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Abstract During mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated protein (HURP) and the mitotic kinesin-8 Kif18A, but the underlying mechanism remains elusive. Using single-molecule imaging in vitro, we demonstrate that Kif18A motility is regulated by HURP. While sparse decoration of HURP activates the motor, higher concentrations hinder processive motility. To shed light on this behavior, we determine the binding mode of HURP to microtubules using cryo-EM. The structure helps rationalize why HURP functions as a microtubule stabilizer. Additionally, HURP partially overlaps with the microtubule-binding site of the Kif18A motor domain, indicating that excess HURP inhibits Kif18A motility by steric exclusion. We also observe that HURP and Kif18A function together to suppress dynamics of the microtubule plus-end, providing a mechanistic basis for how they collectively serve in microtubule length control.

Road noise significantly impacts how customers perceive vehicle noise, especially in electric vehicles, where it becomes more noticeable with the lack of the masking effect of the internal combustion engine. In this study, a novel sound quality (SQ) metric to capture the perception of road noise was established with the help of both objective measurements and subjective evaluations on six different vehicles under smooth and rough road conditions. A jury of 50 individuals participated in subjective evaluations in controlled settings, experiencing road noise on six vehicles under both smooth and rough conditions. The same vehicles were also objectively measured in these conditions. Using subjective responses and objective measurements, this study identified key sound quality parameters influencing perception. These parameters were used to develop a new regression model predicting customer perception of road noise, considering both aspects of comfort and satisfaction to follow as a key indicator for road noise, particularly in electric vehicles. While an R2 of 0.312 was obtained with SPL, R2 of 0.972 and 0.999 were obtained with the new comfort and satisfaction metrics, respectively. The effectiveness of the newly created SQ metrics was further validated across various vehicles.

Abstract Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhibited conformation, but the physiological function of Nde1/Ndel1 remains elusive. Here, we investigate how human Nde1 and Lis1 regulate the assembly and subsequent motility of mammalian dynein using in vitro reconstitution and single molecule imaging. We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. Nde1 can compete with the α2 subunit of platelet activator factor acetylhydrolase 1B (PAF-AH1B) for the binding of Lis1, which suggests that Nde1 may disrupt PAF-AH1B recruitment of Lis1 as a noncatalytic subunit, thus promoting Lis1 binding to dynein. Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. Our results provide a mechanistic explanation for how Nde1 and Lis1 synergistically activate the dynein transport machinery.

Ticari araçların önemli bir parçası olan süspansiyon sistemlerini ana görevi; iyi bir sürüş ve yol tutuş performansı sağlamak, dönüş esnasında direksiyon kontrolü sağlamak ve taşıtın kontrol kuvvetlerine iyi yanıt vermektir. Bu nedenle ticari araçların sürüş güvenliğinin ve konforunun sağlanması ön düzen ve süspansiyon sistemlerinin uyumlu ve sorunsuz çalışması ile ilişkilidir. Taşıtlarda sürüş güvenliği ve konforunun sağlanması ön düzen ve süspansiyon sistemlerinin uyum içinde çalışmasına bağlıdır. Bu çalışmada ağır ticari araçlarda kullanılan süspansiyon sistemlerinde aks (diferansiyel) ve şasiyi birbirine bağlayan klasik X kol yapısına alternatif olarak ayrık boru yapılı bir sistem geliştirilmiş ve bunun sonlu elemanlar analizi ile doğrulanması gerçekleştirilmiştir. Mevcutta var olan sistemde kırılma yaşayabilmekte, bu durumda da parçanın tamamen değiştirilmesi gerekmektedir. Yeni çok kollu tasarımda aynı çalışma şartlarında yeterli mukavemet sağlanmış ayrıca parçalı yapısı sayesinde kırılma durumunda ilgili parçanın değiştirilmesine imkan sağlanmıştır.

This study was designed to examine the development of pre-service teachers' knowledge of concept cartoons for three years within the scope of the courses they took. For three years, pre-service teachers took courses in scientific research methods, instructional technologies and material development, special teaching methods and teaching practice. During these lessons, the learning levels of pre-service teachers towards concept cartoons were examined. In the analysis of the data, the concept cartoons evaluation rubric and the concept cartoons application observation chart were used. Although they were not able to prepare concept cartoons and make applications at the expert level, it was concluded that the education the pre-service teachers received was effective. It is thought that arrangements are necessary to ensure the continuation of communication between teachers and lecturers.

The mechanisms of microtubule-based mitochondrial transport remain poorly understood. Here, the authors show that the mitochondrial TRAK adaptors activate the dynein-dynactin complex, enhance the motility of kinesin, and can scaffold both motors to control bidirectional transport.

Gifted students are individuals who show extraordinary development in at least one area compared to their peers. The common feature of gifted students is their creativity. The gifted students need training to improve their skills. If they do not receive such training, their abilities will fade out over time. Problem posing is one of the activities that promote the creative skills of gifted students. Problem posing activities, which are more effective in the development of creativity than problem solving, have little place in the curriculum. Thus, it is thought that awareness will be created about problem-posing activities in the education of gifted students. In this context, the study aims to examine the problem posing skills of gifted students. The results of the present research reveal that one-third of gifted students' answers are left blank. The problems they pose are not difficult. Solving problems often requires at least three steps. The established problems are grammatically correct in view of Turkish language. The gifted students have used the mathematical language correctly in the problems. These results are compared with the studies in the literature and discussed. As a result of the research, various suggestions have been made to the teachers of gifted students and other teachers who will work in the field in question.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. While the N protein forms spherical assemblies with homopolymeric RNA substrates that do not form base pairing interactions, it forms asymmetric condensates with viral RNA strands. Cross-linking mass spectrometry (CLMS) identified a region that drives interactions between N proteins in condensates, and deletion of this region disrupts phase separation. We also identified small molecules that alter the size and shape of N protein condensates and inhibit the proliferation of SARS-CoV-2 in infected cells. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.

In this paper, a structural design and controller optimization process for a five-bar planar manipulator are studied using three different population-based optimization techniques: particle swarm optimization, genetic algorithm, and differential evolution. First, the desired kinematic properties of the manipulator, such as the position, velocity, and acceleration of the endpoint, are determined using inverse kinematics. Then, an optimization problem is created to minimize the shaking force and moments, and the desired kinematic quantities are implemented as constraints. All the link properties of the manipulator are defined as design variables, and the optimization results are obtained. The results show that it is possible to significantly reduce the shaking force and moment significantly thanks to the optimal design parameters. Finally, the controller is optimized to find the best PID gains considering the forward kinematics of the manipulator. It is observed that the shaking force and shaking moment can be reduced by 99% and 54%, respectively, which has a very positive effect on the accuracy of the trajectory tracking. Moreover, the performances of the optimization methods are compared by using the same number of iterations in the calculations, and thus, it can be seen that the GA method achieves the best results compared to the others. Therefore, the results of this study are of utmost importance for a manufacturer, who wants to design a five-bar planar manipulator and its controller.

Objective Endothelin-1 (ET-1) promotes the progression and induction of sclerotic renal changes in end-stage kidney disease. Membrane-bound endothelin-converting enzyme 1 (ECE-1) is involved in the production of ET-1. The aim of this study was to assess the effects of ECE-1b rs213045 and rs2038089 polymorphisms, which have been shown to be involved in the development of atherosclerosis, hypertension, and nephropathy, on the development of contrast-induced acute kidney injury (CI-AKI) in patients with acute coronary syndrome. Methods Our study included 38 patients with CI-AKI (CI-AKI[+]) and 55 patients without CI-AKI (CI-AKI[−]) who had coronary syndrome. The ECE-1b polymorphisms rs213045 and rs2038089 were assessed using real-time PCR. Serum ET-1 levels were measured by ELISA. Results The distributions of ECE-1b rs213045 and rs2038089 polymorphisms were similar between the two groups. Additionally, the serum ET-1 level did not different between the groups and was not associated with the ECE-1b polymorphisms. Peri-procedural low systolic blood pressure (SBP) was identified as a risk factor for CI-AKI development. Conclusion Our findings indicate that ECE-1b rs213045 and rs2038089 polymorphisms are not associated with CI-AKI development and that peri-procedural low SBP is a risk factor for CI-AKI. However, variations in ECE-1b rs2038089 may contribute to the development of CI-AKI.

CRISPR-Cas9 has been used to image repetitive loci in live cells to explore genome organization. Here the authors demonstrate the imaging of low-repeat regions with a single-guide RNA and the imaging of a non-repetitive region, allowing the tracking of transcriptionally active and inactive regions.

Tracking single molecules in living cells is difficult or impractical owing to their high density. Here the authors introduce a technique of repeatedly photobleaching fluorophores at the boundary of a region of interest, thereby controlling the number of fluorescent particles for observation.

Kinesin-1 and cytoplasmic dynein are microtubule (MT) motors that transport intracellular cargoes. It remains unclear how these motors move along MTs densely coated with obstacles of various sizes in the cytoplasm. Here, we tested the ability of single and multiple motors to bypass synthetic obstacles on MTs in vitro. Contrary to previous reports, we found that single mammalian dynein is highly capable of bypassing obstacles. Single human kinesin-1 motors fail to avoid obstacles, consistent with their inability to take sideways steps on to neighboring MT protofilaments. Kinesins overcome this limitation when working in teams, bypassing obstacles as effectively as multiple dyneins. Cargos driven by multiple kinesins or dyneins are also capable of rotating around the MT to bypass large obstacles. These results suggest that multiplicity of motors is required not only for transporting cargos over long distances and generating higher forces, but also for maneuvering cargos on obstacle-coated MT surfaces.

Today, with the increasing transition to electric vehicles (EVs), the design of highly energy-efficient vehicle architectures has taken precedence for many car manufacturers. To this end, the energy consumption and recovery rates of different powertrain vehicle architectures need to be investigated comprehensively. In this study, six different powertrain architectures—four independent in-wheel motors with regenerative electronic stability control (RESC) and without an RESC, one-stage gear (1G) transmission, two-stage gear (2G) transmission, continuously variable transmission (CVT) and downsized electric motor with CVT—were mathematically modeled and analyzed under real road conditions using nonlinear models of an autonomous hydrogen fuel-cell electric vehicle (HFCEV). The aims of this paper were twofold: first, to compare the energy consumption performance of powertrain architectures by analyzing the effects of the regenerative electronic stability control (RESC) system, and secondly, to investigate the usability of a downsized electrical motor for an HFCEV. For this purpose, all the numerical simulations were conducted for the well-known FTP75 and NEDC urban drive cycles. The obtained results demonstrate that the minimum energy consumption can be achieved by a 2G-based powertrain using the same motor; however, when an RESC system is used, the energy recovery/consumption rate can be increased. Moreover, the results of the article show that it is possible to use a downsized electric motor due to the CVT, and this powertrain significantly reduces the energy consumption of the HFCEV as compared to all the other systems. The results of this paper present highly significant implications for automotive manufacturers for designing and developing a cleaner electrical vehicle energy consumption and recovery system.

In this study, the gas piston actuated opening-closing trunk lid mechanisms used in passenger cars are investigated theoretically and experimentally. First, the position analysis of the mechanism which is a four-bar linkage has been carried out. Then the quasi-static analyzes according to the principle of virtual work have been made, and so the hand force, one of the most important parameters in terms of ergonomics, required for opening and closing the trunk lid has been calculated. In order to verify this developed model, the hand force has been determined also experimentally, performing the physical tests on an existing vehicle at Turkish Automobile Factory Inc. (TOFAŞ). Eventually, it is observed that the results obtained from mathematical model and the experimental measurements are compatible each other. This established model will provide convenience for manufacturers to determine the hand force for different model of vehicles.

Kinesin-1 is a two-headed motor that takes processive 8-nm hand-over-hand steps and transports intracellular cargos toward the plus-end of microtubules. Processive motility requires a gating mechanism to coordinate the mechanochemical cycles of the two heads. Kinesin gating involves neck linker (NL), a short peptide that interconnects the heads, but it remains unclear whether gating is facilitated by the NL orientation or tension. Using optical trapping, we measured the force-dependent microtubule release rate of kinesin monomers under different nucleotide conditions and pulling geometries. We find that pulling NL in the backward direction inhibits nucleotide binding and subsequent release from the microtubule. This inhibition is independent of the magnitude of tension (2–8 pN) exerted on NL. Our results provide evidence that the front head of a kinesin dimer is gated by the backward orientation of its NL until the rear head releases from the microtubule.

Intraflagellar transport (IFT) is essential for the elongation and maintenance of eukaryotic cilia and flagella. Due to the traffic jam of multiple trains at the ciliary tip, how IFT trains are remodeled in these turnaround zones cannot be determined by conventional imaging. Using PhotoGate, we visualized the full range of movement of single IFT trains and motors in Chlamydomonas flagella. Anterograde trains split apart and IFT complexes mix with each other at the tip to assemble retrograde trains. Dynein-1b is carried to the tip by kinesin-II as inactive cargo on anterograde trains. Unlike dynein-1b, kinesin-II detaches from IFT trains at the tip and diffuses in flagella. As the flagellum grows longer, diffusion delays return of kinesin-II to the basal body, depleting kinesin-II available for anterograde transport. Our results suggest that dissociation of kinesin-II from IFT trains serves as a negative feedback mechanism that facilitates flagellar length control in Chlamydomonas.

Objectives: We aimed to investigate the role of oxidative stress related with ischemia- reperfusion damage on the pathogenesis of atrial fibrillation (AF) developing after coronary artery bypass graft (CABG) surgery. Study design: In our prospective, single-center study, 118 patients who underwent elective isolated on-pump CABG surgery were included. Patients were divided into two groups according to the development of postoperative atrial fibrillation (POAF) as Group 1: Patients who developed POAF, and Group 2: Patients who remained in sinus rhythm. In addition to preoperative demographic, laboratory, echocardiographic, intraoperative, and postoperative clinical characteristics, levels of plasma total oxidative status (TOS) after placement and removal of aortic cross clamp (ACC) were compared between the two groups. Predictors of POAF were also investigated by multivariate logistic regression analysis. Results: A comparison of preoperative demographic, laboratory, echocardiographic, and postoperative clinical characteristics between the two groups showed that patients in Group 1 were significantly older (65.6+-7.20 vs. 59.6+-9.07, p

The use of continuously variable transmission systems in many different areas such as aerospace, robotics, machinery and automotive industries as an alternative to conventional speed changers with constant ratio becomes widely.Especially in the automotive industry, these systems have been used increasingly, since they enable that internal combustion engines in vehicles run at optimal speeds, and consequently provide considerable fuel savings and therefore lower emission values and also they provide powerful acceleration and quiet working. CVT systems have several constructive variants such as belted, chained, balled, toroidal etc. In this paper, toroidal CVT systems based on elastohydrodynamic principles are concerned with, and fundamental works of last two decades in this field are reviewed. However, the relevant terminology and dynamics along with the control of these systems are briefly treated for better understanding of the literature mentioned. Attention is drawn to the lack of some significant issues in present research works, and potential future works are pointed out. This paper, to the authors’ knowledge, will be the first review on toroidal CVT systems in Turkish literature

Acute coronary syndromes in patients with presence of ST-segment elevation in the anterior precordial leads indicates left anterior descending coronary artery occlusion. However, anterior ST-segment elevation has also been described in right ventricular myocardial infarction and is thought to be due to right coronary artery (RCA) occlusion. We present a rare case of isolated RVMI presenting with anterior ST-segment elevation due to proximal occlusion of a right coronary artery that was treated by primary coronary angioplasty. Primary coronary angioplasty and stenting of this artery was performed resulting in resolution of the chest pain and ST- segment elevation.

Coronary artery anomalies are usually asymptomatic and associated with other cardiac malformations. Dual left anterior descending coronary artery (LAD) is an uncommon congenital anomaly with four subtypes. This anomaly has been described in the angiographic literature and dual LAD types depending on the origin of major septal and diagonal branches and course within the anterior interventricular sulcus. Type IV expresses the anomaly of a rudimentary LAD artery ending in the mid-portion of the anterior interventricular sulcus, and the presence of other LAD originating from the right coronary artery and continuing to the anterior interventricular sulcus. We report the rare case of a patient with the type IV dual left anterior descending coronary artery.

Telomerase synthesizes chromosome-capping telomeric repeats using an active site in telomerase reverse transcriptase (TERT) and an integral RNA subunit template. The fundamental question of whether human telomerase catalytic activity requires cooperation across two TERT subunits remains under debate. In this study, we describe new approaches of subunit labeling for single-molecule imaging, applied to determine the TERT content of complexes assembled in cells or cell extract. Surprisingly, telomerase reconstitutions yielded heterogeneous DNA-bound TERT monomer and dimer complexes in relative amounts that varied with assembly and purification method. Among the complexes, cellular holoenzyme and minimal recombinant enzyme monomeric for TERT had catalytic activity. Dimerization was suppressed by removing a TERT domain linker with atypical sequence bias, which did not inhibit cellular or minimal enzyme assembly or activity. Overall, this work defines human telomerase DNA binding and synthesis properties at single-molecule level and establishes conserved telomerase subunit architecture from single-celled organisms to humans.

Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo transport along microtubules (MTs). Dynein motility has previously been studied on surface-immobilized MTs in vitro, which constrains the motors to move in two dimensions. In this study, we explored dynein motility in three dimensions using an MT bridge assay. We found that dynein moves in a helical trajectory around the MT, demonstrating that it generates torque during cargo transport. Unlike other cytoskeletal motors that produce torque in a specific direction, dynein generates torque in either direction, resulting in bidirectional helical motility. Dynein has a net preference to move along a right-handed helical path, suggesting that the heads tend to bind to the closest tubulin binding site in the forward direction when taking sideways steps. This bidirectional helical motility may allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo transport.

The assembly and maintenance of all cilia and flagella require intraflagellar transport (IFT) along the axoneme. IFT has been implicated in sensory and motile ciliary functions, but the mechanisms of this relationship remain unclear. Here, we used Chlamydomonas flagellar surface motility (FSM) as a model to test whether IFT provides force for gliding of cells across solid surfaces. We show that IFT trains are coupled to flagellar membrane glycoproteins (FMGs) in a Ca2+-dependent manner. IFT trains transiently pause through surface adhesion of their FMG cargos, and dynein-1b motors pull the cell towards the distal tip of the axoneme. Each train is transported by at least four motors, with only one type of motor active at a time. Our results demonstrate the mechanism of Chlamydomonas gliding motility and suggest that IFT plays a major role in adhesion-induced ciliary signaling pathways.

A 23-year-old female with the diagnosis of idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital with severe chest pain. The electrocardiogram (ECG) revealed acute anterior myocardial infarction. She underwent an immediate cardiac catheterization. An occluded left anterior descending (LAD) was detected by coronary angiography. Reperfusion was performed successfully by angioplasty and stenting with optimal distal flow without any complications. In this report we discussed the management strategies of acute myocardial infarction (AMI) in a patient with ITP.

Abstract Background The implementation of evidence-based practices (EBPs) in healthcare is of critical importance, and nursing leadership plays a significant role in this process; however, there is a lack of validated instruments to measure the effectiveness of implementation leadership for EBPs. This study aims to evaluate the validity and reliability of the Turkish version of the Implementation Leadership Scale (ILS) within the context of nursing. Methods Data were obtained through a cross-sectional study. The original ILS was first translated into Turkish and then back into English. The scale was administered to 343 nurses working in a training and research hospital in Türkiye. Content validity was assessed with input from 10 experts. The data set was randomly divided into two subsamples to evaluate the construct validity of the ILS. Exploratory factor analyse (EFA) was conducted in sub-sample 1 (n = 172) and Confirmatory factor analyse (CFA) was conducted in sub-sample 2 (n = 171). Reliability was assessed using Cronbach’s alpha values, test-retest reliability, item-total statistics, and split-half reliability. Results The content validity index was calculated to be 0.96, indicating high validity. EFA revealed that the scale consists of four factors with eigenvalues greater than 1, and these factors together explained a high proportion of the total variance (77.10%). Confirmatory factor analysis results (χ2 / df = 1.29; CFI = 0.98; GFI = 0.94; AGFI = 0.91; NFI = 0.94; RMSEA = 0.04) confirmed that the Turkish version of the ILS maintains the original four-factor structure (Proactive, Knowledgeable, Supportive, and Perseverant leadership). Cronbach’s alpha values (0.80–0.88) and intraclass correlation coefficients (ICC) (0.78–0.86) were found to be high. Item-total correlations (0.38–0.63) and the Spearman-Brown coefficient (0.75) were above acceptable levels. Conclusion The findings suggest that the Turkish version of the ILS is a valid and reliable tool for assessing implementation leadership in evidence-based practice (EBP) among nurses. This version of the ILS could contribute to further research on implementation leadership in Türkiye, international comparisons of EBP leadership, and the development of EBP practices.