bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of transport logistics in tourism
Authors: Ivasyshyna Nataliia
Published: April 2024

The purpose of the proposed article is a theoretical study of the current state and prospects for the development of transport logistics in Ukraine, determination of the list of factors and limitations that determine the specificity of logistics in tourism. The methodology is based on scientific and special research methods. Methods of analysis, synthesis, systematization, classification, generalization of economic and methodical literature, scientific publications were used. Scientific novely. Research on the development of theoretical and methodological foundations of international transport and, especially, automobile networks in the conditions of world globalization and the substantiation of practical recommendations and approaches for improving the logistics of international road transportation in tourism. Conclusions.. The article deals with important problems of transport logistics in tourism. An analysis of the real state of development of transport logistics in Ukraine and its place in tourism has been carried out. It was determined that the prospects for the development of the logistics services market in Ukraine directly depend on the state of the country’s economy. It has been proven that the use of logistic principles and techniques in the management of tourist firms makes it possible to significantly increase the profitability of the tourist business by reducing costs and increasing the level of logistical coordination of all tourist service operations. The complex of components of the tourist service includes means of accommodation and food for tourists, means of their transportation, software and excursion support, informational and financial services, etc.
Optimization of the parameters on the combined cotton cleaning machine and analysis of cleaning efficiency
Authors: Sayitkulov Sardor , Nurmatova Nigora , Sharipov Jamshid , Salomov Abubakr , Saidova Gulchiroy
Published: April 2024

The article recommended the installation of pile drums and multi-sided grates on a combined cotton cleaner (ССС) unit based on full factor experiments, the results of comparative production tests with respect to the existing design are given. The connection graphs of the parameters were constructed, and on the basis of their analysis their optimal values were determined. Recommendations have been developed to ensure high efficiency of cleaning raw cotton from small and large wastes, to preserve the natural properties of the fiber.
Geospatial analysis of the territory for solving urban planning problems
Authors: Mamonov Kostiantyn , Nesterenko Serhii , Pilicheva Maryna , Afanasiev Aleksandr , Tsyhenko Anna
Published: April 2024

The purpose of the study is to conduct a geospatial analysis of the territory, taking into account urban planning characteristics, for the location of a shopping center. The study characterizes the factors that turn cities into diverse and complex forms of settlements that are constantly changing. The process of urban settlement, which is reflected in their space, is analyzed. It is determined that spatial factors lead to differences in the scale and shape of cities, types of development and methods of spatial planning. The necessity of studying the spatial structure of cities, which has the characteristics of a relatively complete theoretical justification and wide coverage, is established. It is determined that the process of spatial development of cities is multidimensional and complex, which is manifested in spatial planning, transformation of many functions and expansion of the territory. The direction of research on the spatial analysis of the selected city territory is determined. Various characteristics of the site are considered, including views, transport links, access and other constraints that may affect the future development of each approach to the shopping center. A spatial analysis of the shopping center location was conducted. This analysis determines the transport accessibility of the shopping center, the accessible distance to residential development, service areas, etc. It also determines which parts of the territory are suitable for a particular type of use. The results are obtained regarding the location of the shopping center in the city. The estimated number of regular visitors to the projected shopping center is determined, provided that the level of its attractiveness is the same as that of its competitors. The increase in the level of attractiveness of the projected shopping center in comparison with competitors is calculated. Based on the results of the geospatial analysis, the stages of design and survey work were developed to draw up a large-scale topographic basis for the development area.
Historical conditions of Ukraine’s tourism and recreation sector formation and its development in the era of sustainable multimodal mobility
Authors: Tsypko Victoria , Vasylchuk Volodymyr , Gedin Maksim , Kan Den , Lavrynovych Elena
Published: April 2024

The purpose of the proposed article is a show the history of the formation of the sphere of tourism and recreation of Ukraine in the context of world trends. Methodology is base on application of such scientific methods, as literary, historical, chronologic, dichronic (method of division into periods), approach of the systems, івент- and content-analysis, that did possible complex study and selection of the basic historical stages of development of tourism and recreation. Scientific novely. The authors considered the main approaches to the periodization of the formation of tourism and the tourism industry in Ukraine and the main stages of the development of the field of tourism and recreation from the earliest times. It is emphasized that the formation of tourism and recreation in different geographical regions of Ukraine had certain features, and this industry can take place according to the following main models. Conclusions. The processes of the origin and development of tourism and recreation in Ukraine and the world, the emergence of tourist enterprises, the creation of international tourist organizations, and the globalization of tourism are highlighted. The analysis of the points of view of foreign and domestic authors on international tourism market research made it possible to substantiate the historical aspects of the development of the field of tourism and recreation as a factor in the European integration of Ukraine, as well as to determine the current directions of development of the field of tourism and recreation in the context of European integration processes in Ukraine.
Endlich mehr Freiheiten – Blankoverordnung
Authors: Mischner Julia
Published: April 2024

Lange haben Ergothera-peut*innen darauf gewartet: die Einführung der Blankoverordnung. Es handelt sich dabei um eine spezielle Verordnungsform, von der Ärzt*innen und Psychotherapeut*innen seit 1. April 2024 Gebrauch machen können. Sie stellen weiterhin eine Indikation für Ergotherapie fest, die behandelnden Therapeut*innen entscheiden jedoch selbst über die Auswahl des Heilmittels, die Dauer der Therapie sowie die Behandlungsfrequenz.
Association between endoscopist adenoma detection rate and serrated polyp detection: Retrospective analysis of over 200,000 screening colonoscopies
Authors: Penz Daniela , Pammer Daniel , Waldmann Elisabeth , Asaturi Arno , Szymanska Aleksrandra , Trauner Michael , Ferlitsch Monika
Published: April 2024

Background and study aims Serrated lesions have been identified as precursor lesions for 20% to 35% of colorectal cancers (CRCs) and may contribute to a significant proportion of interval-cancer. Sessile-serrated-lesions (SSLs), in particular, tend to be flat and located in the proximal colon, making their detection challenging and requiring expertise. It remains unclear whether the detection rate for serrated polyps should be considered as a quality indicator in addition to the adenoma detection rate (ADR). This study sought to assess whether the ADR has an effect on the detection rate for serrated polyps.

atients and methods In this retrospective analysis, prospectively collected data from 212,668 screening colonoscopies performed between 2012 and September 2018 were included. Spearman correlation and Whitney-Mann U-test were used to assess the association of ADR and the detection rate of SSLs with (SDR) and without hyperplastic polyps (SPADRs), the sessile serrated detection rate (SSLDR) as well as the clinically relevant serrated detection rate (CRSDR), including all SSLs and traditional serrated adenoma, hyperplastic polyps (HPs) >10 mm anywhere in the colon or HPs > 5 mm proximal to the sigmoid.

Results The overall mean ADR was 21.78% (standard deviation [SD] 9.27), SDR 21.08% (SD 11.44), SPADR 2.19% (SD 2.49), and CRSDR was 3.81% (3.40). Significant correlations were found between the ADR and the SDR, SPADR, SSLDR, and CRSDR (rho=0.73 vs. rho=0.51 vs. rho=0.51 vs. rho=0.63; all P <0.001). Endoscopists with a mean ADR ≥25% had significantly higher SDR, SPADR, and CRSDR than endoscopists with a mean ADR <25% (all P <0.001; Mann-Whitney U-Test).

Conclusions This study shows that endoscopists with higher ADR detect significantly more serrated lesions than those with a lower ADR.
Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria
Authors: Huseby Douglas L. , Cao Sha , Zamaratski Edouard , Sooriyaarachchi Sanjeewani , Ahmad Shabbir , Bergfors Terese , Krasnova Laura , Pelss Juris , Ikaunieks Martins , Loza Einars , Katkevics Martins , Bobileva Olga , Cirule Helena , Gukalova Baiba , Grinberga Solveiga , Backlund Maria , Simoff Ivailo , Leber Anna T. , Berruga-Fernández Talía , Antonov Dmitry , Konda Vivekananda R. , Lindström Stefan , Olanders Gustav , Brandt Peter , Baranczewski Pawel , Vingsbo Lundberg Carina , Liepinsh Edgars , Suna Edgars , Jones T. Alwyn , Mowbray Sherry L. , Hughes Diarmaid , Karlén Anders
Published: April 2024

Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains ofEscherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogensE. coliandKlebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-β-lactamase, metallo-β-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.
NKS1/ELMO4 is an integral protein of a pectin synthesis protein complex and maintains Golgi morphology and cell adhesion in
Arabidopsis
Authors: Lathe Rahul S. , McFarlane Heather E. , Kesten Christopher , Wang Liu , Khan Ghazanfar Abbas , Ebert Berit , Ramírez-Rodríguez Eduardo Antonio , Zheng Shuai , Noord Niels , Frandsen Kristian , Bhalerao Rishikesh P. , Persson Staffan
Published: April 2024

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific
Arabidopsis
DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The
nks1
mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to
qua1
and
qua2
mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function.
The impact of living with assistance dog placements on quality of life in children and adults with autism spectrum disorder or a physical disability: A longitudinal service evaluation
Authors: Shoesmith Emily , Gibsone Selina , Bracher Ed , Smolkovič Iris , Jennings Kelly , Viles Laura , Easton Kate , Ratschen Elena
Published: April 2024

Assistance dogs are highly trained animals to support individuals with disabilities and medical conditions. Evidence suggests the support provided by an assistance dog can extend beyond physical assistance to therapeutic and communicative domains. However, there is limited research exploring the lived experience of assistance dog placements in the United Kingdom (UK) over an extended period of time. This longitudinal service evaluation was designed to evaluate the placement of assistance dogs, trained by the charity Dogs for Good, with adults and children with autism or a physical disability in the UK. Goals and expectations of being matched with an assistance dog prior to placement, and perceptions of how these dogs have impacted the quality of life of adults and children with autism and/or a physical disability and their families were assessed. Service users who had applied for an assistance dog via the Dogs for Good charity (n = 307) were contacted and invited to complete questionnaires at five different time points (pre-dog placement, and 6-, 12-, 24-, and 36-months post dog-placement). Repeated-measures ANOVAs were conducted to determine if there were significant changes to quality of life over time. Mean quality of life scores improved significantly for all service users. Responses to free-text questions were thematically analysed, and three main themes were identified from the free-text responses: goals and expectations for assistance dog pre-placement (e.g., enhancing independence, physical functioning and wellbeing), the positive impact of the assistance dog post-placement (e.g., promoting independence, development of the human-animal bond, improving wider family dynamics, and reducing stigma), and satisfaction with the service. The findings complement and extend previous insights into the impact of assistance dogs on people with autism or a physical disability. They also highlight some challenges associated with the placement of assistance dogs and indicate the need to consider the development of further targeted support strategies.
Finite-size effects in hyperuniform vortex matter
Authors: Milagros Besana Rocío , Elías Federico , Puig Joaquín , Aragón Sánchez Jazmín , Nieva Gladys , Benedykt Kolton Alejandro , Fasano Yanina
Published: April 2024

Novel hyperuniform materials are emerging as an active field of applied and basic research since they can be designed to have exceptional physical properties. This ubiquitous state of matter presents a hidden order that is characterized by the density of constituents of the system being uniform at large scales, as in a perfect crystal, although they can be isotropic and disordered like a liquid. In the quest for synthesizing hyperuniform materials in experimental conditions, the impact of finite-size effects remains as an open question to be addressed. We use vortex matter in type-II superconductors as a toy model system to study this issue. We previously reported that vortex matter nucleated in samples with point disorder is effectively hyperuniform and thus presents the interesting physical properties inherent to hyperuniform systems. In this work we present experimental evidence that on decreasing the thickness of the vortex system its hyperuniform order is depleted. By means of hydrodynamic arguments we show that the experimentally observed depletion can be associated to two crossovers that we describe within a hydrodynamic approximation. The first crossover length is thickness-dependent and separates a class-II hyperuniform regime at intermediate lengthscales from a regime that can become asymptotically non-hyperuniform for large wavelengths in very thin samples. The second crossover takes place at smaller lengthscales and marks the onset of a faster increase of density fluctuations due to the dispersivity of the elastic constants. Our work points to a novel mechanism of emerging hyperuniformity controlled by the thickness of the host sample, an issue that has to be taken into account when growing hyperuniform structures for technological applications.
Geodesic flows of compact higher genus surfaces without conjugate points have expansive factors
Authors: Mamani Edhin Franklin
Published: April 2024

In this paper we show that a geodesic flow of a compact surface without conjugate points of genus greater than one is time-preserving semi-conjugate to a continuous expansive flow which is topologically mixing and has a local product structure. As an application we show that the geodesic flow of a compact surface without conjugate points of genus greater than one has a unique measure of maximal entropy. This gives an alternative proof of Climenhaga–Knieper–War Theorem.
The Optosystem: validation and testing of the high-speed electro-optical conversion system for the readout of the ATLAS ITk Pixel upgrade
Authors: Möbius S. ,   the ATLAS ITk Group
Published: April 2024

After Run III the ATLAS detector will undergo a series of upgrades to cope with the harsher radiation environment and increased number of proton interactions in the High Luminosity-LHC. One of the key projects in this suite of upgrades is the ATLAS Inner Tracker (ITk). The pixel detector of the ITk must be read out accurately and with extremely high rate. The Optosystem performs electro-optical conversion of signals from the pixel modules. This paper presents recent results related to the performance of the data transmission chain with a focus on the Optoboards and to the design, testing and production of the Optopanels.
Functionally graded structures in the involucre of Job’s tears
Authors: Kuwada Rikima , Ishii Daisuke
Published: April 2024

Nature is filled with materials that are both strong and light, such as bones, teeth, bamboo, seashells, arthropod exoskeletons, and nut shells. The insights gained from analyzing the changing chemical compositions and structural characteristics, as well as the mechanical properties of these materials, have been applied in developing innovative, durable, and lightweight materials like those used for impact absorption. This research concentrates on the involucres of Job’s tears (Coix lacryma-jobi var. lacryma-jobi), which are rich in silica, hard, and serve to encase the seeds. The chemical composition and structural characteristics of involucres were observed using scanning electron microscopy and energy-dispersive x-ray spectroscopy and optical microscopy with safranin staining. The hardness of the outer and inner surfaces of the involucre was measured using the micro-Vickers hardness test, and the Young’s modulus of the involucre’s cross-section was measured using nanoindentation. Additionally, the breaking behavior of involucres was measured through compression test and three-point bending tests. The results revealed a smooth transition in chemical composition, as well as in the orientation and dimensions of the tissues from the outer to the inner layers of involucres. Furthermore, it was estimated that the spatial gradient of the Young’s modulus is due to the gradient of silica deposition. By distributing the hard, brittle silica in the outer layer and elastoplastic organic components in the middle and inner layers, the involucres effectively respond to compressive and tensile stresses that occur when loads are applied to the outside of the involucre. Furthermore, the involucres are reinforced in both meridional and equatorial directions by robust fibrovascular bundles, fibrous bundles, and the inner layer’s sclerenchyma fibers. From these factors, it was found that involucres exhibit high toughness against loads from outside, making it less prone to cracking.
Increased harvested carbon of cropland in China
Authors: Ren Peiyang , Wang Daju , Xia Xiaosheng , Chen Xiuzhi , Qin Zhangcai , Wei Jing , Liu Shuguang , O’Sullivan Mike , Yuan Wenping
Published: April 2024

Crop harvested carbon (HC) is one of the most important components of the carbon cycle in cropland ecosystems, with a significant impact on the carbon budget of croplands. China is one of the most important crop producers, however, it is still unknown on the spatial and temporal variations of HC. This study collected statistical data on crop production at the province and county levels in China for all ten crop types from 1981 to 2020 and analyzed the magnitude and long-term trend of harvested crop carbon. Our results found a substantial increase of HC in cropland from 0.185 Gt C yr−1 in 1981 to 0.423 Gt C yr−1 in 2020 at a rate of 0.006 Gt C yr−1. The results also highlighted that the average annual carbon sink removal from crop harvesting in China from 1981 to 2020 was 0.32 Gt C yr−1, which was comparable to the net carbon sink of the entire terrestrial ecosystems in China. This study further generated a gridded dataset of HC from 2001 to 2019 in China by using jointly the statistical crop production and distribution maps of cropland. In addition, a model-data comparison was carried out using the dataset and results from seven state-of-the-art terrestrial ecosystem models, revealing substantial disparities in HC simulations in China compared to the dataset generated in the study. This study emphasized the increased importance of HC for estimating cropland carbon budget, and the produced dataset is expected to contribute to carbon budget estimation for cropland ecosystems and the entire China.
Increasing risks of the explosive extratropical cyclones over the North Atlantic storm track: a perspective from their surface wind maxima
Authors: Fu Shen-Ming , Ma Hui , Jiang Li-Zhi
Published: April 2024

Extratropical cyclones play a crucial role in balancing the global momentum, energy, and moisture, and also, they shape the extreme weather events over the extra-tropics. As the strongest category of the extratropical cyclones, the explosive extratropical cyclones (EECs) frequently induce severe disasters through their strong surface winds. During the entire lifespan of an EEC, there is a maximum value of its surface wind (i.e. the maximum surface wind; MSW), which processes the greatest destructive power. After nearly a century of research on the EECs, key features about their MSWs still remain vague. In this study, we systematically investigate the EECs’ MSWs over the North Atlantic storm track (NAST) based on the ERA-Interim reanalysis. It is found that, the average intensity of EECs’ MSWs shows a significant increasing trend of ∼0.3 m s−1 per 10a. More importantly, for the last 20 years, even larger increasing rates of 1.5 m s−1 and 3.5 m s−1 per 10a are found in the average and maximum intensities of the EECs’ MSWs, respectively, implying the EECs’ risks increase notably for the NAST. We further clarify the physical mechanisms governing the production of EECs’ MSWs, and then establish a mechanism-based statistical model, which has the potential to predict the MSWs’ annual average intensity. In summary, our study fills a knowledge gap for the EECs’ MSWs, which would have broad implication of the economics and society.
Light Activism: alternative urban nightscapes
Authors: Flugelman Martin
Published: April 2024

Since their beginnings, artificial lighting technologies have been used as a tool by those in power to express their authority and ensure their control of cities. State and commercial hegemony determine urban lighting, which has a substantial spatial, semiotic, emotional, and physiological effect on us. Lighting conditions imposed from the top down inform our bodily experience of the night.

LED technology is revolutionizing artificial public lighting. Nevertheless, critical inquiry about its potential uses is sorely lacking. This research will explore the capacity of collective light interventions to turn public spaces into more inclusive nightscapes. It will focus on community-driven projects where the use of lighting contributes to the production of alternative urban experiences. The research engages methodological issues by asking how lighting tools can potentially contribute to community empowerment. Can lighting actions in public spaces propose other ways of interacting and other ways of experiencing the night?

This paper revolves around critical lighting practices. It shows how the use of light can foster citizen engagement and ignite new nocturnal imaginaries as the perception of the night is reshaped to restore communities’ right to the city. The intention is to bolster critical awareness regarding the use of light and the power underpinning its instrumentalization. This text will also shed light on the effect ephemeral collective light interventions have on public spaces and its perception.
Numerical Investigations on the Seismic Behavior of a Reinforced Concrete Frame Structure
Authors: Taranu G , Venghiac V M , Banu O M , Florea V
Published: April 2024

Recent seismic events that took place during the past two decades and struck densely populated areas caused significant material losses and, sometimes, casualties. Taking into account the ageing of the building stock around the world coupled with unavoidable degradations, urgent measures need to be taken to either strengthen or retrofit such structures based on data obtained from analytical, experimental or numerical investigations. The present paper presents the results of numerical simulations, using time-history analyses, on a scaled-down reinforced concrete (RC) frame structure subjected to two multidirectional seismic scenarios. The obtained results are discussed from the point of view of maximum displacements, accelerations and equivalent stresses. Considering the dynamic characteristics of the model, neither considered seismic event were able to produce large lateral displacements or accelerations. Damages were localized at the beam-column joints in case of Turkey 2023 earthquake scenario.
High-temperature behavior of zeolite-containing mortar. Experiment and modelling
Authors: Alexa-Stratulat M S , Bunea G , Banu O M , Maxineasa S G , Toma I O
Published: April 2024

High temperature experiments were carried out on cylindrical-shaped specimens of mortar containing different concentrations of either cement-replacing zeolite or aggregate-replacing zeolite. The behavior was compared with that of plain mortar. Furthermore, finite-element models were designed, based on material characteristics obtained on the real specimens, to test the temperature exposure effect when similar conditions were applied.
Time history comparative analyses of a thin-walled cold-formed steel structure considering P-D effect
Authors: Tăranu G. , Movilă M. , Luca S.G. , Pastia C. , Toma I.O.
Published: April 2024

The paper presents a comparative time history analysis based on the 1D-beam Finite Element Method (FEM) for a thin-walled cold-formed steel structure previously investigated both theoretically and experimentally. The recent earthquake which occurred in Turkey with 7.8Mw and a Peak Ground Acceleration (PGA) of almost 0.5g showed numerous collapses of different types of buildings. Romania has an active seismic area located in the Vrancea region where, in 1977 a 7.5Mw earthquake also occurred. In this context, this paper presents a comparative analysis with time history accelerograms of the recorded earthquake in North – South and East - West directions. The structural model was analyzed in Robot Structural Analysis software in two scenarios of the time history accelerograms considering also the P-Δ effect. The finite elements of the structure were defined as 1-D beam elements with hinged joints and limited axial stiffness previously obtained in past studies. The results showed a substantial increase in terms of displacements and stresses.
Variable diameter pile foundations – advantages and disadvantages
Authors: Colţ O E , Neagu C P , Motău A , Dmitriev I , Chercheja L
Published: April 2024

Variable diameter pile foundations can be an efficient foundation solution used for special structures, mainly for the ones with increased heights. For economic efficiency in land use, especially in urban areas, there is a tendency to build very high constructions with very small footprint related to their height, which transmit large loads to the foundation soil. Based on these aspects, it is necessary to consider pile foundations in order to ensure the desired safety and stability requirements. The technologies for piles constructions evolved a lot and a main objective was to better use the interaction between the soil and the pile. From this point a view the paper presents a comparison between the bearing capacities of a constant diameter pile and a variable diameter pile, considering different soil conditions. All the calculations were performed using finite element analyses.
Exploring the connection between adaptive architecture and artificial intelligence
Authors: Dohotariu I
Published: April 2024

Interactive adaptive architecture refers to the design of systems that can adapt to changes in their operating environment through interaction with users or other agents in the system. Artificial intelligence, on the other hand, refers to the ability of computer systems to perform tasks that would otherwise require human intelligence. Interactive adaptive architecture and artificial intelligence are two interconnected concepts that have evolved with the development of cybernetics. The development of interactive architecture based on the use of artificial intelligence will not mean the disappearance of architecture, as we know it, but rather a change in the way it is perceived. In the future, architecture will be participatory, with an active role of inhabitants in shaping and transforming architectural habitats, but there will always be a need for a moderator, the architect, to design and set the rules of the game for humans.
The use of microphysiological systems to model metastatic cancer
Authors: Jackson Caitlin E , Green Nicola H , English William R , Claeyssens Frederik
Published: April 2024

Cancer is one of the leading causes of death in the 21st century, with metastasis of cancer attributing to 90% of cancer-related deaths. Therefore, to improve patient outcomes there is a need for better preclinical models to increase the success of translating oncological therapies into the clinic. Current traditional static in vitro models lack a perfusable network which is critical to overcome the diffusional mass transfer limit to provide a mechanism for the exchange of essential nutrients and waste removal, and increase their physiological relevance. Furthermore, these models typically lack cellular heterogeneity and key components of the immune system and tumour microenvironment. This review explores rapidly developing strategies utilising perfusable microphysiological systems (MPS) for investigating cancer cell metastasis. In this review we initially outline the mechanisms of cancer metastasis, highlighting key steps and identifying the current gaps in our understanding of the metastatic cascade, exploring MPS focused on investigating the individual steps of the metastatic cascade before detailing the latest MPS which can investigate multiple components of the cascade. This review then focuses on the factors which can affect the performance of an MPS designed for cancer applications with a final discussion summarising the challenges and future directions for the use of MPS for cancer models.
Analytical solution to second-harmonic generation of ultrashort laser pulse
Authors: Peng Yufei , Hu Chenyang , Hong Lihong , Li Zhiyuan
Published: April 2024

We present an analytical method to evaluate the second-harmonic generation (SHG) process of ultrashort laser pulses in a nonlinear medium within the small-signal regime. Building upon the broadband nonlinear coupled wave theory, we derive an analytical solution that allows one to investigate the fundamental physics and detailed dynamics of the nonlinear interaction between ultrashort laser pulses. We find that SHG for ultrashort laser pulses in a nonlinear crystal arises from a series of self-SHG and self sum-frequency generation processes involving different frequency components. We have applied the analytical method to investigate specific pulse profiles with Gaussian and sech functions and found good agreement between analytical theory and numerical simulations, validating the accuracy of the analytical approach. The analytical method enables one to explore the evolution of the second-harmonic wave under various pulse profiles, pulse widths, and crystal thicknesses, and offers a more efficient and insightful approach to study the nonlinear optical dynamics of ultrashort laser pulses.
Research on the grouped orthonormalization method in ghost imaging
Authors: Yin Longfei , Liu Tiantian , Mai Xinlong , Sun Shilun , Yin Pengqi , Wu Guohua , Luo Bin
Published: April 2024

Ghost imaging (GI) has found application across diverse fields owing to its distinctive benefits. When employing the rotating ground-glass scheme and utilizing second-order correlation for image reconstruction, the efficiency of imaging is hindered by the multiple sampling of reference patterns. To address this, the orthonormalization method has been employed to enhance image quality and reduce the required number of measurements. Despite its effectiveness, the original orthonormalization method is prone to accumulating imaging noise and errors as the number of measurements increases, leading to a significant degradation in image quality. To overcome this limitation, this paper introduces the grouped orthonormalization method (GO-GI) as an extension of the orthonormalization technique. By adjusting the ‘group size’, this method enables control over the accumulation of errors, resulting in an improvement in image quality. The evaluation of image quality in terms of Contrast-to-Noise demonstrates the significant advantages of the GO-GI method in both simulation and experimental results. This study establishes the GO-GI method as a simple yet practical approach in the realm of GI.
Invited commentary: where do the causal DAGS come from?
Authors: Didelez Vanessa
Published: April 2024

How do we construct our causal directed acyclic graphs (DAGs)—for example, for life-course modeling and analysis? In this commentary, I review how the data-driven construction of causal DAGs (causal discovery) has evolved, what promises it holds, and what limitations or caveats must be considered. I find that expert- or theory-driven model-building might benefit from some more checking against the data and that causal discovery could bring new ideas to old theories.
A machine-readable specification for genomics assays
Authors: Booeshaghi Ali Sina , Chen Xi , Pachter Lior
Published: April 2024

Motivation

Understanding the structure of sequenced fragments from genomics libraries is essential for accurate read preprocessing. Currently, different assays and sequencing technologies require custom scripts and programs that do not leverage the common structure of sequence elements present in genomics libraries.

Results

We present seqspec, a machine-readable specification for libraries produced by genomics assays that facilitates standardization of preprocessing and enables tracking and comparison of genomics assays.

Availability and implementation

The specification and associated seqspec command line tool is available at https://www.doi.org/10.5281/zenodo.10213865.
Designing efficient randstrobes for sequence similarity analyses
Authors: Karami Moein , Soltani Mohammadi Aryan , Martin Marcel , Ekim Barış , Shen Wei , Guo Lidong , Xu Mengyang , Pibiri Giulio Ermanno , Patro Rob , Sahlin Kristoffer
Published: April 2024

Motivation

Substrings of length k, commonly referred to as k-mers, play a vital role in sequence analysis. However, k-mers are limited to exact matches between sequences leading to alternative constructs. We recently introduced a class of new constructs, strobemers, that can match across substitutions and smaller insertions and deletions. Randstrobes, the most sensitive strobemer proposed in Sahlin (Effective sequence similarity detection with strobemers. Genome Res 2021a;31:2080–94. https://doi.org/10.1101/gr.275648.121), has been used in several bioinformatics applications such as read classification, short-read mapping, and read overlap detection. Recently, we showed that the more pseudo-random the behavior of the construction (measured in entropy), the more efficient the seeds for sequence similarity analysis. The level of pseudo-randomness depends on the construction operators, but no study has investigated the efficacy.

Results

In this study, we introduce novel construction methods, including a Binary Search Tree-based approach that improves time complexity over previous methods. To our knowledge, we are also the first to address biases in construction and design three metrics for measuring bias. Our evaluation shows that our methods have favorable speed and sampling uniformity compared to existing approaches. Lastly, guided by our results, we change the seed construction in strobealign, a short-read mapper, and find that the results change substantially. We suggest combining the two results to improve strobealign’s accuracy for the shortest reads in our evaluated datasets. Our evaluation highlights sampling biases that can occur and provides guidance on which operators to use when implementing randstrobes.

Availability and implementation

All methods and evaluation benchmarks are available in a public Github repository at https://github.com/Moein-Karami/RandStrobes. The scripts for running the strobealign analysis are found at https://github.com/NBISweden/strobealign-evaluation.
Practical causal mediation analysis: extending nonparametric estimators to accommodate multiple mediators and multiple intermediate confounders
Authors: Rudolph Kara E , Williams Nicholas T , Diaz Ivan
Published: April 2024

Mediation analysis is appealing for its ability to improve understanding of the mechanistic drivers of causal effects, but real-world data complexities challenge its successful implementation, including (i) the existence of post-exposure variables that also affect mediators and outcomes (thus, confounding the mediator-outcome relationship), that may also be (ii) multivariate, and (iii) the existence of multivariate mediators. All three challenges are present in the mediation analysis we consider here, where our goal is to estimate the indirect effects of receiving a Section 8 housing voucher as a young child on the risk of developing a psychiatric mood disorder in adolescence that operate through mediators related to neighborhood poverty, the school environment, and instability of the neighborhood and school environments, considered together and separately. Interventional direct and indirect effects (IDE/IIE) accommodate post-exposure variables that confound the mediator–outcome relationship, but currently, no readily implementable nonparametric estimator for IDE/IIE exists that allows for both multivariate mediators and multivariate post-exposure intermediate confounders. The absence of such an IDE/IIE estimator that can easily accommodate both multivariate mediators and post-exposure confounders represents a significant limitation for real-world analyses, because when considering each mediator subgroup separately, the remaining mediator subgroups (or a subset of them) become post-exposure intermediate confounders. We address this gap by extending a recently developed nonparametric estimator for the IDE/IIE to allow for easy incorporation of multivariate mediators and multivariate post-exposure confounders simultaneously. We apply the proposed estimation approach to our analysis, including walking through a strategy to account for other, possibly co-occurring intermediate variables when considering each mediator subgroup separately.
When the homo deamon went digital: writing Africa’s transgender refugee diaspora
Authors: Camminga B
Published: April 2024

From an online African lesbian, gay, bisexual, transgender and intersex (LGBTI) news and information website, launched in 2000, called Behind the Mask (BtM) to Sokari Ekine’s foundational 2004 blog Blacklooks, the digital has been crucial to queer African studies and, indeed, queer Africa. In this brief exploration, I navigate through the realms of queer African studies, African digital humanities, and African literary studies, using them as my guiding framework to uncover the digital emergence of an African transgender refugee diaspora. I suggest that this diaspora is producing content explicitly aimed back at the African continent to shape and deploy the reality of what it means to be transgender and African. In so doing, they are actively authoring themselves into existence.
Liveness Attacks On HotStuff: The Vulnerability Of Timer Doubling Mechanism
Authors: Guo Kaiwen , Hu Kexin , Zhang Zhenfeng
Published: April 2024

Byzantine fault-tolerant (BFT) consensus protocols are essential in distributed computing. Most partially synchronous BFT protocols proceed in views and rely on a view synchronizer module to guarantee liveness by synchronizing honest replicas to the same view. HotStuff is a leading BFT consensus protocol known for achieving linear view change and optimistic responsiveness. To achieve these desirable properties, HotStuff relies on a candidate solution for the view synchronizer based on a recomposed timer doubling mechanism. However, a formal analysis of this mechanism is currently lacking. This paper delves into HotStuff with the recomposed timer doubling mechanism. To facilitate accurate analysis, we introduce a new specification for the view synchronizer, incorporating two paths for view switching as in HotStuff’s setting. Surprisingly, we observe that the adversary can disrupt the view synchronization and launch a liveness attack, stalling the confirmation process. Besides, the adversary can further recover or control the confirmation process at will. A repairment that retains the desirable feature of HotStuff is also presented. We simulate the liveness attack and the repairment, demonstrating their effectiveness. Specifically, the liveness attack can cause HotStuff’s throughput to drop and remain at 0. When equipped with our repairment, HotStuff can resist the attack and retain the throughput performance.
Heterozygous gain of function variant in GUCY1A2 may cause autonomous ovarian hyperfunction
Authors: Wittrien Theresa , Ziegler Alban , Rühle Anne , Stomberg Svenja , Meyer Ruben , Bonneau Dominique , Rodien Patrice , Prunier-Mirebeau Delphine , Coutant Régis , Behrends Sönke
Published: April 2024

Purpose

The purpose of this study was to characterize the phenotype associated with a de novo gain-of-function variant in the GUCY1A2 gene.

Methods

An individual carrying the de novo heterozygous variant c.1458G>T p.(E486D) in GUCY1A2 was identified by exome sequencing. The effect of the corresponding enzyme variant α2E486D/β1 was evaluated using concentration-response measurements with wild-type enzyme and the variant in cytosolic fractions of HEK293 cells, UV-vis absorbance spectra of the corresponding purified enzymes, and examination of overexpressed fluorescent protein-tagged constructs by confocal laser scanning microscopy.

Results

The patient presented with precocious peripheral puberty resembling the autonomous ovarian puberty seen in McCune-Albright syndrome. Additionally, the patient displayed severe intellectual disability. In vitro activity assays revealed an increased nitric oxide affinity for the mutant enzyme. The response to carbon monoxide was unchanged, while thermostability was decreased compared to wild type. Heme content, susceptibility to oxidation, and subcellular localization upon overexpression were unchanged.

Conclusion

Our data define a syndromic autonomous ovarian puberty likely due to the activating allele p.(E486D) in GUCY1A2 leading to an increase in cGMP. The overlap with the ovarian symptoms of McCune-Albright syndrome suggests an impact of this cGMP increase on the cAMP pathway in the ovary. Additional cases will be needed to ensure a causal link.
Coming of age: governance challenges in updated AMR national action plans in the EU
Authors: Carelli Daniel E , Ogne Josefin B , Pierre Jon
Published: April 2024

Background

National action plans (NAPs) are key instruments for governing antimicrobial resistance (AMR). In Europe, we can now observe many countries updating their NAPs which raise two key research questions; what substantial modifications are states opting for, and how do they wish to address challenges related to AMR governance in a comparative perspective?

Methods

Building on a previous analytical classification, we address these two questions by examining data of updated versions of NAPs in 13 European Union member states covering seventeen elements related to AMR governance.

Results

Our results substantiate the large variation with regard to both substantive issues and governance-related matters. Most tellingly, they highlight the growing importance of the One Health approach in updated versions of NAPs. Our analysis also shows that while substantive issues remain important, One Health and the coordination and collaboration issues it entails are becoming more salient in the second or third generation of NAPs.

Conclusions

Updated NAPs suggest that EU member states are becoming increasingly knowledgeable on the causes and consequences of AMR and how it needs to be addressed. The enhanced level of knowledge also leads these countries to address the next set of issues and challenges; to improve domestic and international coordination and collaboration. Thus, the revised NAPs present a noticeable development from substantive issues towards governance issues.
Microbial community structures and bacteria-Cylindrospermopsis raciborskii interactions in Yilong Lake
Authors: Jin Yuanpei , Ren Sanguo , Wu Yichi , Zhang Xu , Chen Zhengjun , Xie Bo
Published: April 2024

Cylindrospermopsis raciborskii-dominated harmful algae blooms have been reported globally in recent years. However, our understanding of the ecology of C. raciborskii in natural conditions is still poor. In this study, we collected the water samples from a C. raciborskii-blooming lake, Yilong Lake, in Yunnan province, China, and used both culture-dependent and culture-independent approaches to investigate their microbial communities and the interactions between C. raciborskii and the other bacteria. The composition and diversity of microbial communities were revealed with 16S rRNA gene high-throughput sequencing data analysis. Microbial co-occurrences analysis suggests C. raciborskii may have complex associations with other bacteria. Based on co-inoculation tests, we obtained 14 strains of bacterial strains from the water samples that exhibited either algicidal or promoting effects on a strain of C. raciborskii. Two bacterial isolates exhibited a consistent performance between co-occurrence analysis and experimental results. Effects of these bacteria-algae interspecies interactions on the bloom event are discussed. All these results may provide new insights into the C. raciborskii-dominated blooms and how its interspecies relationships with other bacteria may influence the bloom events in eutrophic waters throughout the world.