Cell-Free DNA and Active Rejection in Kidney Allografts

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P1% indicate a probability of active rejection

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Member of ION and AIG, Associate Fellow Member of RIN and a Senior Member of the IEEE, Com Soc, and

privately held company for developing Global Navigation Software, and Web Solutions (Giftet) in Pomona, California. He was also an Associate Professor with th

Maximum-likelihood GPS parameter estimation

ABSTRACT: Recently we proposed an acquisition process for a maximum-likelihood GPS receiver that considers the joint processing of all GPS satellite waveforms. The resulting estimator was shown to provide an elegant solution to the near -far problem and to perform better than the suboptimal sliding-correlator estimator. However, the proposed acquisition model included only the code search, which estimates just the time of arrival (TOA) between a GPS satellite and a maximum-likelihood GPS receiver. In this paper we enhance the acquisition process by including the estimation of Doppler along with the estimation of the TOA, which results in a two-dimensional Doppler and code search. A maximum-likelihood GPS receiver would require only one front-end hardware section for processing all GPS signals in view, thus simplifying the entire architecture of a GPS receiver. An assessment based on theoretical performance and simulation results indicates that a maximum-likelihood GPS receiver can achieve an order-of-magnitude performance improvement relative to a sliding-correlator GPS receiver. Simulation data will be validated in the near future using GPS acquisition data from the Novatel ProPack AG-G2ϩDB9-RT2 , and the results of this work will be presented in a future publication

A Solution to the Recursive Generalized Eigenvalue Problem

Dr. Matthew Bromberg is an independent consultant. For the last 6 years Dr. Bromberg has been involved in the research and development of array processing algorithms for reuse enhancement for wireless communication systems and for interference mitigation for both commercial and military applications while he was at Radix Technologies. Dr. Bromberg was a key inventor of the technology that led to the formation and funding of Beam Reach Networks and the formation of Protean Radio Networks. He has authored several papers and patents in this area. Abstract Previously, we have discussed a recursive solution to the vector normal equation utilizing the recursive Cholesky and Modified Gram-Schmidt Orthogonalization (MGSO) algorithms. Previously, we have also discussed a blind adaptive approach for detection and extraction of signals of interest in the presence of noise and interference without relying on preamble or training sequences. The heart of the blind adaptive algorithm is based upon solving the recursive generalized eigenvalue problem, the solution of which is discussed in this paper based on the recursive Cholesky or QR factors and the Householder and QL algorithm with implicit shifts. Even though, the solution to the recursive generalized eigenvalue problem is slightly more efficient than the solution to the direct generalized eigenvalue when all the eigenvalues and eigenvectors are required, the improvement is more noticeable when only one eigenvalue and the corresponding eigenvector are required. Therefore, the solution that is proposed here serves well for recursive generalized eigenvalue problems that require only one eigenvalue and the corresponding eigenvector