bluuebunny/crossref_metadata_2025 huggingface dataset:
Strengthening Biomedical Research in Yemen: A Pressing Need for Raising Research Funding
Authors: Abdul-Ghani Rashad
Published: January 2024

This editorial emphasizes the need to secure funding for biomedical research in Yemen, considering the ongoing challenges faced by the research community in the country due to the war and humanitarian crises in the recent years and the lack of domestic research funding. It raises some issues related to improving the fundraising capacity of research institutions and highlights the success story of the University of Science and Technology in Sana’a in raising international funding for research projects on infectious diseases over the past decade.
Investigation of low-cycle fatigue in adhesively-bonded single-lap joints
Authors: İSPİRLİOĞLU KARA Gamze , ÖZEL Adnan
Published: January 2024

Adhesively bonded joints are used as an alternative to classical mechanical joining methods, e.g., bolts, rivets, welding, and soldering, due to their advantages such as high strength, uniform stress distribution, and good fatigue resistance. These adhesively bonded joints are becoming more and more important, especially in fields where weight is critical, such as aviation and aerospace. Adhesively bonded joints are preferred because they offer highly reliable connections. In the present study, the low-cycle fatigue of materials joined together as adhesively bonded single-lap joints were investigated experimentally and numerically. Joints of aluminum and steel samples were subjected to variable loads that were lower than the experimentally obtained average breaking loads, and the number of cycles was determined. As a result, the fatigue life of adhesively bonded single-lap stainless steel samples was observed to be higher than that of aluminum samples. In addition, it was also observed that smudging adhesive around the endpoints of the joint significantly increased the fatigue life of steel samples.
Early-stage heart failure disease prediction with deep learning approach
Authors: DEMİR Emin , BOZKURT Ferhat , AYIK Yusuf Ziya
Published: January 2024

Cardiovascular diseases rank the highest among diseases in terms of mortality rate and cause millions of deaths every year. Heart failure is a type of cardiovascular disease and its early diagnosis is extremely important for its prevention. It may be vitally important to understand to what extent which body values, characteristics and factors (age, gender, blood pressure, sugar, etc.) affect this disease and to predict whether the individual will have a possible heart attack in the future. In this study, firstly, the correlation level of the relevant body values with the disease is extracted and in the second stage, a method that predicts heart attack with DNN (Deep Neural Network) and CNN (Convolutional Neural Network) deep learning models is proposed. In the study, 918 observations obtained from the kaggle site were used. Firstly, missing data, categorical data, non-numerical features were checked. Then, outliers were cleaned and the relationship of the features in the dataset with the disease state was revealed by feature engineering operations on the data. Finally, deep neural network models were built and the model was trained and hyperparameter adjustment was performed with GridSearhCV to achieve the highest success rate. As a result of the study, Accuracy, Precision, Recall and F1-Score values were found as 0.9375, 0.9629, 0.9176, 0.9397 for DNN and 0.9312, 0.9512, 0.9176, 0.9340 for CNN respectively. The AUC value calculated from the ROC curve was found to be equal to 0.96 in both deep learning models.
Investigation of temperature effects in RC-Steel composite industrial building model with FEM
Authors: GÜNDAY Furkan
Published: January 2024

Today, composite structure design has become very popular. The most important goal in composite structure design is to create the most efficient structural system under load by using materials that respond positively to different cross-section effects. Industrial type buildings, on the other hand, consist of very wide openings. In addition, industrial buildings are required to be designed to be constructed quickly and simply. For all these reasons, there has been an increase in the construction of industrial buildings in the form of reinforced concrete-steel composite structures. The effect of temperature in buildings is a parameter that should be considered both in design and use. It is a scientific fact that the expansion and contraction coefficients of reinforced concrete and steel are different. The temperature effect has an even more important place in composite construction systems where both are used together. For all these reasons, in this study, a reinforced concrete-steel composite industrial building model was created and its responses at -50°C and 50°C were examined. As a result of the findings obtained, the effect of temperature in reinforced concrete-steel composite industrial structures should definitely be taken into account both in the design and in the use and maintenance stages.
Rusting Away (or: packing the entire Crossref database into a SQLite file)
Authors: Eve Martin Paul
Published: January 2024

Over the past few weeks I've been working to pack the entire Crossref database into a distributable SQLite file. While this sounds somewhat insane -- the resulting file is 900GB -- it's quite a cool project for, say, embedded systems work in situations where no internet connection is available. It also provides speedy local indexed lookups, working faster than the internet-dependent API ever could.
Participación Latinoamérica en el Programa de Campeonas y Campeones de rOpenSci
Authors: Saibene Yanina Bellini , Campitelli Elio , Prunello Marcos , Lepore Mauro , Svab Haydee , Milz Beatriz , Pradier Carolina , Camacho Cesar Luis Aybar , Corrales Pao
Published: January 2024

Las personas

campeonas

de una comunidad son

personas que asumen una mayor responsabilidad en el éxito, la sostenibilidad y/o el funcionamiento de una comunidad

.

1

rOpenSci desarrolla un programa de campeones y campeonas enfocado y pensado para que participen personas que pertenecen a grupos histórica y sistemáticamente excluidos de las comunidades de software abierto y de software de investigación.
New Varieties of Fast Air-Assisted Boats
Authors: Matveev Konstantin
Published: January 2024

Marine vehicles intended for ultra-high-speed applications can beneficially use the air for drag reduction and lift augmentation. New types of air-assisted marine craft include air-lubricated boats, aerodynamically supported multi-hulls, and ram craft with jet-induced lift. This paper reviews the current state of these technologies, full-scale specifications of some existing boats, experimental data, relevant mathematical theories, and future research directions.
Design & Analysis of Integrated Propulsion Systems for High Speed Craft
Authors: Savander Brant R. , Kamphuis Ryan J. , Thill Cornel , Herman Kevin D. , Woodruff Scott
Published: January 2024

The work documented herein has resulted from a collaborative research program funded by MTU Detroit Diesel in the high speed craft area with an emphasis on design and analysis of open shaft, strut, propeller, and rudder systems for recreational applications. The program combined both numerical and experimental hydrodynamic analyses throughout the research process. The two primary areas of this effort were associated with planing hull and propulsor hydrodynamics. Numerical results from various ideal flow theories for both planing hulls and cavitating propellers are compared with model test results conducted at the Maritime Research Institute of the Netherlands (MARIN). The model testing program included the traditional experimental matrix of EHP, appended EHP, SHP, and nominal wake survey all in the absence of any influence of cavitation. Cavitation number effects were included through a series of experiments in both a cavitation tunnel and depressurized towing tank at MARIN. Both the numerical and experimental findings are compared with full scale sea trial data from the subject craft, a 70 foot planing hull with a top speed of 50 knots. Research program challenges and areas for further development are presented and discussed.
On High Speed Monohulls in Shallow Water
Authors: Radojcic Dejan , Bowles Jeffrey
Published: January 2024

The hydrodynamic performance of marine craft has long been known to be influenced by water depth. When operating in shallow water at subcritical speeds (typical for displacement vessels), they slow down at constant power. On the contrary, when operating in shallow water at supercritical speeds (typical for planing vessels), vessel speeds increase at constant power. Additionally, surface waves generated by the hull vary radically with vessel speed and water depth.

In recent years, mega yachts are being designed for length Froude numbers (FnL) greater than 0.4, with many operating between 0.5 and 1.0, and some have even higher non-dimensional speeds. As these modern mega yachts being delivered have overall lengths up to and often exceeding 100 meters, shallow water effects are being observed by their captains in relatively deep water. Thus, it is the intent of this paper to refresh, for the mega and high speed yacht community, what defines shallow water, the impact on performance and a general discussion on the responsibilities for hull-generated waves and wake occurring due to shallow water. A power prediction procedure applicable in everyday engineering practice is outlined and an underpinned by a numerical example.
A Detailed Validation of Numerical Flow Analysis (NFA) to Predict the Hydrodynamics of a Deep-V Planing Hull
Authors: O'Shea Thomas T. , Brucker Kyle A. , Wyatt Donald , Dommermuth Douglas G. , Fu Thomas C.
Published: January 2024

The focus of this paper is to describe and document the recent effort to validate the computer code Numerical Flow Analysis (NFA) for the prediction of hydrodynamic forces and moments associated with deep-V planing craft. This detailed validation effort was composed of three parts. The first part focuses on assessing NFA’s ability to predict pressures on the surface of a 10 degree deadrise wedge during impact with an undisturbed free surface. Detailed comparisons to pressure gauges are presented for two different drop heights, 6 inches and 10 inches. Results show NFA accurately predicted pressures during the slamming event. The second part examines NFA’s ability to match sinkage, trim and resistance from experiments performed on constant deadrise planing hulls, detailed in Fridsma (1969). Simulations were preformed on two 20 degree deadrise hullforms of varying length to beam ratios (4 and 5) over a range of speed-length ratios (2, 3, 4, 5, and 6 knots-ft -1/2). Results show good agreement with experimentally measured values, as well as values calculated using Savitsky’s parametric equations, detailed in Savistsky (1964). The final part of the validation study focused on assessing how well NFA was able to accurately model the complex multiphase flow associated with high Froude number flows, specifically the formation of the spray sheet. NFA simulations of a planing hull fixed at various angles of roll (0 degrees, 10 degrees, 20 degrees, and 30 degrees) were compared to experiments from Judge (2012). Comparisons to underwater photographs illustrate NFA’s ability to model the formation of the spray sheet and the free surface turbulence associated with planing boat hydrodynamics.
Investigation of Factors leading to Dynamic Instabilities in High-Speed, Shallow Draft Boats
Authors: Morabito Michael G.
Published: January 2024

This paper summarizes portions of a multi-year collaborative study on the dynamic stability of high-speed, shallow draft recreational boats, in which the author has played a small role. These boats are powered by outboard engines, and sometimes fitted with propeller tunnels to permit raising the outboard to reduce draft. Some of these boats have been known to exhibit a dynamic instability referred to as “swapping ends” or “spinout,” in which the boat enters into a moderate turn and then suddenly completes a 180-degree turn in a few seconds, pivoting about a location somewhere near the middle of the boat. During these incidents, occupants sitting in the boat can be ejected and then struck by the boat. Some other shallow-draft, high-speed boats have also been shown to have limited or intermittent helm control, also leading to passenger ejection. The danger of intermittent controllability is compounded by the lack of railings, lifelines, or well-defined seating on these boats to prevent ejection.
Legal Means to Counter the Phenomenon of Child Begging in Palestine
Authors: Alhamouri Hala , Awawdeh Osayd
Published: January 2024

The phenomenon of child begging has been largely spreading lately and has impacted society and child beggars alike. Nevertheless, there are many ways to counter this phenomenon in all its aspects. Since this research paper is limited to studying the legal aspect of this phenomenon, the focus has been placed on the lawful means to achieve that purpose. This research paper analyses the legal rules in international conventions and domestic laws enacted to counter this phenomenon. It found a considerable insufficiency of legal regulations in both procedural and substantive rules at the domestic level that would hinder the process of countering this phenomenon.
Constructing Identities and Negotiating Relationships in Late Eighteenth-century England
Authors: Oudesluijs Tino , Yáñez-Bouza Nuria
Published: January 2024

During the eighteenth century, language became an increasingly valuable commodity for the construction of identities and the negotiation of relationships with others. Additionally, letter writing had emerged as a crucial means of maintaining relationships and forging deeper intimacy between individuals, and correspondence thus constitutes a rich resource for the study of language variation and change in relation to (social) identity, with forms of address as a key strategy in this respect. The current paper examines expressions of direct address and self-reference in Late Modern English ego-documents, more specifically two sets of letters involving Mary Hamilton (1756–1816), sub-governess at Court and a member of the Bluestocking circle. For each set, we discuss intra-speaker variation in the context of both the individual participants involved and the structure of the letters. The findings reveal different strategies through which Hamilton and her correspondents construct their identities and negotiate their relationships with each other, for example by using nicknames and terms of endearment, omitting signatures, or through changes in lexical choices over time.
ASISTENCIA COMPARTIDA Y MANEJO INTERDISCIPLINARIO EN PACIENTES QUIRÚRGICOS. ESTUDIO OBSERVACIONAL EN UN HOSPITAL DE AGUDOS DE ARGENTINA
Authors: Dodero Romina Natalia
Published: January 2024

Introducción. La asistencia compartida (AC) o comanejo es la organización asistencial por la cual el internista se hace responsable de los problemas médicos, desde que ingresa el paciente en el servicio quirúrgico hasta su alta hospitalaria, sin necesidad de ser avisado. Objetivo. Describir las característicassocioepidemiológicas de los pacientes evaluados por un médico clínico durante la internación quirúrgica en el Hospital Municipal de Agudos Dr. Leónidas Lucero. Material y métodos. Estudio observacional,descriptivo, transversal. Se incluyeron los pacientes internados en sala quirúrgica evaluados por clínicamédica, durante seis meses. Resultados. Se estableció AC a 278 pacientes quirúrgicos internados. El 47,1% fue evaluado por iniciativa del equipo clínico de AC y 196 tenían antecedentes patológicos. El motivo de la solicitud de evaluación clínica en 151 pacientes fue el seguimiento de las comorbilidades; en68, por mal manejo del dolor. El diagnóstico clínico más frecuente fue dolor perioperatorio (97 pacientes), seguido de los cardiovasculares (54) y psiquiátricos (41). Se modificaron indicaciones a 255 pacientes, en 128 se cambió el tratamiento analgésico y se realizaron ajustes en el control glucémico de 38 diabéticos.El equipo de AC realizó el seguimiento durante el 67,7% de los días de internación. Conclusiones. En nuestra experiencia, el acompañamiento del paciente quirúrgico por el médico clínico o internista modifica las indicaciones terapéuticas y prioriza el dolor como diagnóstico. La formación del internista influye en lavaloración global del paciente, detectando tempranamente las emergencias médicas. Palabras clave. Asistencia compartida, comanejo, pacientes quirúrgicos, medicina interna, interconsulta.
Pembagian Waris Menurut Hukum Adat Pada Keluarga Beda Agama
Authors: Darmansyah  , Ilyas  , Zuhrah
Published: January 2024

Desa Mbawa Kecamatan Donggo Kabupaten Bima merupakan desa adat yang mengedepankan hukum positif nasional, namun dalam pemasalahan pembagian waris beda agama yang belum diatur secara jelas sehinga masyarakat desa mbawa membagi berdasarkan musyawarah yang menjadi kebiasaan adat desa tersebut. Metode penelitian yang digunakan adalah metode empiris dengan pendekatan sosiologis dan teknik analisis data deskriptif kualitatif.

Hasil penelitian menunjukkan bahwa persoalan waris di desa Mbawa memiliki tata cara pembagian waris dengan ketentuan warisan berdasarkan garis keturunan yang memiliki kesamaan agama hal tersebut memiliki kesamaan dengan sumber yang merujuk pada hukum Islam dalam hal ini dapat dikatakan merujuk pada Pasal 171 huruf c KHI bahwa pewaris dan ahli waris harus dalam keadaan beragama Islam maka diantara keduanya, apabila salah satunya tidak beragama Islam maka diantara keduanya tidak dapat saling mewarisi, maka dalam ketentuan hak kewarisan otomatis terputus ketika berkaitan dengan perbedaan agama. Permasalahan juga muncul ialah ahli waris yang memilik agama berbeda menuntut waris yang menurut hukum adat Desa Mbawa tidak memiliki hak, namun hal tersebut dapat diselesaikan dengan musyawarah mufakat dan apabila ahli waris yang memiliki kesamaan agama memilik rasa iba dapat memberikan sebagian kecil warisannya terhadap ahli waris yang tidak memiliki hak dalam hal ini yang berbeda agama dengan pewaris.
FinTech and Pakistan’s Banking Industry: An Exploratory Study
Authors: Wahga Aqueel Imtiaz , Majid Safyan , Ahmad Nisar , Aftab Irfa , Awais Muhammad
Published: January 2024

Technological development in the financial sector has influenced different segments of consumers differently. In the last decade, like other industries, driven by technological adaptation, the banking industry has also undergone regulatory changes and has, therefore, influenced how consumers interact with traditional financial services. FinTech has contributed to some of this transformation. Numerous new startups are already transforming the financial technology sector by creating cutting-edge financial services and products for consumers. This study provides a better understanding of the current position and FinTech implementation strategy in Pakistan's commercial banking sector. It also investigates the barriers to adopting Fintech and its impact on the banking sector. Twelve in-depth interviews were conducted with the assistant manager, operations manager, and bank branch manager as part of the qualitative study. These interviews provided insights into the current situation of the banking industry to Fintech. The factors reported in this study are Challenges and Barriers to the adoption of Fintech. Factors are Lack of Budget, Lack of Rules and Regulations, Cybercrimes, and Hacking. Requirements for the adoption of Fintech factors are E-commerce activities, SBP Role, Training, and Advanced ICT Infrastructure. The impact of Fintech on Pakistan's banking sector is efficiency, innovation, competitiveness, and customer service. The study contributes to the knowledge of practice-related stakeholders, offering valuable insights into Fintech and its effects on the banking industry in Pakistan. The study thus offers valuable insights for policy managers who are engaged with promoting Fintech in Pakistan's banking sector to offer better services to customers and upgrade industry practices.
Under Pressure? A Study of Heart Rate and Heart-Rate Variability Using SmarTerp
Authors: Olalla-Soler Christian , Spinolo Nicoletta , Muñoz Martín Ricardo
Published: January 2024

The results of a quasi-experimental, intra-subject study are reported on the effects of the use of SmarTerp on physiological stress levels of twelve second-year students of the MA in Interpreting at the University of Bologna during a simultaneous interpreting task. The study, part of a broader project, explores the rendition of terminological units, proper names, and numbers and its correlation with stress levels, to provide insights into SmarTerp’s practical usefulness in the field. Physiological stress levels were measured through heart rate and heart-rate variability indicators with Empatica E4 wristbands. Participants took part in three data-collection sessions over a month. In sessions 1 and 3 the participants interpreted two speeches, one with SmarTerp and another one without it. Descriptive findings hinted at a potential stress-alleviating effect of interpreting with SmarTerp, especially when interpreting into a second language. However, all inferential statistical results consistently revealed non-significant outcomes. Furthermore, stress levels did not decrease significantly over time when using SmarTerp. While the non-significant reduction in stress may cast doubt on the tool’s efficacy, the complexity and multiple variables influencing stress in interpreting tasks should be factored in. SmarTerp may serve its primary purpose in aiding accurate rendition of terminological units, proper names, and numbers.
Non-reciprocal topological photonics
Authors: Wang Zi-Yao , Chen Fu-Jia , Xi Xiang , Gao Zhen , Yang Yi-Hao ,   Department of Electronic and Electrical Engineering, Southern University of Science and Technology, Shenzhen 518055, China,   Interdisciplinary Center for Quantum Information, ZJU-Hangzhou Global Scientific and Technological Innovation Center, State Key Laboratory of Extreme Photonics and Instrumentation, Zhejiang University, Hangzhou 310027, China,   State Key Laboratory of Optical Fiber and Cable Manufacture Technology, Southern University of Science and Technology, Shenzhen 518055, China
Published: January 2024

The proposal and development of topological photonics have provided a new approach to fundamentally addressing the susceptibility of traditional photonic devices to defects or disorders, significantly enhancing the transmission efficiency and robustness of photonic devices. Among them, non-reciprocal topological photonics which break time-reversal symmetry and support chiral topological states are crucial branches of topological photonics. Their topological properties are characterized by non-zero Chern numbers in two dimensions or topological Chern vectors in three dimensions, exhibiting a rigorous and complete topological protection beyond that of reciprocal topological photonics. This review focuses on introducing the remarkable achievements of non-reciprocal topological photonics in exploring novel physical phenomena (chiral/antichiral edge/surface states, two-dimensional/three-dimensional photonic Chern insulators, magnetic Weyl photonics crystals, etc.) and constructing non-reciprocal robust topological photonic devices (unidirectional waveguides, broadband slow-light delay lines, arbitrarily shaped topological lasers, high-orbital-angular-momentum coherent light sources, etc.). Finally, the present status, potential challenges, and possible breakthroughs in the development of non-reciprocal topological photonics are discussed.
A translational MRI approach to validate acute axonal damage detection as an early event in multiple sclerosis
Authors: Cerdán Cerdá Antonio , Toschi Nicola , Treaba Constantina A , Barletta Valeria , Herranz Elena , Mehndiratta Ambica , Gomez-Sanchez Jose A , Mainero Caterina , De Santis Silvia
Published: January 2024

Axonal degeneration is a central pathological feature of multiple sclerosis and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity and clinical applicability, and by the lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin damaging the neuronal terminal of axons. We then applied the same MRI protocol to map axonal integrity in the brain of multiple sclerosis relapsing-remitting patients and age-matched healthy controls. AxCaliber is sensitive to acute axonal damage in rats, as demonstrated by a significant increase in the mean axonal caliber along the targeted tract, which correlated with neurofilament staining. Electron microscopy confirmed that increased mean axonal diameter is associated with acute axonal pathology. In humans with multiple sclerosis, we uncovered a diffuse increase in mean axonal caliber in most areas of the normal-appearing white matter, preferentially affecting patients with short disease duration. Our results demonstrate that MRI-based axonal diameter mapping is a sensitive and specific imaging biomarker that links noninvasive imaging contrasts with the underlying biological substrate, uncovering generalized axonal damage in multiple sclerosis as an early event.
ARHGAP18-ezrin functions as an autoregulatory module for RhoA in the assembly of distinct actin-based structures
Authors: Lombardo Andrew T , Mitchell Cameron AR , Zaman Riasat , McDermitt David J , Bretscher Anthony
Published: January 2024

The location of different actin-based structures is largely regulated by Rho GTPases through specific effectors. We use the apical aspect of epithelial cells as a model system to investigate how RhoA is locally regulated to contribute to two distinct adjacent actin-based structures. Assembly of the non-muscle myosin-2 filaments in the terminal web is dependent on RhoA activity, and assembly of the microvilli also requires active RhoA for phosphorylation and activation of ezrin. We show that the RhoGAP, ARHGAP18, is localized by binding active microvillar ezrin, and this interaction enhances ARHGAP18’s RhoGAP activity. We present a model where ezrin-ARHGAP18 acts as a negative autoregulatory module to locally reduce RhoA activity in microvilli. Consistent with this model, loss of ARHGAP18 results in disruption of the distinction between microvilli and the terminal web including aberrant assembly of myosin-2 filaments forming inside microvilli. Thus, ARHGAP18, through its recruitment and activation by ezrin, fine-tunes the local level of RhoA to allow for the appropriate distribution of actin-based structures between the microvilli and terminal web. As RhoGAPs vastly outnumber Rho GTPases, this may represent a general mechanism whereby individual Rho effectors drive specific actin-based structures.
Unraveling the developmental dynamic of visual exploration of social interactions in autism
Authors: Kojovic Nada , Cekic Sezen , Castañón Santiago Herce , Franchini Martina , Sperdin Holger Franz , Sandini Corrado , Jan Reem Kais , Zöller Daniela , Ben Hadid Lylia , Bavelier Daphné , Schaer Marie
Published: January 2024

Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
DePARylation is critical for S phase progression and cell survival
Authors: Nie Litong , Wang Chao , Huang Min , Liu Xiaoguang , Feng Xu , Tang Mengfan , Li Siting , Hang Qinglei , Teng Hongqi , Shen Xi , Ma Li , Gan Boyi , Chen Junjie
Published: January 2024

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.Poly(ADP-ribosyl)ation is a reversible post-translational modification. Although PARG may have a protective effect against excessive PARP1 engagement, detailed knowledge of PARG’s mechanism of action remains elusive. Here, we showed that PARG participates in DNA replication, especially in Okazaki fragment maturation. Moreover, PARG level is critically important for cellular sensitivity to PARG inhibition, which is a valuable biomarker for PARGi-based therapy.
Notch signaling and Bsh homeodomain activity are integrated to diversify Drosophila lamina neuron types
Authors: Xu Chundi , Ramos Tyler B , Marshall Owen J , Doe Chris Q
Published: January 2024

Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the Drosophila lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates. We show asymmetric Notch signaling between newborn L4 and L5 neurons, but they are not siblings; rather, Notch signaling in L4 is due to Delta expression in adjacent L1 neurons. While Notch signaling and Bsh expression are mutually independent, Notch is necessary and sufficient for Bsh to specify L4 fate over L5. The NotchON L4, compared to NotchOFF L5, has a distinct open chromatin landscape which allows Bsh to bind distinct genomic loci, leading to L4-specific identity gene transcription. We propose a novel model in which Notch signaling is integrated with the primary HDTF activity to diversify neuron types by directly or indirectly generating a distinct open chromatin landscape that constrains the pool of genes that a primary HDTF can activate.
BRAIDing receptors for cell-specific targeting
Authors: Chen Hui , Lee Sung-Jin , Li Ryan , Sura Asmiti , Suen Nicholas , Dilip Archana , Pomogov Yan , Vuppalapaty Meghah , Suen Timothy T , Lu Chenggang , Post Yorick , Li Yang
Published: January 2024

Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular Division) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called ‘bridging receptor’ on the target cell. This concept was validated using the WNT/β-catenin signaling system, demonstrating that a multivalent WNT agonist molecule divided into two inactive components assembled from different epitopes via the hepatocyte receptor βKlotho induces signaling specifically on hepatocytes. These data provide proof of concept for this cell-specific targeting strategy, and in principle, this may also allow activation of multiple signaling pathways where desirable. This approach has broad application potential for other receptor systems.
Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis
Authors: Busby Lara , Serrano Nájera Guillermo , Steventon Benjamin John
Published: January 2024

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single-cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. However, by grafting varied sizes of tissue, we find that small heterochronic grafts disperse more readily and contribute to more anterior portions of the body axis while still maintaining Hox gene expression. This enhanced dispersion is not replicated in explant culture, suggesting that it is a consequence of interaction between host and donor tissue and thus extrinsic to the donor tissue. Therefore, we demonstrate that the timing of cell dispersion and resulting axis contribution is impacted by a combination of both intrinsic and extrinsic cues.
Ym1 protein crystals promote type 2 immunity
Authors: Heyndrickx Ines , Deswarte Kim , Verstraete Kenneth , Verschueren Koen HG , Smole Ursula , Aegerter Helena , Dansercoer Ann , Hammad Hamida , Savvides Savvas N , Lambrecht Bart N
Published: January 2024

Spontaneous protein crystallization is a rare event, yet protein crystals are frequently found in eosinophil-rich inflammation. In humans, Charcot-Leyden crystals (CLCs) are made from galectin-10 (Gal10) protein, an abundant protein in eosinophils. Although mice do not encode Gal10 in their genome, they do form pseudo-CLCs, made from the chitinase-like proteins Ym1 and/or Ym2, encoded by Chil3 and Chil4 and made by myeloid and epithelial cells respectively. Here, we investigated the biological effects of pseudo-CLCs since their function is currently unknown. We produced recombinant Ym1 crystals which were shown to have identical crystal packing and structure by X-ray crystallography as in vivo native crystals derived from murine lung. When administered to the airways of mice, crystalline but not soluble Ym1 stimulated innate and adaptive immunity and acted as a type 2 immune adjuvant for eosinophilic inflammation via triggering of dendritic cells (DCs). Murine Ym1 protein crystals found at sites of eosinophilic inflammation reinforce type 2 immunity and could serve as a surrogate model for studying the biology of human CLCs.
A single-cell transcriptomic atlas reveals resident dendritic-like cells in the zebrafish brain parenchyma
Authors: Rovira Mireia , Ferrero Giuliano , Miserocchi Magali , Montanari Alice , Wittamer Valérie
Published: January 2024

Recent studies have highlighted the heterogeneity of the immune cell compartment within the steady-state murine and human CNS. However it is not known whether this diversity is conserved among non mammalian vertebrates, especially in the zebrafish, a model system with increasing translational value. Here, we reveal the complexity of the immune landscape of the adult zebrafish brain. Using single-cell transcriptomics, we characterized these different immune cell subpopulations, including cell types that have not been -or have been poorly-characterized in zebrafish so far. By histology, we found that, despite microglia being the main immune cell type in the parenchyma, the zebrafish brain is also populated by a distinct myeloid population that shares a gene signature with mammalian dendritic cells (DC). Notably, zebrafish DC-like cells rely on
batf3
, a gene essential for the development of conventional DC1 in the mouse. Using specific fluorescent reporter lines that allowed us to reliably discriminate DC-like cells from microglia, we quantified brain myeloid cell defects in commonly used

irf8
-/-

,

csf1ra
-/-

and

csf1rb
-/-

mutant fish, revealing previously unappreciated distinct microglia and DC-like phenotypes. Overall, our results suggest a conserved heterogeneity of brain immune cells across vertebrate evolution and also highlights zebrafish-specific brain immunity characteristics.
Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth
Authors: Qin Lianhua , Xu Junfang , Chen Jianxia , Wang Sen , Zheng Ruijuan , Cui Zhenling , Liu Zhonghua , Wu Xiangyang , Wang Jie , Huang Xiaochen , Wang Zhaohui , Wang Mingqiao , Pan Rong , Kaufmann Stefan HE , Meng Xun , Zhang Lu , Sha Wei , Liu Haipeng
Published: January 2024

Deeper understanding of the crosstalk between host cells and Mycobacterium tuberculosis (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as a critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9. Here, we demonstrate that galectin-9 directly inhibited mycobacterial growth through AG-binding property of carbohydrate-recognition domain 2. Furthermore, IgG antibodies with AG specificity were detected in the serum of TB patients. Based on the interaction between galectin-9 and AG, we developed a monoclonal antibody (mAb) screening assay and identified AG-specific mAbs which profoundly inhibit Mtb growth. Mechanistically, proteomic profiling and morphological characterizations revealed that AG-specific mAbs regulate AG biosynthesis, thereby inducing cell wall swelling. Thus, direct AG-binding by galectin-9 or antibodies contributes to protection against TB. Our findings pave the way for the rational design of novel immunotherapeutic strategies for TB control.
Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B
Authors: Celis Mike , Navarro Yohanna , Serrano Norma , Martínez Daniel , Nieto Wendy
Published: January 2024

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B.Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana.Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años.Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/μl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa.Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.
Parasitic Array Based Radiation Pattern Reconfigurable Patch Antenna for WLAN Application
Authors: Saikia B. , Borah K.
Published: January 2024

This article presents a radiation pattern reconfigurable patch antenna using three rectangular parasitic elements for WLAN (5.8 GHz) application. A rectangular driven patch with two parasitic elements placed parallel to both non-radiating edges and the third parasitic element is located on the radiating edge of driven element. The parasitic elements located on non-radiating edges are loaded with shorting posts. The electrical connection between the post and ground plane is controlled by an RF PIN diode switch. Based on switching state (ON/OFF) of the PIN diodes, post loaded parasitic elements, switch their function between director and reflector to produce beam reconfiguration in the proposed antenna. For different switching combinations of the PIN diodes, beam steering directions in H-plane are obtained at 0˚, +50˚, –50˚ for E-plane radiation maximum at +30˚, while fourth beam steering angle is found at ±50˚ with corresponding E-plane radiation maximum at ±40˚. Measured peak gain of the proposed antenna varies between 3.46 dBi and 3.74 dBi for different beam steering modes. With measured resonant frequency around 5.85 GHz throughout the reconfiguration process, the proposed antenna is considered as a potential candidate for WLAN application.
DDoS attack detection in smart grid network using reconstructive machine learning models
Authors: Naqvi Sardar Shan Ali , Li Yuancheng , Uzair Muhammad
Published: January 2024

Network attacks pose a significant challenge for smart grid networks, mainly due to the existence of several multi-directional communication devices coupling consumers to the grid. One of the network attacks that can affect the smart grid is the distributed denial of service (DDoS), where numerous compromised communication devices/nodes of the grid flood the smart grid network with false data and requests, leading to disruptions in smart meters, data servers, and the state estimator, ultimately effecting the services for end-users. Machine learning-based strategies show distinctive benefits in resolving the challenge of securing the network from DDoS attacks. Regardless, a notable hindrance in deploying machine learning-based techniques is the requirement of model retraining whenever new attack classes arise. Practically, disrupting the normal operations of smart grid is really discouraged. To handle this challenge effectively and detect DDoS attacks without major disruptions, we propose the deployment of reconstructive deep learning techniques. A primary benefit of our proposed technique is the minimum disruption during the introduction of a new attack class, even after complete deployment. We trained several deep and shallow reconstructive models to get representations for each attack type separately, and we performed attack detection by class-specific reconstruction error-based classification. Our technique experienced rigid evaluation via multiple experiments using two well-acknowledged standard databases exclusively for DDoS attacks, including their subsets. Later, we performed a comparative estimation of our outcomes against six methods prevalent within the same domain. Our outcomes reveal that our technique attained higher accuracy, and notably eliminates the requirement of a complete model retraining in the event of the introduction of new attack classes. This method will not only boost the security of smart grid networks but also ensure the stability and reliability of normal operations, protecting the critical infrastructure from ever-evolving network attacks. As smart grid is advancing rapidly, our approach proposes a robust and adaptive way to overcome the continuous challenges posed by network attacks.
Identification and Speciation of Various Fungal Co-infections in COVID-19 Patients by Different Laboratory Diagnostic Methods: A Retrospective Observational Study
Authors: Patel Alpa , Sukaramwala Tanvi , Mullan Summaiya
Published: January 2024

Introduction: Respiratory illness caused by a novel coronavirus was first noted in December 2019 in Wuhan, Hubei Province, China. Later, the novel coronavirus was referred to as Severe and critical Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) by the International Committee on Taxonomy of Viruses (ICTV). However, the types of co-infected pathogens and the proportion of co-infection in SARS-CoV-2-positive patients were unclear. Co-infection with certain pathogens may also hinder accurate disease diagnosis. Aim: To determine the most suitable sample type for a better culture outcome and to identify the various opportunistic fungal infections related to Coronavirus Disease 2019 (COVID-19) patients. Materials and Methods: This retrospective observational study was conducted between November 2021 to January 2022 at Department of Microbiology, Government Medical College, Surat, Gujarat, India. The data collection was done in the month of November 2021 followed by data analysis in December 2021 to January 2022. A total of 252 suspected cases of fungal co-infection were sampled (including swabs, tissues, skin scrapings, Cerebrospinal fluid (CSF), sputum, pus, and drain) from different wards for fungal wet mount Potassium Hydroxide (KOH) and culture. The data was entered into Microsoft Excel (Windows 10), and analysis was performed using Microsoft Excel, including frequency distribution and percentage. Results: A total of 252 samples were received. Demographic details showed that individuals aged 41-50 years were more commonly affected, and males were affected more than females. Among the sample types, tissue samples showed the highest positivity 43 (17%), followed by scraping materials 14 (6%). Out of the total 252 cultures performed, 70 were positive. In terms of fungal speciation, Mucor species accounted for 24 (34.28%) isolates, while Aspergillus flavus accounted for 26 (37.14%), followed by other isolated fungal species. Conclusion: Fungal co-infection is observed in COVID-19 positive patients, which not only contributes to morbidity but also increases mortality. Tissue samples demonstrated the highest culture positivity. The culture results showed a higher frequency of Mucor species isolates and Aspergillus flavus compared to other isolates.