Ultracold polar molecules as qudits Sawant, Rahul; Blackmore, Jacob A; Gregory, Philip D ...
New journal of physics,
01/2020, Volume:
22, Issue:
1
Journal Article
Peer reviewed
Open access
We discuss how the internal structure of ultracold molecules, trapped in the motional ground state of optical tweezers, can be used to implement qudits. We explore the rotational, fine and hyperfine ...structure of 40Ca19F and 87Rb133Cs, which are examples of molecules with 2 and 1 electronic ground states, respectively. In each case we identify a subset of levels within a single rotational manifold suitable to implement a four-level qudit. Quantum gates can be implemented using two-photon microwave transitions via levels in a neighboring rotational manifold. We discuss limitations to the usefulness of molecular qudits, arising from off-resonant excitation and decoherence. As an example, we present a protocol for using a molecular qudit of dimension d = 4 to perform the Deutsch algorithm.
Understanding and controlling collisions is crucial to the burgeoning field of ultracold molecules. All experiments so far have observed fast loss of molecules from the trap. However, the dominant ...mechanism for collisional loss is not well understood when there are no allowed 2-body loss processes. Here we experimentally investigate collisional losses of nonreactive ultracold
Rb
Cs molecules, and compare our findings with the sticky collision hypothesis that pairs of molecules form long-lived collision complexes. We demonstrate that loss of molecules occupying their rotational and hyperfine ground state is best described by second-order rate equations, consistent with the expectation for complex-mediated collisions, but that the rate is lower than the limit of universal loss. The loss is insensitive to magnetic field but increases for excited rotational states. We demonstrate that dipolar effects lead to significantly faster loss for an incoherent mixture of rotational states.
The development of the mammalian cerebral cortex depends on careful orchestration of proliferation, maturation, and migration events, ultimately giving rise to a wide variety of neuronal and ...non-neuronal cell types. To better understand cellular and molecular processes that unfold during late corticogenesis, we perform single-cell RNA-seq on the mouse cerebral cortex at a progenitor driven phase (embryonic day 14.5) and at birth-after neurons from all six cortical layers are born. We identify numerous classes of neurons, progenitors, and glia, their proliferative, migratory, and activation states, and their relatedness within and across age. Using the cell-type-specific expression patterns of genes mutated in neurological and psychiatric diseases, we identify putative disease subtypes that associate with clinical phenotypes. Our study reveals the cellular template of a complex neurodevelopmental process, and provides a window into the cellular origins of brain diseases.
Gene Length Matters in Neurons Zylka, Mark J.; Simon, Jeremy M.; Philpot, Benjamin D.
Neuron (Cambridge, Mass.),
04/2015, Volume:
86, Issue:
2
Journal Article
Peer reviewed
Open access
A recent study by Gabel et al. (2015) found that Mecp2, the gene mutated in Rett syndrome, represses long (> 100 kb) genes associated with neuronal physiology and connectivity by binding to ...methylated CA sites in DNA. This study adds to a growing body of literature implicating gene length and transcriptional mechanisms in neurodevelopmental and neurodegenerative disorders.
A recent study by Gabel et al. (2015) found that Mecp2, the gene mutated in Rett syndrome, represses long (> 100 kb) genes associated with neuronal physiology and connectivity by binding to methylated CA sites in DNA. This study adds to a growing body of literature implicating gene length and transcriptional mechanisms in neurodevelopmental and neurodegenerative disorders.
Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5- CD11c+ cells (DN2) representing ...pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased Toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7. DN2 cells shared with activated naive cells (aNAV), phenotypic and functional features, and similar transcriptomes. Their PC differentiation and autoantibody production was driven by TLR7 in an interleukin-21 (IL-21)-mediated fashion. An in vivo developmental link between aNAV, DN2 cells, and PC was demonstrated by clonal sharing. This study defines a distinct differentiation fate of autoreactive naive B cells into PC precursors with hyper-responsiveness to innate stimuli, as well as establishes prominence of extra-follicular B cell activation in SLE, and identifies therapeutic targets.
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•Autoreactive CD27- IgD- CXCR5- CD11c+ (DN2) B cells expand in lupus patients•DN2 cells derive from naive cells and are poised to generate plasmablasts•DN2 B cells are hyper-responsive to Toll-like receptor-7 signaling•The properties of SLE DN2 B cells stem from distinct transcriptional networks
The role of extrafollicular B cells in human systemic lupus is unknown. Jenks et al. define the main components of this pathway and its prominence in severe disease. Its activation is mediated by hyper-responsiveness to Toll-like receptor-7 and leads to the generation of autoreactive antibody-secreting plasmablasts.
Appropriate axonal growth and connectivity are essential for functional wiring of the brain. Joubert syndrome-related disorders (JSRD), a group of ciliopathies in which mutations disrupt primary ...cilia function, are characterized by axonal tract malformations. However, little is known about how cilia-driven signaling regulates axonal growth and connectivity. We demonstrate that the deletion of related JSRD genes, Arl13b and Inpp5e, in projection neurons leads to de-fasciculated and misoriented axonal tracts. Arl13b deletion disrupts the function of its downstream effector, Inpp5e, and deregulates ciliary-PI3K/AKT signaling. Chemogenetic activation of ciliary GPCR signaling and cilia-specific optogenetic modulation of downstream second messenger cascades (PI3K, AKT, and AC3) commonly regulated by ciliary signaling receptors induce rapid changes in axonal dynamics. Further, Arl13b deletion leads to changes in transcriptional landscape associated with dysregulated PI3K/AKT signaling. These data suggest that ciliary signaling acts to modulate axonal connectivity and that impaired primary cilia signaling underlies axonal tract defects in JSRD.
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•Chemogenetic and/or optogenetic activation of primary cilia alters axonal behavior•Ciliary activity modulates axonal growth cones and filopodial-lamellipodial balance•Arl13b-Inpp5e activity in cilia facilitates axonal tract formation and targeting•Disrupted ciliary signaling contributes to axonal tract malformations in JSRD
Guo et al. show that primary cilia-driven signaling regulates growth cone dynamics and axonal tract development. Ciliary signaling receptor activation and associated changes in signaling cascades (PI3K, AKT, and AC3) and transcriptional landscape affect axons. Disrupted ciliary signaling following mutations in Arl13b or Inpp5e leads to axonal tract malformations in JSRD.
A proposal for new diagnostic criteria for ALS Shefner, Jeremy M.; Al-Chalabi, Ammar; Baker, Mark R. ...
Clinical neurophysiology,
August 2020, 2020-08-00, 20200801, Volume:
131, Issue:
8
Journal Article
There is little systematic operational guidance about how best to develop complex interventions to reduce the gap between practice and evidence. This article is one in a Series of articles ...documenting the development and use of the Theoretical Domains Framework (TDF) to advance the science of implementation research.
The intervention was developed considering three main components: theory, evidence, and practical issues. We used a four-step approach, consisting of guiding questions, to direct the choice of the most appropriate components of an implementation intervention: Who needs to do what, differently? Using a theoretical framework, which barriers and enablers need to be addressed? Which intervention components (behaviour change techniques and mode(s) of delivery) could overcome the modifiable barriers and enhance the enablers? And how can behaviour change be measured and understood?
A complex implementation intervention was designed that aimed to improve acute low back pain management in primary care. We used the TDF to identify the barriers and enablers to the uptake of evidence into practice and to guide the choice of intervention components. These components were then combined into a cohesive intervention. The intervention was delivered via two facilitated interactive small group workshops. We also produced a DVD to distribute to all participants in the intervention group. We chose outcome measures in order to assess the mediating mechanisms of behaviour change.
We have illustrated a four-step systematic method for developing an intervention designed to change clinical practice based on a theoretical framework. The method of development provides a systematic framework that could be used by others developing complex implementation interventions. While this framework should be iteratively adjusted and refined to suit other contexts and settings, we believe that the four-step process should be maintained as the primary framework to guide researchers through a comprehensive intervention development process.
Peripheral nerve injury induces long-term pro-inflammatory responses in spinal cord glial cells that facilitate neuropathic pain, but the identity of endogenous cells that resolve spinal inflammation ...has not been determined. Guided by single-cell RNA sequencing (scRNA-seq), we found that MRC1+ spinal cord macrophages proliferated and upregulated the anti-inflammatory mediator Cd163 in mice following superficial injury (SI; nerve intact), but this response was blunted in nerve-injured animals. Depleting spinal macrophages in SI animals promoted microgliosis and caused mechanical hypersensitivity to persist. Conversely, expressing Cd163 in spinal macrophages increased Interleukin 10 expression, attenuated micro- and astrogliosis, and enduringly alleviated mechanical and thermal hypersensitivity in nerve-injured animals. Our data indicate that MRC1+ spinal macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following a superficial injury. Moreover, we show that spinal macrophages from nerve-injured animals mount a dampened anti-inflammatory response but can be therapeutically coaxed to promote long-lasting recovery of neuropathic pain.
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•Single-cell RNA-seq of spinal cord in mouse neuropathic pain model•Anti-inflammatory spinal macrophage responses are blunted following nerve injury•Spinal macrophages suppress microgliosis and pain hypersensitivity•CD163 promotes resolution of neuroinflammation and hypersensitivity
Peripheral nerve injury causes inflammation in the spinal cord and neuropathic pain. Guided by single-cell RNA-seq, Niehaus et al. identify a class of spinal macrophages that can be therapeutically coaxed to resolve microgliosis and promote long-lasting recovery of neuropathic pain.
Interrupted time series (ITS) designs are frequently used in public health to examine whether an intervention or exposure has influenced health outcomes. Few reviews have been undertaken to examine ...the design characteristics, statistical methods, and completeness of reporting of published ITS studies.
We used stratified random sampling to identify 200 ITS studies that evaluated public health interventions or exposures from PubMed (2013–2017). Study characteristics, details of statistical models and estimation methods used, effect metrics, and parameter estimates were extracted. From the 200 studies, 230 time series were examined.
Common statistical methods used were linear regression (31%, 72/230) and autoregressive integrated moving average (19%, 43/230). In 17% (40/230) of the series, we could not determine the statistical method used. Autocorrelation was acknowledged in 63% (145/230) of the series. An estimate of the autocorrelation coefficient was given for only 1% of the series (3/230). Measures of precision were reported for 63% of effect measures (541/852).
Many aspects of the design, methods, analysis, and reporting of ITS studies can be improved, particularly description of the statistical methods and approaches to adjust for and estimate autocorrelation. More guidance on the conduct and reporting of ITS studies is needed to improve this study design.
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