Biofluid Markers for Prodromal Parkinson's Disease:Evidence From a Catecholaminergic Perspective

Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of α-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years before the actual parkinsonism that are closely associated with profound deficiency of myocardial noradrenaline content and peripheral sympathetic denervation, as evidenced by neuroimaging experiments in recent years. Additionally, there is an inherent autotoxicity of catecholamines in the neuronal cells in which they are produced, forming toxic catecholaldehyde intermediates that make α-synuclein prone to aggregation, initiating a cascade of events that ultimately leads to neuronal death. The etiopathogenesis of PD and related synucleinopathies thus may well be a prototypical example of a catecholamine-regulated neurodegeneration, given that the synucleinopathy in PD spreads in synergy with central and peripheral catecholaminergic dysfunction from the earliest phases onward. That is why catecholamines and their metabolites, precursors, or derivatives in cerebrospinal fluid or plasma could be of particular interest as biomarkers for prodromal and de novo PD. Because there is great demand for such markers, this mini-review summarizes all catecholamine-related studies to date, in addition to providing profound neurochemical evidence on a systemic and cellular level to further emphasize this hypothesis and with emphasis on extracellular vesicles as a novel diagnostic and therapeutic incentive

Noise screen for attitude control system

An attitude control system comprising a controller and a noise screen device coupled to the controller. The controller is adapted to control an attitude of a vehicle carrying an actuator system that is adapted to pulse in metered bursts in order to generate a control torque to control the attitude of the vehicle in response to a control pulse. The noise screen device is adapted to generate a noise screen signal in response to the control pulse that is generated when an input attitude error signal exceeds a predetermined deadband attitude level. The noise screen signal comprises a decaying offset signal that when combined with the attitude error input signal results in a net attitude error input signal away from the predetermined deadband level to reduce further control pulse generation

210Po and 210Pb distributions during a phytoplankton bloom in the North Atlantic: Implications for POC export

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Horowitz, E. J., Cochran, J. K., Bacon, M. P., & Hirschberg, D. J. 210Po and 210Pb distributions during a phytoplankton bloom in the North Atlantic: implications for POC export. Deep-Sea Research Part I: Oceanographic Research Papers, 164, (2020): 103339, doi:10.1016/j.dsr.2020.103339.During the North Atlantic Bloom Experiment (NABE) of the Joint Global Ocean Flux Study (JGOFS), water column sampling for particulate and dissolved 210Po and 210Pb was performed four times (26 April and 4, 20, 30 May 1989) during a month-long Lagrangian time-series occupation of the NABE site, as well as one-time samplings at stations during transit to and from the site. There are few prior studies documenting short-term changes in 210Po and 210Pb profiles over the course of a phytoplankton bloom, and we interpret the profiles in terms of the classical “steady-state” (SS) approach used in most studies, as well as by using a non-steady state approach suggested by the temporal evolution of the profiles. Changes in 210Po profiles during a bloom are expectable as this radionuclide is scavenged and exported. During NABE, 210Pb profiles also displayed non-steady state, with significant increases in upper water column inventory occurring midway through the experiment. Export of 210Po from the upper 150 m using the classic “steady-state” model shows increases from 0.5 ± 8.5 dpm m−2 d−1 to 68.2 ± 4.2 dpm m−2 d−1 over the ~one-month occupation. Application of a non-steady state model, including changes in both 210Pb and 210Po profiles, gives higher 210Po export fluxes. Detailed depth profiles of particulate organic carbon (>0.8 μm) and particulate 210Po (>0.4 μm) are available from the 20 and 30 May samplings and show maxima in POC/Po at ~37 m. Applying the POC/210Po ratios at 150 m to the “steady state” 210Po fluxes yields POC export from the upper 150 m of 8.2 ± 1.5 mmol C m− 2 d−1 on 20 May and 6.0 ± 1.6 mmol C m−2 d−1 on 30 May. The non-steady state model applied to the interval 20 to 30 May yields POC export of 24.3 mmol C m−2 d−1. The non-steady state (NSS) 210Po-derived POC fluxes are comparable to, but somewhat less than, those estimated previously from 234Th/238U disequilibrium for the same time interval (37.3 and 45.0 mmol m−2 d−1, depending on the POC/Th ratio used). In comparison, POC fluxes measured with a floating sediment trap deployed at 150 m from 20 to 30 May were 11.6 mmol m−2 d−1. These results suggest that non-steady state Po-derived POC fluxes during the NABE agree well with those derived from 234Th/238U disequilibrium and agree with sediment trap fluxes within a factor of ~2. However, unlike the 234Th-POC flux proxy, non-steady stage changes in profiles of 210Pb, the precursor of 210Po, must be considered.We are grateful to T. Hammar and A. Fleer (WHOI) for assistance at sea and in the laboratory. This work was supported originally by National Science Foundation (United States) grant OCE-8819544 to JKC and more recently by OCE-1736591. We thank Stephen Thurston (American Museum of Natural History) for graphics assistance Robert Aller, Steven Beaupre, and two anonymous reviewers for helpful comments

Improved Algorithms for Approximate String Matching (Extended Abstract)

The problem of approximate string matching is important in many different areas such as computational biology, text processing and pattern recognition. A great effort has been made to design efficient algorithms addressing several variants of the problem, including comparison of two strings, approximate pattern identification in a string or calculation of the longest common subsequence that two strings share. We designed an output sensitive algorithm solving the edit distance problem between two strings of lengths n and m respectively in time O((s-|n-m|)min(m,n,s)+m+n) and linear space, where s is the edit distance between the two strings. This worst-case time bound sets the quadratic factor of the algorithm independent of the longest string length and improves existing theoretical bounds for this problem. The implementation of our algorithm excels also in practice, especially in cases where the two strings compared differ significantly in length. Source code of our algorithm is available at http://www.cs.miami.edu/\~dimitris/edit_distanceComment: 10 page

Iterated maps for clarinet-like systems

The dynamical equations of clarinet-like systems are known to be reducible to a non-linear iterated map within reasonable approximations. This leads to time oscillations that are represented by square signals, analogous to the Raman regime for string instruments. In this article, we study in more detail the properties of the corresponding non-linear iterations, with emphasis on the geometrical constructions that can be used to classify the various solutions (for instance with or without reed beating) as well as on the periodicity windows that occur within the chaotic region. In particular, we find a regime where period tripling occurs and examine the conditions for intermittency. We also show that, while the direct observation of the iteration function does not reveal much on the oscillation regime of the instrument, the graph of the high order iterates directly gives visible information on the oscillation regime (characterization of the number of period doubligs, chaotic behaviour, etc.)

Idealized digital models for conical reed instruments, with focus on the internal pressure waveform

International audienceTwo models for the generation of self-oscillations of reed conical woodwinds are presented. They use the fewest parameters (of either the resonator or the ex-citer), whose influence can be quickly explored. The formulation extends iterated maps obtained for loss-less cylindrical pipes without reed dynamics. It uses spherical wave variables in idealized resonators, with one parameter more than for cylinders: the missing length of the cone. The mouthpiece volume equals that of the missing part of the cone, and is implemented as either a cylindrical pipe (first model) or a lumped element (second model). Only the first model adds a length parameter for the mouthpiece and leads to the solving of an implicit equation. For the second model, any shape of nonlinear characteristic can be directly considered. The complex characteristics impedance for spherical waves requires sampling times smaller than a round trip in the resonator. The convergence of the two models is shown when the length of the cylindrical mouthpiece tends to zero. The waveform is in semi-quantitative agreement with experiment. It is concluded that the oscillations of the positive episode of the mouthpiece pressure are related to the length of the missing part, not to the reed dynamics

From the zero-field metal-insulator transition in two dimensions to the quantum Hall transition: a percolation-effective-medium theory

Effective-medium theory is applied to the percolation description of the metal-insulator transition in two dimensions with emphasis on the continuous connection between the zero-magnetic-field transition and the quantum Hall transition. In this model the system consists of puddles connected via saddle points, and there is loss of quantum coherence inside the puddles. The effective conductance of the network is calculated using appropriate integration over the distribution of conductances, leading to a determination of the magnetic field dependence of the critical density. Excellent quantitative agreement is obtained with the experimental data, which allows an estimate of the puddle physical parameters