The Length of an SLE - Monte Carlo Studies

The scaling limits of a variety of critical two-dimensional lattice models are equal to the Schramm-Loewner evolution (SLE) for a suitable value of the parameter kappa. These lattice models have a natural parametrization of their random curves given by the length of the curve. This parametrization (with suitable scaling) should provide a natural parametrization for the curves in the scaling limit. We conjecture that this parametrization is also given by a type of fractal variation along the curve, and present Monte Carlo simulations to support this conjecture. Then we show by simulations that if this fractal variation is used to parametrize the SLE, then the parametrized curves have the same distribution as the curves in the scaling limit of the lattice models with their natural parametrization.Comment: 18 pages, 10 figures. Version 2 replaced the use of "nu" for the "growth exponent" by 1/d_H, where d_H is the Hausdorff dimension. Various minor errors were also correcte

The replicative lifespan-extending deletion of SGF73 results in altered ribosomal gene expression in yeast.

Sgf73, a core component of SAGA, is the yeast orthologue of ataxin-7, which undergoes CAG-polyglutamine repeat expansion leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73-mediated RLS extension, we performed ChIP-Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)-encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5' regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73-occupied, RLS-linked RP genes displayed significantly reduced expression in sgf73Δ mutants, and double null strains lacking SGF73 and a Sgf73-regulated, RLS-linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration

Improving Communication between Doctors and Parents after Newborn Screening

Background: Newborn screening (NBS) enables early treatment, and some consider it a natural vehicle for genetic screening. Bioethicists argue for caution since families of infants with carrier status can develop psychosocial complications. This paper describes the methods and feasibility of Wisconsin’s statewide project for quality improvement of communication and psychosocial outcomes after NBS. Methods: When NBS identifies carrier status for cystic fibrosis or sickle cell, we contact primary care providers (PCPs), answer questions, and invite them to rehearse informing the parents. Three months later, we telephone the parents, assess knowledge and psychosocial outcomes, provide counseling, and assist with self-referral to further resources. Afterward, evaluation surveys are provided to the parents, to be returned anonymously. Results: Birthing facilities provided accurate PCP names for 73% of 817 infants meeting inclusion criteria; we identified PCPs for 21% more. We reached 47.3% of PCPs in time to invite a rehearsal; 60% of these accepted. We successfully called 50.2% of eligible parents; 61% recalled a PCP explanation, and 48.5% evaluated the explanation favorably. Evaluations by parents with limited health literacy were less favorable. Conclusion: It is feasible to follow parents for psychosocial outcomes after NBS. Preliminary data about communication is mixed, but further data will describe psychosocial outcomes and investigate outcomes’ associations with communication

Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis

Background: Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. Methodology/Principal findings: The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. Conclusions/Significance: The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis

The Shifting Origins of International Law

Both state-centrism and Euro-centrism are under challenge in international law today and this double challenge, this work argues, is being fruitfully mirrored back into the study of the history of international law. It examines, in the first section, the effects of the rise of positivism as a method of norm-identification and the role of methodological nationalism over the study of the history of international law in the modern foundational period of international law. This is extended by an examination of how this bequeathed a double exclusionary bias regarding time and space to the study of the history of international law as well as a reiterative focus on a series of canonical events and authors to the exclusion of others such as those related to the Islamic history of international law. In the second section, the analysis turns to address why this state of historiographical affairs is changing, specifically highlighting intra-disciplinary developments within the field of the history of international law and the effects that the “international turn in the writing of history” is having on the writing of a new history of international law for a global age. The conclusion reflects on some of the tasks ahead by providing a series of historiographical signposts for the history of international law as a field of new research

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Galaxy And Mass Assembly (GAMA): galaxy colour gradients versus colour, structure, and luminosity

Using single-component fits to SDSS/UKIDSS images of galaxies in the G09 region of the GAMA survey we study radial colour gradients across the galaxy population. We use the multi-wavelength information provided by MegaMorph analysis of galaxy light profiles to calculate intrinsic colour gradients, and divide into six subsamples split by overall Sérsic index (n) and galaxy colour. We find a bimodality in the colour gradients of high- and low-n galaxies in all wavebands which varies with overall galaxy luminosity. Global trends in colour gradients therefore result from combining the contrasting behaviour of a number of different galaxy populations. The ubiquity of strong negative colour gradients supports the picture of inside-out growth through gas accretion for blue, low-n galaxies, and through dry minor mergers for red, high-n galaxies. An exception is the blue high-n population which has properties indicative of dissipative major mergers

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa\u27s effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered

A Direct Interaction of Axonin-1 with NgCAM-related Cell Adhesion Molecule (NrCAM) Results in Guidance, but not Growth of Commissural Axons

An interaction of growth cone axonin-1 with the floor-plate NgCAM-related cell adhesion molecule (NrCAM) was shown to play a crucial role in commissural axon guidance across the midline of the spinal cord. We now provide evidence that axonin-1 mediates a guidance signal without promoting axon elongation. In an in vitro assay, commissural axons grew preferentially on stripes coated with a mixture of NrCAM and NgCAM. This preference was abolished in the presence of anti–axonin-1 antibodies without a decrease in neurite length. Consistent with these findings, commissural axons in vivo only fail to extend along the longitudinal axis when both NrCAM and NgCAM interactions, but not when axonin-1 and NrCAM or axonin-1 and NgCAM interactions, are perturbed. Thus, we conclude that axonin-1 is involved in guidance of commissural axons without promoting their growth