Integrated photonic quantum gates for polarization qubits

Integrated photonic circuits have a strong potential to perform quantum information processing. Indeed, the ability to manipulate quantum states of light by integrated devices may open new perspectives both for fundamental tests of quantum mechanics and for novel technological applications. However, the technology for handling polarization encoded qubits, the most commonly adopted approach, is still missing in quantum optical circuits. Here we demonstrate the first integrated photonic Controlled-NOT (CNOT) gate for polarization encoded qubits. This result has been enabled by the integration, based on femtosecond laser waveguide writing, of partially polarizing beam splitters on a glass chip. We characterize the logical truth table of the quantum gate demonstrating its high fidelity to the expected one. In addition, we show the ability of this gate to transform separable states into entangled ones and vice versa. Finally, the full accessibility of our device is exploited to carry out a complete characterization of the CNOT gate through a quantum process tomography.Comment: 6 pages, 4 figure

A new metric for quantifying the relative impact of risk factors on loss of working life illustrated in a population of working dogs

In a resource-limited world, organisations attempting to reduce the impact of health or behaviour issues need to choose carefully how to allocate resources for the highest overall impact. However, such choices may not always be obvious. Which has the biggest impact? A large change to a small number of individuals, or a small change to a large number of individuals? The challenge is identifying the issues that have the greatest impact on the population so potential interventions can be prioritised. We addressed this by developing a score to quantify the impact of health conditions and behaviour problems in a population of working guide dogs using data from Guide Dogs, UK. The cumulative incidence of different issues was combined with information about their impact, in terms of reduction in working life, to create a work score. The work score was created at population-level to illustrate issues with the greatest impact on the population and to understand contributions of breeds or crossbreeds to the workforce. An individual work deficit score was also created and means of this score used to illustrate the impact on working life within a subgroup of the population such as a breed, or crossbreed generation. The work deficit scores showed that those removed for behavioural issues had a greater impact on the overall workforce than those removed for health reasons. Additionally trends over time illustrated the positive influence of interventions Guide Dogs have made to improve their workforce. Information highlighted by these scores is pertinent to the effort of Guide Dogs to ensure partnerships are lasting. Recognising that the scores developed here could be transferable to a wide variety of contexts and species, most notably human work force decisions; we discuss possible uses and adaptations such as reduction in lifespan, quality of life and yield in production animals

Ibudilast, a Pharmacologic Phosphodiesterase Inhibitor, Prevents Human Immunodeficiency Virus-1 Tat-Mediated Activation of Microglial Cells

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorders (HAND) occur, in part, due to the inflammatory response to viral proteins, such as the HIV-1 transactivator of transcription (Tat), in the central nervous system (CNS). Given the need for novel adjunctive therapies for HAND, we hypothesized that ibudilast would inhibit Tat-induced excess production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) in microglial cells. Ibudilast is a non-selective cyclic AMP phosphodiesterase inhibitor that has recently shown promise as a treatment for neuropathic pain via its ability to attenuate glial cell activation. Accordingly, here we demonstrate that pre-treatment of both human and mouse microglial cells with increasing doses of ibudilast inhibited Tat-induced synthesis of TNFα by microglial cells in a manner dependent on serine/threonine protein phosphatase activity. Ibudilast had no effect on Tat-induced p38 MAP kinase activation, and blockade of adenosine A2A receptor activation did not reverse ibudilast's inhibition of Tat-induced TNFα production. Interestingly, ibudilast reduced Tat-mediated transcription of TNFα, via modulation of nuclear factor-kappa B (NF-κB) signaling, as shown by transcriptional activity of NF-κB and analysis of inhibitor of kappa B alpha (IκBα) stability. Together, our findings shed light on the mechanism of ibudilast's inhibition of Tat-induced TNFα production in microglial cells and may implicate ibudilast as a potential novel adjunctive therapy for the management of HAND

Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases

Nuclear Factor-Kappa B Family Member RelB Inhibits Human Immunodeficiency Virus-1 Tat-Induced Tumor Necrosis Factor-Alpha Production

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat). Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-κB) family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFα) production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFα synthesis in a manner that involved transcriptional repression of the TNFα promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFα promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFα cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFα production. Moreover, because Tat activates both RelB and TNFα in microglia, and because Tat induces inflammatory TNFα synthesis via NF-κB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-κB activation. These findings identify a novel regulatory pathway for controlling HIV-induced microglial activation and cytokine production that may have important therapeutic implications for the management of HAND

Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis

The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits

Rab11 and Actin Cytoskeleton Participate in Giardia lamblia Encystation, Guiding the Specific Vesicles to the Cyst Wall

The encystation process is crucial for survival and transmission of Giardia lamblia to new hosts. During this process, vesicular trafficking and the cytoskeleton play important roles. In eukaryotic cells, intracellular transport is regulated by proteins, including Rab-GTPases and SNAREs, which regulate vesicle formation along with recognition of and binding to the target membrane. Cytoskeletal structures are also involved in these processes. In this study, we demonstrate the participation of Rab11 in the transport of encystation-specific vesicles (ESVs). Additionally, we demonstrate that disruption of actin microfilaments affects ESVs transport. The modification of actin dynamics was also correlated with a reduction in rab11 and cwp1 expression. Furthermore, down-regulation of rab11 mRNA by a specific hammerhead ribozyme caused nonspecific localization of CWP1. We thus provide new information about the molecular machinery that regulates Giardia lamblia encystation. Given our findings, Rab11 and actin may be useful targets to block Giardia encystation

The potential utility of B cell-directed biologic therapy in autoimmune diseases

Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV- and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm2; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p < 0.05-0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p < 0.01-0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04-p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration