Complex Program Research Articles

Neural circuit mechanisms underlying context-specific halting in Drosophila

Walking is a complex motor programme involving coordinated and distributed activity across the brain and the spinal cord. Halting appropriately at the correct time is a critical component of walking control. Despite progress in identifying neurons driving halting1–6, the underlying neural circuit mechanisms responsible for overruling the competing walking state remain unclear. Here, using connectome-informed models7–9 and functional studies, we explain two fundamental mechanisms by which Drosophila implement context-appropriate halting. The first mechanism (‘walk-OFF’) relies on GABAergic neurons that inhibit specific descending walking commands in the brain, whereas the second mechanism (‘brake’) relies on excitatory cholinergic neurons in the nerve cord that lead to an active arrest of stepping movements. We show that two neurons that deploy the walk-OFF mechanism inhibit distinct populations of walking-promotion neurons, leading to differential halting of forward walking or turning. The brake neurons, by constrast, override all walking commands by simultaneously inhibiting descending walking-promotion neurons and increasing the resistance at the leg joints. We characterized two behavioural contexts in which the distinct halting mechanisms were used by the animal in a mutually exclusive manner: the walk-OFF mechanism was engaged for halting during feeding and the brake mechanism was engaged for halting and stability during grooming.

Multiple Swaps Tested: Rehearsal for Triple and Five Liver Paired Exchanges

Despite several advances in living donor liver transplant (LDLT), many potential living liver donors cannot donate their organs to their relatives because of blood group incompatibility and unsuitable anatomy. Liver paired exchange (LPE) can be used to overcome incompatibilities between living donor-recipient pairs. In this study, we report the early and late results of three and five LDLTs performed simultaneously to initiate the more complex LPE program. By demonstrating that our center is capable of performing up to five LDLTs, we have taken an essential step for establishing a complex LPE program.

Transitioning an implementation research intervention to a sustained clinical service: Telehealth primary care mental health integration implementation in Veterans Health Administration.

Often in implementation science efforts, an intervention originated by research funding does not continue in clinical practice after funding ends, or if it does, the process by which it was sustained remains known only to the implementation research or clinical teams. From 2018 to 2020, we implemented a complex telehealth interdisciplinary behavioral health program supported by research funding. The intervention was Primary Care Mental Health Integration (PCMHI) delivered via televideo from a large parent medical facility to rural satellite clinics (tele-PCMHI) within the Veterans Health Administration. Two implementation facilitators worked closely with clinical leaders and staff to plan, launch, and sustain tele-PCMHI across four sites. The intervention is still maintained by the clinical service and has spread to eight sites. Based on ethnographic and qualitative data collected weekly over 2 years, we categorized sustainment strategies across distinct time periods for this complex program, theoretically grounded in the Dynamic Sustainability Framework, emphasizing changes to adapt intervention fit to rapidly changing context. To contextualize, we identified barriers and strengths, such as difficulty training staff to use new equipment, restructuring clinic workflow, and determining suicide risk management remotely. New barriers arose, and, thus, new strategies were needed to continue implementing at the onset of the COVID-19 pandemic in 2020. Different strategies at different stages of implementation allowed sustainment to be a dynamic and evolving process. Plus, proactive and persistent planning for sustainment early in the effort, along with alignment with performance metrics and national policy, supported continued delivery in real-world organized care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multifaceted profile of PTH excess-related secondary osteoporosis: customized therapy and rehabilitation approach

Many causes of secondary osteoporosis have been identified; endocrine types (such as those linked to male hypogonadism, Cushing’s syndrome, acromegaly, thyrotoxicosis, primary hyperparathyroidism, etc.) represent one of the most challenging ailments since a personalized approach of the endocrine disease is simultaneous required. We aimed to introduce the case of a senior lady who was diagnosed with secondary osteoporosis that was associated with primary hyperparathyroidism and a conservative approach was decided, from anti-osteoporosis drug and calcium lowering agents to the physical rehabilitation and lifestyle recommendations. She also presented double unilateral adrenal incidentaloma and a pituitary incidentaloma as well as a suspected ovarian cyst that she further declined to investigate. Mitigating the non-surgical management in primary hyperparathyroidism showcase (in addition to the zoledronic acid for both osteoporosis and hypercalcemia) a complex program of rehabilitation that included a diet intervention in terms of an adequate hydration and a personalized nutrition for kidney stones primary and secondary prevention, mild physical exercise, avoidance of calcium supplements and keeping a daily chole-calciferol replacement.

Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN

Recent insights into the mechanisms controlling gene expression identified enhancer-associated long non-coding RNAs (elncRNAs) as master players of transcription in cancers. RUNX2, a mammalian RUNT-related transcription factor, is increasingly recognized in cancer biology for its role in supporting survival and progression also in thyroid cancer (TC). We recently identified, within the RUNX2 locus, a novel elncRNA that we named RAIN (RUNX2 associated intergenic lncRNA). We showed that RAIN and RUNX2 expression correlate in TC, both in vitro and in vivo, and that RAIN promotes RUNX2 expression by interacting with and affecting the activity of the RUNX2 P2 promoter through two distinct mechanisms. Here, we took forward these observations to explore the genome-wide transcriptional function of RAIN and its contribution to the RUNX2-dependent gene expression program in TC. By combining multiple omics data, we demonstrated that RAIN functionally cooperates with RUNX2 to the regulation of a subset of functionally related genes involved in promoting matrix remodeling, migration, and loss of differentiation. We showed that RAIN interacts with RUNX2 and its expression is required for the efficient recruitment of this TF to its target regulatory regions. In addition, our data revealed that besides RUNX2, RAIN governs a hierarchically organized complex transcriptional program by controlling a core of cancer-associated TFs that, in turn, orchestrate the expression of downstream genes. This evidence indicates that the functional cooperation observed between RAIN and RUNX2 can be a diffuse work mechanism for this elncRNA.

Plant Immunity Modulation in Arbuscular Mycorrhizal Symbiosis and Its Impact on Pathogens and Pests

Arbuscular mycorrhizal (AM) symbiosis is the oldest and most widespread mutualistic association on Earth and involves plants and soil fungi belonging to Glomeromycotina. A complex molecular, cellular, and genetic developmental program enables partner recognition, fungal accommodation in plant tissues, and activation of symbiotic functions such as transfer of phosphorus in exchange for carbohydrates and lipids. AM fungi, as ancient obligate biotrophs, have evolved strategies to circumvent plant defense responses to guarantee an intimate and long-lasting mutualism. They are among those root-associated microorganisms able to boost plants’ ability to cope with biotic stresses leading to mycorrhiza-induced resistance (MIR), which can be effective across diverse hosts and against different attackers. Here, we examine the molecular mechanisms underlying the modulation of plant immunity during colonization by AM fungi and at the onset and display of MIR against belowground and aboveground pests and pathogens. Understanding the MIR efficiency spectrum and its regulation is of great importance to optimizing the biotechnological application of these beneficial microbes for sustainable crop protection.

Uncovering the key working mechanisms of a complex community-based obesity prevention programme in the Netherlands using ripple effects mapping

BackgroundMuch remains unknown about how complex community-based programmes can successfully achieve long-term impact. More insight is needed to understand the key mechanisms through which these programmes work. Therefore, we conducted an in-depth study in five communities that implemented the Healthy Youth, Healthy Future (JOGG) approach, a Dutch community-based obesity prevention programme. We aimed to identify perceived outcomes and long-term impacts among local stakeholders and explore potential causal pathways and working mechanisms.MethodsWe used ripple effects mapping (REM), a qualitative participatory method to map outcomes and identify causal pathways, in five communities. We involved 26 stakeholders, professionals and policy-makers affiliated with the local JOGG approach, spread over eight REM sessions and conducted individual interviews with 24 additional stakeholders. To uncover working mechanisms, we compared outcomes and causal pathways across communities.ResultsOver 5–9 years of implementation, participants perceived that JOGG had improved ownership of local stakeholders, health policies, intersectoral collaboration and social norms towards promoting healthy lifestyles. Causal pathways comprised small initial outcomes that created the preconditions to enable the achievement of long-term impact. Although exact JOGG actions varied widely between communities, we identified five common working mechanisms through which the JOGG approach contributed to causal pathways: (1) creating a positive connotation with JOGG, (2) mobilizing stakeholders to participate in the JOGG approach, (3) facilitating projects to promote knowledge and awareness among stakeholders while creating successful experiences with promoting healthy lifestyles, (4) connecting stakeholders, thereby stimulating intersectoral collaboration and (5) sharing stakeholder successes that promote healthy lifestyles, which gradually created a social norm of participation.ConclusionsThe JOGG approach seems to work through activating initial stakeholder participation and bolstering the process towards ownership, policy change, and intersectoral collaboration to promote healthy lifestyles. Key working mechanisms can inform further development of JOGG as well as other complex community-based prevention programmes.

Using technology to reduce learning costs and improve program comprehension: Lessons from a survey experiment on Supplemental Nutrition Assistance Program

AbstractThe Supplemental Nutrition Assistance Program (SNAP) provides food assistance to those in need, and while the program reaches many who are eligible, program participation falls short of reaching all who are eligible. One factor contributing to this gap in participation is difficulty understanding program eligibility, a common challenge with means‐tested benefit programs. Governments have attempted to improve public understanding of these complex programs using a range of tools to reduce learning costs, yet we know little about the extent to which these tools work and why. This preregistered survey experiment tests three commonly used methods of communicating SNAP program information, including a flyer, screening tool, and video. Cumulatively, our findings demonstrate that efforts to reduce SNAP learning costs are generally effective at improving comprehension recall and that the type of intervention matters, with the video increasing comprehension scores more than the flyer and screening tool. However, the impact of the intervention does not vary substantially according to household income.

AI chatbots in programming education: Students’ use in a scientific computing course and consequences for learning

Teaching and learning in higher education require adaptation following students' inevitable use of AI chatbots. This study contributes to the empirical literature on students' use of AI chatbots and how they influence learning. The aim of this study is to identify how to adapt programming education in higher engineering education. A mixed-methods case study was conducted of a scientific computing course in a Mechanical Engineering Master's program at a Eindhoven University of Technology in the Netherlands. Data consisted of 29 student questionnaires, a semi-structured group interview with three students, a semi-structured interview with the teacher, and 29 students' grades. Results show that students used ChatGPT for error checking and debugging of code, increasing conceptual understanding, generating, and optimizing solution code, explaining code, and solving mathematical problems. While students reported advantages of using ChatGPT, the teacher expressed concerns over declining code quality and student learning. Furthermore, both students and teacher perceived a negative influence from ChatGPT usage on pair programming, and consequently on student collaboration. The findings suggest that learning objectives should be formulated in more detail, to highlight essential programming skills, and be expanded to include the use of AI tools. Complex programming assignments remain appropriate in programming education, but pair programming as a didactic approach should be reconsidered in light of the growing use of AI Chatbots.

Факторы и уровень суммарного сердечно-сосудистого риска у населения северо-востока России

In northern regions, cardiovascular pathology tends to be more aggressive, is likely to occur at a young age already and often results in disability and even mortality among people who have not yet reached the retirement age. The aim of this study was to assess the structure and age-specific dynamics of basic factors able to cause cardiovascular diseases in men living in northern regions and the total cardiovascular risk. We conducted a one-center experimental cross-sectional comparative one-sample study of 116 men living in the north of the Magadan region. The complex study program included questioning, anthropometric examination, laboratory biochemical tests and molecular-genetic screening of candidate genes of essential hypertension (AGT (rs 4762), AGTR1 (rs5186), ADD1 (rs4961), NOS3 (rs2070744), and АСЕ (rs4340)). Genotyping was performed using real-time polymerase chain reaction. The total cardiovascular risk was calculated using the SCORE scale. The structure of basic risk factors that can cause cardiovascular diseases in men in the Magadan region includes both modifiable (smoking, obesity, essential hypertension, and dyslipidemia) and non-modifiable ones (climatic-geographic and genetic risk factors) in various age groups. With age, risk factors exert stronger influence on each other thus aggravating the clinical course of cardiovascular diseases and increasing risks of fatal cardiac events. This is especially important for northern regions where people are exposed to such non-modifiable risk factors as extreme climate. Moderate risk of cardiovascular diseases (according to the SCORE scale) was established for all men living in the North already at a young age. Therefore, a key task is to develop a strategy for active prevention of cardiovascular pathology that covers public at large starting from younger age groups.

Factors and level of the total cardiovascular risk for people in the north-eastern Russia

In northern regions, cardiovascular pathology tends to be more aggressive, is likely to occur at a young age already and often results in disability and even mortality among people who have not yet reached the retirement age. The aim of this study was to assess the structure and age-specific dynamics of basic factors able to cause cardiovascular diseases in men living in northern regions and the total cardiovascular risk. We conducted a one-center experimental cross-sectional comparative one-sample study of 116 men living in the north of the Magadan region. The complex study program included questioning, anthropometric examination, laboratory biochemical tests and molecular-genetic screening of candidate genes of essential hypertension (AGT (rs 4762), AGTR1 (rs5186), ADD1 (rs4961), NOS3 (rs2070744), and АСЕ (rs4340)). Genotyping was performed using real-time polymerase chain reaction. The total cardiovascular risk was calculated using the SCORE scale. The structure of basic risk factors that can cause cardiovascular diseases in men in the Magadan region includes both modifiable (smoking, obesity, essential hypertension, and dyslipidemia) and non-modifiable ones (climatic-geographic and genetic risk factors) in various age groups. With age, risk factors exert stronger influence on each other thus aggravating the clinical course of cardiovascular diseases and increasing risks of fatal cardiac events. This is especially important for northern regions where people are exposed to such non-modifiable risk factors as extreme climate. Moderate risk of cardiovascular diseases (according to the SCORE scale) was established for all men living in the North already at a young age. Therefore, a key task is to develop a strategy for active prevention of cardiovascular pathology that covers public at large starting from younger age groups.

Efficient grid management: smart forecasting of short-term power load using PSO-LSTM

Recent load forecasting techniques combining machine learning models and hyperparameter optimization algorithms have shown success for short-term load forecasting (STLF) task, but they often require complex programming, higher computational costs, and greater parameter tuning. In this paper, we introduce an improved STLF model that combines Long Short-Term Memory (LSTM) neural network with Particle Swarm Optimization (PSO) for enhanced performance. In the proposed approach, the number of hidden neurons in different LSTM layers, learning rate and the number of iterations for training are optimized using the PSO algorithm. To validate the effectiveness of this method, meteorological data and historical load data from a real-world power grid are used as input. The experimental results reveal PSO significantly enhances hyperparameter tuning for LSTM neural networks, leading to improved predictive modelling. The PSO-LSTM model performed better than the LSTM model by more than 20% (in terms of Mean Absolute Error), and showed low sensitivity to hyperparameters. Comparative analysis with alternative approaches from the literature further validates the PSO-LSTM’s effectiveness in STLF. Additionally, the model achieved stable multi-step prediction capabilities, with average errors of 3.6445 for MAE, 4.6509 for RMSE, and 4.6519 for MAPE over a 1–4 day ahead lead times. This study highlights PSO-LSTM’s enhanced robustness and accuracy in power load prediction while addressing hyperparameter tuning challenges through self-optimization.

Disinhibition enables vocal repertoire expansion after a critical period

The efficiency of motor skill acquisition is age-dependent, making it increasingly challenging to learn complex manoeuvres later in life. Zebra finches, for instance, acquire a complex vocal motor programme during a developmental critical period after which the learned song is essentially impervious to modification. Although inhibitory interneurons are implicated in critical period closure, it is unclear whether manipulating them can reopen heightened motor plasticity windows. Using pharmacology and a cell-type specific optogenetic approach, we manipulated inhibitory neuron activity in a premotor area of adult zebra finches beyond their critical period. When exposed to auditory stimulation in the form of novel songs, manipulated birds added new vocal syllables to their stable song sequence. By lifting inhibition in a premotor area during sensory experience, we reintroduced vocal plasticity, promoting an expansion of the syllable repertoire without compromising pre-existing song production. Our findings provide insights into motor skill learning capacities, offer potential for motor recovery after injury, and suggest avenues for treating neurodevelopmental disorders involving inhibitory dysfunctions.

Secreted Particle Information Transfer (SPIT) - A Cellular Platform for In Vivo Genetic Engineering.

A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for in vivo genetic engineering, Secreted Particle Information Transfer (SPIT) that utilizes human cells as delivery vectors for in vivo genetic engineering. We demonstrate the application of SPIT for cell-cell delivery of Cre recombinase and CRISPR-Cas9 enzymes, we show that genetic logic can be incorporated into SPIT and present the first demonstration of human cells as a delivery platform for in vivo genetic engineering in immunocompetent mice. We successfully applied SPIT to genetically modify multiple organs and tissue stem cells in vivo including the liver, spleen, intestines, peripheral blood, and bone marrow. We anticipate that by harnessing the large packaging capacity of a human cell's nucleus, the ability of human cells to engraft into patients' long term and the capacity of human cells for complex genetic programming, that SPIT will become a paradigm shifting approach for in vivo genetic engineering.

Enhancing energy hub efficiency through advanced modelling and optimization techniques: A case study on micro-refinery output products and parking lot integration

A new model of energy carriers (micro-refinery output products) in the concept of an energy hub is presented. In addition, in the presented model, the effect of different models of parking lot in an energy hub is analyzed. In this study, the uncertainty of the number of electric vehicles was modeled using the Monte Carlo method, and then considering the same conditions, the uncertainty of the number of electric vehicles was calculated using the Probability-Possibility hybrid method. In addition, the study uses a scenario-based approach to address uncertainties related to multi-carrier energy demand and multi-carrier energy prices. In the present paper, ensuring water demand is of great importance, which is why the proposed energy hub structure of a sea desalination unit and sour water treatment that is extracted from the micro refinery output was analyzed. The optimization model presented in this paper for the energy hub is a complex integer linear programming (MILP) that is solved using a CPLEX solver in the GAMS environment. The results show that the use of the Probability-Possibility method resulted in an 8 % reduction in the final energy supply cost in the energy hub compared to the Monte Carlo method.

The main ways and methods of the development of the information bibliographic services of the complex programs

The article is devoted to the problem of the information bibliographic service of complex programs. The information bibliographic experience is analyzed in this article. The author offers to develop the information bibliographic services on the basis of problem-oriented systems.

Complex scientific and technical programs and information requirements

The peculiarities of modern social development have determined the increase in national economy management and planning standards. Complex scientific and technical programs serve the timely and effective solution of major social and economic problems. In this connection, the chief task of all state systems of scientific and technical information (TI) links is to supply information for objective complex programs. The most worthwhile and effective means to supply the objective complex programs with information is to establish problem-oriented data banks (PODB). The article points out the major shortcomings in the existing methods of information requirements (IR) study from the point of view of PODB establishment: PODB can be initiated only after work on the objective complex program has begun. The prognostication of information required by the complex scientific and technical programs' executors is the first step in the establishment of PODB. Its aim is to determine the thematic boundaries of the particular database using the information carried by planning projects and obtained through the opinions of planning bodies and program executors.

Creation of problem-oriented data bases

Program objective method is currently employed for planning the directions of overall industrial intensification and introduction of scientific and technical achievements into practice. Objective complex programs demand respective reorganization of information activities. The fundamentally new approach to data organization lies in the creation of data banks (DB) representing problem-oriented systems for collective use. The accomplished analysis of practice in creation of oriented DB shows that at present there are possibilities to create DB resting upon information resources either provided or generated on the spot, as well as on information and technological, linguistic, program, and technical supply arranged by the Republican automatic system and technical information.

RANCANG BANGUN TRAINABLE ROBOT ARM BERBASIS ARDUINO MEGA 2560 SEBAGAI MEDIA PRAKTIKUM DI LABORATORIUM TEKNIK ELEKTRO UNIVERSITAS PEMBANGUNAN PANCABUDI MEDAN

The design of the Trainable Robot Arm is carried out as a learning medium in the lab. Electrical Engineering University of Development Pancabudi Medan. Trainable Robot Arm is a robotic arm designed to facilitate the process of robot applications in carrying out object transfer tasks without the need to do complex programming every time you want to change the robot's movements. The design of this arm robot is divided into 3 parts, the first is the design and manufacture of robot mechanics, the second is the design and manufacture of robot control/electricity and the third is the manufacture of robot software/programs. The mechanical design of the robot begins with making a 3D design of the robot frame utilizing the non-commercial version of the Fusion360 CAD software, then the 3D design is printed using a 3D Printing machine with PETG (Polyethylene Terephthalate) plastic material. The robot arm is designed to have a 5-DOF (Deegre of Freedom) system, namely Base, Shoulder, Elbow, Wrist and Gripper. As a drive, 5 servo motors with torque are used each, 25 kg/cm for Base and Shoulder, 11kg/cm for Elbow and Wrist, and 1.8 kg/cm for Gripper. From the test results, the Trainable robot arm successfully stores and repeats movements that have been trained to move objects with a mass of 100 grams at a position of 23cm from the axis of the robot arm to the x-axis to a position of 20cm from the axis of the robot to the y-axis as many as 8 repetitions without failure.

Enhancing athletic performance with complex contrast training: A Delphi study of elite strength and conditioning coaches

This Delphi study identifies how elite strength and conditioning coaches prescribe complex contrast training to team sport athletes. Thirty-eight elite strength and conditioning coaches with experience working in high performance settings participated in a three-round survey. Round one was used to collect open-ended responses regarding the programming of complex contrast training. Responses were formulated into statements for rounds two and three, where participants rated their level of agreement using a 9-point Likert scale (agreement threshold ≥80%). In round one, 139 statements were formulated. Twenty-seven statements reached consensus in round two, and four more in round three. Based upon consensus, complex contrast training is best used during the season and dedicated power blocks. It was recommended that strength and power exercises within complex contrast training pairings be performed for 3–4 sets of 3–4 repetitions. Loading of 85–90% of one repetition maximum (1RM) was recommended for strength exercises, with ∼two repetitions in reserve, and BW–30% 1RM for power exercises, with three minutes of rest between contrast sets. Upper body pressing, upper body throwing, lower body squatting and hinging, and lower body jumping and bounding exercises were recommended. Coaches reported using complex contrast training to enhance power-focused training, and because it is more time efficient. Complex contrast training may be a time efficient method of improving athletic performance when training time is limited. Results from this study can guide the development of complex contrast training programs for team-sport athletes, and provides valuable insight into how elite coaches enhance performance.