scholarly journals Noradrenergic regulation of Win-Stay/Lose-Shift policy and choice determinism in a two-armed bandit task

2020 ◽  
Author(s):  
Kyra Swanson ◽  
Bruno B. Averbeck ◽  
Mark Laubach
Keyword(s):  
Adrenergic System ◽  
Inverse Temperature ◽  
Reward Schedule ◽  
General Role ◽  
Learning Rates ◽  
Feedback Sensitivity ◽  
Decision Policies ◽  
Measure Of Performance ◽  
Primary Measure

AbstractRecent studies have established that one-trial-back decision policies (Win-Stay/Lose-Shift) and measures of reinforcement learning (RL), e.g. learning rate, can explain how animals perform two-armed bandit tasks. In many published studies, outcomes reverse after one option is selected repeatedly (e.g. 8 selections in a row), and the primary measure of performance is the number of reversals completed. Performance and Win-Stay likelihood are confounded by using recent performance to drive reversals. An alternative design reverses outcomes across options over fixed blocks of trials. We used this blocked design and tested rats in a spatial two-armed bandit task. We analyzed performance using Win-Stay/Lose-Shift (WSLS) metrics and a RL algorithm. We found that WSLS policies remain stable with increasing reward uncertainty, while choice accuracy decreases. Within test sessions, learning rates increased as rats adapted their strategies over the first few reversals but inverse temperature remains stable. We found that muscimol inactivation of medial orbital cortex (mOFC) mediates task performance and negative feedback sensitivity. Finally, we examined the role of the adrenergic system in bandit performance, and found yohimbine (2 mg/kg) dramatically decreased sensitivity to positive feedback, leading to decreases in accuracy and inverse temperature. These effects are partially dependent on a2 adrenergic receptors in OFC. Our findings demonstrate a correspondence between reward schedule, WSLS policies and RL metrics in a task design that is free of the confound between Wins and reversals, and that the noradrenergic influence of mOFC on WSLS policy is dissociable from the regions general role in cognitive flexibility.

Dissent in the Atlantic World, 1787–1830

2018 ◽  
Author(s):  
Katherine Carté Engel
Keyword(s):  
United States ◽  
African Americans ◽  
First Amendment ◽  
Church And State ◽  
State Level ◽  
The United States ◽  
American Population ◽  
Simple Fact ◽  
General Role

The very term ‘Dissenter’ became problematic in the United States, following the passing of the First Amendment. The formal separation of Church and state embodied in the First Amendment was followed by the ending of state-level tax support for churches. None of the states established after 1792 had formal religious establishments. Baptists, Congregationalists, Presbyterians, and Methodists accounted for the majority of the American population both at the beginning and end of this period, but this simple fact masks an important compositional shift. While the denominations of Old Dissent declined relatively, Methodism grew quickly, representing a third of the population by 1850. Dissenters thus faced several different challenges. Primary among these were how to understand the idea of ‘denomination’ and also the more general role of institutional religion in a post-establishment society. Concerns about missions, and the positions of women and African Americans are best understood within this context.

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

scholarly journals Knockout of Arabidopsis thaliana VEP1, Encoding a PRISE (Progesterone 5β-Reductase/Iridoid Synthase-Like Enzyme), Leads to Metabolic Changes in Response to Exogenous Methyl Vinyl Ketone (MVK)

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 11
Author(s):  
Jan Klein ◽  
Mona Ernst ◽  
Alexander Christmann ◽  
Marina Tropper ◽  
Tim Leykauf ◽  
...  
Keyword(s):  
Metabolic Networks ◽  
Vinyl Ketone ◽  
Methyl Vinyl Ketone ◽  
General Role ◽  
Methyl Vinyl ◽  
Knockout Mutants ◽  
Number Of Genes ◽  
Vein Patterning ◽  
And Function

Small or specialized natural products (SNAPs) produced by plants vary greatly in structure and function, leading to selective advantages during evolution. With a limited number of genes available, a high promiscuity of the enzymes involved allows the generation of a broad range of SNAPs in complex metabolic networks. Comparative metabolic studies may help to understand why—or why not—certain SNAPs are produced in plants. Here, we used the wound-induced, vein patterning regulating VEP1 (AtStR1, At4g24220) and its paralogue gene on locus At5g58750 (AtStR2) from Arabidopsis to study this issue. The enzymes encoded by VEP1-like genes were clustered under the term PRISEs (progesterone 5β-reductase/iridoid synthase-like enzymes) as it was previously demonstrated that they are involved in cardenolide and/or iridoid biosynthesis in other plants. In order to further understand the general role of PRISEs and to detect additional more “accidental” roles we herein characterized A. thaliana steroid reductase 1 (AtStR1) and compared it to A. thaliana steroid reductase 2 (AtStR2). We used A. thaliana Col-0 wildtype plants as well as VEP1 knockout mutants and VEP1 knockout mutants overexpressing either AtStR1 or AtStR2 to investigate the effects on vein patterning and on the stress response after treatment with methyl vinyl ketone (MVK). Our results added evidence to the assumption that AtStR1 and AtStR2, as well as PRISEs in general, play specific roles in stress and defense situations and may be responsible for sudden metabolic shifts.

Spatial and Temporal Sequence Learning in Patients with Parkinson's Disease or Cerebellar Lesions

2003 ◽  
Vol 15 (8) ◽  
pp. 1232-1243 ◽  
Author(s):  
Jacqueline C. Shin ◽  
Richard B. Ivry
Keyword(s):  
Sequence Learning ◽  
Functional Role ◽  
Phase Relationship ◽  
Reaction Time Task ◽  
Training Sequence ◽  
Temporal Sequence ◽  
General Role ◽  
Cerebellar Damage ◽  
Patient Groups

The functional role of different subcortical areas in sequence learning is not clear. In the current study, Parkinson's patients, patients with cerebellar damage, and age-matched control participants performed a serial reaction time task in which a spatial sequence and a temporal sequence were presented simultaneously. The responses were based on the spatial sequence, and the temporal sequence was incidental to the task. The two sequences were of the same length, and the phase relationship between them was held constant throughout training. Sequence learning was assessed comparing performance when both sequences were present versus when the dimension of interest was randomized. In addition, sequence integration was assessed by introducing phase-shift blocks. A functional dissociation was found between the two patient groups. Whereas the Parkinson's patients learned the spatial and temporal sequences individually, they did not learn the relationship between the two sequences, suggesting the basal ganglia play a functional role in sequence integration. In contrast, the cerebellar patients did not show any evidence of sequence learning at all, suggesting the cerebellum might play a general role in forming sequential associations.

Measuring Moros

2020 ◽  
pp. 65-87
Author(s):  
Michael C. Hawkins
Keyword(s):  
Human Evolution ◽  
Human Potential ◽  
World's Fair ◽  
The Real ◽  
Olympic Athletes ◽  
Double Function ◽  
Human Difference ◽  
Biological Development ◽  
Primary Measure

This chapter examines the role of Moro bodies in the quantification of humanity at the St. Louis World's Fair. Although Moro bodies were routinely quantified in a variety of contexts, the real measure of the Moros' physical prowess was to be established in a grand athletic spectacle known as “Anthropology Days.” With the 1904 Olympics as a backdrop, anthropologist William J. McGee hoped the Anthropology Days would provide an undeniable comparison between “savage” and “civilized” athletes, thus diminishing emphasis on biological development and endorsing culture and technology as the primary measure of human difference. Ultimately, the Moros' role in the quantification of humanity served an important double function. The “semi-civilized” Moros allowed for notions of Caucasian superiority while simultaneously offering an analogy of physical and cultural improvement for all people, thus affirming the efficacy of colonial tutelage and universal human potential. In this way, the Moros were embedded firmly within the central arch of human evolution rather than on its extremes. Unlike “savage” live exhibits or indeed the exceptional Olympic athletes, Moros were more akin to average American patrons.

scholarly journals IL DIRITTO SOCIETARIO TRA DIRITTO COMPARATO E DIRITTO STRANIERO

2013 ◽  
Author(s):  
Giuseppe B. Portale
Keyword(s):  
Comparative Law ◽  
Corporate Law ◽  
Private Company ◽  
General Role ◽  
Foreign Law ◽  
Specific Regulation ◽  
The One ◽  
Substantive Law ◽  
Theoretical Foundations

The article tackles the issues related to the use of comparative law a source of substantive law in a specific legal system, with specific regard to corporate law. Expanding on previous studies on the general role of comparative law in the framework of sources of law (§ 1), the study argues that the comparative argument may be used to regulate purely domestic cases and as well as a play a crucial role in interpreting internal laws (§§ 1.1, 1.2) and analyzes the theoretical foundations of such process (§ 1.3) as well as the problems caused by the application of foreign law by a domestic judge (§ 2). Subsequently, two examples of such usage of the comparative legal argument are provided, drawn from the Italian corporate law experience (§ 3): on the one hand, the introduction of a specific regulation of a simplified private company (società a responsabilità limitata semplificata), representing a circulation of German (Unternehmergesellschaft- UG) and Belgian (société privée a responsabilité limitée starter) models (§ 3.1); on the other hand, the use of comparative law by in the interpretation of the organization structure in the Italian dualistic system (§ 3.2).

Sign in / Sign up

Export Citation Format

Share Document