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2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Marzieh Khani ◽  
Elizabeth Gibbons ◽  
Jose Bras ◽  
Rita Guerreiro

AbstractThe search for rare variants in Alzheimer’s disease (AD) is usually deemed a high-risk - high-reward situation. The challenges associated with this endeavor are real. Still, the application of genome-wide technologies to large numbers of cases and controls or to small, well-characterized families has started to be fruitful.Rare variants associated with AD have been shown to increase risk or cause disease, but also to protect against the development of AD. All of these can potentially be targeted for the development of new drugs.Multiple independent studies have now shown associations of rare variants in NOTCH3, TREM2, SORL1, ABCA7, BIN1, CLU, NCK2, AKAP9, UNC5C, PLCG2, and ABI3 with AD and suggested that they may influence disease via multiple mechanisms. These genes have reported functions in the immune system, lipid metabolism, synaptic plasticity, and apoptosis. However, the main pathway emerging from the collective of genes harboring rare variants associated with AD is the Aβ pathway. Associations of rare variants in dozens of other genes have also been proposed, but have not yet been replicated in independent studies. Replication of this type of findings is one of the challenges associated with studying rare variants in complex diseases, such as AD. In this review, we discuss some of these primary challenges as well as possible solutions.Integrative approaches, the availability of large datasets and databases, and the development of new analytical methodologies will continue to produce new genes harboring rare variability impacting AD. In the future, more extensive and more diverse genetic studies, as well as studies of deeply characterized families, will enhance our understanding of disease pathogenesis and put us on the correct path for the development of successful drugs.


Author(s):  
Hadrien Oliveri ◽  
Alain Goriely

AbstractThe establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites—axons and dendrites—to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.


2021 ◽  
Vol 2089 (1) ◽  
pp. 012056
Author(s):  
K.A. Sunitha ◽  
Ganti Sri Giri Sai Suraj ◽  
G Atchyut Sriram ◽  
N Savitha Sai

Abstract The proposed robot aims to serve as a personal assistant for visually impaired people in obstacle avoidance, in identifying the person (known or unknown) with whom they are interacting with and in navigating. The robot has a special feature in truly locating the subject’s location using GPS. The novel feature of this robot is to identify people with whom the subject interacts. Facial detection and identification in real-time has been a challenge and achieved with accurate image processing using viola jones and SURF algorithms. An obstacle avoidance design has been implanted in the system with many sensors to guide in the correct path. Hence, the robot is a fusion of providing the best of the comfort and safety with minimal cost.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Sinchai Chinvorarat ◽  
Pumyos Vallikul

Purpose The purpose of this paper is to present a novel retractable main landing gear for a light amphibious airplane, while the design, synthesis and analysis are given in details for constructing the main landing gear. Design/methodology/approach The constraint three-position synthesis has given the correct path of all linkages that suitably fit the landing gear into the compartment. The additional lock-link is introduced into the design to ensure the securement of the mechanism while landing. Having the telescopic gas-oil shock strut as a core element to absorb the impact load, it enhances the ability and efficiency to withstand higher impact than others type of light amphibious airplane. Findings By kinematics bifurcation analysis, the optimized value of the unlock spring stiffness at 90 N/m can be found to tremendously reduce the extended-retracted linear actuator force from 500 N to 150 N at the beginning of the retraction sequence. This could limit the size and weight of the landing gear actuator of the light amphibious airplane. Practical implications The drop test of the landing gear to comply with the ASTM f-2245 (Standard Specification for Design and Performance of a Light Sport Airplane) reveals that the novel landing gear can withstand the impact load at the drop height determined by the standard. The maximum impact loading 4.8 G occurs at the drop height of 300 mm, and there is no sign of any detrimental or failure of the landing gear or the structure of the light amphibious airplane. The impact settling time response reaches the 2% of steady-state value in approximately 1.2 s that ensure the safety and stability of the amphibious airplane if it subjects to an accidentally hard landing. Originality/value This paper presents unique applications of a retractable main landing gear of a light amphibious airplane. The proposed landing gear functions properly and complies with the drop test standard, ensuring the safety and reliability of the airplane and exploiting the airworthiness certification process.


Author(s):  
Dhara P. Mehta ◽  
Purva C. Shah ◽  
Meena Daveshwar

Background: Malaria is a major cause of morbidity in the tropics, being a disease of global importance that results in 300-500 million cases annually. Liver involvement manifests as jaundice, hyperbilirubinemia, hepatomegaly and elevated enzymes (transaminases and alkaline phosphatase). Our objective in this study was to evaluate the role of liver function as an indicator of malaria in endemic regions and as a marker of disease severity.Methods: This was an observational cross-sectional study conducted in central laboratory, department of pathology, central laboratory, department of biochemistry, and out-patient department, department of medicine, medical college Baroda and SSG hospital over a period of ten months, from February, 2019 to November, 2019 and included 137 microscopy proven malaria positive cases. The parasite density on peripheral smear was graded as scanty, moderate and heavy.  After procuring the records of serum bilirubin, SGPT and SGOT, statistical analysis of the data was performed.Results: All the 3 parameters show maximum derangement in severe parasitemia with mean values of 3.57, 81.44, and 92.9. While comparing vivax and falciparum malaria, all the LFTs studied show greater derangement in Plasmodium Falciparum when compared to Plasmodium vivax, with greatest difference seen in bilirubin levels (27.78% cases with hyperbilirubinemia in Plasmodium vivax versus 71.43% cases of Plasmodium falciparum showing hyperbilirubinemia).Conclusions: We conclude that altered liver function in form of hyperbilirubinemia and increased liver enzymes in a patient with acute febrile illness increase the probability of malaria, hence directing the clinician along the correct path of further work-up and accurate treatment.


2021 ◽  
Vol 2 (2) ◽  
pp. p12
Author(s):  
Shen Qunying

Sakya’s Aphorisms and Bacon’s Essays make a profound observation of social reality, comment on various social phenomena, and convey their rational meditation and political views on social and political life. Here is a comparative study of the two classic literary works with a distance of more than 300 years so as to inherit and carry forward the excellent traditional culture at home and abroad, nourish and enlighten today’s officials to take the right way, follow the law and the correct path of cadre growth, and reserve the corresponding competences.


2021 ◽  
Author(s):  
Yuqi Tan ◽  
Abby Spangler ◽  
Michael Farid ◽  
Da Peng ◽  
Patrick Cahan

Stem cell engineering is a powerful platform to address numerous challenges in regenerative medicine and developmental biology. Typically, engineered populations are derived by exposing pluripotent stem cells to a series of signaling cues meant to recapitulate developmental milestones, such as the induction of the primitive streak. Morphologic, genetic, transcriptomic, and functional differences between fully differentiated in vivo and engineered populations have long been recognized. However, the correspondence between engineered and native embryonic progenitors has been relatively less well characterized, largely due to their transient and highly heterogenous nature, and therefore many studies have relied on expression of a few canonical markers to ensure that their cells are on the correct path. To address this challenge, we first generated an in vivo gastrulation mouse single cell RNA sequencing (scRNA-seq) reference data set and used it to train a collection of computational tools for comparing cell types, states, regulators, and trajectories across studies. Then we used these tools to evaluate a commonly used protocol designed to promote mesoderm derivation, as well as four previously published biomimetic protocols. Finally, we diversified our toolkits to reach a broader scientific community by implementing our primary analysis tool in Python and as an interactive web application.


2021 ◽  
Vol 5 ◽  
Author(s):  
Marianella Herrera-Cuenca ◽  
Maritza Landaeta Jimenez ◽  
Yaritza Sifontes

Food security in Venezuela presents signs of individual, family, community and national deterioration. The food and nutrition system has been weakened by the decrease in the production and the installation of parallel, irregular and insufficient distribution networks. Economic turmoil, political instability, hyperinflation, and poverty, the highest in recent history, limit the population's income and the access to quality food. The transition from capitalism to state-centered socialism has not been successful in ensuring enough foods for Venezuelans and the effect on the well-being of the population has been detrimental. This study proposes to design a public policy model based on the analysis of food security indicators, to generate an integrated framework of actions. The proposed model considers Dunn's classic public policy approach (2017) and the criteria of the Public Health Tools/Community Nutrition Program-Nutritional Care Process: Nutrition Care Process (NCP) of the Academy of Nutrition and Dietetics, 2012. The World Food Program survey on food security in Venezuela 2019, and the HumVenezuela.com 2020 platform were used. The integrated model includes two levels, one for bringing assistance to the most vulnerable and the other for strategic planning of structural, legal and institutional problems, and health and food safety gaps, in an ethical and moral framework that challenges corruption and promotes education and culture of peace. It is necessary for public policies to have parallel levels of actions to assist those most in need and to face long-term structural changes, which should begin as soon as possible, to ensure the correct path toward development.


2021 ◽  
Author(s):  
Thomas Stephen Collett ◽  
Andrew O Philippides

Wood ants were trained indoors to follow a route in a chosen magnetic direction from the centre of a small, circular arena to find a drop of sucrose at the edge. The arena, surrounded by a white cylindrical wall, was in the centre of a 3D coil system that generated an inclined Earth strength magnetic field in any horizontal direction. Between trials, the chosen magnetic training direction was rotated to a new orientation. Tests were given without food and with fresh or reversed paper on the floor of the arena. In a significant number of tests, ants left the centre facing the goal, or in the opposite direction, but they mostly failed to reach the goal. Tests given early in the day, before any training, show that ants remember the magnetic route direction overnight. On some training trials, the position of the sucrose was also indicated by a black stripe. Not uncommonly, ants first moved in the opposite direction to the stripe before switching to the correct direction. Travel away from the reward seems to express the ant's uncertainty about the correct path to take. Tests show that this uncertainty may stem from competing directional cues linked to the room, suggesting that ants are reluctant to rely on magnetic information alone. We conclude that ants can remember a route direction defined by an Earth-strength magnetic field and that they express any uncertainty about the correct direction by moving for a stretch in the opposite direction. In a second experiment, an upright and an inverted triangle were fixed 90° from each other to the inside of the cylinder. Sucrose was placed beneath one of the triangles, dependent on the direction of the magnetic field. Ants failed to master this task and to approach the magnetically cued triangle. Instead, they preferred to approach the upright triangle. The ants were again uncertain of the correct direction and expressed this uncertainty through paths that had segments directed towards both the inverted and the upright triangles.


2021 ◽  
Vol 2020 (67) ◽  
pp. 51-74
Author(s):  
زيد حبيب حسين ◽  
أ. د. وفاء جعفر المهداوي

In a country exhausted by conflicts, and successive circumstances weakened it, to produce a situation that is least described as "outside of time" at all levels. This research comes in the form of a scenario that shows the correct path that the Iraqi state must follow if it wants for itself and its society to return to time. He stresses that the first step of correction begins with the state itself. It is a choice coupled with the extent of the seriousness of the state in its obligations towards its citizens and people to recover and recover from the accumulated effects of conflicts. It is a scenario based on the assumption that the development state will adopt it as the ideal solution for the Iraqi economy in the post-conflict period. Research has proven this assumption. Therefore, the research recommends building a new social contract between the state and the citizen-based on: 1- human rights. 2- Governance. 3- Citizenship. 4- Participation. And adopting the state's development method with social responsibility, which aims to ensure the achievement of sustainable development priorities.


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