50 research outputs found
Quantum Gravity Witness via Entanglement of Masses: Casimir Screening
A recently proposed experimental protocol for Quantum Gravity induced
Entanglement of Masses (QGEM) requires in principle realizable, but still very
ambitious, set of parameters in matter-wave interferometry. Motivated by easing
the experimental realization, in this paper, we consider the parameter space
allowed by a slightly modified experimental design, which mitigates the Casimir
potential between two spherical neutral test-masses by separating the two
macroscopic interferometers by a thin conducting plate. Although this set-up
will reintroduce a Casimir potential between the conducting plate and the
masses, there are several advantages of this design. First, the quantum gravity
induced entanglement between the two superposed masses will have no Casimir
background. Secondly, the matter-wave interferometry itself will be greatly
facilitated by allowing both the mass kg and the
superposition size m to be a one-two order of magnitude
smaller than those proposed earlier, and thereby also two orders of magnitude
smaller magnetic field gradient of Tm to create that superposition
through the Stern-Gerlach effect. In this context, we will further investigate
the collisional decoherences and decoherence due to vibrational modes of the
conducting plate.Comment: 13 Pages, 6 Figure
Relative acceleration noise mitigation for nanocrystal matter-wave interferometry: Applications to entangling masses via quantum gravity
Matter-wave interferometers with large momentum transfers, irrespective of specific implementations, will face a universal dephasing due to relative accelerations between the interferometric mass and the associated apparatus. Here we propose a solution that works even without actively tracking the relative accelerations: putting both the interfering mass and its associated apparatus in a freely falling capsule, so that the strongest inertial noise components vanish due to the equivalence principle. In this setting, we investigate two of the most important remaining noise sources: (a) the noninertial jitter of the experimental setup and (b) the gravity-gradient noise. We show that the former can be reduced below desired values by appropriate pressures and temperatures, while the latter can be fully mitigated in a controlled environment. We finally apply the analysis to a recent proposal for testing the quantum nature of gravity [S. Bose et al., Phys. Rev. Lett. 119, 240401 (2017)] through the entanglement of two masses undergoing interferometry. We show that the relevant entanglement witnessing is feasible with achievable levels of relative acceleration noise
Promiscuous recognition of MR1 drives self-reactive mucosal-associated invariant T cell responses
Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA
Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents
Biogeography of Southern Ocean prokaryotes: a comparison of the Indian and Pacific sectors
18 pages, 5 figures.-- This is an open access article under the terms of the Creative Commons Attribution LicenseWe investigated the Southern Ocean (SO) prokaryote community structure via zero-radius operational taxonomic unit (zOTU) libraries generated from 16S rRNA gene sequencing of 223 full water column profiles. Samples reveal the prokaryote diversity trend between discrete water masses across multiple depths and latitudes in Indian (71–99°E, summer) and Pacific (170–174°W, autumn-winter) sectors of the SO. At higher taxonomic levels (phylum-family) we observed water masses to harbour distinct communities across both sectors, but observed sectorial variations at lower taxonomic levels (genus-zOTU) and relative abundance shifts for key taxa such as Flavobacteria, SAR324/Marinimicrobia, Nitrosopumilus and Nitrosopelagicus at both epi- and bathy-abyssopelagic water masses. Common surface bacteria were abundant in several deep-water masses and vice-versa suggesting connectivity between surface and deep-water microbial assemblages. Bacteria from same-sector Antarctic Bottom Water samples showed patchy, high beta-diversity which did not correlate well with measured environmental parameters or geographical distance. Unconventional depth distribution patterns were observed for key archaeal groups: Crenarchaeota was found across all depths in the water column and persistent high relative abundances of common epipelagic archaeon Nitrosopelagicus was observed in deep-water masses. Our findings reveal substantial regional variability of SO prokaryote assemblages that we argue should be considered in wide-scale SO ecosystem microbial modellingThis work was funded by a CSIRO Office of the Chief Executive Science Leader Fellowship (R-04202) to L.B. as well as the Antarctic Science International Bursary 2017 to S.L.S.S.Peer reviewe
Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit/hyperactivity disorder: study protocol for a randomized controlled trial
Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day– night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD. Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up. This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.The trial is funded by the EU Framework Programme for Research and
Innovation, Horizon 2020 (Project no. 667302). Funding period: January
2016–December 2020. This funding source had no role in the design of this
study and will not have any role during its execution, analyses, interpretation
of the data, or decision to submit results.
Some local funds additionally contributed to carry out this study, especially for
the preparation of the interventions: FBO research activity is by the Spanish
Ministry of Economy and Competitiveness – MINECO (RYC-2011-09011) and by
the University of Granada, Plan Propio de Investigación 2016, Excellence actions:
Unit of Excellence on Exercise and Health (UCEES)
Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients
Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences
The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported
by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on
18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based
researchers who signed it in the short time span from 20 September to 6 October 2016
Coupling of Protonation, Reduction, and Conformational Change in azurin from Pseudomonas aeruginosa Investigated with Free Energy Measures of Cooperativity
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference