26,544 research outputs found
Measurement-device-independent quantum key distribution with ensemble-based memories
Quantum memories are enabling devices for extending the reach of quantum key distribution (QKD) systems. The required specifications for memories are, however, often considered too demanding for available technologies. One can change this mindset by introducing memory-assisted measurement-device-independent QKD (MDI-QKD), which imposes less stringent conditions on the memory modules. It has been shown that, in the case of fast single-qubit memories, we can reach rates and distances not attainable by single no-memory QKD links. Single-qubit memories, such as single atoms or ions, have, currently, too slow of an access time to offer an advantage in practice. Here, we relax that assumption, and consider ensemble-based memories, which satisfy the main two requirements of having short access times and large storage-bandwidth products. Our results, however, suggest that the multiple-excitation effects in such memories can be so detrimental that they may wash away the scaling improvement offered by memory-equipped systems. We then propose an alternative setup that can in principle remedy the above problem. As a prelude to our main problem, we also obtain secret key generation rates for MDI-QKD systems that rely on imperfect single-photon sources with nonzero probabilities of emitting two photons
Questioning flecainide's mechanism of action in the treatment of catecholaminergic polymorphic ventricular tachycardia
Differential peripheral B cell phenotype in patients with primary Sjögren’s syndrome (pSS) compared to secondary Sjögren’s syndrome associated with systemic lupus erythematosus (SS/SLE)
Introduction: Peripheral B-cell abnormalities, a feature of both systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS), are implicated in the pathogenesis of both diseases and correlate with disease activity. This study aims to investigate how the defective B-cell phenotype in pSS patients compares to patients with SS and SLE (SS/SLE), and whether abnormalities in B-cell phenotype could be related to differential B-cell lipid-raft expression and B-cell activating factor (BAFF) receptor function in patients with pSS and SLE and secondary SS (SS/SLE). Methods: Blood samples and clinical and laboratory parameters from 32 patients with pSS and SS/SLE and 13 age/sex matched HC were obtained. We used flow-cytometry to perform B-cell immunophenotyping and analysed lipid-raft expression (marker of B-cell activation). In vitro cultures were also used to assess lipid-raft expression in response to BAFF. Results: Patients with SS/SLE had a significantly decreased Bm1 and Bm5 and increased Bm2 populations compared to HC (p=0.031, p=0.035 and p=0.01, respectively), and increased Bm2 compared to pSS (p=0.027). Bm1-cells were decreased in both pSS and SS/SLE patients compared to HC (p=0.028 and p= 0.031, respectively). Both age and disease duration correlated strongly with Bm2’ cells in SS/SLE patients (r=0.9572, p= 0.0428), and the immunosuppressive treatment correlated negatively with the number of circulating Bm2 and Bm2’ cell in pSS (r = -0.54, p=0.01 and r = -0.56, p=0.008, respectively). B-cells from patients with pSS had a significant increase in lipid-raft expression compared to HC (p=0.01) and patients with SS/SLE (p<0.05). Lipid-raft levels correlated with BAFF-receptor expression in HC and SS/SLE B-cells (p=0.17, r=0.694) but not in pSS patients. Both disease activity score (ESSDAI) and IgG level correlated positively with lipid rafts expression in B cells from patients with pSS (r = 0.79, p=0.004 and r =0.53, p=0.04, respectively). Conclusion: Patients with SS/SLE had more significant B-cell abnormalities compared to HC and pSS, detectable even in a small number of patients. Also the relationship between lipid-raft and BAFF-receptor expression was altered between pSS and SS/SLE patients, and correlated with the disease activity and IgG levels in pSS group, suggesting that therapies targeting BAFF might be particularly successful in the SS/SLE sub-group of patients
Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape
A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular ‘arms races.’ Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2’-5’-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted to circumvent viral-encoded inhibitors
REDD+ on the rocks? Conflict over forest and politics of justice in Vietnam
In Vietnam, villagers involved in a REDD+ (reduced emissions from deforestation and forest degradation) pilot protect areas with rocks which have barely a tree on them. The apparent paradox indicates how actual practices differ from general ideas about REDD+ due to ongoing conflict over forest, and how contestations over the meaning of justice are a core element in negotiations over REDD+. We explore these politics of justice by examining how the actors involved in the REDD+ pilot negotiate the particular subjects, dimensions, and authority of justice considered relevant, and show how politics of justice are implicit to practical decisions in project implementation. Contestations over the meaning of justice are an important element in the practices and processes constituting REDD+ at global, national and local levels, challenging uniform definitions of forest justice and how forests ought to be managed
Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.
The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit
Resting state connectivity of the human habenula at ultra-high field
The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network
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