Continuous mode cooling and phonon routers for phononic quantum networks

We study the implementation of quantum state transfer protocols in phonon networks, where in analogy to optical networks, quantum information is transmitted through propagating phonons in extended mechanical resonator arrays or phonon waveguides. We describe how the problem of a non-vanishing thermal occupation of the phononic quantum channel can be overcome by implementing optomechanical multi- and continuous mode cooling schemes to create a 'cold' frequency window for transmitting quantum states. In addition, we discuss the implementation of phonon circulators and switchable phonon routers, which rely on strong coherent optomechanical interactions only, and do not require strong magnetic fields or specific materials. Both techniques can be applied and adapted to various physical implementations, where phonons coupled to spin or charge based qubits are used for on-chip networking applications.Comment: 33 pages, 8 figures. Final version, a few minor changes and updated reference

Master Equation for the Motion of a Polarizable Particle in a Multimode Cavity

We derive a master equation for the motion of a polarizable particle weakly interacting with one or several strongly pumped cavity modes. We focus here on massive particles with complex internal structure such as large molecules and clusters, for which we assume a linear scalar polarizability mediating the particle-light interaction. The predicted friction and diffusion coefficients are in good agreement with former semiclassical calculations for atoms and small molecules in weakly pumped cavities, while the current rigorous quantum treatment and numerical assessment sheds a light on the feasibility of experiments that aim at optically manipulating beams of massive molecules with multimode cavities.Comment: 30 pages, 5 figure

Duration of environmental enrichment determines astrocyte number and cervical lymph node T lymphocyte proportions but not the microglial number in middle-aged C57BL/6 mice

Published: 18 March 2020Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short- and long-term EE were associated with underlying immune changes. Hence, at the end of behavioral testing, mice were sacrificed, and brains and cervical lymph nodes were collected to investigate the differential effects of the duration of EE (short- and long-term) on the number of immunopositive glial cells in the dentate gyrus, CA1, CA2, and CA3 regions of the hippocampus and proportions of T cell subsets in the cervical lymph nodes using immunohistochemistry and flow cytometry, respectively. EE, regardless of duration, caused an increase in microglia number within the dentate gyrus, CA1 and CA3 hippocampal regions, but only long-term EE increased astrocytes number within the dentate gyrus and CA3 hippocampal regions. A significantly higher proportion of CD8+ naive T cells was observed after long-term EE vs. short-term EE. No significant differences were observed in the proportion of central memory and effector memory T cells or early activated CD25+ cells between any of the test groups. Our results suggest that EE, irrespective of duration, enhances the numbers of microglia, but long-term EE is required to modify astrocyte number and peripheral T cell proportions in middle-aged mice. Our findings provide new insights into the therapeutic effects of EE on various brain disorders, which may be at least partly mediated by glial and neuroimmune modulation.Gaurav Singhal, Julie Morgan1, Magdalene C. Jawahar, Frances Corrigan, Emily J. Jaehne, Catherine Toben ... et al

microRNA-146a modulates behavioural activity, neuroinflammation, and oxidative stress in adult mice

Small non-coding miRNA act as key regulators of several physiological processes due to their ability to interact with numerous target mRNA within a network. Whilst several miRNA can act in concert to regulate target mRNA expression, miR-146a has emerged as a critical modulator of inflammation by targeting key upstream signalling proteins of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and reductions in this miRNA have been observed in several neurological and neurodegenerative disorders. However, a targeted assessment of behaviour and neural tissues following the loss of miR-146a has not been documented. In this study, we examined the behavioural and neuroinflammatory phenotype of mice lacking miR-146a to determine the role of this miRNA in neurological function. Adult miR-146a−/− mice displayed no overt developmental phenotype with the exception of enlarged spleens. Behavioural testing revealed a mild but significant reduction in exploratory locomotor activity and increase in anxiety-like behaviour, with no changes in short-term spatial memory, fear conditioning, or sensorimotor gating. In the brain, the lack of miR-146a resulted in a significant compensatory miR-155 expression with no significant changes in expression of the target Interleukin 1 Receptor Associated Kinase (Irak) gene family. Despite these effects on upstream NF-κB mediators, downstream expression of cytokine and chemokine messengers was significantly elevated in miR-146a−/− mice compared to wild-type controls. Moreover, this increase in inflammatory cytokines was observed alongside an induction of oxidative stress, driven in part by nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, and included reduced thiol antioxidant concentrations and increased oxidised protein carbonyl concentrations. In female miR-146a mice, this increase in oxidative stress resulted in an increased expression of superoxide dismutase 1 (SOD1). Together, this suggests miR-146a plays a key role in regulating inflammation even in the absence of inflammatory stimuli and reduced levels of this miRNA have the capacity to induce limited behavioural effects whilst exacerbating both inflammation and oxidative stress in the brain

Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression

The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.Gaurav Singhal, Julie Morgan, Magdalene C.Jawahar, Frances Corrigan, Emily J.Jaehn

Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis.

Background: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. Methods: The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. Results: Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. Conclusions: To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool

Degenerative Veränderungen im alternden Innenohr, mit besonderer Berücksichtigung der vasculären Veränderungen, in Flächenpräparaten der menschlichen Cochlea dargestellt

Temporal bones from 150 patients, ranging in age from fetuses and newborn to 97 years, were studied by the technique of microdissection and the use of surface specimens stained with OSO 4 . Hair cell and nerve degeneration were seen in the extreme basal turn of the cochlea even in children. In the fetal cochlea vascularization is very dense, in the newborn and infant somewhat less so. A gradual involution of blood vessels occurs postnatally and continues with maturity and aging. Involution is seen especially in the membranous wall of the cochlea and in the system of spiral vessels of the basilar membrane and vestibular lip. During the first decade the radiating arterioles and the outer spiral vessel in the basal turn are reduced to their adult size. In presbycusis material we observed a marked loss of capillaries and of some of the radiating arterioles in the spiral ligament. Other arterioles had thickened walls. This devascularization was accompanied by atrophy and acellularity of the spiral ligament and atrophy of the stria. Atrophy of the spiral vessels was seen, especially in the lower half of the basal turn. Most of the cochlear blood vessels have clearly distinguishable perivascular spaces. Vessels which had become occluded and disappeared left behind them intervascular strands and/or avascular channels . Such channels were seen to connect the perivascular space of one capillary with that of another, representing the perivascular space of the vessel which had atrophied. The hair cell and nerve degeneration seen in presbycusis may be caused, at least in part, by microangiopathy of this type. Similar vascular changes have been observed in retinal vessels. It is possible that the gradual reduction of blood supply through the disappearance of capillaries occurs in many tissues of the body and plays an important role in the aging process. Mit Hilfe der Oberflächenpräparation wurden von uns 150 menschliche Labyrinthe aller Altersgruppen untersucht. Es wurde eine Haarzellen-und Nervendegeneration schon im Kindesalter beobachtet. Blutgefäße in der Schnecke haben perivasculdre Spalten; Gefäße atrophieren and werden zu „avascular channels”, leeren Spaltrdumen oder Striingen. Bei Presbyakusis fällt neben der Haarzell- and Nervendegeneration in der Basalwindung der Schnecke die Gefäßatrophie im Ligamentum spirale und der Membrana basilaris auf. Dazu kommt noch eine beträchtliche Atrophie des Ligamentum spirale und der Stria vascularis. Bemerkenswert ist, daß die Devascularisation schon im Kindesalter beginnt.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47255/1/405_2004_Article_BF00373313.pd

Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1

Renal systems biology of patients with systemic inflammatory response syndrome

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate were inversely correlated with the majority of significantly down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness