Determining knot groups by finite quotients

We prove that hyperbolic 2-bridge knots are determined amongst all compact 3-manifolds by the profinite completions of their knot groups.Comment: 8 page

Non-perturbative approach for the time-dependent symmetry breaking

We present a variational method which uses a quartic exponential function as a trial wave-function to describe time-dependent quantum mechanical systems. We introduce a new physical variable $y$ which is appropriate to describe the shape of wave-packet, and calculate the effective action as a function of both the dispersion $\sqrt{}$ and $y$. The effective potential successfully describes the transition of the system from the false vacuum to the true vacuum. The present method well describes the long time evolution of the wave-function of the system after the symmetry breaking, which is shown in comparison with the direct numerical computations of wave-function.Comment: 8 pages, 3 figure

Pansynaptic Enlargement at Adult Cortical Connections Strengthened by Experience

Behavioral experience alters the strength of neuronal connections in adult neocortex. These changes in synaptic strength are thought to be central to experience-dependent plasticity, learning, and memory. However, it is not known how changes in synaptic transmission between neurons become persistent, thereby enabling the storage of previous experience. A long-standing hypothesis is that altered synaptic strength is maintained by structural modifications to synapses. However, the extent of synaptic modifications and the changes in neurotransmission that the modifications support remain unclear. To address these questions, we recorded from pairs of synaptically connected layer 2/3 pyramidal neurons in the barrel cortex and imaged their contacts with high-resolution confocal microscopy after altering sensory experience by whisker trimming. Excitatory connections strengthened by experience exhibited larger axonal varicosities, dendritic spines, and interposed contact zones. Electron microscopy showed that contact zone size was strongly correlated with postsynaptic density area. Therefore, our findings indicate that whole synapses are larger at strengthened connections. Synaptic transmission was both stronger and more reliable following experience-dependent synapse enlargement. Hence, sensory experience modified both presynaptic and postsynaptic function. Our findings suggest that the enlargement of synaptic contacts is an integral part of long-lasting strengthening of cortical connections and, hence, of information storage in the neocorte

Molecular chaperones and neuronal proteostasis.

Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms

Soft case-based reasoning

Author name used in this publication: Simon ShiuVersion of RecordPublishe

Syncytial Hepatitis of Tilapia (Oreochromis niloticus L.) is Associated With Orthomyxovirus-Like Virions in Hepatocytes

Using transmission electron microscopy (TEM), the presented work expands on the ultrastructural findings of an earlier report on “syncytial hepatitis,” a novel disease of tilapia (SHT). Briefly, TEM confirmed the presence of an orthomyxovirus-like virus within the diseased hepatocytes but not within the endothelium. This was supported by observing extracellular and intracellular (mostly intraendosomal), 60–100 nm round virions with a trilaminar capsid containing up to 7 electron-dense aggregates. Other patterns noted included enveloped or filamentous virions and virion-containing cytoplasmic membrane folds, suggestive of endocytosis. Patterns atypical for orthymyxovirus included the formation of syncytia and the presence of virions within the perinuclear cisternae (suspected to be the Golgi apparatus). The ultrastructural morphology of SHT-associated virions is similar to that previously reported for tilapia lake virus (TiLV). A genetic homology was investigated using the available reverse transcriptase polymerase chain reaction (RT-PCR) probes for TiLV and comparing clinically sick with clinically normal fish and negative controls. By RT-PCR analysis, viral nucleic acid was detected only in diseased fish. Taken together, these findings strongly suggest that a virus is causally associated with SHT, that this virus shares ultrastructural features with orthomyxoviruses, and it presents with partial genetic homology with TiLV (190 nucleotides). </jats:p

In vivo targeted DamID identifies CHD8 genomic targets in fetal mouse brain.

Funder: Royal SocietyFunder: Agouron InstituteGenetic studies of autism have revealed causal roles for chromatin remodeling gene mutations. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeler with significant de novo mutation rates in sporadic autism. However, relationships between CHD8 genomic function and autism-relevant biology remain poorly elucidated. Published studies utilizing ChIP-seq to map CHD8 protein-DNA interactions have high variability, consistent with technical challenges and limitations associated with this method. Thus, complementary approaches are needed to establish CHD8 genomic targets and regulatory functions in developing brain. We used in utero CHD8 Targeted DamID followed by sequencing (TaDa-seq) to characterize CHD8 binding in embryonic mouse cortex. CHD8 TaDa-seq reproduced interaction patterns observed from ChIP-seq and further highlighted CHD8 distal interactions associated with neuronal loci. This study establishes TaDa-seq as a useful alternative for mapping protein-DNA interactions in vivo and provides insights into the regulatory targets of CHD8 and autism-relevant pathophysiology associated with CHD8 mutations

Developing a catalogue of explainability methods to support expert and non-expert users.

Organisations face growing legal requirements and ethical responsibilities to ensure that decisions made by their intelligent systems are explainable. However, provisioning of an explanation is often application dependent, causing an extended design phase and delayed deployment. In this paper we present an explainability framework formed of a catalogue of explanation methods, allowing integration to a range of projects within a telecommunications organisation. These methods are split into low-level explanations, high-level explanations and co-created explanations. We motivate and evaluate this framework using the specific case-study of explaining the conclusions of field engineering experts to non-technical planning staff. Feedback from an iterative co-creation process and a qualitative evaluation is indicative that this is a valuable development tool for use in future company projects