Nonlinear Proportional Plus Integral Control of Optical Traps for Exogenous Force Estimation

This article explores nonlinear proportional plus integral (PI) feedback for controlling the position of an object held in an optical trap. In general, nonlinearities in the spatial dependence of the optical force complicate feedback control for optical traps. Nonlinear PI control has been shown to provide all of the benefits of integral control: disturbance rejection, servo tracking, and force estimation. The controller also linearizes the closed-loop system. More importantly, the nonlinear controller is shown to be equivalent to an estimator of the exogenous force. The ability of nonlinear PI control to lower the measurement SNR is evaluated and compared to the variational open-loop case. A simulation demonstrating the performance of the nonlinear PI control is presented

Southern Massive Stars at High Angular Resolution: Observational Campaign and Companion Detection

Multiplicity is one of the most fundamental observable properties of massive O-type stars and offers a promising way to discriminate between massive star formation theories. Nevertheless, companions at separations between 1 and 100 mas remain mostly unknown due to intrinsic observational limitations. [...] The Southern MAssive Stars at High angular resolution survey (SMASH+) was designed to fill this gap by providing the first systematic interferometric survey of Galactic massive stars. We observed 117 O-type stars with VLTI/PIONIER and 162 O-type stars with NACO/SAM, respectively probing the separation ranges 1-45 and 30-250mas and brightness contrasts of Delta H < 4 and Delta H < 5. Taking advantage of NACO's field-of-view, we further uniformly searched for visual companions in an 8''-radius down to Delta H = 8. This paper describes the observations and data analysis, reports the discovery of almost 200 new companions in the separation range from 1mas to 8'' and presents the catalog of detections, including the first resolved measurements of over a dozen known long-period spectroscopic binaries. Excluding known runaway stars for which no companions are detected, 96 objects in our main sample (DEC < 0 deg; H<7.5) were observed both with PIONIER and NACO/SAM. The fraction of these stars with at least one resolved companion within 200mas is 0.53. Accounting for known but unresolved spectroscopic or eclipsing companions, the multiplicity fraction at separation < 8'' increases to f_m = 0.91 +/- 0.03. The fraction of luminosity class V stars that have a bound companion reaches 100% at 30mas while their average number of physically connected companions within 8'' is f_c = 2.2 +/- 0.3. This demonstrates that massive stars form nearly exclusively in multiple systems. Additionally, the nine non-thermal (NT) radio emitters observed by SMASH+ are all resolved [...]Comment: 57 pages, 20 figures, 7 tables; accepted for publication in ApJ

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range

Automorphism groups of polycyclic-by-finite groups and arithmetic groups

We show that the outer automorphism group of a polycyclic-by-finite group is an arithmetic group. This result follows from a detailed structural analysis of the automorphism groups of such groups. We use an extended version of the theory of the algebraic hull functor initiated by Mostow. We thus make applicable refined methods from the theory of algebraic and arithmetic groups. We also construct examples of polycyclic-by-finite groups which have an automorphism group which does not contain an arithmetic group of finite index. Finally we discuss applications of our results to the groups of homotopy self-equivalences of K(\Gamma, 1)-spaces and obtain an extension of arithmeticity results of Sullivan in rational homotopy theory

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Corrigendum to: Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from EUROAPS registry

Rheumatology 2020;59:1306–1314. doi:https://doi.org/10.1093/rheumatology/kez419 In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record

Unity through truth

Renewed worries about the unity of the proposition have been taken as a crucial stumbling block for any traditional conception of propositions. These worries are often framed in terms of how entities independent of mind and language can have truth conditions: why is the proposition that Desdemona loves Cassio true if and only if she loves him? I argue that the best understanding of these worries shows that they should be solved by our theory of truth and not our theory of content. Specifically, I propose a version of the redundancy theory according to which ‘it is true that Desdemona loves Cassio’ expresses the same proposition as ‘Desdemona loves Cassio’. Surprisingly, this variant of the redundancy theory treats ‘is true’ as an ordinary predicate of the language, thereby defusing many standard criticisms of the redundancy theory

5-HT2C Receptors Localize to Dopamine and GABA Neurons in the Rat Mesoaccumbens Pathway

The serotonin 5-HT2C receptor (5-HT2CR) is localized to the limbic-corticostriatal circuit, which plays an integral role in mediating attention, motivation, cognition, and reward processes. The 5-HT2CR is linked to modulation of mesoaccumbens dopamine neurotransmission via an activation of γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA). However, we recently demonstrated the expression of the 5-HT2CR within dopamine VTA neurons suggesting the possibility of a direct influence of the 5-HT2CR upon mesoaccumbens dopamine output. Here, we employed double-label fluorescence immunochemistry with the synthetic enzymes for dopamine (tyrosine hydroxylase; TH) and GABA (glutamic acid decarboxylase isoform 67; GAD-67) and retrograde tract tracing with FluoroGold (FG) to uncover whether dopamine and GABA VTA neurons that possess 5-HT2CR innervate the nucleus accumbens (NAc). The highest numbers of FG-labeled cells were detected in the middle versus rostral and caudal levels of the VTA, and included a subset of TH- and GAD-67 immunoreactive cells, of which >50% also contained 5-HT2CR immunoreactivity. Thus, we demonstrate for the first time that the 5-HT2CR colocalizes in DA and GABA VTA neurons which project to the NAc, describe in detail the distribution of NAc-projecting GABA VTA neurons, and identify the colocalization of TH and GAD-67 in the same NAc-projecting VTA neurons. These data suggest that the 5-HT2CR may exert direct influence upon both dopamine and GABA VTA output to the NAc. Further, the indication that a proportion of NAc-projecting VTA neurons synthesize and potentially release both dopamine and GABA adds intriguing complexity to the framework of the VTA and its postulated neuroanatomical roles

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing