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Sensorless Adaptive Optics

Karen Mary Hampson, Jacopo Antonello, Richard Lane, Martin Booth
2020 Zenodo  
This tutorial describes the principles and practical implementation of sensorless adaptive optics.
doi:10.5281/zenodo.4065529 fatcat:cksu2nqxvjfevcr4vrestbwdsm

Sensorless Adaptive Optics

Karen Mary Hampson, Jacopo Antonello, Richard Lane, Martin Booth
2020 Zenodo  
This tutorial describes the principles and practical implementation of sensorless adaptive optics.
doi:10.5281/zenodo.4271425 fatcat:d666fx5fyfhflbiapp4qasa2am

Sensorless Adaptive Optics

Karen Mary Hampson, Jacopo Antonello, Richard Lane, Martin Booth
2020 Zenodo  
This tutorial describes the principles and practical implementation of sensorless adaptive optics.
doi:10.5281/zenodo.4066425 fatcat:hmrppjijj5at3insrzddsipy3e

Selecting Informative Contexts Improves Language Model Finetuning [article]

Richard Antonello, Nicole Beckage, Javier Turek, Alexander Huth
2022 arXiv   pre-print
Language model fine-tuning is essential for modern natural language processing, but is computationally expensive and time-consuming. Further, the effectiveness of fine-tuning is limited by the inclusion of training examples that negatively affect performance. Here we present a general fine-tuning method that we call information gain filtration for improving the overall training efficiency and final performance of language model fine-tuning. We define the information gain of an example as the
more » ... rovement on a test metric after training on that example. A secondary learner is then trained to approximate this quantity. During fine-tuning, this learner selects informative examples and skips uninformative ones. We show that our method has consistent improvement across datasets, fine-tuning tasks, and language model architectures. For example, we achieve a median perplexity of 54.0 on a books dataset compared to 57.3 for standard fine-tuning. We present statistical evidence that offers insight into the improvements of our method over standard fine-tuning. The generality of our method leads us to propose a new paradigm for language model fine-tuning -- we encourage researchers to release pretrained secondary learners on common corpora to promote efficient and effective fine-tuning, thereby improving the performance and reducing the overall energy footprint of language model fine-tuning.
arXiv:2005.00175v3 fatcat:g5yr2yc45rf43hv3lfzhmo6s2y

Uniqueness of Protected Areas for Conservation Strategies in the European Union

Samuel Hoffmann, Carl Beierkuhnlein, Richard Field, Antonello Provenzale, Alessandro Chiarucci
2018 Scientific Reports  
Protected areas (PAs) constitute major tools in nature conservation. In the European Union (EU), the Birds and Habitats Directives are the most important policies for conservation strategy, legally preserving Europe's characteristic, rare, endemic and threatened biota. We used occurrence data for species listed in the directives' Annexes to assess the uniqueness of major PAs in the EU (National Parks, Biosphere Reserves); this is important for preserving the EU's focal species. We developed a
more » ... vel, multifunctional approach to calculate different metrics of conservation value that represent different components of species diversity within the PAs, involving inventory diversity, deviation from the species-area relationship, species rarity and differentiation diversity. Applying it, we found that individual PAs frequently vary considerably in their scores on different components, which are often disconnected from PA size. PAs around the EU periphery, often containing few species, are key to conserving species that are rare in the EU. Because our analysis focuses on EU priority species and includes different components of diversity, it allows more appropriate estimation of conservation value inside PAs in context of the EU than recent, high-profile, global-level research. We offer tools to evaluate, and information to regulate, the representativeness, persistence and efficiency of PAs.
doi:10.1038/s41598-018-24390-3 pmid:29691423 pmcid:PMC5915414 fatcat:cmmllgpluvgp7fkm2xz5ywylby

Role of NMDA Receptors in Dopamine Neurons for Plasticity and Addictive Behaviors

Larry S. Zweifel, Emanuela Argilli, Antonello Bonci, Richard D. Palmiter
2008 Neuron  
A single exposure to drugs of abuse produces an NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA receptor (AMPAR) currents in DA neurons; however, the importance of LTP for various aspects of drug addiction is unclear. To test the role of NMDAR-dependent plasticity in addictive behavior, we genetically inactivated functional NMDAR signaling exclusively in DA neurons (KO mice). Inactivation of NMDARs results in increased AMPAR-mediated transmission that is indistinguishable
more » ... om the increases associated with a single cocaine exposure, yet locomotor responses to multiple drugs of abuse were unaltered in the KO mice. The initial phase of locomotor sensitization to cocaine is intact; however, the delayed sensitization that occurs with prolonged cocaine withdrawal did not occur. Conditioned behavioral responses for cocaine-testing environment were also absent in the KO mice. These findings provide evidence for a role of NMDAR signaling in DA neurons for specific behavioral modifications associated with drug seeking behaviors.
doi:10.1016/j.neuron.2008.05.028 pmid:18701073 pmcid:PMC2556153 fatcat:r7sxq4jrnrgclga7tf2kjxihve

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines

Lucy E. Dawson, Luca D'Agostino, Abraham A. Hakim, Richard D. Lackman, Spencer A. Brown, Richard B. Sensenig, Zeus A. Antonello, Igor I. Kuzin
2020 Sarcoma  
Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment is believed to be intratumoral heterogeneity. In this study, we investigated the myogenic determination factor 1 (MYOD1) and Noggin (NOG) markers in an embryonal RMS (ERMS) cell line and an RT cell line and
more » ... he differential response of the MYOD1 and NOG expressing subpopulations to chemotherapy. Importantly, we found that these markers together identify a subpopulation of cells (MYOD1+ NOG+ cells) with primary resistance to Vincristine and Doxorubicin, two commonly used chemotherapies for ERMS and RT. The chemoresistant MYOD1+ NOG+ cells express markers of undifferentiated cells such as myogenin and ID1. Combination of Vincristine with TPA/GSK126, a drug combination shown to induce differentiation of RMS cell lines, is able to partially overcome MYOD1/NOG cells chemoresistance.
doi:10.1155/2020/8647981 pmid:32300280 pmcid:PMC7136814 fatcat:kpasqx3nffctvk2v5dnuukolsq

Stroke Volume/Pulse Pressure Ratio and Cardiovascular Risk in Arterial Hypertension

Giovanni de Simone, Mary J. Roman, Michael J. Koren, George A. Mensah, Antonello Ganau, Richard B. Devereux
1999 Hypertension  
Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has been proposed as an estimate of total arterial compliance and has been shown to be related to body size, age, and heart rate in normal adults. SV/PP was estimated in 294 hypertensive patients (98 women) as a raw value by use of SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a previously developed equation (%SV/PP). At baseline, the 50 patients who had cardiovascular events over the
more » ... lowing 10 years exhibited higher PP and lower SV/PP, SVi/PP, and %SV/PP (all PϽ0.008) than patients without events. Crude risk of follow-up total and fatal cardiovascular events increased with increasing level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all PϽ0.002). In multivariate logistic regression models with continuous covariates, the risk of total cardiovascular events was independently related to increasing age (PϽ0.0001) and left ventricular (LV) mass index (PϽ0.003) and decreasing values of %SV/PP (PϽ0.006) but not to increasing systolic, pulse, or mean blood pressure or gender. Similar although less strong results were obtained with the use of SVi/PP (PϽ0.02), whereas SV/PP did not enter the model as an independent predictor. Risk of cardiovascular death was only predicted by age and LV mass index. The %SV/PP was also an independent predictor of total cardiovascular events in Cox proportional hazards analysis (exp[b]: 2.49, PϽ0.001) independent of age (exp[b]: 1.05, PϽ0.003) and LV mass index (exp[b]: 1.02, PϽ0.0003), whereas no effect was detected for height. Thus, in patients with arterial hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage of the value predicted by demographic variables is a predictor of cardiovascular morbid events independent of age and LV mass index. (Hypertension. 1999;33:800-805.)
doi:10.1161/01.hyp.33.3.800 pmid:10082490 fatcat:yffv5rpf3va5flifhzh3y3pota

Inflammation Increases Neuronal Sensitivity to General Anesthetics

Sinziana Avramescu, Dian-Shi Wang, Irene Lecker, William T. H. To, Antonello Penna, Paul D. Whissell, Lia Mesbah-Oskui, Richard L. Horner, Beverley A. Orser
2016 Anesthesiology  
What We Already Know about This Topic • Inflammation increases the surface expression of receptors for the inhibitory transmitter γ-aminobutyric acid in neurons. • γ-Aminobutyric acid receptors are sensitive to most anesthetics, suggesting that inflammatory states might increase anesthetic sensitivity. What This Article Tells Us That Is New • The inflammatory cytokine interleukin-1β increased γ-aminobutyric acidergic inhibitory currents in the presence of etomidate or isoflurane in cultured
more » ... e hippocampal and cortical neurons. • In a mouse model of sepsis, behavioral sensitivity to both anesthetics was increased. The clinical relevance of these findings will require studies of specific anesthetic endpoints in patients with systemic inflammation. ABSTRACT Background: Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of γ-aminobutyric acid type A (GABA A ) receptors expressed on the surface of neurons, which supports the hypothesis that inflammation increases upregulation of GABA A receptor activity by anesthetics, thereby enhancing the behavioral sensitivity to these drugs. Methods: To mimic inflammation in vitro, cultured hippocampal and cortical neurons were pretreated with interleukin (IL)-1β. Whole cell patch clamp methods were used to record currents evoked by γ-aminobutyric acid (GABA) (0.5 μM) in the absence and presence of etomidate or isoflurane. To mimic inflammation in vivo, mice were treated with lipopolysaccharide, and several anesthetic-related behavioral endpoints were examined. Results: IL-1β increased the amplitude of current evoked by GABA in combination with clinically relevant concentrations of either etomidate (3 μM) or isoflurane (250 μM) (n = 5 to 17, P < 0.05). Concentration-response plots for etomidate and isoflurane showed that IL-1β increased the maximal current 3.3-fold (n = 5 to 9) and 1.5-fold (n = 8 to 11), respectively (P < 0.05 for both), whereas the half-maximal effective concentrations were unchanged. Lipopolysaccharide enhanced the hypnotic properties of both etomidate and isoflurane. The immobilizing properties of etomidate, but not isoflurane, were also increased by lipopolysaccharide. Both lipopolysaccharide and etomidate impaired contextual fear memory. Conclusions: These results provide proof-of-concept evidence that inflammation increases the sensitivity of neurons to general anesthetics. This increase in anesthetic up-regulation of GABA A receptor activity in vitro correlates with enhanced sensitivity for GABA A receptor-dependent behavioral endpoints in vivo. . Information on purchasing reprints may be found at www.anesthesiology. org or on the masthead page at the beginning of this issue. ANESTHESIOLOGy's articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
doi:10.1097/aln.0000000000000943 pmid:26566283 fatcat:uqkucugurnbsjakpox5o4sf7ci

Hepatic epithelioid hemangioendothelioma: a report from three university centers

Antonello Giardino, Frank H. Miller, Bobby Kalb, Miguel Ramalho, Diego R. Martin, Karina Rodacki, John T. Woosley, Richard C. Semelka
2016 Radiologia Brasileira  
Objective: To determine common imaging findings of hepatic epithelioid hemangioendothelioma on magnetic resonance images. Materials and Methods: A search was made of three institutional databases between January 2000 and August 2012. Seven patients (mean age, 47 years; range, 21-66 years; 6 women) with pathology-confirmed diagnosis of hepatic epithelioid hemangioendothelioma who had undergone magnetic resonance imaging were identified. None of the patients had received any treatment for hepatic
more » ... epithelioid hemangioendothelioma at the time of the initial magnetic resonance imaging examination. Results: Hepatic epithelioid hemangioendothelioma tumors appeared as focal masses in 7/7 patients, greater than 5 in number, with a coalescing lesion in 1/5, and peripheral localization in 6/7. Capsular retraction was present in 4/7, and was associated with peripherally located lesions. Early ring enhancement was appreciated in the majority of lesions in 7/7 patients. Centripetal progressive enhancement was shown in 5/7 patients on venous phase that exhibited a distinctive thick inner border of low signal on venous phase images, and a central core of delayed enhancement. Small lesions did not show this. Conclusion: The combination of multifocal round-configuration lesions that are predominantly peripheral and exhibit early peripheral ring enhancement and late appearance of an inner thick border of low signal and central core of high signal may represent an important feature for hepatic epithelioid hemangioendothelioma.
doi:10.1590/0100-3984.2015.0059 pmid:27818541 pmcid:PMC5094816 fatcat:emqm2v5wojc2jcvk4rniiirkhy

Neural Estimates of Imagined Outcomes in the Orbitofrontal Cortex Drive Behavior and Learning

Yuji K. Takahashi, Chun Yun Chang, Federica Lucantonio, Richard Z. Haney, Benjamin A. Berg, Hau-Jie Yau, Antonello Bonci, Geoffrey Schoenbaum
2013 Neuron  
Imagination, defined as the ability to interpret reality in ways that diverge from past experience, is fundamental to adaptive behavior. This can be seen at a simple level in our capacity to predict novel outcomes in new situations. The ability to anticipate outcomes never before received can also influence learning if those imagined outcomes are not received. The orbitofrontal cortex is a key candidate for where the process of imagining likely outcomes occurs; however, its precise role in
more » ... ating these estimates and applying them to learning remain open questions. Here we address these questions by showing that single-unit activity in the orbitofrontal cortex reflects novel outcome estimates. The strength of these neural correlates predicted both behavior and learning, learning that was abolished by temporally specific inhibition of orbitofrontal neurons. These results are consistent with the proposal that the orbitofrontal cortex is critical for integrating information to imagine future outcomes.
doi:10.1016/j.neuron.2013.08.008 pmid:24139047 pmcid:PMC3806218 fatcat:sijnsfnakndhdpeigwfgxrdvyq

Regulation of Elastinolytic Cysteine Proteinase Activity in Normal and Cathepsin K–Deficient Human Macrophages

Antonello Punturieri, Sergey Filippov, Edward Allen, Ingrid Caras, Richard Murray, Vivek Reddy, Stephen J. Weiss
2000 Journal of Experimental Medicine  
Human macrophages mediate the dissolution of elastic lamina by mobilizing tissue-destructive cysteine proteinases. While macrophage-mediated elastin degradation has been linked to the expression of cathepsins L and S, these cells also express cathepsin K, a new member of the cysteine proteinase family whose elastinolytic potential exceeds that of all known elastases. To determine the relative role of cathepsin K in elastinolysis, monocytes were differentiated under conditions in which they
more » ... itulated a gene expression profile similar to that observed at sites of tissue damage in vivo. After a 12-d culture period, monocyte-derived macrophages (MDMs) expressed cathepsin K in tandem with cathepsins L and S. Though cysteine proteinases are acidophilic and normally confined to the lysosomal network, MDMs secreted cathepsin K extracellularly in concert with cathepsins L and S. Simultaneously, MDMs increased the expression of vacuolar-type H ϩ -ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form. MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity. Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.
doi:10.1084/jem.192.6.789 pmid:10993910 pmcid:PMC2193285 fatcat:bx3dqepc5nh4nnzovxvgzlxtyy

Reduced expression of α5GABA A receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior

Lia Mesbah-Oskui, Antonello Penna, Beverley A. Orser, Richard L. Horner
2017 Neurotoxicology and Teratology  
A reduction in the activity of GABA A receptors, particularly α5 subunit-containing GABA A receptors (α5GABA A Rs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABA A Rs (Gabra5 −/− ) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5 −/− mice and
more » ... mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125 mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5 −/− mice (n = 3) exhibited elevated 0-2 Hz EEG activity during all sleep-wake states (all p b 0.04), decreased 8-12 Hz EEG activity during REM sleep (p = 0.04), and decreased sleep spindles under baseline conditions compared to wild-type controls (n = 4) (all p ≤ 0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5 −/− mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced α5GABA A R activity contributes to an ASD phenotype. The results also suggest that Gabra5 −/− mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors.
doi:10.1016/ pmid:27793660 fatcat:47uzsijspvf4tmgkumvjr7ixbm

Development of a human papillomavirus competitive luminex immunoassay for 9 HPV types

Christine Roberts, Tina Green, Erica Hess, Katie Matys, Martha J Brown, Richard M Haupt, Alain Luxembourg, Scott Vuocolo, Alfred Saah, Joseph Antonello
2014 Human Vaccines & Immunotherapeutics  
The quadrivalent human papillomavirus (HPV) type 6/11/16/18 (abbreviated as qHPV) vaccine (Gardasil®) has been marketed since 2006 and is widely used and recommended for the prevention of HPV6, 11, 16, and 18-related disease. An investigational nine-valent HPV (abbreviated as 9vHPV) vaccine targeting HPV6/11/16/18, as well as 5 of the next most frequent HPV types found in cervical cancers worldwide (HPV31/33/45/52/58) 1 is currently under development (Merck, V503, NCT00543543). The qHPV and
more » ... V vaccines are composed of virus-like-particles (VLPs), which are made by expressing the L1 major capsid protein of the respective-HPVtypes in eukaryotic cells. Vaccination with L1 VLPs induces a broad polyclonal antibody response directed against conformational and linear epitopes displayed on the VLP surface. [2] [3] [4] In the clinical trials of the qHPV vaccine, antibodies to the L1 VLPs were measured by an HPV-4 competitive Luminex immunoassay (cLIA). 5, 6 This type-specific multiplexed assay measures the competition for antibody binding to a single neutralizing epitope for each VLP. Subsequently, a multiplexed HPV-9 cLIA was developed for use in the clinical development program of the investigational 9vHPV vaccine. Here we describe the specificity of the 9 typespecific monoclonal antibodies (mAbs) used in the HPV-9 cLIA, as well as the assignment of antibody values for the HPV-9 cLIA reference standard. The HPV-9 cLIA is a competitive immunoassay that measures HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 specific antibodies to neutralizing epitopes on VLPs from a single serum sample. The assay is an extension of the previously developed and validated HPV-4 cLIA which was used in the clinical development of the qHPV vaccine (Gardasil). 5,6 The HPV-9 cLIA uses yeast-derived VLPs that have been coupled to a set of 9 distinct fluorescent Luminex microspheres. The type-specific HPV-VLP antibody responses are associated with specific Luminex microspheres that In the clinical trials of the quadrivalent human papillomavirus (qHPV) vaccine, antibodies were measured by a competitive Luminex immunoassay (HPV-4 cLIA). A nine-valent HPV (9vHPV) vaccine targeting the types in the qHPV vaccine (HPV6/11/16/18), as well as 5 of the next most frequent HPV types found in cervical cancers worldwide (HPV31/33/45/52/58) is under development. To support the 9vHPV vaccine program, a nine-multiplexed cLIA (HPV-9 cLIA) was developed. Antibody titers were determined in a competitive format, where type-specific phycoerythrin (Pe)-labeled, neutralizing mAbs (mAbs-Pe) compete with an individual's serum antibodies for binding to conformationally sensitive, neutralizing epitopes on the VLPs. Neutralizing antibody levels were quantitated against a reference standard -a pool of sera from 6 Rhesus macaques that were immunized with the 9vHPV vaccine. specificity of the mAbs was assessed by measuring their individual binding capacities to the type-specific and non-type-specific VLPs at alternative concentrations of the mAbs. Antibody assignments to the HPV-9 cLIA reference standard for HPV6/11/16/18 were determined to provide for a measure of consistency in serostatus assignment between the HPV-4 and HPV-9 cLIAs. Antibody assignments to the HPV-9 reference standard for HPV31/33/45/52/58 were obtained by calibration to HPV11 using a direct binding IgG assay. For each HPV VLP type, the cross-reactivity of the mAb-Pes in the HPV-9 cLIA was <1% (i.e., the mAb-Pes result in <1% non-specific binding). The antibody concentrations assigned to the HPV-9 cLIA reference standard for types 6/11/16/18/31/33/45/52/58 were 3, 817, 2, 889, 23,061, 5, 271, 3, 942, 2, 672, 1, 489, 1274, and 2263 mMU/mL, respectively.
doi:10.4161/hv.29205 pmid:25424920 pmcid:PMC4896759 fatcat:iy6fycrv3jf5bdlhswl3hrljnq

Carotid anatomy and stiffness is not affected by hypercholesterolemia in uncomplicated essential hypertension

Pier S. Saba, Mary J. Roman, Riccardo Pini, Richard B. Devereux, Antonello Ganau
1996 Journal of the American College of Cardiology  
Roman 1, Riccardo Pint 1, Richard B.  ... 
doi:10.1016/s0735-1097(96)80400-1 fatcat:sebff34wr5hvfhrwdwlbvwzu7e
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