Multiple Actions Research Articles

Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet.

The incretin axis is an essential component of postprandial insulin secretion and glucose homeostasis. There are two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which exert multiple actions throughout the body. A key cellular target for the incretins are pancreatic β-cells, where they potentiate nutrient-stimulated insulin secretion. This feature of incretins has made this system an attractive target for therapeutic interventions aimed at controlling glycemia. Here, we discuss the role of GIP in both β-cells and α-cells within the islet, to stimulate insulin and glucagon secretion, respectively. Moreover, we discuss how glucagon secretion from α-cells has important insulinotropic actions in β-cells through an axis termed α- to β-cell communication. These recent advances have elevated the potential of GIP and glucagon as a therapeutic targets, coinciding with emerging compounds that pharmacologically leverage the actions of these two peptides in the context of diabetes and obesity.

A large-scale demonstration and sustainability evaluation of ductile-porous vascular networks for self-healing concrete

Self-healing cementitious materials show potential to reduce material consumption, maintenance costs, and environmental impacts within the construction sector. This study explores the feasibility of installing a ductile-porous vascular network in a series of retaining walls under realistic construction conditions, with the objective of both assessing the efficacy of the self-healing system and addressing any constructability issues that may arise. Numerical modelling was performed first to determine a suitable mix design and wall configuration that would promote cracking, so cracks would appear without mechanical intervention. The predicted crack distribution informed the optimal network configuration. Healing and sustainability considerations are discussed, and the benefits of implementing this technology are evaluated. When comparing a single maintenance activity using a vascular network versus manual repair, there is no significant benefit of using a vascular network. However, environmental impacts are substantially reduced when using a vascular network once multiple repair actions are considered.

Prioritization of Ecological Conservation and Restoration Areas through Ecological Networks: A Case Study of Nanchang City, China

Rapid urbanization has led to ecosystem fragmentation, conversion, and degradation, posing great threats to natural habitat and biodiversity. The utilization of ecological networks has gained importance in ecological restoration planning to mitigate the negative impacts of urbanization on ecosystems. This study focused on Nanchang City, China, as a case study area to examine the application of integrated ecological networks in 2000, 2010 and 2020. This study analyzed the dynamic characteristics and spatial differences in landscape connectivity, providing evidence-based support for ecological conservation and restoration. The results indicate the following: (1) a decrease in the number of ecological sources and corridors, especially general sources and corridors, along with a decreasing trend in their importance; (2) an increase in ecological barrier points and breakpoints over time, especially in the southeastern region of the study area; and (3) the identification of ecological conservation priority areas, ecological improvement priority areas, and ecological restoration points based on connectivity and dynamic analysis. Multiple priority actions were proposed, which remarkably improved network connectivity and strengthened biodiversity conservation. Our research provides a valuable reference for identifying ecological priorities and developing ecological protection and ecological restoration actions in highly urbanized areas.

Comparison of european surveillance and control programs for Salmonella in broiler and Turkey chains

For the past years, Salmonella has been one of the major foodborne pathogens in Europe, leading to the development of several control efforts to reduce its impact on human health. Poultry meat has been consistently implicated in foodborne cases of salmonellosis. One of the strategies to lessen the burden of salmonellosis in humans was the implementation of national control programs (NCPs) for Salmonella in broilers and turkeys aiming for reductions in these animal populations. In this paper, a description and comparison of the Salmonella surveillance and control programs that are currently implemented for the broiler and turkey chains in different European countries was performed.All the countries studied have set multiple surveillance and control actions for Salmonella at different stages of the broiler and turkey chains, namely the feed, farm and meat levels. Although most of the control programs are aligned with European Union (EU) regulations, some differences were observed, mostly regarding feed controls, farm surveillance schemes, target serovars and the handling of positive flocks. Overall, these differences had a regional pattern, with the Nordic countries having more detailed control programs with a zero-tolerance in meat. The remaining countries generally follow EU legislation, but in some cases, additional specifications were identified by this study.Despite the positive impact of these control programs on the reduction of human cases of salmonellosis, the decreasing tendency has reached a stall. The authors suggest that the NCPs are regularly revised within the framework of risk-based meat assurance systems, and the inclusion of additional target serovars which are simultaneously prevalent in broiler and turkey flocks and relevant in terms of public health within a country or a region. Furthermore, within the revision of NCPs, sampling schemes and strategies need to be consistent, following the risk management approach that has led to very low prevalences of Salmonella in poultry meat in some European countries.

How Platform Ecosystems Can Turbocharge Your Strategy To Address Societal Challenges

As societal value creation gains importance, there is a growing realisation that some complex challenges facing society are hard to tackle by the corporate or even through a public-private partnership. To effectively tackle grand challenges such as food security, clean energy or cybersecurity threats, to name a few, value creation needs to look beyond the organisation’s boundary for multiple stakeholder collective action. So how best to organise for this? A recent research article by Finnish academic Paavo Ritala says, ‘by developing scalable online-cum-physical platforms that engage diverse stakeholders focused on the challenge to be addressed’1

Surprise-minimization as a solution to the structural credit assignment problem.

The structural credit assignment problem arises when the causal structure between actions and subsequent outcomes is hidden from direct observation. To solve this problem and enable goal-directed behavior, an agent has to infer structure and form a representation thereof. In the scope of this study, we investigate a possible solution in the human brain. We recorded behavioral and electrophysiological data from human participants in a novel variant of the bandit task, where multiple actions lead to multiple outcomes. Crucially, the mapping between actions and outcomes was hidden and not instructed to the participants. Human choice behavior revealed clear hallmarks of credit assignment and learning. Moreover, a computational model which formalizes action selection as the competition between multiple representations of the hidden structure was fit to account for participants data. Starting in a state of uncertainty about the correct representation, the central mechanism of this model is the arbitration of action control towards the representation which minimizes surprise about outcomes. Crucially, single-trial latent-variable analysis reveals that the neural patterns clearly support central quantitative predictions of this surprise minimization model. The results suggest that neural activity is not only related to reinforcement learning under correct as well as incorrect task representations but also reflects central mechanisms of credit assignment and behavioral arbitration.

Synthesis and DFT-optimized structures of hydrazonal-based compound: Biological activity and molecular docking

Distinctive quinolinyl hydrazonal-based compound was synthesized by an azo-coupling reaction of an enaminonitrile (piperidinylacrylonitrile) with the diazonium salt of 8-aminoquinoline. The synthesized compound was characterized by different spectroscopic methods and displayed distinctive solvatochromism. The possible tautomeric transformation of the arylhydrazonal was studied using DFT quantum chemical calculations revealing that the E→Z tautomerization was a spontaneous exothermic process and its equilibrium constant (Keq) was high with positive power. Thus, the Z-tautomer is more favorable than E-tautomer. This study looks at arylhydrazonal's multiple biological actions, showing its substantial promise in antibacterial, antifungal, anticancer, and enzyme inhibition applications. The arylhydrazonal exhibited concentration-dependent strong antibacterial action against Gram-positive and negative bacteria. Moreover, it showed a comparable concentration-dependent antifungal efficiency against C. albicans and A. fumigatus, and close to fluconazole's potency against A. fumigatus. The arylhydrazonal exhibits significant anticancer action, targeting skin and breast cancer cells, suggesting lesser harm to normal cells. In comparison with acetazolamide (AZA), It inhibited carbonic anhydrase isozymes IX and XII with substantial potency against CA-XII. Molecular docking investigations demonstrated the compound's interactions with proteins such 1D2S, 1AS0, 4WW8, and 5Fl4, revealing different binding energies, RMSD values, and stable configurations via hydrogen bonding and π-H stacking interactions. These results highlight the compound's potential as a therapeutic agent in a variety of clinical applications, calling for more study into its development and clinical usage.

Commentary on Carroll & Esposito Amideo “Gender Equality: Opportunities and challenges for the OR community”

This article comprises a set of commentaries for the paper written by Carroll and Esposito Amideo from different scholars and OR practitioners. The commentaries agree on the importance of documenting the gender situation across the OR community and the need to address it through multiple actions.

Androcin 18−1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18−1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18−1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18−1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18−1 in drug development for glioblastoma treatment.

It’s not distance but similarity of distance: changing stimulus relations affect the control of action sequences

Interacting with our environment happens on different levels of complexity: While there are individual and simple actions like an isolated button press, most actions are more complex and involve sequences of simpler actions. The degree to which multiple simple actions are represented as one action sequence can be measured via so-called response-response binding effects. When two or more responses are executed consecutively, they are integrated into one representation so that repetition of one response can start retrieval of the other. Executing such an action sequence typically involves responding to multiple objects or stimuli. Here, we investigated whether the spatial relation of these stimuli affects action sequence execution. To that end, we varied the distance between stimuli in a response-response binding task. Stimulus distance might affect response-response binding effects in one of two ways: It might directly affect the representation of the response sequence, making integration and retrieval between responses more likely if the responses relate to close stimuli. Alternatively, the similarity of stimulus distribution during integration and retrieval might be decisive, leading to larger binding effects if stimulus distance is identical during integration and retrieval. We found stronger binding effects with constant than with changing stimulus distance, indicating that action integration and retrieval can easily affect performance also if responses refer to separated objects. However, this effect on performance is diminished by changing spatial distribution of stimuli at the times of integration and retrieval.

Street Evangelists and Transgender Saints

Abstract This article historicizes the religious fervor of the 1969 Stonewall riots—multiple direct actions against the anti-Black and homo- and transphobic NYPD and white-owned bars in Greenwich Village—by examining the political organizing of Marsha P. Johnson and Sylvia Rivera, cofounders of Street Transvestite Action Revolutionaries. This article queries and queers the field’s preoccupation with the cisgender and heterosexual regarding religious affiliation and the formation of liberation theologies, and probes at the heart of Johnson’s and Rivera’s critical absences in religious studies on the one hand, and the critical absence of their religious sensibilities in narrations of queer and trans politics on the other.

Development of the Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology: a qualitative synthesis of interventions in randomised controlled trials.

Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology. We developed our typology by qualitatively synthesising community-based complex interventions to sustain independence in older people, evaluated in randomised controlled trials (RCTs), in four stages: (i) systematically identifying relevant RCTs; (ii) extracting descriptions of interventions (including control) using the Template for Intervention Description and Replication; (iii) generating categories of key intervention features and (iv) grouping the interventions based on these categories. PROSPERO registration: CRD42019162195. Our search identified 129 RCTs involving 266 intervention arms. The Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology comprises 14 action components and 5 tailoring components. Action components include procedures for treating patients or otherwise intended to directly improve their outcomes; regular examples include formal homecare; physical exercise; health education; activities of daily living training; providing aids and adaptations and nutritional support. Tailoring components involve a process that may result in care planning, with multiple action components being planned, recommended or prescribed. Multifactorial action from care planning was the most common tailoring component. It involves individualised, multidomain assessment and management, as in comprehensive geriatric assessment. Sixty-three different intervention types (combinations) were identified. Our typology provides an empirical basis for service planning and evidence synthesis. We recommend better reporting about organisational aspects of interventions and usual care.

IPSC-derived NK cells with site-specific integration of CAR19 and IL24 at the multi-copy rDNA locus enhanced antitumor activity and proliferation.

The generation of chimeric antigen receptor-modified natural killer (CAR-NK) cells using induced pluripotent stem cells (iPSCs) has emerged as one of the paradigms for manufacturing off-the-shelf universal immunotherapy. However, there are still some challenges in enhancing the potency, safety, and multiple actions of CAR-NK cells. Here, iPSCs were site-specifically integrated at the ribosomal DNA (rDNA) locus with interleukin 24 (IL24) and CD19-specific chimeric antigen receptor (CAR19), and successfully differentiated into iPSC-derived NK (iNK) cells, followed by expansion using magnetic beads in vitro. Compared with the CAR19-iNK cells, IL24 armored CAR19-iNK (CAR19-IL24-iNK) cells showed higher cytotoxic capacity and amplification ability in vitro and inhibited tumor progression more effectively with better survival in a B-cell acute lymphoblastic leukaemia (B-ALL) (Nalm-6 (Luc1))-bearing mouse model. Interestingly, RNA-sequencing analysis showed that IL24 may enhance iNK cell function through nuclear factor kappa B (NFκB) pathway-related genes while exerting a direct effect on tumor cells. This study proved the feasibility and potential of combining IL24 with CAR-iNK cell therapy, suggesting a novel and promising off-the-shelf immunotherapy strategy.

Association of natriuretic peptides and receptor activity with cardio-metabolic health at middle age

Natriuretic peptides (NP) have multiple actions benefitting cardiovascular and metabolic health. Although many of these are mediated by Guanylyl Cyclase (GC) receptors NPR1 and NPR2, their role and relative importance in vivo is unclear. The intracellular mediator of NPR1 and NPR2, cGMP, circulates in plasma and can be used to examine relationships between receptor activity and tissue responses targeted by NPs. Plasma cGMP was measured in 348 participants previously recruited in a multidisciplinary community study (CHALICE) at age 50 years at a single centre. Associations between bio-active NPs and bio-inactive aminoterminal products with cGMP, and of cGMP with tissue response, were analysed using linear regression. Mediation of associations by NPs was assessed by Causal Mediation Analysis (CMA). ANP’s contribution to cGMP far exceed those of other NPs. Modelling across three components (demographics, NPs and cardiovascular function) shows that ANP and CNP are independent and positive predictors of cGMP. Counter intuitively, findings from CMA imply that in specific tissues, NPR1 responds more to BNP stimulation than ANP. Collectively these findings align with longer tissue half-life of BNP, and direct further therapeutic interventions towards extending tissue activity of ANP and CNP.

은유적 사상의 부분성(2) - 구조적 은유 ‘죽음’의 은유적 활용을 중심으로 -

The purpose of this study is to examine the partiality of metaphorical utilization in the thought of the conceptual metaphor 'death'. Applying the proposed multifaceted cognitive model (MCM) for this purpose, the results are as follows. First, in terms of the frequency of occurrence of the elements of the MCM, the source aspect in which both single and multiple actions occurred was more diverse than the goal aspect, death, and they were generally in the order of 'goal aspect> shape aspect> action aspect>material aspect'. Second, in terms of the subject's agentic power, we could distinguish between active (12.5%) and passive (87.5%) attitudes, which was consistent with the subject's loss of control in the goal aspect. This allowed us to infer that death is being controlled by the subject's passive attitude rather than being controlled by the subject's active attitude. Third, the identification of the partiality of metaphorical utilization ultimately led to a broader understanding of the target domain of death.

CCL14 testing to guide clinical practice in patients with AKI: Results from an international expert panel

PurposeUrinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown. MethodsWe assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results. ResultsThe strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category). ConclusionsMost recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.

Nanoparticles on pathogenic strains of Staphylococcus aureus and Escherichia coli

Background: Nanoparticles are increasingly being used as an alternative antibiotic to target microorganisms, particularly for treating bacterial infections. In current study it was recognized processes such as metal ion release, induction of oxidative stress, and non-oxidative mechanisms. Developing resistance to nanoparticles is challenging for bacterial cells due to the multiple simultaneous actions against microorganisms, and require several simultaneous gene alterations within the same bacterial cell. Objective: To determine the effect of the titanium dioxide nanoparticles (TiO2NPs) on the activity of the same bacteria that participate in dental caries (Staphylococcus aureus and Escherichia coli). Patients and Methods: The study included 50 patients who attended the dental clinic and took the samples by the wooden swap from the molar area (cervical area of inflamed gingiva and same samples taken from occlusal surface of molar). The collected samples were cultured on “Mannitol salt agar, Blood agar, and MacConkey's agar plates” for separation of the needed bacteria (Staphylococcus aureus and Escherichia coli) that showed wide spreading in the oral cavities and dental carries. TiO2NPs are then created using pulse laser ablation, followed by coating preparation the nanoparticles materials (using a hybrid sol-gel and organ silicate nanoparticles), and finally the prepared nanoparticles to the coating solution and local paint were used for antimicrobial activity of the separated bacteria using different concentrations of TiO2 in the cultures. Results: Characterization showed the phase of the TiO2NPs was spherical, with very few irregularly shaped particles, and had an average small size in millimeters. Antimicrobial activity results showed a strong bactericidal effect against Gram-positive bacteria and demonstrated greater sensitivity to TiO2 nanoparticles at lower concentrations when compared to Gram-negative bacteria. Conclusion: It was shown that nanotechnology promise in treating various infections caused by bacteria, including dental caries. Notably, nanoparticles have demonstrated broad-spectrum antibacterial effects against Gram-positive bacteria. Keywords: TiO2, nanoparticles, Staphylococcus aureus, and E. coli

Electron Microscope Scanning, and Antibacterial Activity of Tio2 Nanoparticles on pathogenic strains of Staphylococcus aureus and Escherichia coli

Background: Nanoparticles are increasingly being used as an alternative antibiotic to target microorganisms, particularly for treating bacterial infections. In current study it was recognized processes such as metal ion release, induction of oxidative stress, and non-oxidative mechanisms. Developing resistance to nanoparticles is challenging for bacterial cells due to the multiple simultaneous actions against microorganisms, and require several simultaneous gene alterations within the same bacterial cell. Objective: To determine the effect of the titanium dioxide nanoparticles (TiO2NPs) on the activity of the same bacteria that participate in dental caries (Staphylococcus aureus and Escherichia coli). Patients and Methods: The study included 50 patients who attended the dental clinic and took the samples by the wooden swap from the molar area (cervical area of inflamed gingiva and same samples taken from occlusal surface of molar). The collected samples were cultured on “Mannitol salt agar, Blood agar, and MacConkey's agar plates” for separation of the needed bacteria (Staphylococcus aureus and Escherichia coli) that showed wide spreading in the oral cavities and dental carries. TiO2NPs are then created using pulse laser ablation, followed by coating preparation the nanoparticles materials (using a hybrid sol-gel and organ silicate nanoparticles), and finally the prepared nanoparticles to the coating solution and local paint was used for antimicrobial activity of the separated bacteria using different concentrations of TiO2 in the cultures. Results: Characterization showed the phase of the TiO2NPs was spherical, with very few irregularly shaped particles, and had an average small size in millimeters. Antimicrobial activity results showed a strong bactericidal effect against Gram-positive bacteria and demonstrated greater sensitivity to TiO2 nanoparticles at lower concentrations when compared to Gram-negative bacteria. Conclusion: It was shown that nanotechnology promise in treating various infections caused by bacteria, including dental caries. Notably, nanoparticles have demonstrated broad-spectrum antibacterial effects against Gram-positive bacteria.

Effect of Warm-Up Exercise on Functional Regulation of Motor Unit Activation during Isometric Torque Production.

In this study, we tested several hypotheses related to changes in motor unit activation patterns after warm-up exercise. Fifteen healthy young men participated in the experiment and the main task was to produce voluntary torque through the elbow joint under the isometric condition. The experimental conditions consisted of two directions of torque, including flexion and extension, at two joint angles, 10° and 90°. Participants were asked to increase the joint torque to the maximal level at a rate of 10% of the maximum voluntary torque. The warm-up protocol followed the ACSM guidelines, which increased body temperature by approximately 1.5°C. Decomposition electromyography electrodes, capable of extracting multiple motor unit action potentials from surface signals, were placed on the biceps and triceps brachii muscles, and joint torque was measured on the dynamometer. The mean firing rate and the recruitment threshold of the decomposed motor units were quantified. In addition, a single motor unit activity from the spike train was quantified for each of five selected motor units. The magnitude of joint torque increased with the warm-up exercise for all the experimental conditions. The results of the motor unit analyses showed a positive and beneficial effect of the warm-up exercise, with an increase in both the mean firing rate and the recruitment threshold by about 56% and 33%, respectively, particularly in the agonist muscle. Power spectral density in the gamma band, which is thought to be the dominant voluntary activity, was also increased by the warm-up exercise only in the high threshold motor units.

Research Progress on Multiple Effects and Clinical Application of Proprotein Convertase Subtilisin-kexin9 Inhibitors

PCSK9 inhibitors (Proprotein convertase subtilisin-kexin9 inhibitors) not only have a good lipid-lowering effect but also have the effects of improving cardiovascular outcome, anti-inflammation, reducing oxidative stress and improving vascular endothelium. In recent years, the continuous research and development of PCSK9 inhibitors have provided new ideas for the treatment of cardiovascular diseases. This article reviews the multiple action mechanisms of PCSK9 inhibitors and their research in kidney disease and cerebrovascular diseases.