Photon Bound States in Coupled Waveguides

Photon bound states have been identified as particular solutions to the scattering of two photons from a single emitter, but from these results the full nature of these states remains elusive. We study a novel, clear and unambiguous signature that these bound states are truly bound. To this end we consider a new configuration of close-by waveguides, each chirally coupled to two-level emitters. We show that in this system the photon bound states behave like rigid molecules, where photons do not tunnel individually but rather collectively, such that there is rarely a single photon in each waveguide. We further identify new classes of bound states in this system.Comment: 8 pages, 7 figure

A Bio-Logical Theory of Animal Learning

This article provides the foundation for a new predictive theory of animal learning that is based upon a simple logical model. The knowledge of experimental subjects at a given time is described using logical equations. These logical equations are then used to predict a subject’s response when presented with a known or a previously unknown situation. This new theory suc- cessfully anticipates phenomena that existing theories predict, as well as phenomena that they cannot. It provides a theoretical account for phenomena that are beyond the domain of existing models, such as extinction and the detection of novelty, from which “external inhibition” can be explained. Examples of the methods applied to make predictions are given using previously published results. The present theory proposes a new way to envision the minimal functions of the nervous system, and provides possible new insights into the way that brains ultimately create and use knowledge about the world

Using a Tablet-Based App to Deliver Evidence-Based Practices for Suicidal Patients in the Emergency Department: Pilot Randomized Controlled Trial

BACKGROUND: Emergency departments (EDs) have the potential to provide evidence-based practices for suicide prevention to patients who are acutely suicidal. However, few EDs have adequate time and personnel resources to deliver recommended evidence-based assessment and interventions. To raise the clinical standard of care for patients who are suicidal and seeking psychiatric crisis services in the ED, we developed Jaspr Health, a tablet-based app for direct use by such patients, which enables the delivery of 4 evidence-based practices. OBJECTIVE: This study aims to evaluate the feasibility, acceptability, and effectiveness of Jaspr Health among suicidal adults in EDs. METHODS: Patients who were acutely suicidal and seeking psychiatric crisis services participated in an unblinded pilot randomized controlled trial while in the ED. Participants were randomly assigned to Jaspr Health (n=14) or care as usual (control; n=17) groups. Participants were assessed at baseline, and a 2-hour posttest using self-report measures and a semistructured interview were conducted. RESULTS: Conditions differed significantly at baseline with regard to age but not other demographic variables or baseline measures. On average, participants had been in the ED for 17 hours before enrolling in the study. Over their lifetime, 84% (26/31) of the sample had made a suicide attempt (mean 3.4, SD 6.4) and 61% (19/31) had engaged in nonsuicidal self-injurious behaviors, with an average rate of 8.8 times in the past 3 months. All established feasibility and acceptability criteria were met: no adverse events occurred, participants\u27 app use was high, Jaspr Health app user satisfaction ratings were high, and all participants using Jaspr Health recommended its use for other suicidal ED patients. Comparisons between study conditions provide preliminary support for the effectiveness of the app: participants using Jaspr Health reported a statistically significant increase in receiving 4 evidence-based suicide prevention interventions and overall satisfaction ratings with their ED experience. In addition, significant decreases in distress and agitation, along with significant increases in learning to cope more effectively with current and future suicidal thoughts, were observed among participants using Jaspr Health compared with those receiving care as usual. CONCLUSIONS: Even with limited statistical power, the results showed that Jaspr Health is feasible, acceptable, and clinically effective for use by ED patients who are acutely suicidal and seeking ED-based psychiatric crisis services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03584386; https://clinicaltrials.gov/ct2/show/NCT03584386

Protein Expr Purif

E6 is a small oncoprotein involved in tumorigenesis induced by papillomaviruses (PVs). E6 often recognizes its cellular targets by binding to short motifs presenting the consensus LXXLL. E6 proteins have long resisted structural analysis. We found that bovine papillomavirus type 1 (BPV1) E6 binds the N-terminal LXXLL motif of the cellular protein paxillin with significantly higher affinity as compared to other E6/peptide interactions. Although recombinant BPV1 E6 was poorly soluble in the free state, provision of the paxillin LXXLL peptide during BPV1 E6 biosynthesis greatly enhanced the protein's solubility. Expression of BPV1 E6/LXXLL peptide complexes was carried out in bacteria in the form of triple fusion constructs comprising, from N- to C-terminus, the soluble carrier protein maltose binding protein (MBP), the LXXLL motif and the E6 protein. A TEV protease cleavage site was placed either between MBP and LXXLL motif or between LXXLL motif and E6. These constructs allowed us to produce highly concentrated samples of BPV1 E6, either covalently fused to the C-terminus of the LXXLL motif (intra-molecular complex) or non-covalently bound to it (inter-molecular complex). Heteronuclear NMR measurements were performed and showed that the E6 protein was folded with similar conformations in both covalent and non-covalent complexes. These data open the way to novel structural and functional studies of the BPV1 E6 in complex with its preferential target motif

No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. METHODS: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. RESULTS: No evidence of association of ADHD with either polymorphism in this population was observed. CONCLUSION: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations

Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins

E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses in vertebrates, including cervical cancer in humans. E6 proteins target many host proteins by specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus E6 proteins bound to LxxLL peptides from the focal adhesion protein paxillin and the ubiquitin ligase E6AP, respectively. In both E6 proteins, two zinc domains and a linker helix form a basic-hydrophobic pocket, which captures helical LxxLL motifs in a way compatible with other interaction modes. Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins

Bacterial Flagella: Twist and Stick, or Dodge across the Kingdoms

The flagellum organelle is an intricate multiprotein assembly best known for its rotational propulsion of bacteria. However, recent studies have expanded our knowledge of other functions in pathogenic contexts, particularly adherence and immune modulation, e.g., for Salmonella enterica, Campylobacter jejuni, Pseudomonas aeruginosa, and Escherichia coli. Flagella-mediated adherence is important in host colonisation for several plant and animal pathogens, but the specific interactions that promote flagella binding to such diverse host tissues has remained elusive. Recent work has shown that the organelles act like probes that find favourable surface topologies to initiate binding. An emerging theme is that more general properties, such as ionic charge of repetitive binding epitopes and rotational force, allow interactions with plasma membrane components. At the same time, flagellin monomers are important inducers of plant and animal innate immunity: variation in their recognition impacts the course and outcome of infections in hosts from both kingdoms. Bacteria have evolved different strategies to evade or even promote this specific recognition, with some important differences shown for phytopathogens. These studies have provided a wider appreciation of the functions of bacterial flagella in the context of both plant and animal reservoirs

The Devil is in the Definition - Definitions and their Limited Use in Legal Problem Solving

The lawyer’s usual attempt to catch the meaning of a thing by entangling it in a net of words is based on a common misapprehension of the way words work. The great minds of the ages have since time immemorial reminded us that words do not contain essences, that meanings are social constructs, and that the relation between words and meanings is slippery at best. Definitions presuppose that words have simple meanings attached to them in something like a one-to-one relationship, which is why the law can sometimes be so obtuse. It is the use of the law in a tribunal that provides the eventual understanding of how the law works. Decisions handed down in courts are embedded in a particular time and a particular set of circumstances and are the products of minds informed by a set of social experiences which other lawyers accept as qualifying those particular persons to pronounce on the law. Our legislature would do well when framing legislation to imitate those who drafted the Constitution of the Republic of South Africa, 1996 which is sufficiently specific, without the support of pages of definitions, to lead to very precise argument in the Constitutional Court, and yet sufficiently general to allow the law to develop with the flux of time

The devil is in the definition - definitions and their limited use in legal problem solving

The lawyer’s usual attempt to catch the meaning of a thing by entangling it in a net of words is based on a common misapprehension of the way words work. The great minds of the ages have since time immemorial reminded us that words do not contain essences, that meanings are social constructs, and that the relation between words and meanings is slippery at best. Definitions presuppose that words have simple meanings attached to them in something like a one-to-one relationship, which is why the law can sometimes be so obtuse. It is the use of the law in a tribunal that provides the eventual understanding of how the law works. Decisions handed down in courts are embedded in a particular time and a particular set of circumstances and are the products of minds informed by a set of social experiences which other lawyers accept as qualifying those particular persons to pronounce on the law. Our legislature would do well when framing legislation to imitate those who drafted the Constitution of the Republic of South Africa, 1996 which is sufficiently specific, without the support of pages of definitions, to lead to very precise argument in the Constitutional Court, and yet sufficiently general to allow the law to develop with the flux of time

The Devil is in the Definition – Definitions and their Limited Use in Legal Problem Solving

The lawyer’s usual attempt to catch the meaning of a thing by entangling it in a net of words is based on a common misapprehension of the way words work. The great minds of the ages have since time immemorial reminded us that words do not contain essences, that meanings are social constructs, and that the relation between words and meanings is slippery at best. Definitions presuppose that words have simple meanings attached to them in something like a one-to-one relationship, which is why the law can sometimes be so obtuse. It is the use of the law in a tribunal that provides the eventual understanding of how the law works. Decisions handed down in courts are embedded in a particular time and a particular set of circumstances and are the products of minds informed by a set of social experiences which other lawyers accept as qualifying those particular persons to pronounce on the law. Our legislature would do well when framing legislation to imitate those who drafted the Constitution of the Republic of South Africa, 1996 which is sufficiently specific, without the support of pages of definitions, to lead to very precise argument in the Constitutional Court, and yet sufficiently general to allow the law to develop with the flux of time.KEYWORDS: Definitions in law; essences; positivism; flux; words; meaning