bluuebunny/crossref_metadata_2025 huggingface dataset:
How you describe procurement calls matters: Predicting outcome of public procurement using call descriptions
Authors: Acikalin Utku Umur , Gorgun Mustafa Kaan , Kutlu Mucahid , Tas Bedri Kamil Onur
Published: August 2023

A competitive and cost-effective public procurement (PP) process is essential for the effective use of public resources. In this work, we explore whether descriptions of procurement calls can be used to predict their outcomes. In particular, we focus on predicting four well-known economic metrics: (i) the number of offers, (ii) whether only a single offer is received, (iii) whether a foreign firm is awarded the contract, and (iv) whether the contract price exceeds the expected price. We extract the European Union’s multilingual PP notices, covering 22 different languages. We investigate fine-tuning multilingual transformer models and propose two approaches: (1) multilayer perceptron (MLP) models with transformer embeddings for each business sector in which the training data are filtered based on the procurement category and (2) a k-nearest neighbor (KNN)-based approach fine-tuned using triplet networks. The fine-tuned MBERT model outperforms all other models in predicting calls with a single offer and foreign contract awards, whereas our MLP-based filtering approach yields state-of-the-art results in predicting contracts in which the contract price exceeds the expected price. Furthermore, our KNN-based approach outperforms all the baselines in all tasks and our other proposed models in predicting the number of offers. Moreover, we investigate cross-lingual and multilingual training for our tasks and observe that multilingual training improves prediction accuracy in all our tasks. Overall, our experiments suggest that notice descriptions play an important role in the outcomes of PP calls.
The experiences of families of children with cancer during the COVID-19 pandemic: A qualitative exploration
Authors: Sutherland-Foggio Malcolm S. , Stanek Charis J. , Buff Kimberly , Nahata Leena , Foster-Akard Terrah , Gerhardt Cynthia A. , Skeens Micah A.
Published: August 2023

Objectives

The COVID-19 pandemic posed new challenges to physical and psychological well-being. Families with pediatric cancer patients were particularly vulnerable due to changes like children staying at home, hospital policy shifts, and caring for an immunocompromised child. Limited research exists on COVID-19's effects on these families. This study aimed to assess the pandemic's impact and identify psychosocial support gaps.

Methods

Participants (N = 256) were parents of children with cancer recruited via Facebook in partnership with Momcology®, a community-based organization for pediatric cancer, between February and May 2021. Qualitative analyses used open-ended responses about the pandemic’s impact on the family.

Results

Analysis revealed 6 themes, with positive and negative sentiments: family changes (n = 169; 61% negative), social isolation (n = 154; 100% negative), emotional impact (n = 143; 89% negative), school changes (n = 126; 80% negative), health-care changes (n = 111; 96% negative), and physical health (n = 49; 73% negative). Family changes overarched all themes and included financial strains, at-home schooling, and family bonding. Parents highlighted social isolation and the emotional impact of pandemic-related changes. School changes forced parents to balance remote-work and childcare. Health-care changes limited resources and visitation. Parents reported their children were less active and slept less but had fewer illnesses.

Significance of results

Many common pandemic challenges were exacerbated by the stress of caring for a child with cancer. Parents struggled most with loss of social support and feelings of isolation. Careful consideration should be given to providing resources for parents of children with cancer and their families.
Knowledge, goals, and misperceptions about palliative care in adults with chronic disease or cancer
Authors: Ramos Katherine , Kaufman Brystana G. , Winger Joseph G. , Boggins Abby , Van Houtven Courtney H. , Porter Laura S. , Hastings S. Nicole
Published: August 2023

Objectives

Limited evidence investigates how knowledge, misconceptions, and beliefs about palliative care vary across patients with cancerous versus non-cancerous chronic disease. We examined the knowledge of and misconceptions about palliative care among these groups.

Methods

We used weighted data from the National Cancer Institute Health Information National Trends Survey 5 (Cycle 2) for nationally representative estimates and logistic regression to adjust for respondent characteristics. We identified respondents who reported having (1) cancer ([n = 585]; breast, lung, and colorectal), (2) chronic conditions ([n = 543]; heart failure, lung disease, or chronic obstructive pulmonary disorder), or (3) neither cancer nor other chronic conditions (n = 2,376).

Results

Compared to cancer respondents, chronic condition respondents were more likely to report being Black or Hispanic, report a disability, and have lower socioeconomic status. In the sample, 65.6% of cancer respondents and 72.8% chronic conditions respondents reported they had never heard of palliative care. Chronic condition respondents were significantly (p < 0.05) less likely to report high palliative care knowledge than cancer respondents (9.1% vs. 16.6%, respectively). In adjusted analyses, cancer respondents had greater odds of high palliative care knowledge (odd ratio [OR] = 1.70; 95% confidence interval [CI] = 1.01, 2.86) compared to respondents with neither cancer nor chronic disease; chronic condition respondents did not have increased odds (OR = 0.96; CI = 0.59, 1.54).

Significance of results

Disparities in palliative care knowledge exist among people with non-cancerous chronic disease compared to cancer. Supportive educational efforts to boost knowledge about palliative care remains urgent and is critical for promoting equity, particularly for underserved people with chronic illnesses.
More Foxes than Hedgehogs: The Case for Nitrogen Fixation in Coastal Marine Sediments
Authors: Fulweiler Robinson W.
Published: August 2023

Nitrogen fixation is an important process connecting the vast atmospheric pool of di‐nitrogen gas to the biosphere. Nitrogen fixation is an energy intensive process, and it is historically thought to occur only to meet nitrogen demands. However, over the last two decades, research has demonstrated that sediment nitrogen fixation occurs in a variety of coastal environments, including those where reduced nitrogen is abundant. This can be met with skepticism when nitrogen fixation is viewed solely as a nitrogen limitation relief mechanism. Here, I propose that coastal sediments are actually ideal environments for nitrogen fixation and synthesize ideas on why this is the case. My goal is to help the community embrace a new paradigm for sediment nitrogen fixation and to see it as an important and even expected process. In doing so, I hope to motivate future research on the spatial and temporal rate dynamics of sediment nitrogen fixation as well as on the sediment nitrogen fixation community composition and activity.
Variability of the Auroral Footprint of Io Detected by Juno‐JIRAM and Modeling of the Io Plasma Torus
Authors: Moirano A. , Mura A. , Bonfond B. , Connerney J. E. P. , Dols V. , Grodent D. , Hue V. , Gérard J.‐C. , Tosi F. , Migliorini A. , Adriani A. , Altieri F. , Castagnoli C. , Cicchetti A. , Dinelli B. M. , Grassi D. , Moriconi M. L. , Noschese R. , Piccioni G. , Plainaki C. , Scarica P. , Sindoni G. , Sordini R. , Turrini D. , Zambon F.
Published: August 2023

One of the auroral features of Jupiter is the emission associated with the orbital motion of its moon Io. The relative velocity between Io and the surrounding plasma trigger perturbations that travels as Alfvén waves along the magnetic field lines toward the Jovian ionosphere. These waves can accelerate electrons into the atmosphere and ultimately produce an auroral emission, called the Io footprint. The speed of the Alfvén waves—and hence the position of the footprint—depends on the magnetic field and on the plasma distribution along the field line passing through Io, whose SO2‐rich atmosphere is the source of a dense plasma torus around Jupiter. Since 2016, the Jovian InfraRed Auroral Mapper (JIRAM) onboard Juno has been observing the Io footprint with a spatial resolution of ∼few tens of km/pixel. JIRAM detected evidences of variability in the Io footprint position that are not dependent on the System III longitude of Io. The position of the Io footprint in the JIRAM images is compared with the position predicted by a model of the Io Plasma Torus and of the magnetic field. This is the first attempt to retrieve quantitative information on the variability of the torus by looking at the Io footprint. The results are consistent with previous observations of the density and temperature of the Io Plasma Torus. However, we found that the plasma density and temperature exhibit considerable non‐System III variability that can be due either to local time asymmetry of the torus or to its temporal variability.
Evidence of CME‐Magnetospheric Shock Disturbance of the D‐Region Observed in the VLF Signal
Authors: NaitAmor S. , Ikhlef R. , Ammar A. , Ghalila H.
Published: August 2023

The observation of the D‐region response to the interplanetary shock (IS) during the storm of 17 March 2015 is carried out using two very low frequency (VLF) transmitter signals (NRK and GQD) recorded at Algiers and Tunis. Data from THEMIS‐E and RBSP are used to correlate between the ground and satellite observations. The important finding is the wavy structure of the perturbations observed on the two VLF signals tens of seconds after the space detection of the shock, in concordance with the RBSP electric field measurements. The measured VLF signal amplitude and phase perturbations were: −0.65 dB, 5.81° for NRK and −0.12 dB, −126° for GQD measured at Algiers. For Tunis receiver, the perturbations were: −0.58 dB, 4.7° for NRK and 0.15 dB, −1.19° for GQD. In addition to the observations, simulations of the NRK signal perturbations were done using the long wavelength propagating capability code to determine the electron density modification that lead to the measured perturbations. The simulation results showed that the modified Wait's parameters above the NRK transmitter were: 80.391 km for h′ and 0.43 km−1 for β in the case of NRK‐Tunis path. Concerning the NRK‐Algiers path, the simulation gave 80.316 km for h′ and 0.431 km−1 for β. From these parameters values, the modified electron density was not important to explain the observed perturbations. Therefore, the IS effect could be explained by induced heating of the ionosphere due to the penetration of the electric field which leads to the changes of the ionospheric conductivity.
A D‐Region Ionospheric Imaging Method Using Sferic‐Based Tomography
Authors: Richardson David K. , McCormick Jackson C. , Cohen Morris B.
Published: August 2023

We present a tomographic imaging technique for the D‐region electron density using a set of spatially distributed very low frequency (VLF) remote sensing measurements. The D‐region ionosphere plays a critical role in many long‐range and over‐the‐horizon communication systems; however, it is unreachable by most direct measurement techniques such as balloons and satellites. Fortunately, the D region, combined with Earth's surface, forms what is known as the Earth‐Ionosphere waveguide allowing VLF and low frequency (LF) radio waves to propagate to global distances. By measuring these signals, we can estimate a path measurement of the electron density, which we assume to be a path‐averaged electron density profile of the D region. In this work, we use path‐averaged inferences from lightning‐generated radio atmospherics (sferics) with a tomographic inversion to produce 3D models of electron density over the Southeastern United States and the Gulf of Mexico. The model begins with two‐dimensional great circle path observations, each of which is parameterized so it includes vertical profile information. The tomography is then solved in two dimensions (latitude and longitude) at arbitrarily many altitude slices to construct the 3D electron density. We examine the model's performance in the synthetic case and determine that we have an expected percent error better than 10% within our area of interest. We apply our model to the 2017 “Great American Solar Eclipse” and find a clear relationship between sunlight percentage and electron density at different altitudes.
Electron Lifetimes Measured at LEO: Comparison With RBSP Estimates and Pitch Angle Resolved Lifetimes
Authors: Shane A. D. , Marshall R. A. , Claudepierre S. G. , Pettit J. M.
Published: August 2023

Electron lifetimes are important for understanding the dominant loss processes of radiation belt electrons to the atmosphere and for accurate radiation belt modeling. We estimate electron lifetimes from the precipitating population measured in Low Earth Orbit (LEO) from the Polar Orbiting Environmental Satellites (POES). We compare our estimates to previous estimates from the Radiation Belt Storm Probes (RBSP) by Claudepierre et al. (2020b, https://doi.org/10.1029/2019GL086053). We also present the first complete pitch angle resolved lifetimes in the radiation belts. Quasi‐linear theory predicts the pitch angle distribution decays uniformly, therefore if steady‐state decay is realized, POES and RBSP should measure similar lifetimes. Lifetime estimates from LEO are shown to be in good agreement with those from Van Allen Probes in the outer belt and pitch angle resolved lifetimes indicate that steady‐state decay is realized. However, a systematic slight overestimation of the POES lifetimes reveal that the POES instruments may suffer from bremsstrahlung contamination. At L = 2–3, no decay intervals were identified in the POES electron fluxes and the near loss cone RBSP electron fluxes. We show that at these L‐shells, where lifetimes are long, there is an apparent decoupling of the perpendicular and parallel flux. Large pitch angle anisotropy and processes that affect low pitch angle electrons are two explanations for this apparent decoupling. Electron lifetime models that use pitch angle independent lifetimes, derived from the equatorially mirroring electron flux, likely underestimate the amount of precipitating flux and may not capture the dynamics of low equatorial pitch angle electrons at L < 3.
Eddy Tracking From In Situ and Satellite Observations
Authors: Erickson Zachary K. , Fields Erik , Johnson Leah , Thompson Andrew F. , Dove Lilian A. , D’Asaro Eric , Siegel David A.
Published: August 2023

Mesoscale eddies are a dominant source of spatial variability in the surface ocean and play a major role in the biological marine carbon cycle. Satellite altimetry is often used to locate and track eddies, but this approach is rarely validated against in situ observations. Here we compare measurements of a small (under 25 km radius) mode water anticyclonic eddy over the Porcupine Abyssal Plain in the northeastern Atlantic Ocean using CTD and Acoustic Doppler Current Profiler (ADCP) measurements from three ships, two gliders, two profiling floats, and one Lagrangian float with those derived from sea level anomaly (SLA). In situ estimates of the eddy center were estimated from maps of the thickness of its central isopycnal layer, from ADCP velocities at a reference depth, and from the trajectory of the Lagrangian float. These were compared to three methods using altimetric SLA: one based on maximizing geostrophic rotation, one based on a constant SLA contour, and one which maximizes geostrophic velocity speed along the eddy boundary. All algorithms were used to select CTD profiles that were within the eddy. The in‐situ metrics agreed to 97%. The altimetry metrics showed only a small loss of accuracy, giving >90% agreement with the in situ results. This suggests that current satellite altimetry is adequate for understanding the spatial representation of even relatively small mesoscale eddies.
Wind Fields in Category 1–3 Tropical Cyclones Are Not Fully Represented in Wind Turbine Design Standards
Authors: Sanchez Gomez M. , Lundquist J. K. , Deskos G. , Arwade S. R. , Myers A. T. , Hajjar J. F.
Published: August 2023

Offshore wind energy deployment in the U.S. is expected to increase in the years to come, with proposed wind farm sites located in regions with high risk for tropical cyclones. Yet, the wind turbine design criteria outlined by the International Electrotechnical Commission for extreme events may not account for wind field characteristics unique to tropical cyclones. To evaluate if current design standards capture the extreme conditions of these storms, we perform idealized large‐eddy simulations of three tropical cyclones (one Category 1, one Category 2, and one Category 3 storms) using the Weather Research and Forecasting model. Wind conditions near the eyewall of Cat‐1, Cat‐2, and Cat‐3 storms can exceed current design standards for offshore wind turbines. Winds at 90 m can be faster than outlined in the design criteria for Class I and Class T turbines for 50‐year recurrence periods. Wind speed shear across the turbine rotor layer is also larger than assumed in design specifications. Moreover, vertical variations in wind direction across the turbine rotor layer are large for tropical cyclones of all intensity levels, suggesting design standards should include veer, which can amplify loads in wind turbines. The existence of hurricane wind field characteristics that are not represented in design standards does not imply that damage or failure will certainly occur. Engineering safety factors incorporated in the design of the turbine's blades and structural components may prevent damage from occurring.
Genetic etiology of progressive pediatric neurological disorders
Authors: Aaltio Juho , Etula Anna , Ojanen Simo , Brilhante Virginia , Lönnqvist Tuula , Isohanni Pirjo , Suomalainen Anu
Published: August 2023

Background

The aim of the study was to characterize molecular diagnoses in patients with childhood-onset progressive neurological disorders of suspected genetic etiology.

Methods

We studied 48 probands (age range from newborn to 17 years old) with progressive neurological disorders of unknown etiology from the largest pediatric neurology clinic in Finland. Phenotypes included encephalopathy (54%), neuromuscular disorders (33%), movement disorders (11%), and one patient (2%) with hemiplegic migraine. All patients underwent whole-exome sequencing and disease-causing genes were analyzed.

Results

We found 20 (42%) of the patients to have variants in genes previously associated with disease. Of these, 12 were previously reported disease-causing variants, whereas eight patients had a novel variant on a disease-causing gene: ATP7A, CHD2, PURA, PYCR2, SLC1A4, SPAST, TRIT1, and UPF3B. Genetics also enabled us to define atypical clinical presentations of Rett syndrome (MECP2) and Menkes disease (ATP7A). Except for one deletion, all findings were single-nucleotide variants (missense 72%, truncating 22%, splice-site 6%). Nearly half of the variants were de novo.

Conclusions

The most common cause of childhood encephalopathies are de novo variants. Whole-exome sequencing, even singleton, proved to be an efficient tool to gain specific diagnoses and in finding de novo variants in a clinically heterogeneous group of childhood encephalopathies.

Impact

Whole-exome sequencing is useful in heterogeneous pediatric neurology cohorts.

Our article provides further evidence for and novel variants in several genes.

De novo variants are an important cause of childhood encephalopathies.
Interspecific competition can drive plasmid loss from a focal species in a microbial community
Authors: Sünderhauf David , Klümper Uli , Gaze William H , Westra Edze R , van Houte Stineke
Published: August 2023

Plasmids are key disseminators of antimicrobial resistance genes and virulence factors, and it is therefore critical to predict and reduce plasmid spread within microbial communities. The cost of plasmid carriage is a key metric that can be used to predict plasmids’ ecological fate, and it is unclear whether plasmid costs are affected by growth partners in a microbial community. We carried out competition experiments and tracked plasmid maintenance using a model system consisting of a synthetic and stable five-species community and a broad host-range plasmid, engineered to carry different payloads. We report that both the cost of plasmid carriage and its long-term maintenance in a focal strain depended on the presence of competitors, and that these interactions were species specific. Addition of growth partners increased the cost of a high-payload plasmid to a focal strain, and accordingly, plasmid loss from the focal species occurred over a shorter time frame. We propose that the destabilising effect of interspecific competition on plasmid maintenance may be leveraged in clinical and natural environments to cure plasmids from focal strains.
B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer
Authors: Garg Ritu , Endzhievskaya Sofia , Williamson Magali
Published: August 2023

Resistance to anti-androgen therapy for metastatic prostate cancer is a major clinical problem. Sema3C promotes resistance to androgen withdrawal via its receptor, PlexinB1. Activation of PlexinB1 promotes the ligand-independent nuclear translocation of the androgen receptor (AR), which may contribute to resistance to androgen deprivation therapy. However, the mechanism by which PlexinB1 promotes nuclear translocation is unclear. We show here that PlexinB1 and B2 regulate nuclear import by acting as GTPase activating proteins (GAPs) for the small RasGTPase Ran, a key regulator of nuclear trafficking. Purified PlexinB1/B2 protein catalyses the hydrolysis of RanGTP, and mutations in the GAP domain of PlexinB1 inhibit this activity. Activation of PlexinB1/B2 with Sema4D decreases the levels of RanGTP, while PlexinB1 or B2 depletion increases the levels of activated Ran in the cell. Ran directly associates with B-type plexins in a GTP-dependent manner. Sema4D is internalised by endocytosis, and PlexinB1 and Ran display overlapping patterns of expression. Furthermore, Sema4D/PlexinB1-induced AR nuclear translocation is dependent on the GAP domain of PlexinB1 and is blocked by the expression of non-functional Ran mutants. Depletion of PlexinB1 decreases the nuclear/cytoplasmic ratio of Ran, indicative of a higher RanGTP/GDP ratio. Plexins may promote the growth of androgen-independent prostate cancer through their activity as RanGAPs.
Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis
Authors: Zheng Kang , Hao Fengjie , Medrano-Garcia Sandra , Chen Chaobo , Guo Feifei , Morán-Blanco Laura , Rodríguez-Perales Sandra , Torres-Ruiz Raúl , Peligros María Isabel , Vaquero Javier , Bañares Rafael , Gómez del Moral Manuel , Regueiro José R. , Martínez-Naves Eduardo , Mohamed Mohamed Ramadan , Gallego-Durán Rocío , Maya Douglas , Ampuero Javier , Romero-Gómez Manuel , Gilbert-Ramos Albert , Guixé-Muntet Sergi , Fernández-Iglesias Anabel , Gracia-Sancho Jordi , Coll Mar , Graupera Isabel , Ginès Pere , Ciudin Andreea , Rivera-Esteban Jesús , Pericàs Juan M. , Frutos María Dolores , Ramos Molina Bruno , Herranz José María , Ávila Matías A. , Nevzorova Yulia A. , Fernández-Malavé Edgar , Cubero Francisco Javier
Published: August 2023

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.
Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice
Authors: Rosenberg Ayelet M. , Saggar Manish , Monzel Anna S. , Devine Jack , Rogu Peter , Limoges Aaron , Junker Alex , Sandi Carmen , Mosharov Eugene V. , Dumitriu Dani , Anacker Christoph , Picard Martin
Published: August 2023

The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity, and exhibited distinct molecular mitochondrial phenotype signatures. This work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the male mouse brain.
Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates
Authors: Poulet-Benedetti Jérémy , Tonnerre-Doncarli Caroline , Valton Anne-Laure , Laurent Marc , Gérard Marie , Barinova Natalja , Parisis Nikolaos , Massip Florian , Picard Franck , Prioleau Marie-Noëlle
Published: August 2023

Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce the assembly of an efficient minimal replication origin without inducing transcription in avian DT40 cells. Dimeric pG4s in replication origins are associated with formation of an NFR next to precisely-positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest that dimeric pG4s are important for the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.
Structural basis of agonist specificity of α1A-adrenergic receptor
Authors: Su Minfei , Wang Jinan , Xiang Guoqing , Do Hung Nguyen , Levitz Joshua , Miao Yinglong , Huang Xin-Yun
Published: August 2023

α1-adrenergic receptors (α1-ARs) play critical roles in the cardiovascular and nervous systems where they regulate blood pressure, cognition, and metabolism. However, the lack of specific agonists for all α1 subtypes has limited our understanding of the physiological roles of different α1-AR subtypes, and led to the stagnancy in agonist-based drug development for these receptors. Here we report cryo-EM structures of α1A-AR in complex with heterotrimeric G-proteins and either the endogenous common agonist epinephrine or the α1A-AR-specific synthetic agonist A61603. These structures provide molecular insights into the mechanisms underlying the discrimination between α1A-AR and α1B-AR by A61603. Guided by the structures and corresponding molecular dynamics simulations, we engineer α1A-AR mutants that are not responsive to A61603, and α1B-AR mutants that can be potently activated by A61603. Together, these findings advance our understanding of the agonist specificity for α1-ARs at the molecular level, opening the possibility of rational design of subtype-specific agonists.
Decision making for implementing non-traditional water sources: a review of challenges and potential solutions
Authors: Quon Hunter , Jiang Sunny
Published: August 2023

The effects of climate change, population growth, and future hydrologic uncertainties necessitate increased water conservation, new water resources, and a shift towards sustainable urban water supply portfolios. Diversifying water portfolios with non-traditional water sources can play a key role. Rooftop harvested rainwater (RHRW), atmospheric and condensate harvesting, stormwater, recycled wastewater and greywater, and desalinated seawater and brackish water are all currently utilized and rapidly emerging non-traditional water sources. This review explores the status and trends around these non-traditional water sources, and reviews approaches and models for prioritizing, predicting, and quantifying metrics of concern. The analysis presented here suggests that understanding the challenges of location specific scenarios, socioeconomic knowledge gaps, water supply technologies, and/or water management structure is the crucial first step in establishing a model or framework approach to provide a strategy for improvement going forward. The findings of this study also suggest that clear policy guidance and onsite maintenance is necessary for variable water quality concerns of non-traditional sources like harvested rainwater and greywater. In addition, use of stormwater or reuse of wastewater raises public health concerns due to unknown risks and pathogen levels, thus rapid monitoring technologies and transparent reporting systems can facilitate their adoption. Finally, cost structure of desalination varies significantly around the world, largely due to regulatory requirements and local policies. Further reduction of its capital cost and energy consumption is identified as a hurdle for implementation. Overall, models and process analyses highlight the strength of comparative assessments across scenarios and water supply options.
First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial
Authors: Thibaudin Marion , Fumet Jean-David , Chibaudel Benoist , Bennouna Jaafar , Borg Christophe , Martin-Babau Jerome , Cohen Romain , Fonck Marianne , Taieb Julien , Limagne Emeric , Blanc Julie , Ballot Elise , Hampe Léa , Bon Marjorie , Daumoine Susy , Peroz Morgane , Mananet Hugo , Derangère Valentin , Boidot Romain , Michaud Henri-Alexandre , Laheurte Caroline , Adotevi Olivier , Bertaut Aurélie , Truntzer Caroline , Ghiringhelli François
Published: August 2023

Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated the safety and efficacy of durvalumab plus tremelimumab combined with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable metastatic CRC. Safety was the primary objective of phase Ib; no safety issue was observed. The phase 2 primary objective of efficacy in terms of 3-month progression-free survival (PFS) in patients with MSS tumors was met, with 3-month PFS of 90.7% (95% confidence interval (CI): 79.2–96%). For secondary objectives, response rate was 64.5%; median PFS was 8.2 months (95% CI: 5.9–8.6); and overall survival was not reached in patients with MSS tumors. We observed higher tumor mutational burden and lower genomic instability in responders. Integrated transcriptomic analysis underlined that high immune signature and low epithelial–mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor-specific T cell response associated with better PFS. The combination of durvalumab–tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC. Clinicaltrials.gov identifier: NCT03202758.
Supervised machine learning classification of psychosis biotypes based on brain structure: findings from the Bipolar-Schizophrenia network for intermediate phenotypes (B-SNIP)
Authors: Koen Joshua D. , Lewis Leslie , Rugg Michael D. , Clementz Brett A. , Keshavan Matcheri S. , Pearlson Godfrey D. , Sweeney John A. , Tamminga Carol A. , Ivleva Elena I.
Published: August 2023

Traditional diagnostic formulations of psychotic disorders have low correspondence with underlying disease neurobiology. This has led to a growing interest in using brain-based biomarkers to capture biologically-informed psychosis constructs. Building upon our prior work on the B-SNIP Psychosis Biotypes, we aimed to examine whether structural MRI (an independent biomarker not used in the Biotype development) can effectively classify the Biotypes. Whole brain voxel-wise grey matter density (GMD) maps from T1-weighted images were used to train and test (using repeated randomized train/test splits) binary L2-penalized logistic regression models to discriminate psychosis cases (n = 557) from healthy controls (CON, n = 251). A total of six models were evaluated across two psychosis categorization schemes: (i) three Biotypes (B1, B2, B3) and (ii) three DSM diagnoses (schizophrenia (SZ), schizoaffective (SAD) and bipolar (BD) disorders). Above-chance classification accuracies were observed in all Biotype (B1 = 0.70, B2 = 0.65, and B3 = 0.56) and diagnosis (SZ = 0.64, SAD = 0.64, and BD = 0.59) models. However, the only model that showed evidence of specificity was B1, i.e., the model was able to discriminate B1 vs. CON and did not misclassify other psychosis cases (B2 or B3) as B1 at rates above nominal chance. The GMD-based classifier evidence for B1 showed a negative association with an estimate of premorbid general intellectual ability, regardless of group membership, i.e. psychosis or CON. Our findings indicate that, complimentary to clinical diagnoses, the B-SNIP Psychosis Biotypes may offer a promising approach to capture specific aspects of psychosis neurobiology.
Combining a parsimonious mathematical model with infection data from tailor-made experiments to understand environmental transmission
Authors: Gamża Anna M. , Hagenaars Thomas J. , Koene Miriam G. J. , de Jong Mart C. M.
Published: August 2023

Although most infections are transmitted through the environment, the processes underlying the environmental stage of transmission are still poorly understood for most systems. Improved understanding of the environmental transmission dynamics is important for effective non-pharmaceutical intervention strategies. To study the mechanisms underlying environmental transmission we formulated a parsimonious modelling framework including hypothesised mechanisms of pathogen dispersion and decay. To calibrate and validate the model, we conducted a series of experiments studying distance-dependent transmission of Campylobacter jejuni in broilers. We obtained informative simultaneous estimates for all three model parameters: the parameter of C. jejuni inactivation, the diffusion coefficient describing pathogen dispersion, and the transmission rate parameter. The time and distance dependence of transmission in the fitted model is quantitatively consistent with marked spatiotemporal patterns in the experimental observations. These results, for C. jejuni in broilers, show that the application of our modelling framework to suitable transmission data can provide mechanistic insight in environmental pathogen transmission.
Locational memory of macrovessel vascular cells is transcriptionally imprinted
Authors: Spanjersberg Talitha C. F. , Oosterhoff Loes A. , Kruitwagen Hedwig S. , van den Dungen Noortje A. M. , Vernooij Johannes C. M. , Asselbergs Folkert W. , Mokry Michal , Spee Bart , Harakalova Magdalena , van Steenbeek Frank G.
Published: August 2023

Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.
Adaptive filtering and smoothing algorithm based on variable structure interactive multiple model
Authors: Hu Kai-Yu , Wang Jiaming , Cheng Yuqing , Yang Chunxia
Published: August 2023

For maneuvering target tracking, a novel adaptive variable structure interactive multiple model filtering and smoothing (AVSIMMFS) algorithm is proposed in this paper. Firstly, an accurate model of the variable structure interactive multiple model algorithm is established. Secondly, by constructing a new model subset based on the original model subsets, the matching accuracy between the model subset and the actual maneuvering mode of the target is improved. Then, the AVSIMMFS algorithm is obtained by smoothing the filtered data of the new model subset. Because of the combination of forward filtering and backward smoothing, the target tracking accuracy is further improved. Finally, in order to verify the effectiveness of the algorithm, the simulation is carried out on two cases. The simulation results show that the tracking performance of AVSIMMFS algorithm is better than other methods and has lower calculation cost.
Sex differences in the kinematics and kinetics of the foot and plantar aponeurosis during drop-jump
Authors: Matsumoto Yuka , Ogihara Naomichi , Kosuge Sachiko , Hanawa Hiroki , Kokubun Takanori , Kanemura Naohiko
Published: August 2023

Plantar fasciitis is one of the most common musculoskeletal injuries in runners and jumpers, with a higher incidence in females. However, mechanisms underlying sex-associated differences in its incidence remain unclear. This study investigated the possible differences in landing and jumping kinematics and kinetics of the foot between sexes during drop-jump activities. Twenty-six participants, including 13 males and 13 females, performed drop-jumps from a platform onto force plates. Nineteen trials including ten males and nine females were selected for inverse dynamics analysis. The patterns of stretch and tensile force generated by the plantar aponeurosis (PA) were estimated using a multi-segment foot model incorporating the PA. Our results demonstrated that dorsiflexion, angular velocity, and normalized plantarflexion moment of the midtarsal joint right after the heel landed on the floor were significantly larger in females than in males. Consequently, the PA strain rate and tensile stress tended to be larger in females than in males. Such differences in the kinematics and kinetics of the foot and the PA between sexes could potentially lead to a higher prevalence of foot injuries such as plantar fasciitis in females.
FPGA realization of four chaotic interference cases in a terrestrial trajectory model and application in image transmission
Authors: Estudillo-Valdez Miguel-Angel , Adeyemi Vincent-Ademola , Tlelo-Cuautle Esteban , Sandoval-Ibarra Yuma , Nuñez-Perez Jose-Cruz
Published: August 2023

This article presents a technique to integrate two dynamical models, a four-wing spherical chaotic oscillator and the elliptical path described by the planet Earth during its translation movement around the sun. Four application cases are derived from the system by varying the dynamics of the chaotic oscillator and these can be applied in information encryption to transmit RGB and grayscale images modulated by CSK. Consequently, the three main contributions of this work are (1) the emulation of the trajectories of the planet Earth with chaotic interference, (2) the CSK modulation and image encryption in a master-slave synchronization topology, and (3) the CSK demodulation for decryption without loss of information with respect to the original information. The three contributions are based on VHDL code implementation. The results of the synchronization, encryption and decryption technique were verified by means of time series and the encrypted images showed a correlation less than − 0.000142 and − 0.0003439 for RGB and grayscale format, respectively, while the retrieved image shows a complete correlation with the image original. In this work, the co-simulations were performed between MATLAB/Simulink and Vivado, using the VHDL language on two FPGA boards from different manufacturers, namely, Xilinx Artix-7 AC701 and Intel Cyclone IV.
Microplastics in gastrointestinal tracts of gentoo penguin (Pygoscelis papua) chicks on King George Island, Antarctica
Authors: Kim Youmin , Kim Hankyu , Jeong Min-Su , Kim Dowoon , Kim Juyang , Jung Jaehak , Seo Hae-Min , Han Hyun-Jin , Lee Woo-Shin , Choi Chang-Yong
Published: August 2023

Microplastics (< 5 mm) have been found in marine ecosystems worldwide, even in Antarctic ecosystems. In this study, the stomach and upper intestines of 14 dead gentoo penguin (Pygoscelis papua) chicks were collected and screened for microplastics on King George Island, a gateway to Antarctic research and tourism. A total of 378 microplastics were identified by Fourier-transform infrared spectroscopy, with 27.0 ± 25.3 microplastics per individual. The detected number of microplastics did not increase with the mass of penguin chicks, suggesting no permanent accumulation of microplastics. However, the concentration of microplastics was much higher (9.1 ± 10.8 microplastics per individual within the size range 100–5000 μm) than the previously reported concentration in the penguin feces, and a greater number of smaller microplastics were found. Marine debris surveys near the breeding colony found various plastic (79.3%) to be the most frequent type of beached debris, suggesting that local sources of marine plastic waste could have contributed to microplastic contamination of penguin chicks being fed by parents that forage in nearby seas. This finding confirms the presence of microplastics in an Antarctic ecosystem and suggests the need for stronger waste management in Antarctica and a standardized scheme of microplastic monitoring in this once-pristine ecosystem.
Real-time jellyfish classification and detection algorithm based on improved YOLOv4-tiny and improved underwater image enhancement algorithm
Authors: Gao Meijing , Li Shiyu , Wang Kunda , Bai Yang , Ding Yan , Zhang Bozhi , Guan Ning , Wang Ping
Published: August 2023

The outbreak of jellyfish blooms poses a serious threat to human life and marine ecology. Therefore, jellyfish detection techniques have earned great interest. This paper investigates the jellyfish detection and classification algorithm based on optical images and deep learning theory. Firstly, we create a dataset comprising 11,926 images. A MSRCR underwater image enhancement algorithm with fusion is proposed. Finally, an improved YOLOv4-tiny algorithm is proposed by incorporating a CBMA module and optimizing the training method. The results demonstrate that the detection accuracy of the improved algorithm can reach 95.01%, the detection speed is 223FPS, both of which are better than the compared algorithms such as YOLOV4. In summary, our method can accurately and quickly detect jellyfish. The research in this paper lays the foundation for the development of an underwater jellyfish real-time monitoring system.
Realization of a pulsed optically pumped Rb clock with a frequency stability below $$10^{-15}$$
Authors: Gozzelino Michele , Micalizio Salvatore , Calosso Claudio E. , Belfi Jacopo , Sapia Adalberto , Gioia Marina , Levi Filippo
Published: August 2023

We present the frequency stability performances of a vapor cell Rb clock based on the pulsed optically pumping (POP) technique. The clock has been developed in the frame of a collaboration between INRIM and Leonardo SpA, aiming to realize a space-qualified POP frequency standard. The results here reported were obtained with an engineered physics package, specifically designed for space applications, joint to laboratory-grade optics and electronics. The measured frequency stability expressed in terms of Allan deviation is$$1.2\times 10^{-13}$$1.2×10-13at 1s and achieves the value of$$6\times 10^{-16}$$6×10-16for integration times of 40000 s (drift removed). This is, to our knowledge, a record result for a vapor-cell frequency standard. In the paper, we show that in order to get this result, a careful stabilization of microwave and laser pulses is required.
A metacontinuum model for phase gradient metasurfaces
Authors: Palma Giorgio , Iemma Umberto
Published: August 2023

Acoustic metamaterials and metasurfaces often present complex geometries and microstructures. The development of models of reduced complexity is fundamental to alleviate the computational cost of their analysis and derivation of optimal designs. The main objective of this paper is the derivation and validation of a metacontinuum model for phase gradient-based metasurfaces. The method is based on the transformation acoustics framework and defines the metasurface in terms of anisotropic inertia and bulk modulus. Thermal and viscous dissipation effects in the metacontinuum are accounted for by introducing a complex-valued speed of sound. The model is implemented in a commercial FEM code, and its predictions are compared with numerical simulations on the original geometry and also using an equivalent boundary impedance approach. The results are examined for an exterior acoustics benchmark and for an in-duct installation in terms of transmission coefficient with the four-pole matrix method. The metacontinuum model gives solid results for the prediction of the acoustic properties of the examined metasurface samples for all the analyzed configurations, as accurate as the equivalent impedance model on which it is based and outperforming it in some circumstances.