bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Ergonomic Adjustable Welding Work Facilities Using the DFMA Method
Authors: Noveldi Ahmad , Faisal Ashari  , Rio Chandra Pratama
Published: September 2023

In this modern and sophisticated era, the manufacturing industry is developing both service industries and those that produce products with a variety of shapes and models to attract customers. For example, adjustable welding tables, motorbikes, cars, and others. Companies compete with each other in terms of price, product excellence, product innovation, and product convenience in order to find the right consumer market. DFMA (Design for Manufacturing and Assembly) is a method of making products that aims to facilitate the manufacturing and assembly process where existing designs can be simplified and adapted to the capabilities of the manufacturing facility by considering technical aspects. The scope of design and ergonomics activities includes problems related to human needs, including interior design, furniture design, environmental equipment design, transportation equipment design, textile design, graphic design, etc. (Setiawan, M. S. 2022). At this stage, data collection is carried out, and the author needs to design an adjustable welding table. However, first recompose the table components and determine which are assembly parts and subassembly parts. Then identify each component. Product size and components, labor time, manufacturing data, and others to support research. 1. Analysis of Design Needs 2. Preliminary Design Sketching 3. Design Evaluation 4. Final Design Refinement 4. Final Design Refinement 4. Final Design Refinement 4. Final Design Refinement 4. Final Design Refinement 4. Final Design Refinement. 1) In the previous product development, design 3 was completed with a design that is certainly more ergonomic than design 1, because design 3 has been adjusted to body size using ergonomic standards. 2) Based on the results of the development of this adjustable welding table product, option 3 is the one with the lowest cost because it has a smaller number of components and total assembly steps compared to options 1 and 2. The cost of option 1 is around Rp. 1,780,000; option 2 is around Rp. 1,515,000; and option 3 is around Rp. 870,000. The total assembly steps for option 1 are 40; option 2 is 34; and option 3 is 25. The number of components in options 1 and 2 is 10, while option 3 is only 9.
The Effect of Work Environment and Work Discipline on The Effect of Work Environment, Work Discipline on Employee Performance with Communication as an Intermediate Variable
Authors: Wirawan Maryani , Putri Christin
Published: September 2023

This study aims to examine the influence of the work environment and work discipline on employee performance through communication. The population in this study is all employees. The sample in this study consisted of 129 employees. This study uses a census sampling technique. Data collection techniques obtained using interviews and questionnaires. Based on the results of the analysis of hypothesis testing, it can be found that the accepted hypothesis (influence) is that the work environment has an influence on communication, work discipline has an influence on communication, the work environment has an influence on performance, work discipline has an influence on performance, and the work environment and work discipline have an influence on performance through communication as an intervening variable. The hypothesis that is neither rejected nor accepted is that the work environment has an influence on communication
The Influence of Work Motivation and Work Discipline on Employee Performance Using Promotions at the Special Class I Immigration Office in Surabaya
Authors: Budianto Arif
Published: September 2023

This study aims to analyze the effect of work motivation and work discipline on employee performance using promotions at the Special Class I Immigration Office in Surabaya. Using quantitative methods and measuring instruments SPSS version 26. Respondents used were 135 respondents. The results of this The Influence of Work Motivation and Work Discipline on Employee Performance Using Promotions at the Special Class I Immigration Office in Surabaya has a significant effect
“Breaking the mould”: Resisting the stereotypes of being a Black Canadian student-athlete
Authors: Nartey Humphrey , James Carl E.
Published: September 2023

This article examines how stereotypes operate in the social construction of Black Canadian male student-athletes and how those stereotypes frame these students’ lived experiences in relation to race, athletic ability, and academic performance. From qualitative interviews with twenty current and former Black Canadian student-athletes, we found that they largely resisted and challenged the stereotypes of being primarily athletes and less students. In various ways, they sought to demonstrate that they possessed the skills needed to be academically successful students with the ability to balance their athletic and academic responsibilities and commitments. This was evident in their having obtained the required grades to enter university, receiving athletic scholarships, maintaining playing eligibility, graduating from university, and going on to pursue graduate studies.
iTutorGroup: A case study of covert native-speakerism underneath a social justice façade
Authors: Alvarez Hector Sebastian
Published: September 2023

This article examines the covert native-speakerist strategies iTutorGroup utilizes to discriminate against teachers of nationalities the company appears to deem as undesired. Through content analysis of numerous job application submissions to iTutorGroup’s website, results show iTutorGroup’s automatic hiring process offers teachers of these nationalities a much lower potential wage and only a video-recorded asynchronous interview, if not complete refusal to an interview. In contrast, British, Australasian, and North American nationals are afforded a much higher potential wage as well as a one-on-one live interview. The company conceals these nuanced discriminatory strategies with a façade of equality since they are one of TESOL International Association’s Global Partners. As a Global Partner, iTutorGroup follows suit in pretending to uphold TESOL’s nondiscrimination policies.
Validation of the French version of the student engagement instrument
Authors: Lessard Anne , Lopez Amanda , Diallo Thierno
Published: September 2023

The purpose of this study is to explore the psychometric properties of the French version of the Student Engagement Instrument in order to perform a cross-cultural validation of its factorial structure, based on a sample of 919 French Canadian high school students. Results confirm the reliability of the instrument with good internal consistency (Cronbach’s alpha between .76 and .84). Confirmatory factor analysis shows the validity of the six scales composing the French version of the instrument. Results are significant as there were no standardized instruments with which to evaluate student engagement in high school students in French. Student engagement represents an important intervention target towards improving student achievement and preventing dropout.
Class-wide behaviour management practices reported by pre-and elementary school teachers: Relations with individual and contextual characteristics
Authors: Nadeau Marie-France , Massé Line , Lagacé-Leblanc Jeanne , Verret Claudia , Gaudreau Nancy
Published: September 2023

This study examined the use of inclusive practices by 1,373 Quebec teachers to promote prosocial behaviour, according to their individual and contextual characteristics. Two questionnaires were used: a sociodemographic and a validated Classroom Behaviour Management Practices Inventory (N = 68 items; 2 dimensions/7 scales α = .70 to .90). Results from descriptive and univariate variance analysis showed that proactive /positive dimension practices (e.g., rules, instructional, reinforcement-based) are used more frequently than reductive dimension practices (e.g., educational consequences), although some of the latter are frequently used. Hierarchical models indicate significant interrelationships with teachers characteristics and the scales of classroom behaviour management practices, but for a small proportion of explained variance.
Derrière le lutrin… le déséquilibre qui m’inspire
Authors: Provost Terry
Published: September 2023

This response piece engages in the conversation initiated by Maggie McDonnell and Teresa Strong-Wilson on professional identity. It ponders the question of my role as a college-level professor of art history. Whereas numerous academic institutions have started to decolonise curricula to promote diverse perspectives, certain students, believing multiculturalism applies to all across the board, show indifference in learning decolonised points of view. Here, I examine some of these challenges and the several sides of my role as teacher.
Why the brown ghost chirps at night
Authors: Oboti Livio , Pedraja Federico , Ritter Marie , Lohse Marlena , Klette Lennart , Krahe Rüdiger
Published: September 2023

Since the pioneering work by Moeller, Szabo, and Bullock, weakly electric fish have served as a valuable model for investigating spatial and social cognitive abilities in a vertebrate taxon usually less accessible than mammals or other terrestrial vertebrates. These fish, through their electric organ, generate low-intensity electric fields to navigate and interact with conspecifics, even in complete darkness. The brown ghost knifefish is appealing as a study subject due to a rich electric ‘vocabulary’, made by individually variable and sex-specific electric signals. These are mainly characterized by brief frequency modulations of the oscillating dipole moment continuously generated by their electric organ, and are known as chirps. Different types of chirps are believed to convey specific and behaviorally salient information, serving as behavioral readouts for different internal states during behavioral observations. Despite the success of this model in neuroethology over the past seven decades, the code to decipher their electric communication remains unknown. To this aim, in this study we re-evaluate the correlations between signals and behavior offering an alternative, and possibly complementary, explanation for why these freshwater bottom dwellers emit electric chirps. By uncovering correlations among chirping, electric field geometry, and detectability in enriched environments, we present evidence for a previously unexplored role of chirps as specialized self-directed signals, enhancing conspecific electrolocation during social encounters.
Why the brown ghost chirps at night
Authors: Oboti Livio , Pedraja Federico , Ritter Marie , Lohse Marlena , Klette Lennart , Krahe Rüdiger
Published: September 2023

Since the pioneering work by Moeller, Szabo and Bullock, weakly electric fish have been widely used as a model to approach the study of both spatial and social cognitive abilities in a vertebrate taxon typically less approachable than mammals or other terrestrial vertebrates. Through their electric organ, weakly electric fish generate low-intensity electric fields around their bodies with which they scan the environment to orient themselves and interact with conspecifics even in complete darkness. The brown ghost knifefish is probably the most intensely studied species due to the large repertoire of individually variable and sex-specific electric signals it produces. Their rich electric vocabulary is composed of brief frequency modulations - or chirps - of the oscillating dipole moment emitted continuously by their electric organ. Chirps of different types are thought to convey very specific and behaviorally salient information, and are thus used as references to specific internal states during recordings - of either the brain or the electric organ - or during behavioral observations. However, while this notion undoubtedly contributed to the success of this model in neuroethology during the past seven decades, the logic underlying this electric communication still remains unclear.

This study re-evaluates this view in the attempt to provide an alternative, and perhaps complementary, explanation for why these freshwater bottom dwellers emit electric chirps. By revealing correlations between chirping, electric field geometry and detectability in enriched environments, we provide evidence for a previously unexplored role of chirps as specialized self-directed signals used to expand conspecific electrolocation ranges during social encounters.
A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions
Authors: Xue Gang , Zhang Xiaoyi , Li Wanqi , Zhang Lu , Zhang Zongxu , Zhou Xiaolin , Zhang Di , Zhang Lei , Li Zhiyuan
Published: September 2023

Organisms utilize gene regulatory networks (GRNs) to make fate decisions, but the regulatory mechanisms of transcription factors (TFs) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.
A stochastic world model on gravity for stability inference
Authors: Huang Taicheng , Liu Jia
Published: September 2023

The fact that objects without proper support will fall to the ground is not only a natural phenomenon, but also common sense in mind. Previous studies suggest that humans may infer objects’ stability through a world model that performs mental simulations with
a priori
knowledge of gravity acting upon the objects. Here we measured participants’ sensitivity to gravity’s direction, the most critical parameter of gravity in stability inference, to investigate how the world model works. We found that the world model was not a faithful replica of Newton’s law of gravity but rather encoded gravity’s direction as a Gaussian distribution, with the vertical direction as the maximum likelihood. The world model with this stochastic feature fit nicely with participants’ subjective sense of objects’ stability and explained the illusion that taller objects are perceived as more likely to fall. Furthermore, a computational model with reinforcement learning revealed that the stochastic feature likely originated from agent-environment interaction, and computer simulations illustrated the ecological advantage of the stochastic over deterministic representation of gravity’s direction in balancing accuracy and speed for efficient stability inference. In summary, the stochastic world model on gravity provides an example of how
a priori
knowledge of the physical world is implemented in the brain that helps humans operate flexibly in open-ended environments.
Mechanism of substrate binding and transport in BASS transporters
Authors: Becker Patrick , Naughton Fiona B. , Brotherton Deborah H. , Pacheco-Gomez Raul , Beckstein Oliver , Cameron Alexander D.
Published: September 2023

The Bile Acid Sodium Symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here we solve the crystal structure at 2.3 Å of a transporter from
Neisseria Meningitidis
(ASBT
NM
) in complex with pantoate, a potential substrate of ASBT
NM
. The BASS family is characterised by two helices that cross-over in the centre of the protein in an arrangement that is intricately held together by two sodium ions. We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. During molecular dynamics simulations the pantoate remains in this position when sodium ions are present but is more mobile in their absence. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBT
NM
but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.
Dual recognition of multiple signals in bacterial outer membrane proteins enhances assembly and maintains membrane integrity
Authors: Germany Edward M , Thewasano Nakajohn , Imai Kenichiro , Maruno Yuki , Bamert Rebecca S , Stubenrauch Christopher J , Dunstan Rhys A , Ding Yue , Nakajima Yukari , Lai XiangFeng , Webb Chaille T , Hidaka Kentaro , Tan Kher Shing , Shen Hsinhui , Lithgow Trevor , Shiota Takuya
Published: September 2023

Outer membrane proteins (OMPs) are essential components of the outer membrane of Gram-negative bacteria. In terms of protein targeting and assembly, the current dogma holds that a ‘β-signal’ imprinted in the final β-strand of the OMP engages the β-barrel assembly machinery (BAM) complex to initiate membrane insertion and assembly of the OMP into the outer membrane. Here, we revealed an additional rule that signals equivalent to the β-signal are repeated in other, internal β-strands within bacterial OMPs, by peptidomimetic and mutational analysis. The internal signal is needed to promote the efficiency of the assembly reaction of these OMPs. BamD, an essential subunit of the BAM complex, recognizes the internal signal and the β-signal, arranging several β-strands and partial folding for rapid OMP assembly. The internal signal-BamD ordering system is not essential for bacterial viability but is necessary to retain the integrity of the outer membrane against antibiotics and other environmental insults.
Simultaneous Recognition of Multiple Signals in Bacterial Outer Membrane Proteins Enhance Assembly and Maintain Membrane Integrity
Authors: Germany Edward M. , Thewasano Nakajohn , Imai Kenichiro , Maruno Yuki , Bamert Rebecca S. , Stubenrauch Christopher J. , Dunstan Rhys A. , Ding Yue , Nakajima Yukari , Lai XiangFeng , Webb Chaille T. , Hidaka Kentaro , Tan Kher Shing , Shen Hsin-Hui , Lithgow Trevor , Shiota Takuya
Published: September 2023

Outer membrane proteins (OMPs) are essential components of the outer membrane of Gram-negative bacteria. In terms of protein targeting and assembly, the current dogma holds that a “β-signal” imprinted in the final β-strand of the OMP engages the β-barrel assembly machinery (BAM complex) to initiate membrane insertion and assembly of the OMP into the outer membrane. Here, we reveal an additional rule, that signals equivalent to the β-signal are repeated in other, internal β-strands within bacterial OMPs. The internal signal is needed to promote the efficiency of the assembly reaction of these OMPs. BamD, an essential subunit of the BAM complex, recognizes the internal signal and the β-signal, arranging several β-strands for rapid OMP assembly. The internal signal-BamD ordering system is not essential for bacterial viability but is necessary to retain the integrity of the outer membrane against antibiotics and other environmental insults.Bacterial outer membrane proteins are recognized and bound by BamD at specific signals located in multiple β-strands at the C-terminus of these proteins.
Hundreds of myosin 10s are pushed to the tips of filopodia and could cause traffic jams on actin
Authors: Shangguan Julia , Rock Ronald S
Published: September 2023

Myosin 10 (Myo10) is a motor protein known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the absolute number of Myo10 molecules during the filopodial lifecycle. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. We combined SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it enriches at opposite cellular ends. Hundreds of Myo10s are in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Live-cell movies reveal a dense cluster of over a hundred Myo10 molecules that initiates filopodial elongation. Hundreds of Myo10 molecules continue to accumulate during filopodial growth, but accumulation ceases when retraction begins. Rates of filopodial elongation, second-phase elongation, and retraction are inversely related to Myo10 quantities. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane compartments. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.
Pushed to the edge: hundreds of Myosin 10s pack into filopodia and could cause traffic jams on actin
Authors: Shangguan Julia , Rock Ronald S.
Published: September 2023

Myosin 10 (Myo10) is a vertebrate-specific motor protein well known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the numbers of Myo10 in filopodia. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. Here we combined SDS-PAGE analysis with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it tends to be enriched at opposite ends of the cell. Hundreds of Myo10 are found in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane deformations in addition to the numbers of Myo10 required for filopodia initiation. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.
Enhancing CRISPR prime editing by reducing misfolded pegRNA interactions
Authors: Zhang Weiting , Petri Karl , Ma Junyan , Lee Hyunho , Tsai Chia-Lun , Joung J Keith , Yeh Jing-Ruey Joanna
Published: September 2023

CRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here, we show that sequence complementarity between the 5’ and the 3’ regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as sixfold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.
Double and triple thermodynamic mutant cycles reveal the basis for specific MsbA-lipid interactions
Authors: Lyu Jixing , Zhang Tianqi , Marty Michael T , Clemmer David , Russell David H , Laganowsky Arthur
Published: September 2023

Structural and functional studies of the ATP-binding cassette transporter MsbA have revealed two distinct lipopolysaccharide (LPS) binding sites: one located in the central cavity and the other at a membrane-facing, exterior site. Although these binding sites are known to be important for MsbA function, the thermodynamic basis for these specific MsbA-LPS interactions is not well understood. Here, we use native mass spectrometry to determine the thermodynamics of MsbA interacting with the LPS-precursor 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)2-lipid A (KDL). The binding of KDL is solely driven by entropy, despite the transporter adopting an inward-facing conformation or trapped in an outward-facing conformation with adenosine 5’-diphosphate and vanadate. An extension of the mutant cycle approach is employed to probe basic residues that interact with KDL. We find the molecular recognition of KDL is driven by a positive coupling entropy (as large as –100 kJ/mol at 298 K) that outweighs unfavorable coupling enthalpy. These findings indicate that alterations in solvent reorganization and conformational entropy can contribute significantly to the free energy of protein-lipid association. The results presented herein showcase the advantage of native MS to obtain thermodynamic insight into protein-lipid interactions that would otherwise be intractable using traditional approaches, and this enabling technology will be instrumental in the life sciences and drug discovery.
Activity of MukBEF for chromosome management in E. coli and its inhibition by MatP
Authors: Seba Mohammed , Boccard Frédéric , Duigou Stéphane
Published: September 2023

While different features for the activity of the bacterial canonical SMC complex, Smc-ScpAB, have been described in different bacteria, not much is known about the way chromosomes in enterobacteria interact with their SMC complex, MukBEF. Here we used a number of
in vivo
assays in
E. coli
to reveal how MukBEF controls chromosome conformation and how the MatP/
matS
system prevents MukBEF activity. Our results indicate that the loading of MukBEF occurs preferentially in newly replicated DNA, at multiple loci on the chromosome where it can promote long-range contacts in
cis
even though MukBEF can promote long-range contacts in the absence of replication. Using HiC and ChIP-seq analyses in strains with rearranged chromosomes, the prevention of MukBEF activity increases with the number of
matS
sites and this effect likely results from the unloading of MukBEF by MatP. Altogether, our results reveal how MukBEF operates to control chromosome folding and segregation in E. coli.
Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes
Authors: Link Fabian , Borges Alyssa , Karo Oliver , Jungblut Marvin , Müller Thomas , Meyer-Natus Elisabeth , Krüger Timothy , Sachs Stefan , Jones Nicola G , Morphew Mary , Sauer Markus , Stigloher Christian , McIntosh J Richard , Engstler Markus
Published: September 2023

Endocytosis is a common process observed in most eukaryotic cells, although its complexity varies among different organisms. In Trypanosoma brucei, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune evasion. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization. The entire process of membrane recycling occurs exclusively through the flagellar pocket, an extracellular organelle situated at the posterior pole of the spindle-shaped cell. The high-speed dynamics of membrane flux in trypanosomes do not seem compatible with the conventional concept of distinct compartments for early endosomes (EE), late endosomes (LE), and recycling endosomes (RE). To investigate the underlying structural basis for the remarkably fast membrane traffic in trypanosomes, we employed advanced techniques in light and electron microscopy to examine the three-dimensional architecture of the endosomal system. Our findings reveal that the endosomal system in trypanosomes exhibits a remarkably intricate structure. Instead of being compartmentalized, it constitutes a continuous membrane system, with specific functions of the endosome segregated into membrane subdomains enriched with classical markers for EE, LE, and RE. These membrane subdomains can partly overlap or are interspersed with areas that are negative for endosomal markers. This continuous endosome allows fast membrane flux by facilitated diffusion that is not slowed by multiple fission and fusion events.
Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes
Authors: Link Fabian , Borges Alyssa , Karo Oliver , Jungblut Marvin , Müller Thomas , Meyer-Natus Elisabeth , Krüger Timothy , Sachs Stefan , Jones Nicola G. , Morphew Mary , Sauer Markus , Stigloher Christian , McIntosh J. Richard , Engstler Markus
Published: September 2023

Endocytosis is a common process observed in all eukaryotic cells, although its complexity varies among different organisms. In
Trypanosoma brucei
, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune escape. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization. The entire process of membrane recycling occurs exclusively through the flagellar pocket, an extracellular organelle situated at the posterior pole of the spindle-shaped cell. The high-speed dynamics of membrane flux in trypanosomes do not seem compatible with the conventional concept of distinct compartments for early, late and recycling endosomes. To investigate the underlying structural basis for the remarkably efficient membrane traffic in trypanosomes, we employed advanced techniques in light and electron microscopy to examine the three-dimensional architecture of the endosomal system. Our findings reveal that the endosomal system in trypanosomes exhibits a remarkably intricate structure. Instead of being compartmentalized, it constitutes a continuous membrane system, with specific functions of the endosome segregated into membrane subdomains enriched with classical markers for early, late, and recycling endosomes. These membrane subdomains can partly overlap or are interspersed with areas that are negative for endosomal markers. This continuous endosome allows fast membrane flux by facilitated diffusion that is not slowed by multiple fission and fusion events. Our study further suggests that in trypanosomes, the endosome has taken over the role of the trans-Golgi network as the master regulator of membrane trafficking.
Prickle and Ror modulate Dishevelled-Vangl interaction to regulate non-canonical Wnt signaling during convergent extension
Authors: Seo Hwa-seon , Yu Deli , Popov Ivan , Tao Jiahui , Angermeier Allyson , Sha Bingdong , Axelrod Jeffrey D. , Chang Chenbei , Wang Jianbo
Published: September 2023

Convergent extension (CE) is a fundamental morphogenetic process where oriented cell behaviors lead to polarized extension of diverse tissues. In vertebrates, regulation of CE requires both non-canonical Wnt, its co-receptor Ror, and “core members” of the planar cell polarity (PCP) pathway. PCP was originally identified as a mechanism to coordinate the cellular polarity in the plane of static epithelium, where core proteins Frizzled (Fz)/ Dishevelled (Dvl) and Van Gogh-like (Vangl)/ Prickel (Pk) partition to opposing cell cortex. But how core PCP proteins interact with each other to mediate non-canonical Wnt/ Ror signaling during CE is not clear. We found previously that during CE, Vangl cell-autonomously recruits Dvl to the plasma membrane but simultaneously keeps Dvl inactive. In this study, we show that non-canonical Wnt induces Dvl to transition from Vangl to Fz. PK inhibits the transition, and functionally synergize with Vangl to suppress Dvl during CE. Conversely, Ror is required for the transition, and functionally antagonizes Vangl. Biochemically, Vangl interacts directly with both Ror and Dvl. Ror and Dvl do not bind directly, but can be cofractionated with Vangl. We propose that Pk assists Vangl to function as an unconventional adaptor that brings Dvl and Ror into a complex to serves two functions: 1) simultaneously preventing both Dvl and Ror from ectopically activating non-canonical Wnt signaling; and 2) relaying Dvl to Fz for signaling activation upon non-canonical Wnt induced dimerization of Fz and Ror.
High-content microscopy reveals a morphological signature of bortezomib resistance
Authors: Kelley Megan E , Berman Adi Y , Stirling David R , Cimini Beth A , Han Yu , Singh Shantanu , Carpenter Anne E , Kapoor Tarun M , Way Gregory P
Published: September 2023

Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause. We hypothesized that cell morphology could provide an unbiased readout of drug resistance. To test this hypothesis, we used HCT116 cells, a mismatch repair-deficient cancer cell line, to isolate clones that were resistant or sensitive to bortezomib, a well-characterized proteasome inhibitor and anticancer drug to which many cancer cells possess intrinsic resistance. We then expanded these clones and measured high-dimensional single-cell morphology profiles using Cell Painting, a high-content microscopy assay. Our imaging- and computation-based profiling pipeline identified morphological features that differed between resistant and sensitive cells. We used these features to generate a morphological signature of bortezomib resistance. We then employed this morphological signature to analyze a set of HCT116 clones (five resistant and five sensitive) that had not been included in the signature training dataset, and correctly predicted sensitivity to bortezomib in seven cases, in the absence of drug treatment. This signature predicted bortezomib resistance better than resistance to other drugs targeting the ubiquitin-proteasome system, indicating specificity for mechanisms of resistance to bortezomib. Our results establish a proof-of-concept framework for the unbiased analysis of drug resistance using high-content microscopy of cancer cells, in the absence of drug treatment.
Factors associated with the control of arterial hypertension among users assisted in the family health strategy / Fatores associados ao controle da hipertensão arterial entre usuários atendidos na estratégia saúde da família
Authors: Ferreira Maciel Ana Paula , Junior Rene Ferreira da Silva , Pereira Victor Guilherme , Macedo Otávio Henrique Oliveira , Silva Carla Silvana de Oliveira e , Caldeira Antônio Prates
Published: September 2023

Objetivo: analisar o percentual de pacientes sob tratamento anti-hipertensivo que apresentam níveis de pressão arterial controlados e fatores associados. Método: estudo transversal e analítico. A seleção de pacientes ocorreu por amostragem probabilística, por conglomerados tratados de forma descritiva e analítica. Participaram do estudo 720 indivíduos. Resultados: após regressão logística, permaneceram associadas ao não controle da pressão arterial as variáveis sexo, adesão à terapia medicamentosa, história pregressa de doença cardíaca e automedicar-se. Conclusão: a prevalência de controle da pressão arterial foi de 54,3 %, as dificuldades no tratamento anti-hipertensivo relacionam-se a fatores como aspectos pessoais, ao ambiente de vida, ao acesso aos cuidados de saúde, destacando-se como variável modificável a não adesão medicamentosa. Reforça-se a necessidade de incentivo das políticas públicas para o estabelecimento de novas estratégias para abordagem dos fatores modificáveis no manejo da hipertensão.
Monitoring Structural and Electronic Changes of Supported Metal Catalysts Using Combined X‐Ray Techniques
Authors: Sarnello Erik , Li Tao
Published: September 2023

Supported metal nanoparticle catalysts have become increasingly crucial for many catalytic applications. However, long‐term catalyst stability remains a problem due to catalyst deactivation caused by coke formation and sintering. The deposition of a thin overcoating via atomic layer deposition (ALD) onto metal‐supported nanoparticles has shown to greatly inhibit catalyst deactivation. This work utilizes a model catalyst system comprised of Pt nanoparticles supported on Al2O3 to demonstrate the effect of an atomically thin overcoating on supported metal nanoparticles. Continuous operando small‐angle X‐ray scattering (SAXS) and X‐ray absorption near edge spectroscopy (XANES) monitor structural and electronic changes to the catalyst and overcoating during calcination. SAXS data fitting reveals the formation of nanopores in the overcoating at high temperatures, while XANES monitors the oxidation state of the Pt catalyst. Herein, the usefulness of combined X‐ray techniques is demonstrated to characterize supported metal catalysts to further understanding of the synergistic effects of the ALD overcoating to aid in the design of new catalyst materials.
Progression on Oxidative Decyanation Approaches from Secondary Nitriles to Ketones and α‐Aminonitriles to Amides
Authors: Sathyendran Swetha , Senadi Gopal Chandru
Published: September 2023

The functional group transformation associated with nitrile moiety is considered a diligent research topic in the synthetic community as it is a building block for several organic molecules, including ketones and amides. Many synthetic methodologies have been developed for synthesizing ketones and amides, considering them synthetic analogues with exciting biological properties. However, there are limited research articles to synthesize these important classes of compounds via oxidative decyanation of nitriles and α‐aminonitriles. As several protocols are developed in decyanation, base‐induced oxidative decyanation of nitrile functionality to the oxo group via a carbanion formation is an effective but under‐explored area of research. In this context, we wish to present an outline of studies in oxidative decyanation of secondary nitriles and α‐aminonitriles to afford corresponding ketones and amides since its inception.
Strategy of scaled modeling for underwater shaking table tests on cylindrical marine structures under coupled earthquake and wave–current action: A review
Authors: Han Qinghua , Li Mengyu , Wang Zhongxing , Sun Jianjie , Liu Mingjie
Published: September 2023

Marine structures located in earthquake‐prone areas may be subjected to coupled earthquake and wave–current action and the underwater shaking table (UST) model test is one of the most effective methods to investigate the dynamic responses of them. However, the strategy of scaled modeling, including the selection of similitude criterion and the implementation of it, plays an important role in the test design, and hence influences the accuracy of response predictions of the prototype. This paper presents a comprehensive review of the strategy of scaled modeling utilized in UST model tests on marine structures subjected to coupled earthquake and wave–current action. The key performance parameters of USTs in service and being built in the world are first introduced. Then, the strategies of scaled modeling adopted in existing UST model tests of bridges, offshore wind turbines, submarine pipelines, and submerged floating tunnels are summarized. Following this, the applicability of current similitude criteria for UST model tests for different research focuses is fully discussed and the specific measure to realize the similitude criteria is concluded. Finally, recommendations for future work on similitude criteria are set out, providing insights into the improvements of the applicability and accuracy of the similitude criteria for UST model tests.
Adolescent mental health in Japan and Russia: The role of body image, bullying victimisation and school environment
Authors: Zhang Xiao , Slobodskaya Helena R. , Kaneko Hitoshi
Published: September 2023

This study examined associations between self‐reported mental health problems, body image, bullying victimisation and school safety in large adolescent samples in Japan and Russia, considering the effects of gender, culture and their interactions. In both Japan and Russia, girls reported a greater number of mental health problems, less bullying victimisation and much higher body dissatisfaction than boys did. Japanese adolescents rated themselves higher on total difficulties, reported less body dissatisfaction and bullying victimisation, and rated their school safety lower than that of Russian youths. Cross‐cultural differences in total difficulties and body image were qualified by gender. Body dissatisfaction, bullying victimisation and school safety all independently contributed to adolescent mental health problems. The protective effect of school safety on total difficulties was larger for girls than for boys; the strength of the association between bullying victimisation and adolescent mental health problems differed across genders and cultures. The findings indicate a need for a cross‐cultural approach and provide a strong basis for targeted interventions that seek to improve adolescent mental health.
An Approach to Bridging the Gap Between the Attainment of Research Objectives and System Application
Authors: Ruth Susan
Published: September 2023

The aerospace industry has widely adopted the use of technology readiness levels (TRLs), (NASA) which describe the maturity of a technology from earliest stages of research through the operational system. In using TRLs, it has been observed that bridging the gap between research on a technology and its incorporation by engineers into a system is challenging. Nominally, the transition from TRL 4, defined as a component and/or breadboard validation in a laboratory environment, to TRL 7, defined as a system prototype demonstration in an operational environment, is a programmatic gap known as the “valley of death.” The valley of death is a schism whereby the component that incorporates the new technology fails to meet the eventual system requirements. The goal of this paper is to provide a methodology and “language” that enables the researchers and engineers to communicate more effectively to traverse this gap. The basis for this methodology is the combination of established methods for communicating progress for a program combined with the development and application of domain assessments. Domain readiness levels (DRLs), analogs of the TRLs, are specific to the domains relevant to the system of interest. Specifically, the methodology is intended to enable two‐way communication between the domain experts and the systems engineer, with the goal of effective incorporation of a technology. This paper will use an example of the approach to bridge the “valley of death” targeted on the development of a satellite composites optical support structure that must stay in focus across the temperature range of 77‐323 degrees Kelvin. In this example, the communication will use two relevant domains, materials and processes, to illustrate the methodology.
Enhancing Early Systems R&D Capabilities with Systems —Theoretic Process Analysis
Authors: Williams Adam D.
Published: September 2023

Systems engineering today faces a wide array of challenges, ranging from new operational environments to disruptive technological — necessitating approaches to improve research and development (R&D) efforts. Yet, emphasizing the Aristotelian argument that the “whole is greater than the sum of its parts” seems to offer a conceptual foundation creating new R&D solutions. Invoking systems theoretic concepts of emergence and hierarchy and analytic characteristics of traceability, rigor, and comprehensiveness is potentially beneficial for guiding R&D strategy and development to bridge the gap between theoretical problem spaces and engineering‐based solutions. In response, this article describes systems–theoretic process analysis (STPA) as an example of one such approach to aid in early‐systems R&D discussions. STPA—a ‘top‐down’ process that abstracts real complex system operations into hierarchical control structures, functional control loops, and control actions—uses control loop logic to analyze how control actions (designed for desired system behaviors) may become violated and drive the complex system toward states of higher risk. By analyzing how needed controls are not provided (or out of sequence or stopped too soon) and unneeded controls are provided (or engaged too long), STPA can help early‐system R&D discussions by exploring how requirements and desired actions interact to either mitigate or potentially increase states of risk that can lead to unacceptable losses. This article will demonstrate STPA's benefit for early‐system R&D strategy and development discussion by describing such diverse use cases as cyber security, nuclear fuel transportation, and US electric grid performance. Together, the traceability, rigor, and comprehensiveness of STPA serve as useful tools for improving R&D strategy and development discussions. Leveraging STPA as well as related systems engineering techniques can be helpful in early R&D planning and strategy development to better triangulate deeper theoretical meaning or evaluate empirical results to better inform systems engineering solutions.
The Duration of the Cycle of the Seminiferous Epithelium is Altered by Administration of 2,5‐Hexanedione in the Adult Sprague‐Dawley Rat
Authors: ROSIEPEN GIESA , CHAPIN ROBERT E. , WEINBAUER Priv.‐Doz. Dr.GERHARD F.
Published: September 2023

ABSTRACT: The duration of the cycle of the seminiferous epithelium is believed to be under genetic control rather than being influenced by other factors. However, the frequencies of certain spermatogenic stages—reflecting their relative durations—can be altered under various conditions including treatment with the n‐hexane metabolite, 2,5‐hexanedione (HD). To investigate whether HD administration alters the duration of the spermatogenic process, adult Sprague‐Dawley rats were exposed to vehicle (n = 20) or 1% HD dissolved in the drinking water (n = 40) throughout a period of 29 days. On day 17, 100 mg/kg of 5‐bromodeoxyuridine (BrdU) was given intraperitoneally; 3 hours later one testis was removed, and the remaining testis was excised 12 days later. BrdU was localized in Bouin's‐fixed, Paraplast‐embedded testes using immunogold‐silver‐staining, and sections were counterstained with periodic acid‐Schiff and hematoxylin to permit identification of the spermatogenic stages. HD treatment reduced weights of body, testis, and epididymis (P < 0.05) but had no effects on serum levels of follicle‐stimulating hormone or testosterone. The seminiferous epithelium was vacuolized, and spermatogenesis was affected to various degrees. HD significantly reduced the frequency of stage VII tubules (P < 0.01) and increased the frequency of stage IX and stage×tubules (P < 0.05). Furthermore, HD reduced the stage‐dependent progression of BrdU‐labeled germ cells. By day 29, BrdU‐positive germ cells were seen in 13% of stage IX control tubules, whereas in HD‐treated animals BrdU‐labeled germ cells were not present in stage IX tubules and were found in only 2–3% of stage VIII tubules; the calculated duration of the spermatogenic cycle was significantly increased (P < 0.01) in the HD‐administered animals (13.43 ± 0.10 vs. 12.37 ± 0.05 days). These findings demonstrate (1) that the duration of the cycle of the seminiferous epithelium can be altered experimentally in the adult Sprague‐Dawley rat and (2) that changes in the frequency of spermatogenic stages can be associated with a change in the duration of the spermatogenic process.