On the Spin Gap Phase of Strongly-Correlated Electrons

We discuss the possible existence of a spin-gap phase in the low-doping regime of strongly-correlated two-dimensional electrons within the gauge field description of the t-J model. The spin-gap phase was recently shown by Ubbens and Lee to be destroyed by gauge field quantum fluctuations for a single-layer 2D system in the absence of disorder and for a full gap. We show that the same conclusion applies both in the dirty limit and for the case of a gapless spinon condensate.Comment: 7 pages, uuencoded Postscript, including 1 figur

Renormalization group analysis of the 2D Hubbard model

Salmhofer [Commun. Math. Phys. 194, 249 (1998)] has recently developed a new renormalization group method for interacting Fermi systems, where the complete flow from the bare action of a microscopic model to the effective low-energy action, as a function of a continuously decreasing infrared cutoff, is given by a differential flow equation which is local in the flow parameter. We apply this approach to the repulsive two-dimensional Hubbard model with nearest and next-nearest neighbor hopping amplitudes. The flow equation for the effective interaction is evaluated numerically on 1-loop level. The effective interactions diverge at a finite energy scale which is exponentially small for small bare interactions. To analyze the nature of the instabilities signalled by the diverging interactions we extend Salmhofers renormalization group for the calculation of susceptibilities. We compute the singlet superconducting susceptibilities for various pairing symmetries and also charge and spin density susceptibilities. Depending on the choice of the model parameters (hopping amplitudes, interaction strength and band-filling) we find commensurate and incommensurate antiferromagnetic instabilities or d-wave superconductivity as leading instability. We present the resulting phase diagram in the vicinity of half-filling and also results for the density dependence of the critical energy scale.Comment: 16 pages, RevTeX, 16 eps figure

Effects of the field modulation on the Hofstadter's spectrum

We study the effect of spatially modulated magnetic fields on the energy spectrum of a two-dimensional (2D) Bloch electron. Taking into account four kinds of modulated fields and using the method of direct diagonalization of the Hamiltonian matrix, we calculate energy spectra with varying system parameters (i.e., the kind of the modulation, the relative strength of the modulated field to the uniform background field, and the period of the modulation) to elucidate that the energy band structure sensitively depends on such parameters: Inclusion of spatially modulated fields into a uniform field leads occurrence of gap opening, gap closing, band crossing, and band broadening, resulting distinctive energy band structure from the Hofstadter's spectrum. We also discuss the effect of the field modulation on the symmetries appeared in the Hofstadter's spectrum in detail.Comment: 7 pages (in two-column), 10 figures (including 2 tables

MoTE-ECC: Energy-Scalable Elliptic Curve Cryptography for Wireless Sensor Networks

Wireless Sensor Networks (WSNs) are susceptible to a wide range of malicious attacks, which has stimulated a body of research on "light-weight" security protocols and cryptographic primitives that are suitable for resource-restricted sensor nodes. In this paper we introduce MoTE-ECC, a highly optimized yet scalable ECC library for Memsic's MICAz motes and other sensor nodes equipped with an 8-bit AVR processor. MoTE-ECC supports scalar multiplication on Montgomery and twisted Edwards curves over Optimal Prime Fields (OPFs) of variable size, e.g. 160, 192, 224, and 256 bits, which allows for various trade-offs between security and execution time (resp. energy consumption). OPFs are a special family of "low-weight" prime fields that, in contrast to the NIST-specified fields, facilitate a parameterized implementation of the modular arithmetic so that one and the same software function can be used for operands of different length. To demonstrate the performance of MoTE-ECC, we take (ephemeral) ECDH key exchange between two nodes as example, which requires each node to execute two scalar multiplications. The first scalar multiplication is performed on a fixed base point (to generate a key pair), whereas the second scalar multiplication gets an arbitrary point as input. Our implementation uses a fixed-base comb method on a twisted Edwards curve for the former and a simple ladder approach on a birationally-equivalent Montgomery curve for the latter. Both scalar multiplications require about 9*10^6 clock cycles in total and occupy only 380 bytes in RAM when the underlying OPF has a length of 160 bits. We also describe our efforts to harden MoTE-ECC against side-channel attacks (e.g. simple power analysis) and introduce a highly regular implementation of the comb method

Modelling Forced Vital Capacity in Idiopathic Pulmonary Fibrosis: Optimising Trial Design

Introduction: Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. Methods: The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. Results: Power to detect a significant treatment differe

Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones

Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue

Background: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples. Methods: Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq. Results: Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified. Conclusions: We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers

Supplementary Material for: Plasma Endothelin-1 and Vascular Endothelial Growth Factor Levels and Their Relationship to Hemodynamics in Idiopathic Pulmonary Fibrosis

<b><i>Background:</i></b> Pulmonary hypertension (PH) is associated with a poor prognosis in idiopathic pulmonary fibrosis (IPF). Endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) are important in both fibrosis and vascular remodeling. <b><i>Objectives:</i></b> We sought to determine the relationship between ET-1 and VEGF levels and hemodynamics in patients with IPF. We hypothesized that higher levels of ET-1 and VEGF would be associated with higher pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR) in patients with IPF. <b><i>Methods:</i></b> We performed a cross-sectional analysis of 52 adults with IPF enrolled in a prospective cohort with available clinical data, platelet-free plasma, and hemodynamics. ET-1 and VEGF levels were measured via immunoassay. The associations of ET-1 and VEGF with PAP and PVR were examined using generalized additive models adjusted for age, gender, race/ethnicity, and forced vital capacity (% predicted). <b><i>Results:</i></b> Sixteen of 52 (30.8%) had PH (mean PAP ≥25 mm Hg). After multivariable adjustment, higher ET-1 levels were significantly associated with higher systolic (p = 0.01), diastolic (p = 0.02), and mean (p = 0.01) PAP and possibly higher PVR (p = 0.09). There were no significant associations between VEGF levels and hemodynamics. <b><i>Conclusions:</i></b> Higher levels of ET-1 were associated with higher PAP and possibly higher PVR in participants with IPF. In a subgroup of patients, ET-1 may be a contributor to pulmonary vascular disease burden in IPF