, respectively). Pigs responded to AmBisome with pulmonary hypertension and systemic hypotension, and the reaction was not tachyphylactic. The major response of rats was systemic hypotension, leukopenia followed by leukocytosis, and thrombocytopenia. Chol-PEG liposomes caused severe reaction in pigs at 0.1 mg/kg, while the reaction they caused in rats was mild even at 300 mg PL/kg. Importantly, the reaction to Chol-PEG in pigs was partly tachyphylactic. These observations highlight fundamental differences in the immune mechanisms of porcine and rat CARPA, and also show a major impact of liposome surface characteristics, determining the presence or absence of tachyphylaxis. The data suggest that rats are 2–3 orders of magnitude less sensitive to liposomal CARPA than pigs; however, the causes of these differences, the PEG-dependent tachyphylaxis and the massive reactivity of Chol-PEG liposomes remain unclear. [ABSTRACT FROM AUTHOR]

Oil and gas platforms are energy-intensive systems, which operate under changing boundary conditions over time. In this paper, the life performance of an offshore platform is analysed by comparing three representative stages of an oil field (early-life, plateau and end-life productions). The energy requirements are assessed by a process integration study, and the system inefficiencies are pinpointed by performing an exergy accounting. The heating and cooling requirements vary significantly over time, and most inefficiencies take place in processes where chemical exergy is consumed (≃ 50-55%), thermal exergy is transferred (≃ 15-20%), or mechanical exergy is varied (≃ 0-15%). These findings are valid for all production periods: this suggests that more attention should be paid on a proper integration of the processing and utility plants, by, for instance, recovering heat from the turbine exhausts and from the exported gas. Multi-objective optimisations are conducted for evaluating the integration of steam and organic Rankine cycles, considering thermodynamic, economic and environmental performance indicators. They indicate that the profitability of a given improvement measure mainly depends on (i) the field properties, (ii) the platform operating strategy, and (iii) the production stage of the oil field. The implementation of steam networks appears promising, as it results in a better performance of the offshore platform and in larger economic profits. [ABSTRACT FROM AUTHOR]

There are direct and indirect indications that PEGylated liposomal doxorubicin (Doxil), a widely used anticancer nanomedicine, has a subclinical immune suppressive effect. As an example of a seemingly bad pharmacological property turning out to be “not-so-ugly”, but actually beneficial, the authors highlight the potential benefits of Doxil's immune suppressive effect. These include (1) the decreased uptake of the drug by the MPS which may entail enhanced tumor uptake, and, hence, improved therapeutic efficacy; (2) the use of slow infusion protocols in reducing the risk of hypersensitivity (infusion) reactions; and (3), possible protection against hypersensitivity reactions to co-administered reactogenic drugs. To consider immune suppression as useful represents a paradigm shifts in nanotoxicology and anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Approaching object detector structure has been recently identified in mouse retina, and its neural circuit model has been successfully built. A discrete-type mathematical model describing the retinal structure has been synthesized and implemented on a biologically motivated focal-plane mixed-signal sensor-processor device. The model responses have been analyzed, and the critical parameters have been identified, and their roles were studied. The model has been validated in real dynamic surround of a robotic arm, where the geometrical and the kinematic parameters of the movements were known. From the mathematical and experimental analysis, it has been concluded that this retinal structure has a capacity to generate a last second warning signal to avoid collisions. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Kinematic quantities for finite elastic and plastic deformations are defined via an approach that does not rely on auxiliary elements, such as reference frame and reference configuration, and that gives account of the inertial-noninertial aspects explicitly. These features are achieved by working on Galilean spacetime directly. The quantity expressing elastic deformations is introduced according to its expected role: to measure how different the current metric is from the relaxed/stressless metric. Further, the plastic kinematic quantity is the change rate of the stressless metric. The properties of both are analyzed, and their relationship with frequently used elastic and plastic kinematic quantities is discussed. One important result is that no objective elastic or plastic quantities can be defined from the deformation gradient. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We calculate the quantum statistical force acting on a partition wall that divides a one-dimensional box into two halves. The two half boxes containing the same (fixed) number of noninteracting bosons are kept at the same temperature, and admit the same boundary conditions at the outer walls; the only difference is the distinct boundary conditions imposed at the two sides of the partition wall. The net force acting on the partition wall is nonzero at zero temperature and remains almost constant for low temperatures. As the temperature increases, the force starts to decrease considerably, but after reaching a minimum it starts to increase, and tends to infinity with a square-root-of-temperature asympotics. This example demonstrates clearly that distinct boundary conditions cause remarkable physical effects for quantum systems. [ABSTRACT FROM AUTHOR]

On the example of the Poynting–Thomson–Zener rheological model for solids, which exhibits both dissipation and wave propagation, with nonlinear dispersion relation, we introduce and investigate a finite difference numerical scheme. Our goal is to demonstrate its properties and to ease the computations in later applications for continuum thermodynamical problems. The key element is the positioning of the discretized quantities with shifts by half space and time steps with respect to each other. The arrangement is chosen according to the spacetime properties of the quantities and of the equations governing them. Numerical stability, dissipative error, and dispersive error are analyzed in detail. With the best settings found, the scheme is capable of making precise and fast predictions. Finally, the proposed scheme is compared to a commercial finite element software, COMSOL, which demonstrates essential differences even on the simplest—elastic—level of modeling. [ABSTRACT FROM AUTHOR]

The non-Fourier heat conduction phenomenon on room temperature is analyzed from various aspects. The first one shows its experimental side, in what form it occurs, and how we treated it. It is demonstrated that the Guyer-Krumhansl equation can be the next appropriate extension of Fourier's law for room-temperature phenomena in modeling of heterogeneous materials. The second approach provides an interpretation of generalized heat conduction equations using a simple thermo-mechanical background. Here, Fourier heat conduction is coupled to elasticity via thermal expansion, resulting in a particular generalized heat equation for the temperature field. Both aforementioned approaches show the size dependency of non-Fourier heat conduction. Finally, a third approach is presented, called pseudo-temperature modeling. It is shown that non-Fourier temperature history can be produced by mixing different solutions of Fourier's law. That kind of explanation indicates the interpretation of underlying heat conduction mechanics behind non-Fourier phenomena. [ABSTRACT FROM AUTHOR]

An editorial is presented on the 14th Joint European Thermodynamics Conference (JETC) held at the University of Technology and Economics Budapest, Hungary from May 21 to 25, 2017 which was based on the thermodynamics focusing to upgrade interaction and combine deployment-oriented categories to grow a more robust and more relevant discipline. Øivind Wilhelmsen was chosen by an international committee for his thesis on equilibrium and non-equilibrium thermodynamics of planar and curved interfaces.

Rocks are important examples for solid materials where, in various engineering situations, elastic, thermal expansion, rheological /viscoelastic and plastic phenomena each may play a remarkable role. Nonequilibrium continuum thermodynamics provides a consistent way to describe all these aspects in a unified framework. This we present here in a formulation where the kinematic quantities allow arbitrary nonzero initial (e.g., in situ) stresses and such initial configurations which - as a consequence of thermal or remanent stresses - do not satisfy the kinematic compatibility condition. The various characteristic effects accounted by the obtained theory are illustrated via experimental results where loaded solid samples undergo elastic, thermal expansion and plastic deformation and exhibit rheological behaviour. From the experimental data, the rheological coefficients are determined, and the measured temperature changes are also explained by the theory. Dedicated to the memory of Zoltán Szarka (1927-2015). [ABSTRACT FROM AUTHOR]

Senile amyloid plaques are one of the main hallmarks of Alzheimer's disease (AD). They correspond to insoluble deposits of amyloid-β peptides (Aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Aβ possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether Aβ is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted Aβ42 in response to HSV-1 challenge and that U118-MG cells could rapidly internalize Aβ42. Production of pro-inflammatory cytokines TNFα and IL-1β by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFNα. However, extraneous Aβ42 induced strong production of these cytokines. A combination of Aβ42 and HSV-1 induced production of pro-inflammatory cytokines TNFα and IL-1β, and IFNα in the cell lines. The reported anti-viral protection of Aβ42 was revealed in transfer experiments involving conditioned medium (CM) of HSV-1-infected H4 cells. CM conferred Aβ-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced Aβ42 in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD. [ABSTRACT FROM AUTHOR]

We report heat pulse experiments at room temperature that cannot be described by Fourier's law. The experimental data are modeled properly by the Guyer-Krumhansl equation, in its over-diffusion regime. The phenomenon may be due to conduction channels with differing conductivities and parallel to the direction of the heat flux. [ABSTRACT FROM AUTHOR]

Non-equilibrium thermodynamics with internal variables introduces a natural hierarchical arrangement of evolution equations. Three examples are shown: a hierarchy of linear constitutive equations in thermodynamic rheology with a single internal variable, a hierarchy of wave equations in the theory of generalized continua with dual internal variables, and a hierarchical arrangement of the Fourier equation in the theory of heat conduction with current multipliers. [ABSTRACT FROM AUTHOR]

Background: Growing evidence supports that receptor for advanced glycation end products (RAGE) and glyoxalase-1 (GLO-1) are implicated in the pathophysiology of Alzheimer's disease (AD). Extracellular vesicles (EVs) are nanovesicles secreted by almost all cell types, contribute to cellular communication, and are implicated in AD pathology. Recently, EVs are considered as promising tools to identify reliable biomarkers in AD.Objective: The aim of our study was to determine the levels of RAGE and GLO-1 in circulating EVs from mild cognitive impairment (MCI) and AD patients and to analyze their correlation with the clinical Mini-Mental State Examination and Montreal Cognitive Assessment scores. We have studied the possibility that neuronal cells could release and transfer GLO-1 through EVs.Methods: RAGE and GLO-1 levels were measured in circulating EVs, respectively, by Luminex assay and western blot. Released-EVs from SK-N-SH neuronal cells were isolated and GLO-1 levels were determined by western blot.Results: Our data showed higher levels of RAGE in EVs from late AD patients while GLO-1 levels in EVs from early AD were lower as compared to control and MCI patients. Interestingly, levels of RAGE and GLO-1 in EVs were correlated with the cognitive scores regardless of age. For the first time, we demonstrated that GLO-1 was released from neuronal cells through EVs.Conclusion: Although more samples will be needed, our preliminary results support the use of peripheral EVs cargo as new tools for the discovery of peripheral AD biomarkers. [ABSTRACT FROM AUTHOR]

We show that the point interactions on a line can be utilized to provide family of qubit operations for quantum information processing. Qubits are realized as states localized in either side of the point interaction which represents a controllable gate. The qubit manipulation proceeds in a manner analogous to the operation of an abacus. [Copyright &y& Elsevier]

It is a long-lasting task to understand heat conduction phenomena beyond Fourier. Besides the low-temperature experiments on extremely pure crystals, it has turned out recently that heterogeneous materials with macro-scale size can also show thermal effects that cannot be modeled by the Fourier equation. This is called over-diffusive propagation, different from low-temperature observations, and is found in numerous samples made from metal foam, rocks, and composites. The measured temperature history is indeed similar to what Fourier's law predicts but the usual evaluation cannot provide reliable thermal parameters. This paper is a report on our experiments on several rock types, each type having multiple samples with different thicknesses. We show that size-dependent thermal behavior can occur for both Fourier and non-Fourier situations. Moreover, based on the present experimental data, we find an empirical relation between the Fourier and non-Fourier parameters, which may be helpful in later experiments to develop a more robust and reliable evaluation procedure. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, where neuroinflammation and immune cells are key pathological factors. Recently, it was suggested a possible association between AD and human herpesvirus 6 (HHV-6) infection. Since we recently observed that multiple sclerosis patients with KIR2DL2 expression on natural killer (NK) cells are more susceptible to herpesvirus infection, we tested the possible implication of KIR/HLA genetic for HHV-6A infection. We identified, for the first time, a possible implication of a specific KIR/HLA subset in AD. The combination KIR2DS2/KIR2DL2/C1 correlated with a lower MMSEDi score, representative of a severe AD status and an increased susceptibility to HHV-6A infection. Therefore, the results seem to converge on the hypothesis that herpesvirus infection might play a role in AD. If this hypothesis finds experimental confirmation, a new therapeutic strategy, modulating KIR2DL2 expression on NK cells, for AD might be envisaged. [ABSTRACT FROM AUTHOR]

AP@LZ is an electronic organiser that was designed to support the day-to-day activities of persons with Alzheimer's disease. To assess the potential of this technology, three participants (NI, JB, RD) were approached to take part in the study. They benefited from a structured cognitive intervention to learn how to operate AP@LZ; the intervention included the following learning stages: Acquisition, Application and Adaptation. Pre- and post-intervention measures were collected. NI, for whom a longitudinal study was conducted, still continued to use AP@LZ 24 months post-intervention. JB and RD also showed a gradual improvement in their performance throughout the intervention phase (sessions 1 to 19 for JB: performance increased from 50 to 100%; sessions 1 to 25 for RD: from 56 to 89%). The results of the use of AP@LZ in activities of daily living suggest that the application was beneficial for three persons with Alzheimer's disease whose profiles differed notably (age, cognitive and social profiles). Thus, results indicate that they were all able to learn how to operate AP@LZ's functions and to use them in their activities of daily living. Cognitive intervention appears to play an important role for the promotion of learning and adoption of such technology. [ABSTRACT FROM AUTHOR]

Reciprocity is when wave or quantum scattering satisfies a symmetry property, connecting a scattering process with the reversed one. While reciprocity involves the interchange of source and detector, it is fundamentally different from rotational invariance, and is a generalization of time reversal invariance, occurring in absorptive media as well. Due to its presence at diverse areas of physics, it admits a wide variety of applications. For polarization dependent scatterings, reciprocity is often violated, but violation in the phase of the scattering amplitude is much harder to experimentally observe than violation in magnitude. Enabled by the advantageous properties of nuclear resonance scattering of synchrotron radiation, we have measured maximal, i.e., 180-degree, reciprocity violation in the phase. For accessing phase information, we introduced a new version of stroboscopic detection. The scattering setting was devised based on a generalized reciprocity theorem that opens the way to construct new types of reciprocity related devices. [ABSTRACT FROM AUTHOR]

Background: Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits.Objective: To determine whether aerobic exercise training modifies brain energy metabolism in mild AD.Methods: In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program.Results: Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2-3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 μmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop-color naming test (-10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01).Conclusion: In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement. [ABSTRACT FROM AUTHOR]

Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression. [ABSTRACT FROM AUTHOR]

The recent results attained from a thermodynamically conceived numerical scheme applied on wave propagation in viscoelastic/rheological solids are generalized here, both in the sense that the scheme is extended to four spacetime dimensions and in the aspect of the virtues of a thermodynamical approach. Regarding the scheme, the arrangement of which quantity is represented where in discretized spacetime, including the question of appropriately realizing the boundary conditions, is nontrivial. In parallel, placing the problem in the thermodynamical framework proves to be beneficial in regards to monitoring and controlling numerical artefacts—instability, dissipation error, and dispersion error. This, in addition to the observed preciseness, speed, and resource-friendliness, makes the thermodynamically extended symplectic approach that is presented here advantageous above commercial finite element software solutions. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) and glyoxal (GO) are suggested to be associated with the development of neurodegenerative pathologies. However, their peripheral levels in relation to cognitive decline and their effects on key factors in neuronal cells are poorly investigated. The aim of this study was to determine their serum levels in MCI (mild cognitive impairment) and Alzheimer's disease (AD) patients, to analyze their effects on the neurotrophic and inflammatory factors, on neurodegenerative markers in neuronal cells and in neuronal derived-extracellular vesicles (nEVs). Our results show that MG and GO levels in serum, determined by HPLC, were higher in MCI. ROC (receiver-operating characteristic curves) analysis showed that the levels of MG in serum have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. Cells and nEVs levels of BDNF, PRGN, NSE, APP, MMP-9, ANGPTL-4, LCN2, PTX2, S100B, RAGE, Aβ peptide, pTau T181 and alpha-synuclein were quantified by luminex assay. Treatment of neuronal cells with MG or GO reduced the cellular levels of NSE, PRGN, APP, MMP-9 and ANGPTL-4 and the nEVs levels of BDNF, PRGN and LCN2. Our findings suggest that targeting MG and GO may be a promising therapeutic strategy to prevent or delay the progression of AD. [ABSTRACT FROM AUTHOR]

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways. [ABSTRACT FROM AUTHOR]