Major Output Research Articles

1525-P: Ventromedial Hypothalamic Nucleus Subset Stimulates Tissue Thermogenesis via Preoptic Outputs

Changes in energy status ignite neural circuits that maintain body weight by engaging peripheral mechanisms that control energy expenditure; obesity results for when these responses are no longer sufficient. The key neural circuits that stimulate energy expenditure have not yet been established, but previous research has identified several critical sites (e.g. preoptic area (POA) and ventromedial hypothalamus (VMN)) that could be part of an interconnected system that controls tissue thermogenesis, which is essential for body weight control. Activating SF1-cre VMN cells in male diet-induced obese mice reduces body fat by 25% in 72 hours. This function is likely mediated at least in part by release of the peptide pituitary adenylate cyclase-activating polypeptide (PACAP), since knockout of PACAP in the VMN induces obesity at thermoneutrality (30C) and suppresses temperature above both the brown and beige adipose tissue in response to feeding. Because some VMN cells densely project to the POA, we hypothesized that VMN PACAP cells activate tissue thermogenesis via preoptic outputs. We placed temperature-sensing microchips above a traditional brown (interscapular brown adipose tissue (iBAT) and beige (inguinal white adipose tissue (iWAT) adipose tissue in Adcyap1(gene for PACAP)cre mice with DIO-ChR2 in the VMN and fiber optic implants in two major VMN outputs: the POA and the bed nucleus of the stria terminalis (BST). Activating VMN fibers in the POA that contain PACAP in both male and female mice, but not the BST, increased iBAT and iWAT temperature, and the effect was most robust when the mice were fasted. In summary, these data indicate that VMN PACAP connections with the POA is important for the induction of tissue thermogenesis, particularly when feeding conditions change. VMN PACAP, as well as associated signaling targets, are critical components to energy balance by activating adipose tissue mechanisms that stimulate energy expenditure. Disclosure A.J.Elmendorf: Other Relationship; Eli Lilly and Company. C.A.Mahler: Stock/Shareholder; AbbVie Inc., Pfizer Inc., AstraZeneca. B.Lorentz: Research Support; Eli Lilly and Company. J.Flak: Research Support; Eli Lilly and Company. Funding American Diabetes Association (Pathway 17-INI-15 to J.F.); Ralph W. and Grace M. Showalter Research Trust; Indiana University; Indiana Biosciences Research Institute

Sustainable Futures for OA Books: The Open Book Collective

This article describes and explains the need for the work of the Open Book Collective (OBC). The OBC is a major output of the COPIM project (Community-Led Infrastructures for Open Access Monographs). The collective will bring together diverse small-to-medium open access (OA) publishers, open publishing service providers, libraries, and other research institutions to create a new, mutually supportive, and interdependent community space and platform designed to sustainthe future of OA book publishing. The OBC is founded upon equitable, community-led governance and helping publishers move beyond Book Processing Charges (BPCs). Central to the functioning of the Open Book Collective is an online platform that will make it far quicker and easier for libraries and other potential subscribers to compare, evaluate, and subscribe to different OA publishers and open service providers via membership packages. The OBC supports small-to-medium OA publishers by way of the COPIM (Community-Led Publication Infrastructures for Open Access Books) philosophy of “scaling small.” This allows publishers and other members to operate sustainably and collaboratively whilst retaining their diverse and singular editorial missions, rather than operating from philosophies centered on economic growth, competition, and monopoly.

Pharmacological evaluation of lateral habenula and rostromedial tegmental nucleus in the expression of ethanol-induced place preference.

Although ethanol administration produces a range of physiological effects, the rewarding aspect associated with its consumption is a major contributory factor to its abuse liability. Recently, lateral habenula (LHb) has been shown to be engaged by both rewarding and aversive stimuli. Its major glutamatergic output, the fasciculus retroflexus, projects to the rostromedial tegmental nucleus (RMTg) and controls the activity of the ventral tegmental area (VTA) dopaminergic system to promote reward circuitry. While several attempts have been made to understand the relationship between LHb and addiction, there is still a lack of knowledge in relation to ethanol addiction. In the present study, by pharmacologically exacerbating or inhibiting the LHb or RMTg neuronal activity during a post-conditioning test, we investigated the role of LHb-RMTg fasciculus retroflexus in ethanol-induced reward behavior using the conditioned place preference (CPP) test. We found that activation of LHb glutamatergic system by intra-LHb administration of l-trans-2,4-pyrrolidine dicarboxylate (PDC) (glutamate transporter inhibitor) significantly decreased CPP score; on the contrary, lamotrigine (inhibits glutamate release) significantly increased CPP score and showed a rewarding effect in CPP. Instead, intra-RMTg administration of muscimol (GABAA receptor agonist) significantly increased CPP score, whereas bicuculline (GABAA antagonist) treatment decreased CPP score. In immunohistochemistry, we found that PDC administration significantly decreased, whereas lamotrigine treatment significantly increased tyrosine hydroxylase immunoreactivity (TH-ir) in VTA and nucleus accumbens (NAc). Furthermore, while intra-RMTg administration of muscimol increased, the bicuculline treatment significantly decreased the TH-ir in VTA and NAc. Together, our behavioral and immunohistochemical results signify the role of LHb and RMTg in the expression of ethanol-conditioned reward behavior.

Bibliometric analysis of holographic data storage literature

Objectives. Snapshots of data can be stored in a holographic medium at varying depths. Data can be written via a spiral data channel in spinning holographic media in the form of circular disks like CDs or DVDs. This data is then read by shining a reference beam through the refraction following writing. However, holographic storage is distinct from CD/DVD media in the sense that information is encoded in all three dimensions. Two-dimensional data is written using a single laser beam that spirals around the material. Prototype holographic storage solutions use minuscule cones formed by individual snapshots or pages to store one million pixels. As compared with magnetic disks and tapes, which have a finite lifespan of 50 years at most, the longevity and dependability of optical media storage is advantageous for long-term archiving. Holographic technology allows for the portability of data-intensive media such as broadcast or high-definition video. However, the shelf life of holographic media remains low due to its sensitivity to light. The primary goals of most storage devices are more storage space and faster data transport. Holographic storage devices have the potential to outperform traditional optical storage devices both in terms of capacity and performance. The present paper aims to evaluate the current international research trends in Holographic Data Storage (HDS) and produce a graphical mapping of co-authorship and countries.Methods. The major outputs of the dataset were authors, document type, publication, institution, nation, and citations. After exporting 1052 data sources, HistCite software was used to analyze the citations; visualization mapping was carried out using VOSviewer software and R programming language for the analysis of the authorcountry-title association on Holographic Storage Devices.Results. The most prominent authors, papers, journals, organizations, and nations in the field of HDS were identified in HistCite. Then, four clusters were investigated using VOSviewer based on author keywords, citation collaboration networks among different organizations, countries, and the HDS co-authorship network.Conclusions. During the study period from 2000–2020 (21 years), 4636 authors contributed to 1052 publications. The highest number of publications was in 2009, with a linear adjustment of R2 = 0.0136. The most prolific author, Lee J., published 3.14% of the articles on this subject. In terms of country distribution, Japan took first-place ranking, claiming 16.54% of the total number of articles. The “holographic” keyword was used in 62.55% of the articles.

Single-cell RNA sequencing analysis of human chondrocytes reveals cell-cell communication alterations mediated by interactive signaling pathways in osteoarthritis.

Objective: Osteoarthritis (OA) is a common joint disorder characterized by degenerative articular cartilage, subchondral bone remodeling, and inflammation. Increasing evidence suggests that the substantial crosstalk between cartilage and synovium is closely related to Osteoarthritis development, but the events that cause this degeneration remain unknown. This study aimed to explore the alterations in intercellular communication involved in the pathogenesis of Osteoarthritis using bioinformatics analysis. Methods: Single-cell transcriptome sequencing (scRNA-seq) profiles derived from articular cartilage tissue of patients with Osteoarthritis were downloaded from a public database. Chondrocyte heterogeneity was assessed using computational analysis, and cell type identification and clustering analysis were performed using the "FindClusters" function in the Seurat package. Intercellular communication networks, including major signaling inputs and outputs for cells, were predicted, and analyzed using CellChat. Results: Seven molecularly defined chondrocytes clusters (homeostatic chondrocytes, hypertrophic chondrocyte (HTC), pre-HTC, regulatory chondrocytes, fibro-chondrocytes (FC), pre-FC, and reparative chondrocyte) with different compositions were identified in the damaged cartilage. Compared to those in the intact cartilage, the overall cell-cell communication frequency and communication strength were remarkably increased in the damaged cartilage. The cellular communication among chondrocyte subtypes mediated by signaling pathways, such as PTN, VISFATIN, SPP1, and TGF-β, was selectively altered in Osteoarthritis. Moreover, we verified that SPP1 pathway enrichment scores increased, but VISFATIN pathway enrichment scores decreased based on the bulk rna-seq datasets in Osteoarthritis. Conclusion: Our results revealed alterations in cell-cell communication among OA-related chondrocyte subtypes that were mediated by specific signaling pathways, which might be a crucial underlying mechanism associated with Osteoarthritis progression.

Differential vulnerability of neuronal subpopulations of the subiculum in a mouse model for mesial temporal lobe epilepsy.

Selective loss of inhibitory interneurons (INs) that promotes a shift toward an excitatory predominance may have a critical impact on the generation of epileptic activity. While research on mesial temporal lobe epilepsy (MTLE) has mostly focused on hippocampal changes, including IN loss, the subiculum as the major output region of the hippocampal formation has received less attention. The subiculum has been shown to occupy a key position in the epileptic network, but data on cellular alterations are controversial. Using the intrahippocampal kainate (KA) mouse model for MTLE, which recapitulates main features of human MTLE such as unilateral hippocampal sclerosis and granule cell dispersion, we identified cell loss in the subiculum and quantified changes in specific IN subpopulations along its dorso-ventral axis. We performed intrahippocampal recordings, FluoroJade C-staining for degenerating neurons shortly after status epilepticus (SE), fluorescence in situ hybridization for glutamic acid decarboxylase (Gad) 67 mRNA and immunohistochemistry for neuronal nuclei (NeuN), parvalbumin (PV), calretinin (CR) and neuropeptide Y (NPY) at 21 days after KA. We observed remarkable cell loss in the ipsilateral subiculum shortly after SE, reflected in lowered density of NeuN+ cells in the chronic stage when epileptic activity occurred in the subiculum concomitantly with the hippocampus. In addition, we show a position-dependent reduction of Gad67-expressing INs by ∼50% (along the dorso-ventral as well as transverse axis of the subiculum). This particularly affected the PV- and to a lesser extent CR-expressing INs. The density of NPY-positive neurons was increased, but the double-labeling for Gad67 mRNA expression revealed that an upregulation or de novo expression of NPY in non-GABAergic cells with a concomitant reduction of NPY-positive INs underlies this observation. Our data suggest a position- and cell type-specific vulnerability of subicular INs in MTLE, which might contribute to hyperexcitability of the subiculum, reflected in epileptic activity.

Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice

Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 in Shank3B knockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype and Shank3B knockout mice. However, activation of the CA2 enhanced vCA1 theta power in Shank3B knockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.

A role for the fornix in temporal sequence memory.

Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system.

Implementation of the Infrastructure Development Program in the City of Maasin, Southern Leyte: a Case Study

SDG No. 9 envisions building resilient infrastructure, promoting inclusive and sustainable industrialization, and fostering innovation. It is congruent with AmBisyon Natin 2040 and Philippine Development Plan which provides a roadmap towards unlocking sustained and inclusive growth for the Philippine economy by accelerating strategic infrastructure development. Hence, this case study was conducted to explore the experiences of the key informants on the Implementation of the Infrastructure Development Program in Maasin City, Southern Leyte as the basis for policy recommendation and theory generation. Utilizing a descriptive-qualitative research design, the data were gathered through an interview with the fourteen key informants and were analyzed following Creswell's six steps in data analysis. The study found that the LGU was able to implement a comprehensive infrastructure development program that fostered economic, social, and environmental sustainability. Generally, the projects were properly implemented by the local officials through the observance of transparency, accountability, and citizen participation. Furthermore, the LGU officials were found to be compliant concerning their financial, managerial, compliance, and result from accountabilities. Although, there were some slight constraints encountered such as non-involvement of private sectors, bureaucratic processes, unprecedented pandemic, and destructive weather conditions, lack of technical skills and qualified manpower, few competent bidders, conflict of interest, political biases, and insufficient resources. Henceforth, the study concludes that the infrastructure development program of Maasin City, Southern Leyte was well implemented and has complied with the basic requirements of RA 9184. A policy recommendation and theory generation were forwarded as the major outputs of the study.

Collateralizing ventral subiculum melanocortin 4 receptor circuits regulate energy balance and food motivation

Hippocampal dysfunction is associated with major depressive disorder, a serious mental illness characterized by not only depressed mood but also appetite disturbance and dysregulated body weight. However, the underlying mechanisms by which hippocampal circuits regulate metabolic homeostasis remain incompletely understood. Here we show that collateralizing melanocortin 4 receptor (MC4R) circuits in the ventral subiculum (vSUB), one of the major output structures of the hippocampal formation, affect food motivation and energy balance. Viral-mediated cell type- and projection-specific input-output circuit mapping revealed that the nucleus accumbens shell (NAcSh)-projecting vSUBMC4R+ neurons send extensive collateral projections of to various hypothalamic nuclei known to be important for energy balance, including the arcuate, ventromedial and dorsomedial nuclei, and receive monosynaptic inputs mainly from the ventral CA1 and the anterior paraventricular nucleus of thalamus. Chemogenetic activation of NAcSh-projecting vSUBMC4R+neurons lead to increase in motivation to obtain palatable food without noticeable effect on homeostatic feeding. Viral-mediated restoration of MC4R signaling in the vSUB partially restores obesity in MC4R-null mice without affecting anxiety- and depression-like behaviors. Collectively, these results delineate vSUBMC4R+ circuits to the unprecedented level of precision and identify the vSUBMC4R signaling as a novel regulator of food reward and energy balance.

Permanent-Magnetically Amplified Robotic Gripper With Less Clamping Width Influence on Compensation Realized by a Stepless Width Adjustment Mechanism

Machines such as robotic grippers use powerful actuators or gearboxes to exert large loads at the expense of energy consumption, volume, and mass. We propose a stepless force amplification mechanism that assists clamping by a pair of permanent magnets, in which the external control force required to adjust their distance, and thus the output force, is suppressed by compensation springs. For further sophistication, we invented a new width adjuster using a lever. By separating the actuation of fingers and compensated magnets temporarily, the adjuster eliminated the nonlinear influence of the object width on the clamping force. The prototype gripper for proof of concept revealed that the adjuster successfully linearized the width-force characteristic with an inclination of 0.15 N/mm, which is sufficiently insignificant compared to the major output force of approximately 50 N. The force amplification effect coexisted with this phenomenon, such that the clamping force was amplified to 137.5% while maintaining the energy consumption of a DC motor, and the force-energy efficiency was multiplied by 1.39. Thus, able to be driven by a weaker, smaller, and lighter actuator, the gripper contributes to extension of the operation time of robots with limited power.

Using Optimized Three-Band Spectral Indices and a Machine Learning Model to Assess Squash Characteristics under Moisture and Potassium Deficiency Stress

Moisture and potassium deficiency are two of the main limiting variables for squash crop performance in many water-stressed places worldwide. If major output decreases are to be avoided, it is critical to detect signs of crop stress as early as possible in the growth cycle. Proximal remote sensing can be a reliable technique for offering a rapid and precise instrument and localized management tool. This study tested the ability of proximal hyperspectral remotely sensed data to predict squash traits in two successive seasons (spring and fall) with varying moisture and potassium rates. Spectral data were collected from drip-irrigated squash that had been treated to varied rates of irrigation and potassium fertilization over both investigated seasons. To forecast potassium-use efficiency (KUE), chlorophyll meter (Chlm), water-use efficiency (WUE), and seed yield (SY) of squash, different commonly used and newly-introduced spectral index values for three bands (3D-SRIs), as well as a Decision Tree (DT) model, were evaluated. The results revealed that the newly constructed three-band SRIs based on the wavelengths of the visible (VIS), near-infrared (NIR), and red-edge regions were sensitive enough to measure the four tested parameters of squash in this study. For instance, NDI558,646,708 presented the highest R2 of 0.75 for KUE, NDI744,746,738 presented the highest R2 of 0.65 for Chlm, and NDI670,628,392 presented the highest R2 of 0.64 for SY of squash. The results further demonstrated that the principal component analysis (PCA) demonstrated the ability to distinguish moisture stress from potassium deficiency stress at the flowering stage onwards. Combining 3D-SRIs, DT-based bands (DT-b), and the aggregate of all spectral characteristics (ASF) with DT models would be an effective strategy for estimating four observed parameters with appropriate accuracy. For example, the model’s approximately 30 spectral characteristics were extremely important for predicting KUE. Its outputs with R2 were, for the training and validation datasets, 0.967 (RMSE = 0.175) and 0.818 (RMSE = 0.284), respectively. For measuring Chlm, the DT-DT-b-20 model demonstrated the best. In the training and validation datasets, the R2 value was 0.993 (RMSE = 0.522) and 0.692 (RMSE = 2.321), respectively. The overall outcomes showed that proximal-reflectance-sensing-based 3D-SRIs and DT models based on 3D-SRIs, DT-b, and ASF could be used to evaluate the four tested parameters of squash under different levels of irrigation regimes and potassium fertilizer.

Ventral Subiculum Inputs to Nucleus Accumbens Medial Shell Preferentially Innervate D2R Medium Spiny Neurons and Contain Calcium Permeable AMPARs.

Ventral subiculum (vSUB) is the major output region of ventral hippocampus (vHIPP) and sends major projections to nucleus accumbens medial shell (NAcMS). Hyperactivity of the vSUB-NAcMS circuit is associated with substance use disorders and the modulation of vSUB activity alters drug seeking and drug reinstatement behavior in rodents. However, to the best of our knowledge, the cell type-specific connectivity and synaptic transmission properties of the vSUB-NAcMS circuit have never been directly examined. Instead, previous functional studies have focused on total ventral hippocampal (vHIPP) output to NAcMS without distinguishing vSUB from other subregions of vHIPP, including ventral CA1 (vCA1). Using ex vivo electrophysiology, we systematically characterized the vSUB-NAcMS circuit with cell type- and synapse-specific resolution in male and female mice and found that vSUB output to dopamine receptor type-1 (D1R) and type-2 (D2R) expressing medium spiny neurons (MSNs) displays a functional connectivity bias for D2R MSNs. Furthermore, we found that vSUB-D1R and vSUB-D2R MSN synapses contain calcium-permeable AMPA receptors in drug-naive mice. Finally, we find that, distinct from other glutamatergic inputs, cocaine exposure selectively induces plasticity at vSUB-D2R synapses. Importantly, we directly compared vSUB and vCA1 output to NAcMS and found that vSUB synapses are functionally distinct and that vCA1 output recapitulated the synaptic properties previously ascribed to vHIPP. Our work highlights the need to consider the contributions of individual subregions of vHIPP to substance use disorders and represents an important first step toward understanding how the vSUB-NAcMS circuit contributes to the etiologies that underlie substance use disorders.SIGNIFICANCE STATEMENT Inputs to nucleus accumbens (NAc) dopamine receptor type 1 (D1R) and D2R medium spiny neurons (MSNs) are critically involved in reward seeking behavior. Ventral subiculum (vSUB) provides robust synaptic input to nucleus accumbens medial shell (NAcMS) and activity of this circuit is linked to substance use disorders. Despite the importance of the vSUB to nucleus accumbens circuit, the functional connectivity and synaptic transmission properties have not been tested. Here, we systematically interrogated these properties and found that basal connectivity and drug-induced plasticity are biased for D2R medium spiny neurons. Overall, we demonstrate that this circuit is distinct from synaptic inputs from other brain regions, which helps to explain how vSUB dysfunction contributes to the etiologies that underlie substance use disorders.

Optogenetic stimulation of transmission from prelimbic cortex to nucleus accumbens core overcomes resistance to venlafaxine in an animal model of treatment-resistant depression

BackgroundOur earlier study demonstrated that repeated optogenetic stimulation of afferents from ventral hippocampus (vHIP) to the prelimbic region of medial prefrontal cortex (mPFC) overcame resistance to antidepressant treatment in Wistar-Kyoto (WKY) rats. These results suggested that antidepressant resistance may result from an insufficiency of transmission from vHIP to mPFC. Here we examined whether similar effects can be elicited from major output of mPFC; the pathway from to nucleus accumbens core (NAc). MethodWKY rats were subjected to Chronic Mild Stress and were used in two sets of experiments: 1) they were treated acutely with optogenetic stimulation of afferents to NAc core originating from the mPFC, and 2) they were treated with chronic (5 weeks) venlafaxine (10 mg/kg) and/or repeated (once weekly) optogenetic stimulation of afferents to NAc originating from either mPFC or vHIP. ResultsChronic mild stress procedure decreased sucrose intake, open arm entries on elevated plus maze, and novel object recognition test. Acute optogenetic stimulation of the mPFC-NAc and vHIP-NAc pathways had no effect in sucrose or plus maze tests, but increased object recognition. Neither venlafaxine nor mPFC-NAc optogenetic stimulation alone was effective in reversing the effects of CMS, but the combination of chronic antidepressant and repeated optogenetic stimulation improved behaviour on all three measures. ConclusionsThe synergism between venlafaxine and mPFC-NAc optogenetic stimulation supports the hypothesis that the mechanisms of non-responsiveness of WKY rats involves a failure of antidepressant treatment to restore transmission in the mPFC-NAc pathway. Together with earlier results, this implicates insufficiency in a vHIP-mPFC-NAc circuit in non-responsiveness to antidepressant drugs.

DB-HERITAGE Building Materials Data Aggregation in ARIADNE - challenges and opportunities

DB-HERITAGE provides open and free sharing of wide-ranging technical data on hundreds of samples of building materials from diverse periods, extracted from Portuguese built heritage all over the world. It has been developed to improve know-how for historic building materials and as a basis for developing best practices for built heritage conservation. It incorporates both physical and digital repositories for building material samples and related data, providing tools for the systematic recording of data concerning the history, properties, and performance of materials used in Portuguese built heritage. DB-HERITAGE targets different communities, researchers, and stakeholders involved in the preservation of archaeological and architectural heritage. It provides a systematisation of building assets, within their related environmental, social, and cultural contexts, as well as displaying technical and scientific information on structural elements, built components and their constituent materials. Although the rationale of the wide context sustaining the DB-HERITAGE concept, gathering communities and reduced time-to-value represent extra requirements for data quality, improved tools, and an efficient management plan. The participation in ARIADNEplus challenged DB-HERITAGE to get the most out of standardised procedures and the FAIR principles, strengthening its data management plan and practices. Data processing has been improved by deploying a common ontology and further developing standards, shared semantics, and identifiers. Updated protocols for data sharing and detailed information on provenance have also been developed to enhance data reuse. This article presents an overview of the aggregation process of DB-HERITAGE data into ARIADNEplus. It includes a summary of DB-HERITAGE’s strengths and of the challenges faced within the scope of the aggregation process, with examples of some of DB-HERITAGE’s major outputs. Additionally, it considers the benefits and opportunities provided by participation in ARIADNEplus.

A Novel 2D Micromilling FEM simulation strategy to optimize the flow stress law of IN625

The products miniaturization tendency of the last years led to an acceleration of micromilling process development. Considering the high-quality requirements, a deep knowledge of this operation, concerning ploughing-shearing transition, tool run-out, and tool edge radius effects, is mandatory, especially when machining difficult-to-cut materials. For this reason, this paper introduces a novel 2D micromachining Finite Element Method simulation strategy for micromilling forces evaluation, when cutting IN625. The major output of this technique consists in the computation of an optimized flow stress law, suitable for the simulation of high-speed machining. Particle Swarm Optimization method was employed for optimizing the flow stress parameters by comparing the cutting force predicted by an analytical model previously calibrated on experimental data, providing good agreement. This strategy permits the micromilling process predictive analysis, avoiding costly optimization experimental tests.

Neutrosophic MABAC Method for Solutions of Ecotourism Centers (EC) in COVID-19

The Covid-19 epidemic has had devastating effects on the economy and generated many issues for enterprises worldwide. As a result, it is imperative that during periods of pandemic, options be made available to help impacted companies recover and enhance their operations. One industry that has encountered this issue and has had to overcome substantial obstacles is ecotourism centres. In the first part of this study, we offer several valuable and realistic action strategies for ecotourism centres. Tourism professionals, faculty members, executives, proprietors, and some staff from eco-tourism centres got together for brainstorming meetings to come up with implementation plans. The stated action plans are prioritised based on four factors. One MCDM approach, known as Multi-Attributive Border Approximation area Comparison (MABAC), uses distance and area-based computing algorithms to systematically represent a complicated choice. In this study, we suggest a bipolar neutrosophic MABAC that incorporates the three possible memberships truth, indeterminate, and false into a single set. Using a bipolar neutrosophic language scale, a panel of specialists was asked to rate the outcome values of requirements and options. The major output of the suggested approach is the distances of options from the Border Approximation Area of bipolar neutrosophic MABAC.

Evaluating Refresher Training on MA Course to the Coordinators of Rural Development Subject in Tribhuvan University, Nepal

The refresher course training is pivotal for strengthening teachers’ commitment, sharing knowledge, increasing self-confidence, and keeping them up to date on current teaching learning activities. With this consideration, the aim of this paper is to assess the present syllabus of MA in Rural Development and evaluate the refresher course training program based on four levels of evaluation such as reaction, learning, behavior and result of the program. For that purpose, we purposively selected 25 participants who were associated in 21 campuses including Central Department. We applied survey based evaluation research method and Kirkpatrick four levels (reaction, learning, behavior and result) training evaluation model for assessing and examining outcomes of trainings. It reveals that the training program has evolved into an academic platform for students to share their personal experiences with course structure, teaching learning practices, and student performance. It has increased the capacity of the subject coordinators/teacher in terms of networking, course structure/function, performance assessment and constructivist pedagogy. Besides, they have developed a good network amongst the participants and resource persons. The major outputs of the program are SWOC analysis of course structure, 3Rs (Revisit, Revision and Restructure) course concept as well as list of lesson learn and new possible papers (course of study). Therefore, this short term training might brought long term impact improving course structure/function including pedagogical practices. Finally, course function scale, conceptual learning scale, Constructivist Pedagogy/learning theory scale, level four result/outcomes scale and characteristics of the participants are interlinked and associated significantly.

Corticostriatal Projections Relying on GABA Levels Mediate Exercise-Induced Functional Recovery in Cerebral Ischemic Mice.

Stroke is a neurological disorder characterized by high disability and death worldwide. The occlusion of the middle cerebral artery (MCAO) supplying the cortical motor regions and its projection pathway regions can either kill the cortical neurons or block their projections to the spinal cord and subcortical structure. The cerebral cortex is the primary striatal afferent, and the medium spiny neurons of the striatum have been identified as the major output neurons projecting to the substantia nigra and pallidum. Thus, disconnection of the corticostriatal circuit often occurs in the model of MCAO. In this study, we hypothesize that striatal network dysfunction in cerebral ischemic mice ultimately modulates the activity of striatal projections from cortical neurons to improve dysfunction during exercise training. In this study, we observed that the corticostriatal circuit originating from glutamatergic neurons could partially medicate the improvement of motor and anxiety-like behavior in mice with exercise. Furthermore, exercising or activating a single optogenetic corticostriatal circuit can increase the striatal gamma-aminobutyric acid (GABA) level. Using the GABA-A receptor antagonist, bicuculline, we further identified that the striatal glutamatergic projection from the cortical neurons relies on the GABAergic synapse's activity to modulate exercise-induced functional recovery. Overall, those results reveal that the dorsal striatum-projecting subpopulation of cortical glutamatergic neurons can influence GABA levels in the striatum, playing a critical role in modulating exercise-induced improvement of motor and anxiety-like behavior.

Community-Led Infrastructures for Open Access Books: A Sustainable Model and Platform

This paper introduces two major outputs of the Community-led Open Publication Infrastructures for Monographs project, the Open Book Collective (OBC) and platform and the Opening the Future publishing model. The OBC, a charitable entity, will host an infrastructure and revenue management platform for the support, access, distribution, and promotion of open access (OA) books beyond models relying on book processing models. I then discuss a revenue model for publishers who wish to flip to an OA model without book processing charges. This ‘Opening the Future’ model has already been successfully implemented by two publishers, the Central European University Press and Liverpool University Press. This paper relates to the conference theme of sustaining positive change. The international move towards OA book publishing must be approached through models that render OA books equitable and accessible to the widest variety of international readers and authors. This necessitates thinking beyond book processing charges and the potential monopolisation of the OA landscape by major publishers, supporting a diversity of approaches in a networked model we call ‘scaling small.’