Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

Fully Automatic and Real-Time Catheter Segmentation in X-Ray Fluoroscopy

Augmenting X-ray imaging with 3D roadmap to improve guidance is a common strategy. Such approaches benefit from automated analysis of the X-ray images, such as the automatic detection and tracking of instruments. In this paper, we propose a real-time method to segment the catheter and guidewire in 2D X-ray fluoroscopic sequences. The method is based on deep convolutional neural networks. The network takes as input the current image and the three previous ones, and segments the catheter and guidewire in the current image. Subsequently, a centerline model of the catheter is constructed from the segmented image. A small set of annotated data combined with data augmentation is used to train the network. We trained the method on images from 182 X-ray sequences from 23 different interventions. On a testing set with images of 55 X-ray sequences from 5 other interventions, a median centerline distance error of 0.2 mm and a median tip distance error of 0.9 mm was obtained. The segmentation of the instruments in 2D X-ray sequences is performed in a real-time fully-automatic manner.Comment: Accepted to MICCAI 201

Stimulated superconductivity at strong coupling

Stimulating a system with time dependent sources can enhance instabilities, thus increasing the critical temperature at which the system transitions to interesting low-temperature phases such as superconductivity or superfluidity. After reviewing this phenomenon in non-equilibrium BCS theory (and its marginal fermi liquid generalization) we analyze the effect in holographic superconductors. We exhibit a simple regime in which the transition temperature increases parametrically as we increase the frequency of the time-dependent source.Comment: 19 pages, 2 figure. v3: Comments, references and one figure added. Version to appear in JHE

Optical frequency comb generation from a monolithic microresonator

Optical frequency combs provide equidistant frequency markers in the infrared, visible and ultra-violet and can link an unknown optical frequency to a radio or microwave frequency reference. Since their inception frequency combs have triggered major advances in optical frequency metrology and precision measurements and in applications such as broadband laser-based gas sensing8 and molecular fingerprinting. Early work generated frequency combs by intra-cavity phase modulation while to date frequency combs are generated utilizing the comb-like mode structure of mode-locked lasers, whose repetition rate and carrier envelope phase can be stabilized. Here, we report an entirely novel approach in which equally spaced frequency markers are generated from a continuous wave (CW) pump laser of a known frequency interacting with the modes of a monolithic high-Q microresonator13 via the Kerr nonlinearity. The intrinsically broadband nature of parametric gain enables the generation of discrete comb modes over a 500 nm wide span (ca. 70 THz) around 1550 nm without relying on any external spectral broadening. Optical-heterodyne-based measurements reveal that cascaded parametric interactions give rise to an optical frequency comb, overcoming passive cavity dispersion. The uniformity of the mode spacing has been verified to within a relative experimental precision of 7.3*10(-18).Comment: Manuscript and Supplementary Informatio

Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor

The nature of the pseudogap phase is a central problem in the quest to understand high-Tc cuprate superconductors. A fundamental question is what symmetries are broken when that phase sets in below a temperature T*. There is evidence from both polarized neutron diffraction and polar Kerr effect measurements that time- reversal symmetry is broken, but at temperatures that differ significantly. Broken rotational symmetry was detected by both resistivity and inelastic neutron scattering at low doping and by scanning tunnelling spectroscopy at low temperature, but with no clear connection to T*. Here we report the observation of a large in-plane anisotropy of the Nernst effect in YBa2Cu3Oy that sets in precisely at T*, throughout the doping phase diagram. We show that the CuO chains of the orthorhombic lattice are not responsible for this anisotropy, which is therefore an intrinsic property of the CuO2 planes. We conclude that the pseudogap phase is an electronic state which strongly breaks four-fold rotational symmetry. This narrows the range of possible states considerably, pointing to stripe or nematic orders.Comment: Published version. Journal reference and DOI adde

A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure

Sensory Measurements: Coordination and Standardization

Do sensory measurements deserve the label of “measurement”? We argue that they do. They fit with an epistemological view of measurement held in current philosophy of science, and they face the same kinds of epistemological challenges as physical measurements do: the problem of coordination and the problem of standardization. These problems are addressed through the process of “epistemic iteration,” for all measurements. We also argue for distinguishing the problem of standardization from the problem of coordination. To exemplify our claims, we draw on olfactory performance tests, especially studies linking olfactory decline to neurodegenerative disorders

Generalized Uncertainty Principle, Modified Dispersion Relation and Barrier penetration by a Dirac particle

We have studied the energy band structure of a Dirac particle in presence of a generalised uncertainty principle (GUP). We start from defining a modified momentum operator and derive corresponding modified dispersion relation (MDR) and GUP. Apart from the forbidden band within the range $\pm m$, $m$ being the mass of the particle, we find the existence of additional forbidden bands at the both ends of the spectrum. Such band structure forbids a Dirac particle to penetrate a potential step of sufficient height ($\sim E_P$, $E_P$ being Planck energy). This is also true for massless particle. Unlike the relativistic case, a massless particle also can reflect from a barrier of sufficient height. Finally we discuss about the Klein's paradox in presence of the GUP.Comment: 10 pages, 7 figures, LaTe

Intracellular interferons in fish : a unique means to combat viral infection

Peer reviewedPublisher PD