A Case of Intramural Coronary Amyloidosis Associated With Hemodialysis

Dialysis-related amyloidosis predominantly occurs in osteo-articular structures and dialysis-related amyloid (DRA) substances also deposit in extra-articular tissues. Clinical manifestations of DRA include odynophagia, gastrointestinal hemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction, and subcutaneous tumors. The pathological characteristics of DRA in the heart of hemodialysis patients have rarely been reported. We report the case of a 73-year-old female with a history of cerebral palsy and end-stage renal disease status post two failed renal transplants who had been on hemodialysis for 30 years. The patient was admitted with the working diagnosis of pneumonia. An echocardiography showed markedly reduced biventricular function manifested by low blood pressure with systolic in the 70s and elevated pulmonary artery pressure of 45 mmHg, which did not respond to therapy. Following her demise, the autopsy revealed bilateral pulmonary edema and pleural effusions. There was cardiac amyloid deposition exclusively in the coronary arteries but not in the perimyocytic interstitium. Amyloids were also found in pulmonary and intrarenal arteries and the colon wall. Previous case reports showed that beta 2-microglobulin amyloid deposits in various visceral organs but less frequently in the atrial and/or the ventricular myocardium. In the present case, amyloids in the heart were present in the intramural coronary arteries causing myocardial ischemia and infarction, which was the immediate cause of death

The Evolution of HoxD-11 Expression in the Bird Wing: Insights from Alligator mississippiensis

BACKGROUND:Comparative morphology identifies the digits of the wing of birds as 1,2 and 3, but they develop at embryological positions that become digits 2, 3 and 4 in other amniotes. A hypothesis to explain this is that a homeotic frame shift of digital identity occurred in the evolution of the bird wing, such that digits 1,2 and 3 are developing from embryological positions 2, 3 and 4. Digit 1 of the mouse is the only digit that shows no late expression of HoxD-11. This is also true for the anterior digit of the bird wing, suggesting this digit is actually a digit 1. If this is the case, we can expect closer relatives of birds to show no HoxD-11 expression only in digit 1. To test this prediction we investigate HoxD-11 expression in crocodilians, the closest living relatives of birds. METHODOLOGY/PRINCIPAL FINDINGS:Using degenerate primers we cloned a 606 nucleotide fragment of exon 1 of the alligator HoxD-11 gene and used it for whole-mount in-situ detection in alligator embryos. We found that in the pentadactyl forelimbs of alligator, as in the mouse, late expression of HoxD-11 is absent only in digit 1. CONCLUSIONS/SIGNIFICANCE:The ancestral condition for amniotes is that late-phase HoxD-11 expression is absent only in digit 1. The biphalangeal morphology and lack of HoxD-11 expression of the anterior digit of the wing is like digit 1 of alligator and mouse, but its embryological position as digit 2 is derived. HoxD-11 expression in alligator is consistent with the hypothesis that both digit morphology as well as HoxD-11 expression are shifted towards posterior in the bird wing

Cooperative Localization for Autonomous Underwater Vehicles

The absence of GPS underwater makes navigation for Autonomous Underwater Vehicles (AUVs) a difficult challenge. Without an external reference in the form of acoustic beacons at known positions, the vehicle has to rely on proprioceptive information obtained through a compass, a Doppler Velocity Logger (DVL) or an Inertial Navigation System (INS). Independent of the quality of the sensors used, the error in the position estimate based on dead-reckoning information grows without bound. Typical navigation errors are 0.5% to 2% of distance traveled for vehicles traveling within a few hundred meters of the sea floor such that their DVL has a lock on the bottom. Errors as low as 0.1% can be obtained with large and expensive INS systems, but for vehicles relying only on a compass and a speed estimate can be as high as 10%. By surfacing the AUV can obtain a position update through its GPS, but this is impossible (under ice) or undesirable for many applications. The use of static beacons in the form of a Long Baseline (LBL) array limits the operation area to a few km2 and requires a substantial deployment effort before operations, especially in deep water. As underwater vehicles become more reliable and affordable the simultaneous use of several AUVs recently became a viable option and multi-vehicle deployments will become standard in the upcoming years. This will not only make entirely new types of missions which rely on cooperation possible, but will also allow each individual member of the group to benefit from navigation information obtained from other members. For optimal cooperative localization a few dedicated Communication and Navigation Aid-AUVs (CNAs), which maintain an accurate estimate of their position through sophisticated DVL and INS sensors, can enable a much larger group of vehicles with less sophisticated navigation suites to maintain an accurate position

Continuous Humanoid Locomotion over Uneven Terrain using Stereo Fusion

Abstract — For humanoid robots to fulfill their mobility po-tential they must demonstrate reliable and efficient locomotion over rugged and irregular terrain. In this paper we present the perception and planning algorithms which have allowed a humanoid robot to use only passive stereo imagery (as opposed to actuating a laser range sensor) to safely plan footsteps to continuously walk over rough and uneven surfaces without stopping. The perception system continuously integrates stereo imagery to build a consistent 3D model of the terrain which is then used by our footstep planner which reasons about obstacle avoidance, kinematic reachability and foot rotation through mixed-integer quadratic optimization to plan the required step positions. We illustrate that our stereo imagery fusion approach can measure the walking terrain with sufficient accuracy that it matches the quality of terrain estimates from LIDAR. To our knowledge this is the first such demonstration of the use of computer vision to carry out general purpose terrain estimation on a locomoting robot — and additionally to do so in continuous motion. A particular integration challenge was ensuring that these two computationally intensive systems oper-ate with minimal latency (below 1 second) to allow re-planning while walking. The results of extensive experimentation and quantitative analysis are also presented. Our results indicate that a laser range sensor is not necessary to achieve locomotion in these challenging situations. I

An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis

Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a “neuropeptide,” neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane. Disruption of endogenous NK-B signaling promoted angiogenesis. Mechanistic analyses defined a multicomponent pathway in which NK-B signaling converges upon cellular processes essential for angiogenesis. NK-B−mediated ablation of Ca2+ oscillations and elevation of 3′–5′ cyclic adenosine monophosphate (cAMP) reduced cellular proliferation, migration, and vascular endothelial growth factor receptor expression and induced the antiangiogenic protein calreticulin. Whereas NK-B initiated certain responses, other activities required additional stimuli that increase cAMP. Although NK-B is a neurotransmitter/ neuromodulator and NK-B overexpression characterizes the pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular remodeling. These results establish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose vascular remodeling

Cooperative AUV Navigation using a Single Maneuvering Surface Craft

In this paper we describe the experimental implementation of an online algorithm for cooperative localization of submerged autonomous underwater vehicles (AUVs) supported by an autonomous surface craft. Maintaining accurate localization of an AUV is difficult because electronic signals, such as GPS, are highly attenuated by water. The usual solution to the problem is to utilize expensive navigation sensors to slow the rate of dead-reckoning divergence. We investigate an alternative approach that utilizes the position information of a surface vehicle to bound the error and uncertainty of the on-board position estimates of a low-cost AUV. This approach uses the Woods Hole Oceanographic Institution (WHOI) acoustic modem to exchange vehicle location estimates while simultaneously estimating inter-vehicle range. A study of the system observability is presented so as to motivate both the choice of filtering approach and surface vehicle path planning. The first contribution of this paper is to the presentation of an experiment in which an extended Kalman filter (EKF) implementation of the concept ran online on-board an OceanServer Iver2 AUV while supported by an autonomous surface vehicle moving adaptively. The second contribution of this paper is to provide a quantitative performance comparison of three estimators: particle filtering (PF), non-linear least-squares optimization (NLS), and the EKF for a mission using three autonomous surface craft (two operating in the AUV role). Our results indicate that the PF and NLS estimators outperform the EKF, with NLS providing the best performance.United States. Office of Naval Research (Grant N000140711102)United States. Office of Naval Research. Multidisciplinary University Research InitiativeSingapore. National Research FoundationSingapore-MIT Alliance for Research and Technology. Center for Environmental Sensing and Monitorin

Astrometry and geodesy with radio interferometry: experiments, models, results

Summarizes current status of radio interferometry at radio frequencies between Earth-based receivers, for astrometric and geodetic applications. Emphasizes theoretical models of VLBI observables that are required to extract results at the present accuracy levels of 1 cm and 1 nanoradian. Highlights the achievements of VLBI during the past two decades in reference frames, Earth orientation, atmospheric effects on microwave propagation, and relativity.Comment: 83 pages, 19 Postscript figures. To be published in Rev. Mod. Phys., Vol. 70, Oct. 199

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons