bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid UPQC for Power Quality Management of Renewable Energy Penetrated System
Authors: D. Chandra Sekhar
Published: April 2024

Severe voltage sag and radiation pollution is an obstacle for low-voltage intermediate-requirement requiring power facilities, like optical semi conduct, data storage, and precision equipment, like pharmaceuticals and pharmaceuticals, where radiation is involved. As more voltage and economic as well as becoming slower and more difficult to maintain, current equipment is now needed to have higher energy capability. Achieving bi-links for bi-side operation in a medium-voltage condition power-supply application. The first step, followed by the study of a three-phase equivalent circuit and mathematical model, reveals the underlying mechanism of harmonic suppression and voltage control combined with sequence-shunt act phasing and shunt HAPF for continuous phase synthesis (CPS) and the different discrete control and CPS (p-p/Discrete Fourier Transform and Differential Mode Digital Filtration are considered for series, which uses the sliding fourier Phase Lock Loop and its sychronous shunt capability are implemented. The L-C series-filter and passive double-resonant circuits (PDR) are then discussed, along with the key circuit components of the design, the series inductor (LL) circuit, the PDR passive low-pass, and the passive double resonant circuit design for applying the induct filtering. After all, the proof of results in the high voltage delivery validation in MATLAB/Simulink, IHUPC has been demonstrated, 10kV distribution now is supported. With these effects, it being effective in regulating voltage and current and dynamic power generation, the simulation results show the performance of dynamic grid voltage & current regulation and dynamic load-harmonic regulation.
Model Pembelajaran Project Based Learning untuk Meningkatkan Ketuntasan Hasil Belajar Numerasi Siswa Kelas 1 SDN 2 Ngrawan
Authors: Irdani Laili Rahma , Santia Ika
Published: April 2024

This research was motivated by the low level of complete learning outcomes for grade 1 students at SD Negeri 2 Ngrawan regarding numeracy. The aim of this research is to improve the completeness of student learning outcomes. This type of research is classroom action research. Classroom action research was carried out in two cycles. The subjects of this research were class 1 students consisting of 12 students. Techniques for collecting data are tests, observation and documentation. The results of the research show that carrying out learning activities by applying the project based learning model can improve the completeness of students' numeracy learning outcomes. This is indicated by an increase in test results from each cycle. In cycle I, the percentage of student success reached 25%. Meanwhile, in cycle II, the percentage of student success reached 83%. The research can be said to be successful because the percentage of success reaches ≥80%. The conclusion of this research is that the project based learning model can improve the completeness of students' numeracy learning outcomes.
Model Pembelajaran Problem Based Learning sebagai Upaya Peningkatan Prestasi Belajar Mata Pelajaran Pendidikan Kewarganegaraan
Authors: Fathimah Diah Nuraini
Published: April 2024

Learning Pancasila and Citizenship Education in class XI IPA 3 Madrasah Aliyah Negeri 2 Surakarta has problems, including 1) student achievement results are still low 2) not using various learning methods and learning resources, so learning is less interesting and less fun; 3) students tend to be passive when learning takes place; 4) students' understanding of political culture material is still low. The research used classroom action research (CAR) consisting of 2 cycles. The purpose of this study was to improve students' understanding of the subject of political culture and learning achievement of Civics subjects in class XI IPA 3 MAN 2 Surakarta through the Problem Based Learning method. This research was conducted in class XI IPA 3 MAN 2 Surakarta in the academic year 2020/2021 by applying the Problem Based Learning method. Data collection for learning outcomes is done by observing learning activities, observing peers, and writing tests. Validation of this research data using the triangulation method by re-checking with colleagues in order to obtain accurate data. Data analysis in this study used comparative qualitative and quantitative descriptive data analysis. The performance indicator of PPKn MAN 2 Surakarta subjects is getting a score of > 75 and students complete 75% of the total number of students. The research was carried out in two cycles, each cycle consisting of four stages, namely the planning, implementation, observation, and reflection stages. The results of the study showed 1) The students completed Pre-cycle 17 students, increased to 25 students or 83.33% in the first cycle and increased to 31 students or 100% in the second cycle. Unfinished Students: from Pre-cycle 13 students, it decreased to 5 students in Cycle I and decreased to 0 in Cycle II. Highest Value: from Precycle 80, increased to 85 in cycle I and increased again to 90 in Cycle II. The lowest value of the Precycle was 70, remained at 70 in the first cycle, and increased again to 75 in the second cycle. The average value of the Pre-cycle class was 74.33, which increased to 76.33 in the first cycle and increased again to 78.17 in the second cycle. 2) After the application of the problem-based learning model, it can improve from the initial condition to the final condition after the first cycle and continue in the second cycle, there is a significant increase in the understanding of the material understanding of the nature of democracy.
Urgensi Guru Pendidikan Agama Islam, Guru Bimbingan Konseling dan Wali Kelas dalam Mengatasi Dekadensi Moral
Authors: Fitriyah Eni , Syarief Nasrul
Published: April 2024

Decadence or moral decline towards students is an increasingly worrying issue in modern society. The moral degradation caused by the various possible consequences that come from outside and within the student. If it is not addressed immediately, then gradually there will be influence on how students will grow and develop.The objective of this study is to find out about moral decadence and how the efforts of teachers in schools, especially teachers of Islamic education (PAI), mentoring teachers, and classmates. The research methods used in this research are qualitative research, phenomenology, data obtained from interviews, observations, documentation. This article also discusses practices and strategies that can be used by teachers of Islamic education, mentoring teachers, and classmates in supporting the formation of strong student character and good morality. Thus, the three-party collaboration is vital in dealing with the challenges of moral decadence in the contemporary era.
Stock Liquidity, Corporate Governance and Dividend Payout: Evidence From Tehran Stock Exchange
Authors: Filsaraei Mahdi
Published: April 2024

The main goal of this article is the impact of Corporate Governance and Stock Liquidity on the Dividend payout. In order to test the hypotheses, a sample of companies accepted in the Tehran Stock Exchange was selected between 2016 and 2021, which was analyzed using R software. The research method is multivariate regression using panel data. According to the research findings, there is not a meaningful relationship between Corporate Governance, Stock Liquidity and Dividend payout. Companies finance through debt regardless of the stock liquidity, therefore, stock liquidity does not have a decisive role in financing. Better corporate governance mechanisms apply more supervision, so that these mechanisms prevent the opportunistic behavior of managers and preventing them from hiding and manipulating information. By testing the mutual effect of stock liquidity and the quality of corporate governance, a significant relationship was found with the dividend payout of companies accepted in the Tehran Stock Exchange. The study tries to contribute to the current literature of corporate governance and stock liquidity by providing new evidence on the causal impacts of stock liquidity and corporate governance quality on dividend payout. Also, this study contributes to the literature on stock liquidity, corporate governance quality and dividend payout by exploring the mechanism of corporate governance quality and dividend payout from equity financing and internal financing.
Thermal enhancement of the oxidation layer of micron-sized aluminum powder and its anti-oxidation performance
Authors: Liu Yang
Published: April 2024

Micron-sized aluminum powder, with its typical core-shell structure, exhibits oxidation behavior upon slow heating in an oxidative atmosphere that is related to the particle size of the aluminum powder. A particle size-dependent thermal response mechanism for micron-sized aluminum powder is established: a "shell-breaking eruption" thermal response mechanism. The oxide layer is thermally enhanced, and the anti-oxidation reaction behavior mechanism of the enhanced samples is studied. Aluminum powder samples, heated slowly to specific temperatures to obtain changes in the oxide layer structure, are analyzed using a thermal analyzer to compare the slow heating response behavior of aluminum powder before and after the oxidation layer changes. It was found that after thermal enhancement of the aluminum powder oxidation layer, which changed from amorphous to γ-phase and whose thickness increased to twice the original thickness, the slow oxidation process of micron-sized aluminum powder was inhibited, and the aluminum powder was completely deactivated in the slow heating response.
Jablonskis tagset v2
Authors: Rimkutė Erika , Bielinskienė Agnė , Boizou Loic , Utka Andrius , Dadurkevičius Virginijus
Published: April 2024

JABLONSKIS VERSION 2 is a Lithuanian standard morphologiclal tagset that is based on the abbreviations of parts of speech and other grammatical categories commonly used in Lithuanian linguistic works. The tagset is most suitable in applications with human-readable scenarios. The data contains: 1) Lithuanian and English descriptions of the tagset; 2) TSV files with POS categories and values.
Aspects of role models in bullying as a basis for interaction.
Authors: Trufanov Gleb Alekseevich , Evstafev Aleksandr Viktorovich , Tomin Vitalii Vyacheslavovich , Akulina Elena Evgenievna
Published: April 2024

The object of this study is the role models that can be chosen by the participants of the confrontation within the framework of bullying, the subject of the study was social consequences of the application of specific behavioral scenarios in the conflict. These consequences are manifested through the results of the confrontation and the impact of these results on the statuses and positions in the educational environment at different levels, changes in the structure of factions, and interaction between them. Among the applied research methods are comparison, generalization, and synthesis. In the context of conflict methodology, the work is based on the consideration of the theories of conflict functions of Lewis Сoser and the conflict of Ralph Darendorf. The innovative aspect of the research consists of a comprehensive understanding and analysis of Western experience in the field of pedagogy and the development of new conceptual models. It should be emphasized that few studies of bullying in Russian pedagogical conflictology have been carried out. Western researchers often consider the victim of bullying as a passive participant deprived of subjectivity. The authors propose to perceive bullying as a conflict and consider it not only as bullying but also as a situation of negative leadership. The new models considered in our study highlight victim role scripts and assimilation/accommodation of behaviors within the aggressor/victim dichotomy. In addition, the novelty of the study is manifested in the introduction of the concept of role (emotional) benefit and a comprehensive consideration of the aspects of benefit that a "victim" receives in a conflict. The authors propose a system of scenarios and sub-scenarios of victim behavior, taking into account the assimilation/accommodation of certain behavioral patterns when subjects are included in a bullying situation.
Stability of telemedicine legislation: current issues
Authors: Usenkov Ivan Alekseevich
Published: April 2024

The main features and problems of the development of legislative regulation of telemedicine in the Russian Federation are considered. The stages of such development are identified and analyzed: the existence of a concept, the existence of detailed regulation, the establishment of the possibility of deregulation within the framework of a legal experiment, the beginning of a legal experiment. The correlations between changes in the telemedicine services market and changes in legislation and regulated public relations are considered. The probable reasons that prompted the legislative bodies to establish detailed regulation of relations in the field of telemedicine have been identified, given that the provision of telemedicine services has never been prohibited (encouraging participants in civil turnover to use this legal institution, public interest in regulated public relations). The aim of the work was to formulate the problems of non-systemic changes in legislation on telemedicine, their determinants and further optimal development vectors.  The research methodology is based on historical and teleological methods that allow us to consider the problems of legal regulation of telemedicine, based on the peculiarities of the formation of legislation in this area. The paper analyzes statistical data, regulations and materials of judicial practice; using the comparative legal method, general and various trends with the development of other legislative institutions are identified. It is concluded that regular changes in legislation on telemedicine, undermining its stability and predictability of legal regulation, have their reasons for the lack of conditionality of reforms with the current concept of development of legislation on telemedicine, as well as the redundancy of the adopted regulatory regulation. Taking into account the absence of civil law litigation on the provision of telemedicine services, it is proposed to expand deregulation in this area beyond the legal experiment: extending its provisions to the current legislation as a whole. This need is indirectly confirmed by statistical data on a significant increase in the provision of telemedicine services after their legislative consolidation, with its subsequent decrease and the introduction of a legal experiment on deregulation after that. The study is financially supported by the Russian Science Foundation, project No. 23-78-10175, https://rscf.ru/project/23-78-10175/.
Ferrous fumarate nanoliposomes: Formulation, characterization, and diffusion profiles
Authors: Suryani Arman , Laksitorini Marlyn Dian , Sulaiman Teuku Nanda Saifullah
Published: April 2024

To assess the effect of cholesterol concentration in the preparation of ferrous fumarate nanoliposome toward its physicochemical properties and stability. Nanoliposomes were produced with cholesterol concentrations of 8, 12, and 16 mg using the thin film hydration method. The ultrasonic dispersion method and mini extruders were used to reduce the particle size. The nanoliposomes were evaluated for their physical properties, encapsulation efficiency, stability, and transport in the in vitro model of skin absorption. Formula 3 showed the smallest size results, with spherical multilamellar vesicle globules with a relatively dense matrix structure and even distribution between particles with a positive zeta potential value with an encapsulation efficiency percentage value of 61.67% ± 0.50 and a cumulative amount penetrated at the second hour of 442.077 mcg/cm2 ± 17.270 with a flux value of 14.575 mcg/cm−2/hour−1. Formulation 3 with higher cholesterol concentration showed better physical characteristics, encapsulation efficiency, and in vitro skin penetration compared to formulations with lower cholesterol concentration.
Differentially gene expression profiling reveals effect similarities of everolimus, asiaticoside, and asiatic acid on TSC-derived renal angiomyolipoma
Authors: Zulkipli Ninie Nadia , Long Idris , Wahab Habibah A. , Sasongko Teguh Haryo , Azhar Nur Atiqah , Zakaria Rahimah
Published: April 2024

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the development of benign hamartomas in various organs, including renal angiomyolipoma. The current medical standard treatment for TSC-associated renal angiomyolipoma involves the use of a mammalian target of rapamycin (mTOR) inhibitor. To better understand the molecular basis of this treatment approach, our study aimed to identify differentially expressed genes (DEGs) in the UMB1949 cell line following treatment with asiaticoside and asiatic acid and compared them to the effects of everolimus treatment. Using the RT2 Profiler polymerase chain reaction (PCR) array panel, we systematically analyzed the expression patterns of these DEGs, utilizing gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the underlying mTOR inhibitory mechanisms in UMB1949. Our results revealed that all three substances shared five DEGs (four upregulated: CAB39, PRKCE, RRAGC, RPS6KA5, and one downregulated: DEPTOR), as well as seven common GO terms and KEGG pathways, suggesting that the inhibitory activity against mTOR closely mirrors that of everolimus. Moreover, we identified a significant overlap in DEGs involved in cell inhibition via the mTOR pathway across all treated groups. Based on the comprehensive analysis of DEG bioinformatics data, we hypothesized that asiaticoside and asiatic acid exhibit functions comparable to everolimus, with asiaticoside displaying a closer similarity to everolimus than asiatic acid. These findings provide valuable insights into the molecular mechanisms and potential mTOR inhibitors for TSC-associated renal angiomyolipoma and establish a crucial link between our study and the current therapeutic landscape of TSC.
Theoretical calculation of “tune-out” wavelengths for clock states of Al+
Authors: Wei Yuan-Fei , Tang Zhi-Ming , Li Cheng-Bin , Huang Xue-Ren ,   Key Laboratory of Atom Frequency Standards, Innovation Academy for Precision Measurement Science and Technology of Innovation Academy for Precision Measurement Science and Technology, Wuhan 430071, China,   University of Chinese Academy of Sciences, Beijing 100049, China,   Shanghai EBIT Laboratory, Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Institute of Modern Physics, Fudan University, Shanghai 200433, China,   Wuhan Institute of Quantum Technology, Wuhan 430206, China
Published: April 2024

In quantum optical experiments, the polarizabilities of atomic systems play a very important role, which can be used to describe the interactions of atomic systems with external electromagnetic fields. When subjected to a specific electric field such as a laser field with a particular frequency, the frequency-dependent electric-dipole (E1) dynamic polarizability of an atomic state can reach zero. The wavelength corresponding to such a frequency is referred to as the “turn-out” wavelength. In this work, the “turn-out” wavelengths for the 3s2 1S0 and 3s3p 3P0 clock states of Al+ are calculated by using the configuration interaction plus many-body perturbation theory (CI+MBPT) method. The values of energy and E1 reduced matrix elements of low-lying states of Al+ are calculated. By combining these E1 reduced matrix elements with the experimental energy values, the E1 dynamic polarizabilities of the 3s2 1S0 and 3s3p 3P0 clock states are determined in the angular frequency range of (0, 0.42 a.u.). The “turn-out” wavelengths are found at the zero-crossing points of the frequency-dependent dynamic polarizability curves for both the 3s2 1S0 and 3s3p 3P0 states. For the ground state 3s2 1S0, a single “turn-out” wavelength at 266.994(1) nm is observed. On the other hand, the excited state 3s3p 3P0 exhibits four distinct “turn-out” wavelengths, namely 184.56(1) nm, 174.433(1) nm, 121.52(2) nm, and 119.71(2) nm. The contributions of individual resonant transitions to the dynamic polarizabilities at the “turn-out” wavelengths are examined. It is observed that the resonant lines situated near a certain “turn-out” wavelength can provide dominant contributions to the polarizability, while the remaining resonant lines generally contribute minimally. When analyzing these data, we recommend accurately measuring these “turn-out” wavelengths to accurately determine the oscillator strengths or reduced matrix elements of the relevant transitions. This is crucial for minimizing the uncertainty of the blackbody radiation (BBR) frequency shift in Al+ optical clock and suppressing the systematic uncertainty. Meanwhile, precisely measuring these “turn-out” wavelengths is also helpful for further exploring the atomic structure of Al+.
Aberrant cortical activity, functional connectivity, and neural assembly architecture after photothrombotic stroke in mice
Authors: Bandet Mischa V. , Winship Ian R.
Published: April 2024

Despite substantial progress in mapping the trajectory of network plasticity resulting from focal ischemic stroke, the extent and nature of changes in neuronal excitability and activity within the peri-infarct cortex of mice remains poorly defined. Most of the available data have been acquired from anesthetized animals, acute tissue slices, or infer changes in excitability from immunoassays on extracted tissue, and thus may not reflect cortical activity dynamics in the intact cortex of an awake animal. Here,
in vivo
two-photon calcium imaging in awake, behaving mice was used to longitudinally track cortical activity, network functional connectivity, and neural assembly architecture for 2 months following photothrombotic stroke targeting the forelimb somatosensory cortex. Sensorimotor recovery was tracked over the weeks following stroke, allowing us to relate network changes to behavior. Our data revealed spatially restricted but long-lasting alterations in somatosensory neural network function and connectivity. Specifically, we demonstrate significant and long-lasting disruptions in neural assembly architecture concurrent with a deficit in functional connectivity between individual neurons. Reductions in neuronal spiking in peri-infarct cortex were transient but predictive of impairment in skilled locomotion measured in the tapered beam task. Notably, altered neural networks were highly localized, with assembly architecture and neural connectivity relatively unaltered a short distance from the peri-infarct cortex, even in regions within ‘remapped’ forelimb functional representations identified using mesoscale imaging with anaesthetized preparations 8-weeks after stroke. Thus, using longitudinal two photon microscopy in awake animals, these data show a complex spatiotemporal relationship between peri-infarct neuronal network function and behavioural recovery. Moreover, the data highlight an apparent disconnect between dramatic functional remapping identified using strong sensory stimulation in anaesthetized mice compared to more subtle and spatially restricted changes in individual neuron and local network function in awake mice during stroke recovery.
C. elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA
Authors: Consalvo Claudia D. , Aderounmu Adedeji M. , Donelick Helen M. , Aruscavage P. Joe , Eckert Debra M. , Shen Peter S. , Bass Brenda L.
Published: April 2024

Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense,
C. elegans
Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1’s helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.
Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling
Authors: Bolamperti Simona , Saito Hiroaki , Heerdmann Sarah , Hesse Eric , Taipaleenmäki Hanna
Published: April 2024

Osteoblast adherence to bone surfaces is important for remodeling of the bone tissue. This study demonstrates that deficiency of TG-interacting factor 1 (Tgif1) in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matrices
in vitro
. Furthermore, Tgif1 acts as transcriptional repressor of p21-activated kinase 3 (PAK3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased PAK3 expression, which impairs osteoblast spreading. Additionally, Tgif1 is implicated in osteoblast recruitment and activation of bone surfaces in the context of bone regeneration and in response to parathyroid hormone 1-34 (PTH 1-34) treatment
in vivo
. These findings provide important novel insights in the regulation of the cytoskeletal architecture of osteoblasts.
Beyond BioID: Streptavidin outcompetes antibody fluorescence signals in protein localization and readily visualises targets evading immunofluorescence detection
Authors: Odenwald Johanna , Gabiatti Bernardo , Braune Silke , Shen Siqi , Zoltner Martin , Kramer Susanne
Published: April 2024

Immunofluorescence is a common method to localise proteins within their cellular context via fluorophore labelled antibodies and for some applications without alternative. However, some protein targets evade detection due to low protein abundance or accessibility issues. In addition, some imaging methods require a massive reduction in antigen density thus impeding detection of even medium-abundant proteins.Here, we show that the fusion of the target protein to TurboID, a biotin ligase labelling lysine residues in close proximity, and subsequent detection of biotinylation by fluorescent streptavidin offers an “all in one” solution to the above-mentioned restrictions. For a wide range of target proteins tested, the streptavidin signal was significantly stronger than an antibody signal, markedly improving the imaging sensitivity in expansion microscopy and correlative light and electron microscopy, with no loss in resolution. Importantly, proteins within phase-separated regions, such as the central channel of the nuclear pores, the nucleolus or RNA granules, were readily detected with streptavidin, while most antibodies fail to label proteins in these environments. When TurboID is used in tandem with an HA epitope tag, co-probing with streptavidin and anti-HA can be used to map antibody-accessibility to certain cellular regions. As a proof of principle, we mapped antibody access to all trypanosome nuclear pore proteins (NUPs) and found restricted antibody labelling of all FG NUPs of the central channel that are known to be phase-separated, while most non-FG Nups could be labelled. Lastly, we show that streptavidin imaging can resolve dynamic, temporally and spatially distinct sub-complexes and, in specific cases, reveal a history of dynamic protein interaction.In conclusion, streptavidin imaging has major advantages for the detection of lowly abundant or inaccessible proteins and in addition, can provide information on protein interactions and biophysical environment.
Single-cell RNA sequencing of iPSC-derived brain organoids reveals Treponema pallidum infection inhibiting neurodevelopment
Authors: Xu Qiu-Yan , Wang Yong-Jing , He Yun , Zheng Xin-Qi , Tong Man-Li , Lin Yu , Yang Tian-Ci
Published: April 2024

Congenital syphilis is a vertically transmitted bacterial infection caused by Treponema pallidum , often causing multidomain neurodevelopmental disabilities. However, little is known about the pathogenesis of this disease. Brain organoids platform derived from the induced pluripotent stem cell (iPSC) is exposed to T. pallidum infection for modelling congenital neurodevelopmental impairment. Single-cell RNA sequencing is used for identifying the subpopulations of differentially expressed genes and cellular heterogeneity and reconstructing differentiation trajectories following T. pallidum infection. The results reveal that T. pallidum infection influences the formation of neural rosette structures, reduces the cell number of the neural progenitor cell subcluster 1B (subNPC1B) and hindbrain neurons, and affects the neurodevelopment of the brain organoid. Moreover, it is speculated that T. pallidum inhibits the hindbrain neuron cell number through the suppression of subNPC1B subgroup in the organoids and inhibits transcription factor 3 activity in the subNPC1B-hindbrain neuronal axis. This is the first report on the inhibited effects of T. pallidum on the neurodevelopment of the iPSC-derived brain organoid model. T. pallidum could inhibit the differentiation of subNPC1B in brain organoids, thereby reducing the differentiation from subNPC1B to hindbrain neurons, and ultimately affecting the development and maturation of hindbrain neurons.
Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors
Authors: Rasmussen Damien M. , Semonis Manny M. , Greene Joseph T. , Muretta Joseph M. , Thompson Andrew R. , Ramos Silvia Toledo , Thomas David D. , Pomerantz William C.K. , Freedman Tanya S. , Levinson Nicholas M.
Published: April 2024

The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking BRAF dimerization and conformation we built an allosteric model of inhibitor-induced dimerization that resolves the allosteric contributions of inhibitor binding to the two active sites of the dimer, revealing key differences between type I and type II RAF inhibitors. For type II inhibitors the allosteric coupling between inhibitor binding and BRAF dimerization is distributed asymmetrically across the two dimer binding sites, with binding to the first site dominating the allostery. This asymmetry results in efficient and selective induction of dimers with one inhibited and one catalytically active subunit. Our allosteric models quantitatively account for paradoxical activation data measured for 11 RAF inhibitors. Unlike type II inhibitors, type I inhibitors lack allosteric asymmetry and do not activate BRAF homodimers. Finally, NMR data reveal that BRAF homodimers are dynamically asymmetric with only one of the subunits locked in the active αC-in state. This provides a structural mechanism for how binding of only a single αC-in inhibitor molecule can induce potent BRAF dimerization and activation.
A Deep Learning Pipeline for Mapping in situ Network-level Neurovascular Coupling in Multi-photon Fluorescence Microscopy
Authors: Rozak Matthew , Mester James , Attarpour Ahmadreza , Dorr Adrienne , Goubran Maged , Stefanovic Bojana
Published: April 2024

Functional hyperaemia is a well-established hallmark of healthy brain function, whereby local brain blood flow adjusts in response to a change in the activity of the surrounding neurons. Although functional hyperemia has been extensively studied at the level of both tissue and individual vessels, vascular network-level coordination remains largely unknown. To bridge this gap, we developed a deep learning-based computational pipeline that uses two-photon fluorescence microscopy images of cerebral microcirculation to enable automated reconstruction and quantification of the geometric changes across the microvascular network, comprising hundreds of interconnected blood vessels, pre and post-activation of the neighbouring neurons. The pipeline’s utility was demonstrated in the Thy1-ChR2 optogenetic mouse model, where we observed network-wide vessel radius changes to depend on the photostimulation intensity, with both dilations and constrictions occurring across the cortical depth, at an average of 16.1±14.3 μm (mean±stddev) away from the most proximal neuron for dilations; and at 21.9±14.6 μm away for constrictions. We observed a significant heterogeneity of the vascular radius changes within vessels, with radius adjustment varying by an average of 24 ± 28% of the resting diameter, likely reflecting the heterogeneity of the distribution of contractile cells on the vessel walls. A graph theory-based network analysis revealed that the assortativity of adjacent blood vessel responses rose by 152 ± 65% at 4.3 mW/mm
2
of blue photostimulation
vs.
the control, with a 4% median increase in the efficiency of the capillary networks during this level of blue photostimulation in relation to the baseline. Interrogating individual vessels is thus not sufficient to predict how the blood flow is modulated in the network. Our computational pipeline, to be made openly available, enables tracking of the microvascular network geometry over time, relating caliber adjustments to vessel wall-associated cells’ state, and mapping network-level flow distribution impairments in experimental models of disease.
Endocytic recycling is central to circadian collagen fibrillogenesis and disrupted in fibrosis
Authors: Chang Joan , Pickard Adam , Herrera Jeremy A , O'Keefe Sarah , Garva Richa , Hartshorn Matthew , Hoyle Anna , Dingle Lewis , Knox John , Jowitt Thomas A , Coy Madeleine , Wong Jason , Reid Adam , Lu Yinhui , Zeltz Cédric , Venkateswaran Rajamiyer V , Caswell Patrick T , High Stephen , Gullberg Donald , Kadler Karl E
Published: April 2024

Collagen-I fibrillogenesis is crucial to health and development, where dysregulation is a hallmark of fibroproliferative diseases. Here, we show that collagen-I fibril assembly required a functional endocytic system that recycles collagen-I to assemble new fibrils. Endogenous collagen production was not required for fibrillogenesis if exogenous collagen was available, but the circadian-regulated vacuolar protein sorting (VPS) 33b and collagen-binding integrin α11 subunit were crucial to fibrillogenesis. Cells lacking VPS33B secrete soluble collagen-I protomers but were deficient in fibril formation, thus secretion and assembly are separately controlled. Overexpression of VPS33B led to loss of fibril rhythmicity and overabundance of fibrils, which was mediated through integrin α11β1. Endocytic recycling of collagen-I was enhanced in human fibroblasts isolated from idiopathic pulmonary fibrosis, where VPS33B and integrin α11 subunit were overexpressed at the fibrogenic front; this correlation between VPS33B, integrin α11 subunit, and abnormal collagen deposition was also observed in samples from patients with chronic skin wounds. In conclusion, our study showed that circadian-regulated endocytic recycling is central to homeostatic assembly of collagen fibrils and is disrupted in diseases.
Brain white matter pathways of resilience to chronic back pain: a multisite validation
Authors: Mišić Mina , Lee Noah , Zidda Francesca , Sohn Kyungjin , Usai Katrin , Löffler Martin , Uddin Md Nasir , Farooqi Arsalan , Schifitto Giovanni , Zhang Zhengwu , Nees Frauke , Geha Paul , Flor Herta
Published: April 2024

Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have shown that brain characteristics can serve as robust predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking. In two independent longitudinal studies, we examined white matter diffusion imaging data and pain characteristics in patients with subacute back pain (SBP) over six- and 12-month periods. Diffusion data from individuals with CBP and healthy controls (HC) were analyzed for comparison. Whole-brain tract-based spatial statistics analyses revealed that a cluster in the right superior longitudinal fasciculus (SLF) tract had larger fractional anisotropy (FA) values in patients who recovered (SBPr) compared to those with persistent pain (SBPp), and predicted changes in pain severity. The SLF FA values accurately classified patients at baseline and follow-up in a third publicly available dataset (Area under the Receiver Operating Curve ∼ 0.70). Notably, patients who recovered had FA values larger than those of HC suggesting a potential role of SLF integrity in resilience to CBP. Structural connectivity-based models also classified SBPp and SBPr patients from the three data sets (validation accuracy 67%). Our results validate the right SLF as a robust predictor of CBP development, with potential for clinical translation. Cognitive and behavioral processes dependent on the right SLF, such as proprioception and visuospatial attention, should be analyzed in subacute stages as they could prove important for back pain chronicity.
In vitro function, assembly, and interaction of primary cell wall cellulose synthase homotrimers
Authors: Purushotham Pallinti , Ho Ruoya , Zimmer Jochen
Published: April 2024

Plant cell walls contain a meshwork of cellulose fibers embedded into a matrix of other carbohydrate and non-carbohydrate-based biopolymers. This composite material exhibits extraordinary properties, from stretchable and pliable cell boundaries to solid protective shells. Cellulose, a linear glucose polymer, is synthesized and secreted across the plasma membrane by cellulose synthase (CesA). Plants express several CesA isoforms, with different subsets necessary for primary and secondary cell wall biogenesis. The produced cellulose chains can be organized into fibrillar structures and fibrillogenesis likely requires the supramolecular organization of CesAs into pseudo sixfold symmetric complexes (CSCs). Here, we structurally and functionally characterize a set of soybean (Gm) CesA isoforms implicated in primary cell wall biogenesis. Cryogenic electron microscopy analyses of catalytically active GmCesA1, GmCesA3, and GmCesA6 reveal their assembly into homotrimeric complexes, stabilized by a cytosolic plant conserved region. Contrasting secondary cell wall CesAs, a peripheral position of the C-terminal transmembrane helix creates a large, lipid-exposed lateral opening of the enzymes’ cellulose-conducting transmembrane channels. Co-purification experiments reveal that homotrimers of different CesA isoforms interact
in vitro
and that this interaction is independent of the enzymes’ N-terminal cytosolic domains. Our data suggest that cross-isoform interactions are mediated by the class-specific region, which forms a hook-shaped protrusion of the catalytic domain at the cytosolic water-lipid interface. Further, inter-isoform interactions lead to synergistic catalytic activity, suggesting increased cellulose biosynthesis upon homotrimer interaction. Combined, our structural and biochemical data favor a model by which homotrimers of different CesA isoforms assemble into a microfibril-producing CSC.
Deep embedding of sparse multi-band light curves with missing data
Authors:   , Becker Troncoso Ignacio
Published: April 2024

Los telescopios, herramientas que los astrónomos usan para captar luz, han experimentado avances sin precedentes en potencia y automatización, presentando nuevos desafíos en el campo de la astronomía. El Vera C. Rubin Observatory Legacy Survey of Space and Time (Rubin/LSST) es un innovador telescopio de 8.4 metros destinado a revolucionar la astronomía al mapear todo el cielo del hemisferio sur cada tres días en seis filtros ópticos, generando 20 TB de datos y 10 millones de alertas cada noche, superando cualquier telescopio operando actualmente. Para manejar este inmenso volumen de datos y focalizar los esfuerzos de investigación, los sistemas de clasificación automatizados se han vuelto indispensables. Los algoritmos de aprendizaje automático, en particular el aprendizaje profundo, se han erigido como herramientas esenciales, permitiendo a los expertos concentrarse en tareas más exigentes. En esta tesis, presentamos algoritmos basados en aprendizaje profundo que aprenden automáticamente representaciones de curvas de luz para clasificación precisa y automática. Proponemos un método de clasificación supervisada basado en Redes Neuronales Recurrentes (RNNs), capaz de manejar series temporales muestreadas de forma irregular. Nuestros modelos se evalúan en tres conjuntos de datos reales de curvas de luz: OGLE-III, Gaia y WISE, compilados y publicados para la comunidad. Nuestro enfoque requiere un preprocesamiento mínimo de datos, exhibe un bajo costo computacional para actualizaciones con nuevas observaciones, y escala eficientemente a grandes conjuntos de datos. Los resultados demuestran que nuestra arquitectura propuesta logra un rendimiento comparable con los clasificadores basados en descriptores estadísticos, mejorando significativamente los tiempos de predicción. Para prepararnos para los datos de Rubin/LSST, extendemos el modelo de una sola banda creando un conjunto de RNNs capaz de manejar datos multibanda y cadencia no uniforme. El modelo puede aprender los comportamientos en cada banda y unificarlo en una única representación. Esta adaptabilidad permite inferencias sin requerir la curva de luz completa, acelerando el proceso. El modelo se prueba en tres conjuntos de datos reales de curvas de luz: Gaia, Pan-STARRS1 y ZTF, para demostrar su capacidad de generalizar en diferentes condiciones de observación. Además, nuestro modelo propuesto demuestra su versatilidad al realizar no solo clasificación sino también regresión de parámetros físicos como temperatura efectiva y radio. El modelo se destaca en escenarios con menos observaciones, convirtiéndolo en una herramienta prometedora para la clasificación temprana para el Rubin/LSST. En general, nuestros resultados resaltan la eficacia y flexibilidad de nuestro modelo, posicionándolo como una herramienta poderosa para futuras proyectos astronómicos.
Revenue management of customer delivery time offers in on-demand delivery systems
Authors:   , Mendieta Bustos Diego
Published: April 2024

Estudiamos decisiones de revenue management para sistemas de despacho a domicilio on-demand formulando el Problema de los Compradores Personales con Ofertas de Tiempo de Entrega. Consideramos una plataforma crowdsourced de despacho de alimentos que busca maximizar el número de clientes atendidos manteniendo una alta calidad de servicio al cliente. Diseñamos ofertas de ventanas de tiempo de entrega (VTE) para solicitudes dinámicas de clientes. Cuando un cliente ingresa una solicitud de despacho, la plataforma debe diseñar una VTE y ofrecérsela al cliente. Cada cliente acepta o rechaza la oferta de VTE segun sus propias preferencias. Las decisiones del cliente son modeladas utilizando un modelo logit parametrizado por la elasticidad deadline. Si el cliente acepta la oferta, la solicitud debe ser atendida lo mas puntalmente posible. Retrasos con respecto a la VTE conllevan penalizaciones que representan la insatisfacción del cliente. Si el cliente rechaza la oferta, la plataforma incurre en una penalización por pérdida de ingresos. El objetivo es diseñar políıticas de decisión inteligentes que construyan automáticamente ofertas de VTE y tomen decisiones de ruteo que minimicen los costos esperados. Formulamos el problema como un proceso de decisión de Markov y proponemos una política basada en Value Function Approximation entrenada offline. Probamos nuestra política en instancias simuladas y comparamos los resultados con una política de sentido común. Nuestro estudio computacional revela que nuestra política supera al benchmark en todas las instancias de test, logrando ahorros de hasta el 66% en algunas instancias. Ideas clave derivadas de nuestro estudio son que: estrategias de postposición son beneficiosas en entornos con clientes dispuestos a aceptar plazos más largos; políticas proactivas presentan mayores beneficios en entornos con alta estocasticidad en la disponibilidad futura de fuerza de trabajo; entornos con clientes con alta tolerancia a atrasos presentan oportunidades para aprovechar el trade-off entre maximizar el número de clientes atendidos y la calidad del servicio ofrecido a clientes.
Emisiones de gases de efecto invernadero de la dieta chilena y su caracterización por macrozonas en el período 2010-2011
Authors:   , Gutiérrez Fuentes Soledad
Published: April 2024

Antecedentes: Chile se ha comprometido a reducir sus emisiones de gases de efecto invernadero (EGEI) en un 30% al año 2030. La producción de alimentos es la segunda fuente de EGEI del país y un cambio en el consumo de alimentos per cápita tiene el potencial de reducir estas EGEI. No se cuenta con información sobre las EGEI dietarias nacionales. Objetivo: describir las EGEI de la dieta chilena promedio y de sus macrozonas; analizar qué variables, sociodemográficas, antropométricas, y de calidad dietaria, se asocian a mayores EGEI, e identificar los alimentos más emisores. Sujetos y Métodos: se obtuvieron datos dietarios, sociodemográficos y antropométricos de la Encuesta Nacional de Consumo Alimentario (2010-2011) y datos sobre EGEI de los alimentos desde estudios basados en la metodología del Análisis del ciclo de vida. Se calcularon mediana y percentiles 25-75 de las EGEI dietarias expresadas en kilos de CO2 equivalentes por persona diarios(kgCO2eq/persona/d). Se compararon las EGEI entre macrozonas mediante Test de Kruskal Wallis y Dunn. Se calcularon los porcentajes de contribución de los alimentos a esas EGEI. Se identificaron las variables asociadas a mayores EGEI mediante un modelo de regresión logística. Resultados: se incluyeron 4.676 sujetos, edad promedio 40 años, 62% mujeres. La mediana nacional de EGEI fue de 3,89 (2,60-5,67) kgCO2eq/persona/d. Macrozona Sur mostró los mayores niveles, 4,66 (2,89-6,69) kgCO2eq/persona/d, seguido por la Región Metropolitana 4,04 (2,73-5,79) kgCO2eq/persona/d. Las carnes representaron el 56% de las EGEI. Mayores EGEI se asociaron de manera significativa con sexo masculino, edad menor de 65 años, niveles socioeconómicos (NSE) alto y medio y una calidad de la dieta deficiente. Conclusión: las EGEI de la dieta chilena son significativamente más elevadas en la macrozona Sur y la capital debido a la mayor ingesta de carnes. Este pionero estudio establece que mayores EGEI se asocian con NSE, calidad dietaria, sexo y edad, de manera concordante a estudios internacionales.