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### MATTHEW GARDNER

1903 California state journal of medicine
Matthew Gardner. Dr. Gardner was born in Ontario, Canada, in 1845. He died in San Francisco, April 18, 1903.  ...  Gardner soon enjoyed a large practice, which was increased on his removal to Sacramento.  ...

### Editorial

Matthew Gardner, David Vickers
2021 Early Music
Matthew Gardner and David Vickers Downloaded from https://academic.oup.com/em/advance-article/doi/10.1093/em/caab040/6324061 by guest on 21 July 2021  ...  Nevertheless, Matthew Gardner's reexamination of her interests in music and supportiveness towards Handel provides fresh illumination of the patronage Handel received from the monarchy.  ...

### Uncountable Sets and an Infinite Real Number Game [chapter]

Matthew Baker
2009 Mathematical Wizardry for a Gardner
The game. Alice and Bob decide to play the following infinite game on the real number line. A subset S of the unit interval [0, 1] is fixed, and then Alice and Bob alternate playing real numbers. Alice moves first, choosing any real number a 1 strictly between 0 and 1. Bob then chooses any real number b 1 strictly between a 1 and 1. On each subsequent turn, the players must choose a point strictly between the previous two choices. Equivalently, if we let a 0 = 0 and b 0 = 1, then in round n ≥
more » ... Alice chooses a real number a n with a n−1 < a n < b n−1 , and then Bob chooses a real number b n with a n < b n < b n−1 . Since a monotonically increasing sequence of real numbers which is bounded above has a limit (see [8, Theorem 3.14]), α = lim n→∞ a n is a well-defined real number between 0 and 1. Alice wins the game if α ∈ S, and Bob wins if α ∈ S. Countable and uncountable sets. An set X is called countable if it is possible to list the elements of X in a (possibly repeating) infinite sequence x 1 , x 2 , x 3 , . . . Equivalently, X is countable if there is a function from the set {1, 2, 3, . . .} of natural numbers to X which is onto. For example, every finite set is countable, and the set of natural numbers is countable. A set which is not countable is called uncountable. Cantor proved using his famous diagonalization argument that the real interval [0, 1] is uncountable. We will give a different proof of this fact based on Alice and Bob's game. Proposition 1. If S is countable, then Bob has a winning strategy.

### Review of "Handbook of Human Factors in Medical Device Design", edited by Matthew B. Weinger, Michael E. Wiklund and Daryle J. Gardner-Bonneau, Assistant Editor Loir M. Kelly

Jonathan A Gaev
2011 BioMedical Engineering OnLine
Gardner-Bonneau, Assistant Editor Loir M. Kelly. BioMedical Engineering OnLine 2011 10:46.  ...  ISBN: 978-0-8058-5627-9 (Hardcover) this article as: Gaev: Review of "Handbook of Human Factors in Medical Device Design", edited by Matthew B. Weinger, Michael E. Wiklund and Daryle J.  ...

### Rethinking dopamine prediction errors [article]

Matthew P.H. Gardner, Geoffrey Schoenbaum, Samuel J. Gershman
2017 bioRxiv   pre-print
Midbrain dopamine neurons are commonly thought to report a reward prediction error, as hypothesized by reinforcement learning theory. While this theory has been highly successful, several lines of evidence suggest that dopamine activity also encodes sensory prediction errors unrelated to reward. Here we develop a new theory of dopamine function that embraces a broader conceptualization of prediction errors. By signaling errors in both sensory and reward predictions, dopamine supports a form of
more » ... einforcement learning that lies between model-based and model-free algorithms. We show that the theory can account for the role of dopamine in phenomena such as sensory preconditioning and identity unblocking, which ostensibly draw upon knowledge beyond reward predictions.

### Learning from Task Descriptions [article]

Orion Weller, Nicholas Lourie, Matt Gardner, Matthew E. Peters
2020 arXiv   pre-print
., 2019; Gardner et al., 2020) . Teaching a system to learn a task from the description alone would alleviate these biases, as new training data would not be needed to learn a novel task.  ...  Additionally, when tasks are closely related we use a more stringent consistency metric (Gardner et al., 2020 ) that computes whether a model is competent in both tasks at the same time.  ...

### Views

Thomas Dinsdale-Young, Lars Birkedal, Philippa Gardner, Matthew Parkinson, Hongseok Yang
2013 SIGPLAN notices
Dinsdale-Young, Gardner and Yang acknowledge support from EPSRC.  ...

### Prospective representations in rat orbitofrontal ensembles [article]

Jingfeng Zhou, Wenhui Zong, Chunying Jia, Matthew P.H. Gardner, Geoffrey Schoenbaum
2020 bioRxiv   pre-print
The orbitofrontal cortex (OFC) has been proposed to encode expected outcomes, which is thought to be important for outcome-directed behavior. However, such neural encoding can also often be explained by the recall of information about the recent past. To dissociate the retrospective and prospective aspects of encoding in the OFC, we designed a non-spatial, continuous, alternating odor-sequence task that mimicked a continuous T-maze. The task consisted of two alternating sequences of four
more » ... ided trials (2 sequences x 4 positions). In each trial, rats were asked to make a "go" or "no-go" action based on a fixed odor-reward contingency. Odors at both the first and last positions were distinct across the two sequences, such that they resembled unique paths in the past and future, respectively; odors at positions in between were the same and thus resembled a common path. We trained classifiers using neural activity to distinguish between either sequences or positions and asked whether the neural activity patterns in the common path were more like the ones in the past or the future. We found a proximal prospective code for sequence information as well as a distal prospective code for positional information, the latter of which was closely associated with rats' ability to predict future outcomes. This study demonstrates a prospective behaviorally-relevant predictive code in rat OFC.

### eCD4-Ig promotes ADCC activity of sera from HIV-1-infected patients

Meredith E. Davis-Gardner, Matthew R. Gardner, Barnett Alfant, Michael Farzan, Ronald Swanstrom
2017 PLoS Pathogens
Antibody-dependent cell-mediated cytotoxity (ADCC) can eliminate HIV-1 infected cells, and may help reduce the reservoir of latent virus in infected patients. Sera of HIV-1 positive individuals include a number of antibodies that recognize epitopes usually occluded on HIV-1 envelope glycoprotein (Env) trimers. We have recently described eCD4-Ig, a potent and exceptionally broad inhibitor of HIV-1 entry that can be used to protect rhesus macaques from multiple high-dose challenges with
more » ... an immunodeficiency virus AD8 (SHIV-AD8). Here we show that eCD4-Ig bearing an IgG1 Fc domain (eCD4-IgG1) can mediate efficient ADCC activity against HIV-1 isolates with differing tropisms, and that it does so at least 10-fold more efficiently than CD4-Ig, even when more CD4-Ig molecules bound cell surfaceexpressed Env. An ADCC-inactive IgG2 form of eCD4-Ig (eCD4-IgG2) exposes V3-loop and CD4-induced epitopes on cell-expressed trimers, and renders HIV-1-infected cells susceptible to ADCC mediated by antibodies of these classes. Moreover, eCD4-IgG2, but not IgG2 forms of the broadly neutralizing antibodies VRC01 and 10-1074, enhances the ADCC activities of serum antibodies from patients by 100-fold, and significantly enhanced killing of two latently infected T-cell lines reactivated by vorinostat or TNFα. Thus eCD4-Ig is qualitatively different from CD4-Ig or neutralizing antibodies in its ability to mediate ADCC, and it may be uniquely useful in treating HIV-1 infection or reducing the reservoir of latently infected cells. Author summary Antibodies can bind HIV-1-infected cells by recognizing the viral envelope glycoprotein (Env) on the cell surface. Antibody-bound cells then recruit natural killer cells to eliminate these infected cells. Here we demonstrate the unique properties of eCD4-Ig, a potent and exceptionally broad antibody-like HIV-1 entry inhibitor. Like antibodies, eCD4-Ig can efficiently mediate killing of infected cells. However, unlike most antibodies, eCD4-Ig can promote Env conformational changes that then allow abundant but otherwise inert antibodies in patient sera to mediate killing of infected cells. This property may be especially useful in efforts to cure HIV-1 by reactivating virus in latently infected cells and then killing these virus-producing cells.

### eCD4-Ig Variants That More Potently Neutralize HIV-1

Ina Fetzer, Matthew R. Gardner, Meredith E. Davis-Gardner, Neha R. Prasad, Barnett Alfant, Jesse A. Weber, Michael Farzan, Frank Kirchhoff
2018 Journal of Virology
The human immunodeficiency virus type 1 (HIV-1) entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralized all HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates that it has been tested against, suggesting that it may be useful in clinical settings, where antibody escape is a
more » ... oncern. Here, we characterize three new eCD4-Ig variants, each with a different architecture and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as the original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented the promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from those of antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral life cycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the utility of antibodies as a treatment for HIV-1 infection or as part of an effort to eradicate latently infected cells. eCD4-Ig is an antibody-like entry inhibitor that closely mimics HIV-1's obligate receptors. eCD4-Ig appears to be qualitatively different from antibodies, since it neutralizes all HIV-1, HIV-2, and SIV isolates. Here, we characterize three new structurally distinct eCD4-Ig variants and show that each excels in a key property useful to prevent, treat, or cure an HIV-1 infection. For example, one variant neutralized HIV-1 most efficiently, while others best enlisted natural killer cells to eliminate infected cells. These observations will help generate eCD4-Ig variants optimized for different clinical applications.

### Nitric-oxide Dioxygenase Function of Human Cytoglobin with Cellular Reductants and in Rat Hepatocytes

Anne M. Gardner, Matthew R. Cook, Paul R. Gardner
2010 Journal of Biological Chemistry
Cytoglobin (Cygb) was investigated for its capacity to function as a NO dioxygenase (NOD) in vitro and in hepatocytes. Ascorbate and cytochrome b 5 were found to support a high NOD activity. Cygb-NOD activity shows respective K m values for ascorbate, cytochrome b 5 , NO, and O 2 of 0.25 mM, 0.3 M, 40 nM, and ϳ20 M and achieves a k cat of 0.5 s ؊1 . Ascorbate and cytochrome b 5 reduce the oxidized Cygb-NOD intermediate with apparent second order rate constants of 1000 M ؊1 s ؊1 and 3 ؋ 10 6 M
more » ... s ؊1 , respectively. In rat hepatocytes engineered to express human Cygb, Cygb-NOD activity shows a similar k cat of 1.2 s ؊1 , a K m (NO) of 40 nM, and a k cat /K m (NO) (k NOD ) value of 3 ؋ 10 7 M ؊1 s ؊1 , demonstrating the efficiency of catalysis. NO inhibits the activity at [NO]/[O 2 ] ratios >1:500 and limits catalytic turnover. The activity is competitively inhibited by CO, is slowly inactivated by cyanide, and is distinct from the microsomal NOD activity. Cygb-NOD provides protection to the NOsensitive aconitase. The results define the NOD function of Cygb and demonstrate roles for ascorbate and cytochrome b 5 as reductants.

### Donald Barrie Case Reginald ("Rex") Frank Robert Gardner Evan Griffiths Alfred Gordon Heppleston Theodore David Lambert Margaret Joyce Poole Isaac ("Sakkie") Rachman Thomas Rutherford Alexander Marshall Short Jean Margaret Vickers Matthew Westwood John Christopher Wharton

M R Wharton, G. Mackay, L. LeDune, E. Gardner, N. Griffiths, P. Heppleston, G. Conn, C. Cameron, D. Logie, G. Boss, A P. Walker, W A. Johnstone (+4 others)
1998 BMJ (Clinical Research Edition)
[Chris Vickers] Matthew Westwood Former general practitioner and senior hospital medical officer Cirencester Memorial Hospital (b Wolverhampton 1908; q Cambridge/St Bartholomew's 1934; FRCGP) , died  ...

### Deep contextualized word representations [article]

Matthew E. Peters, Mark Neumann, Mohit Iyyer, Matt Gardner, Christopher Clark, Kenton Lee, Luke Zettlemoyer
2018 arXiv   pre-print
A.4 Question Answering Our QA model is a simplified version of the model from Clark and Gardner (2017) .  ...  Our baseline model (Clark and Gardner, 2017) is an improved version of the Bidirectional Attention Flow model in Seo et al. (BiDAF; 2017).  ...

### Concurrent Abstract Predicates [chapter]

Thomas Dinsdale-Young, Mike Dodds, Philippa Gardner, Matthew J. Parkinson, Viktor Vafeiadis
2010 Lecture Notes in Computer Science
Many of our ideas on abstraction originated in Dinsdale-Young, Gardner and Wheelhouse's work on using RGSep to analyse a concurrent B-tree algorithm [6, 22] .  ...

### Conservation must capitalise on climate's moment

Charlie J. Gardner, Matthew J. Struebig, Zoe G. Davies
2020 Nature Communications
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