Discrete Physics and the Dirac Equation

We rewrite the 1+1 Dirac equation in light cone coordinates in two significant forms, and solve them exactly using the classical calculus of finite differences. The complex form yields ``Feynman's Checkerboard''---a weighted sum over lattice paths. The rational, real form can also be interpreted in terms of bit-strings.Comment: LaTex 16 pages, 10 figures. To obtain a copy, send e-mail to [email protected]

Donor Heart Allocation

The limited number of donor hearts is one of the greatest and persistent challenges to heart transplantation. Allocation of this precious resource requires the integration of objective data, clinical intuition, and moral fairness. Institution of an allocation system by UNOS has provided important structure to the allocation methodology. The system must be periodically reviewed and reorganized to ensure it is reflective of current patient disease and clinical practice and builds upon the previous knowledge paradigms. Since the establishment of the 2006 allocation system, not only has there been a dramatic increase in the number of heart transplant candidates, but also a dramatic increase in the number of patients qualifying as high-priority candidates. To address these changes, UNOS Thoracic Organ Transplantation Committee was tasked with providing a revised allocation system. The resulting system aims to improve waitlist mortality and post-transplant outcomes by better prioritizing the highest acuity patients while improving the geographic distribution of organ offers

Globalisation, adjustment and the structural transformation of African economies?: the role of international financial institutions

Under the auspices of the World Bank and IMF, for almost two decades, sub-Saharan African countries have implemented structural adjustment, an orthodox package of economic reform measures. During this period there has been an unprecedented proliferation of technology investment and trade in the world economy. However sub-Saharan Africa has performed poorly under adjustment and has been largely marginalized from the international economy. The paper investigates the problems with the theoretical model underlying structural adjustment policies to explain why the model is not conducive to either African development or Africa’s increasing participation in the global economy. An example is used to illustrate the existence of an alternative set of policies that may be better suited for Africa

Level and Eigenfunction Statistics in Billiards with Surface Scattering

Statistical properties of billiards with diffusive boundary scattering are investigated by means of the supersymmetric sigma-model in a formulation appropriate for chaotic ballistic systems. We study level statistics, parametric level statistics, and properties of electron wavefunctions. In the universal regime, our results reproduce conclusions of the random matrix theory, while beyond this regime we obtain a variety of system-specific results determined by the classical dynamics in the billiard. Most notably, we find that level correlations do not vanish at arbitrary separation between energy levels, or if measured at arbitrarily large difference of magnetic fields. Saturation of the level number variance indicates strong rigidity of the spectrum. To study spatial correlations of wavefunction amplitudes, we reanalyze and refine derivation of the ballistic version of the sigma-model. This allows us to obtain a proper matching of universal short-scale correlations with system-specific ones.Comment: 19 pages, 5 figures included. Minor corrections, references adde

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia. Cell Rep 2018 Mar 6; 22(10):2667-2676

The Impact of Spatial Incongruence on an Auditory-Visual Illusion

The sound-induced flash illusion is an auditory-visual illusion--when a single flash is presented along with two or more beeps, observers report seeing two or more flashes. Previous research has shown that the illusion gradually disappears as the temporal delay between auditory and visual stimuli increases, suggesting that the illusion is consistent with existing temporal rules of neural activation in the superior colliculus to multisensory stimuli. However little is known about the effect of spatial incongruence, and whether the illusion follows the corresponding spatial rule. If the illusion occurs less strongly when auditory and visual stimuli are separated, then integrative processes supporting the illusion must be strongly dependant on spatial congruence. In this case, the illusion would be consistent with both the spatial and temporal rules describing response properties of multisensory neurons in the superior colliculus.status: publishe

Genome-Wide Analysis of Nucleotide-Level Variation in Commonly Used Saccharomyces cerevisiae Strains

Ten years have passed since the genome of Saccharomyces cerevisiae–more precisely, the S288c strain–was completely sequenced. However, experimental work in yeast is commonly performed using strains that are of unknown genetic relationship to S288c. Here, we characterized the nucleotide-level similarity between S288c and seven commonly used lab strains (A364A, W303, FL100, CEN.PK, ∑1278b, SK1 and BY4716) using 25mer oligonucleotide microarrays that provide complete and redundant coverage of the ∼12 Mb Saccharomyces cerevisiae genome. Using these data, we assessed the frequency and distribution of nucleotide variation in comparison to the sequenced reference genome. These data allow us to infer the relationships between experimentally important strains of yeast and provide insight for experimental designs that are sensitive to sequence variation. We propose a rational approach for near complete sequencing of strains related to the reference using these data and directed re-sequencing. These data and new visualization tools are accessible online in a new resource: the Yeast SNPs Browser (YSB; http://gbrowse.princeton.edu/cgi-bin/gbrowse/yeast_strains_snps) that is available to all researchers

IL1RL1 Gene Variants and Nasopharyngeal IL1RL-a Levels Are Associated with Severe RSV Bronchiolitis: A Multicenter Cohort Study

Targets for intervention are required for respiratory syncytial virus (RSV) bronchiolitis, a common disease during infancy for which no effective treatment exists. Clinical and genetic studies indicate that IL1RL1 plays an important role in the development and exacerbations of asthma. Human IL1RL1 encodes three isoforms, including soluble IL1RL1-a, that can influence IL33 signalling by modifying inflammatory responses to epithelial damage. We hypothesized that IL1RL1 gene variants and soluble IL1RL1-a are associated with severe RSV bronchiolitis.We studied the association between RSV and 3 selected IL1RL1 single-nucleotide polymorphisms rs1921622, rs11685480 or rs1420101 in 81 ventilated and 384 non-ventilated children under 1 year of age hospitalized with primary RSV bronchiolitis in comparison to 930 healthy controls. Severe RSV infection was defined by need for mechanical ventilation. Furthermore, we examined soluble IL1RL1-a concentration in nasopharyngeal aspirates from children hospitalized with primary RSV bronchiolitis. An association between SNP rs1921622 and disease severity was found at the allele and genotype level (p = 0.011 and p = 0.040, respectively). In hospitalized non-ventilated patients, RSV bronchiolitis was not associated with IL1RL1 genotypes. Median concentrations of soluble IL1RL1-a in nasopharyngeal aspirates were >20-fold higher in ventilated infants when compared to non-ventilated infants with RSV (median [and quartiles] 9,357 [936-15,528] pg/ml vs. 405 [112-1,193] pg/ml respectively; p<0.001).We found a genetic link between rs1921622 IL1RL1 polymorphism and disease severity in RSV bronchiolitis. The potential biological role of IL1RL1 in the pathogenesis of severe RSV bronchiolitis was further supported by high local concentrations of IL1RL1 in children with most severe disease. We speculate that IL1RL1a modifies epithelial damage mediated inflammatory responses during RSV bronchiolitis and thus may serve as a novel target for intervention to control disease severity