In Vivo Mapping of Vascular Inflammation Using Multimodal Imaging

Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.The multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture

Multivariate statistical integration of satellite infrared and microwave radiometric measurements for rainfall retrieval at the geostationary scale

The objective of this paper is to investigate how the complementarity between low earth orbit (LEO) microwave (MW) and geostationary earth orbit (GEO) infrared (IR) radiometric measurements can be exploited for satellite rainfall detection and estimation. Rainfall retrieval is pursued at the space–time scale of typical geostationary observations, that is at a spatial resolution of few kilometers and a repetition period of few tens of minutes. The basic idea behind the investigated statistical integration methods follows an established approach consisting in using the satellite MW-based rain-rate estimates, assumed to be accurate enough, to calibrate spaceborne IR measurements on sufficiently limited subregions and time windows. The proposed methodologies are focused on new statistical approaches, namely the multivariate probability matching (MPM) and variance-constrained multiple regression (VMR). The MPM and VMR methods are rigorously formulated and systematically analyzed in terms of relative detection and estimation accuracy and computing efficiency. In order to demonstrate the potentiality of the proposed MW–IR combined rainfall algorithm (MICRA), three case studies are discussed, two on a global scale on November 1999 and 2000 and one over the Mediterranean area. A comprehensive set of statistical parameters for detection and estimation assessment is introduced to evaluate the error budget. For a comparative evaluation, the analysis of these case studies has been extended to similar techniques available in literature

High-sensitivity detection of trace gases using dynamic photoacoustic spectroscopy

Lincoln Laboratory of Massachusetts Institute of Technology has developed a technique known as dynamic photoacoustic spectroscopy (DPAS) that could enable remote detection of trace gases via a field-portable laser-based system. A fielded DPAS system has the potential to enable rapid, early warning of airborne chemical threats. DPAS is a new form of photoacoustic spectroscopy that relies on a laser beam swept at the speed of sound to amplify an otherwise weak photoacoustic signal. We experimentally determine the sensitivity of this technique using trace quantities of SF[subscript 6] gas. A clutter-limited sensitivity of ~100  ppt is estimated for an integration path of 0.43 m. Additionally, detection at ranges over 5 m using two different detection modalities is demonstrated: a parabolic microphone and a laser vibrometer. Its utility in detecting ammonia emanating from solid samples in an ambient environment is also demonstrated.United States. Dept. of the Air Force (Contract FA8721-05-C-0002

Chocolate consumers and lymphocyte-to-monocyte ratio: a working hypothesis from a preliminary report of a pilot study in celiac subjects

Background and aim: The aim of this work was to evaluate the relationship between platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) with habitual consumption of dark chocolate in a group of celiac subjects in which chocolate consumption and lower neutrophil-to-lymphocyte ratio (NLR) association had already been observed. Additionally, due to the known anti-nutrient effect on iron absorption, we evaluated red blood cell count (RBC), mean corpuscular volume (MCV) and hemoglobin (Hb) values. Methods: Chocolate consumers and non-consumers were matched for sex, menopausal status, NLR values over the previously suggested cut off (2.32) for celiac patients, and co-morbidities. Results: Chocolate consumers had high LMR compared to non-consumers, whereas no differences were observed between chocolate consumers and non-consumers in RBC, MCV, Hb and PLR. However, similar number of subjects had PLR higher than the previously suggested cut off (143.7) for celiac disease. Conclusions: This preliminary report suggests a working hypothesis for larger studies aimed at establishing cut off values for LMR in celiac patients and the modulation of this marker by dietary antioxidants

Conductive photo-activated porphyrin-ZnO nanostructured gas sensor array

Chemoresistors working at room temperature are attractive for low-consumption integrated sensors. Previous studies show that this feature can be obtained with photoconductive porphyrins-coated ZnO nanostructures. Furthermore, variations of the porphyrin molecular structure alter both the chemical sensitivity and the photoconductivity, and can be used to define the sensor characteristics. Based on these assumptions, we investigated the properties of an array of four sensors made of a layer of ZnO nanoparticles coated with porphyrins with the same molecular framework but different metal atoms. The array was tested with five volatile organic compounds (VOCs), each measured at different concentrations. Results confirm that the features of individual porphyrins influence the sensor behavior, and the differences among sensors are enough to enable the discrimination of volatile compounds disregarding their concentration. © 2017 by the authors; Licensee MDPI, Basel, Switzerland

• ROTHSCHILD ET AL. Recent Trends in Optical Lithography Recent Trends in Optical Lithography

■ The fast-paced evolution of optical lithography has been a key enabler in the dramatic size reduction of semiconductor devices and circuits over the last three decades. Various methods have been devised to pattern at dimensions smaller than the wavelength used in the process. In addition, the patterning wavelength itself has been reduced and will continue to decrease in the future. As a result, it is expected that optical lithography will remain the technology of choice in lithography for at least another decade. Lincoln Laboratory has played a seminal role in the progress of optical lithography; it pioneered 193-nm lithography, which is used in advanced production, and 157-nm lithography, which is under active development. Lincoln Laboratory also initiated exploration of liquidimmersion lithography and studied the feasibility of 121-nm lithography. Many of the challenges related to practical implementation of short-wavelength optical lithography are materials-related, including engineering of new materials, improving on existing materials, and optimizing their photochemistry. This article examines the technical issues facing optical lithography and Lincoln Laboratory’s contributions toward their resolution. Optical lithography, the technology of patterning, has enabled semiconductor devices to progressively shrink since the inception of integrated circuits more than three decades ago. Throughout the 1980s and 1990s, the trend of miniaturization continued unabated and even accelerated. Current semiconductor devices are being mass produced with 130-nm dense features; by 2007 these devices will have 65-nm dense features. Optical lithography has been, and will remain for the foreseeable future, the critical technology that makes this trend possible. (To learn the fundamentals of optical lithography, see the sidebar entitled “Optical Lithograph