bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulations of common-envelope evolution in binary stellar systems: physical models and numerical techniques
Authors: Röpke Friedrich K. , De Marco Orsola
Published: May 2023

When the primary star in a close binary system evolves into a giant and engulfs its companion, its core and the companion temporarily orbit each other inside a common envelope. Drag forces transfer orbital energy and angular momentum to the envelope material. Depending on the efficiency of this process, the envelope may be ejected leaving behind a tight remnant binary system of two stellar cores, or the cores merge retaining part of the envelope material. The exact outcome of common-envelope evolution is critical for in the formation of X-ray binaries, supernova progenitors, the progenitors of compact-object mergers that emit detectable gravitational waves, and many other objects of fundamental astrophysical relevance. The wide ranges of spatial and temporal timescales that characterize common-envelope interactions and the lack of spatial symmetries present a substantial challenge to generating consistent models. Therefore, these critical phases are one of the largest sources for uncertainty in classical treatments of binary stellar evolution. Three-dimensional hydrodynamic simulations of at least part of the common-envelope interaction are the key to gain predictive power in modeling common-envelope evolution. We review the development of theoretical concepts and numerical approaches for such three-dimensional hydrodynamic simulations. The inherent multi-physics, multi-scale challenges have resulted in a wide variety of approximations and numerical techniques to be exercised on the problem. We summarize the simulations published to date and their main results. Given the recent rapid progress, a sound understanding of the physics of common-envelope interactions is within reach and thus there is hope that one of the remaining fundamental problems of stellar astrophysics may be solved before long.
Revaluation of the Portable Art of Northern Iberia: a Magdalenian Decorated Bone Tube from Torre (Basque Country, Spain)
Authors: Erostarbe-Tome Asier , Rivero Olivia , Tejero José-Miguel , Arrizabalaga Alvaro
Published: May 2023

A decorated ulna of a gannet (Morus bassanus) was found in 1966 during the exploration of the archaeological site of Torre cave (Gipuzkoa, northern Iberian Peninsula). The present study offers a new appraisal of this truly outstanding art object through a technological and stylistic analysis enriched by more recent finds. What makes this object extraordinary is the fact that it is one of the most complete specimens in the Iberian Peninsula. Moreover, the Torre tube is one of the few remains with peri-cylindrical decoration displaying a complex combination of motifs. It is profusely decorated with figurative representations (deer, horse, ibex, chamois, aurochs and an anthropomorph) and signs (single lines, parallel lines, zigzags, etc.) in two rows in opposite directions. The tube resembles objects from other Magdalenian sites in Cantabrian Spain and the Pyrenees, which corroborate the exchange of technical and iconographic behaviour.
Mastery-Oriented Students Are Less Stubborn
Authors: Romero Miriam , Hernández José Manuel , Juola James F. , Casadevante Cristina , Santacreu José
Published: May 2023

Goal orientation theory identifies
mastery-oriented people as adaptive and highly persistent when pursuing a goal. Performance-oriented people are described as being less persistent, and tend to show more maladaptive responses. However, previous works that have studied persistence have not always found that performance-oriented participants show the least persistence. In addition, it is not easy to conclude if the persistence measured in the studies implies a stubborn response and therefore if it is a maladaptive response. In this work, we classify participants as mastery- or performance-oriented using an objective test and we employ a behavioral task to study persistence defined as stubbornness. When studying response patterns, we found that performance-oriented students were more stubborn. The behavioral analysis performed in this work offers complement and rich information and provides empirical support for the goal orientation theory.
An empirical analysis of the impact of semiconductor engineer characteristics on outflows and inflows: evidence from six major semiconductor countries
Authors: Fujiwara Ayano
Published: May 2023

The impact of cross-border migration of semiconductor engineers has become an important concern for many countries’ economic policies. There has been limited large-scale data analysis regarding the movement of semiconductor engineers between countries. This study creates an original engineer database for six major semiconductor countries (U.S., China, Taiwan, Japan, Korea, and Germany) using bibliographic information on patents and papers to analyze their transnational migration. Multiple logistic analysis is conducted on the impact of engineers’ characteristics such as age, skills, and areas of expertise on outflows and inflows. The analysis reveals that (1) the United States, Taiwan, Japan, and Germany have excess outflows of engineers, while China and South Korea have excess inflows, (2) the movement of engineers between the United States and China is the most frequent, and (3) there is a significant outflow of engineers from semiconductor fields in which each country specializes.
Measurement of quality of recovery using the postoperative quality of recovery scale (PQRS) in patients undergoing laparoscopic cholecystectomy: A prospective cohort pilot study
Authors: Vu Phan Ton Ngoc , Bang Ho Tat , Hieu Huynh Huu , Chinh Le Hong
Published: May 2023

Abstract

Objectives

Quality of post-operative recovery is an essential end-point for evaluating anesthesia and surgery. Measures must incorporate patient-reported outcomes and satisfaction in addition to physiological indicators of recovery in order to fully assess the effects of anesthesia and surgery. This study is to explore the quality of recovery using the postoperative quality of recovery scale (PQRS) in patients undergoing laparoscopic cholecystectomy.

Methods

This is a single-center, prospective cohort pilot study. Patients undergoing laparoscopic cholecystectomy were divided into two groups: Group D with deep neuromuscular blockade and Group M with moderate neuromuscular blockade. After surgery, patients were assessed by using Post-operative Quality Recovery Scale (PQRS).

Results

60 patients in group D and 60 patients in group M were analyzed. The proportion of patients with excellent surgical conditions in group D was higher than in group M. In the recovery room, at 15 min and 40 min after endotracheal extubation, the recovery of the physiological domain in group D was significantly higher than in group M. In postoperative day 1, the overall recovery percentage was 78.3% in group D and 76.7% in group M.

Conclusion

This is a pilot study showing that it is feasible and appropriate to use the postoperative quality of recovery scale (PQRS) in postoperative recovery assessment. Preliminary assessment of this result shows that anesthesia strategy with deep rocuronium-induced neuromuscular blockade-sugammadex reversal improved postoperative recovery versus the routine care with moderate neuromuscular block-neostigmine.

Highlights
Managed Dissent
Authors: Zick Timothy
Published: May 2023

The mass street demonstrations that followed the 2020 police murder of George Floyd were perhaps the largest in American history. These events confirmed that even in a digital era, people rely on public dissent to communicate grievances, change public discourse, and stand in collective solidarity with others. However, the demonstrations also showed that the laws surrounding public protest make public contention more dangerous, more costly, and less effective. Police fired tear gas into peaceful crowds, used physical force against compliant demonstrators, imposed broad curfews, limited the places where protesters could assemble, and abused 'unlawful assembly' and other public disorder laws. These and other pathologies epitomize a system in which public protest is tightly constrained in the name of public order. Managed Dissent argues that in order to preserve the venerable tradition of public protest in the US, we must reform several aspects of the law of public protest.
Sustainable Value Chains in the Global Garment Industry
Authors: Alexander Rachel , Lund-Thomsen Peter
Published: May 2023

The widespread prevalence of economically, socially, and environmentally unsustainable practices in global value chains is a pressing international challenge. The way to improve systems and practices in the complex networks that characterize contemporary production processes is not clear cut. Finding solutions requires innovation. This Element examines the structures of garment value chains and explores how innovation related to sustainability is taking place in these chains. Furthermore, it identifies barriers and opportunities for innovations to break through and stimulate industry-wide change.
Calibrated river-level estimation from river cameras using convolutional neural networks
Authors: Vandaele Remy , Dance Sarah L. , Ojha Varun
Published: May 2023

Monitoring river water levels is essential for the study of floods and mitigating their risks. River gauges are a well-established method for river water-level monitoring but many flood-prone areas are ungauged and must be studied through gauges located several kilometers away. Taking advantage of river cameras to observe river water levels is an accessible and flexible solution but it requires automation. However, current automated methods are only able to extract uncalibrated river water-level indexes from the images, meaning that these indexes are relative to the field of view of the camera, which limits their application. With this work, we propose a new approach to automatically estimate calibrated river water-level indexes from images of rivers. This approach is based on the creation of a new dataset of 32,715 images coming from 95 river cameras in the UK and Ireland, cross-referenced with gauge data (river water-level information), which allowed us to train convolutional neural networks. These networks are able to accurately produce two types of calibrated river water-level indexes from images: one for continuous river water-level monitoring, and the other for flood event detection. This work is an important step toward the automated use of cameras for flood monitoring.
Decomposition of multicorrelation sequences and joint ergodicity
Authors: DONOSO SEBASTIÁN , FERRÉ MORAGUES ANDREU , KOUTSOGIANNIS ANDREAS , SUN WENBO
Published: May 2023

We show that, under finitely many ergodicity assumptions, any multicorrelation sequence defined by invertible measure-preserving
$\mathbb {Z}^d$
-actions with multivariable integer polynomial iterates is the sum of a nilsequence and a nullsequence, extending a recent result of the second author. To this end, we develop a new seminorm bound estimate for multiple averages by improving the results in a previous work of the first, third, and fourth authors. We also use this approach to obtain new criteria for joint ergodicity of multiple averages with multivariable polynomial iterates on
${\mathbb Z}^{d}$
-systems.
Molecular characterization of a suspected IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreak reveals two simultaneous outbreaks in a tertiary-care hospital
Authors: Gual-de-Torrella Ana , López-Causape Carla , Alejo-Cancho Izaskun , Rojo-Molinero Estrella , Sanchez-García Gonzalo , Cortés-Lara Sara , Rodríguez Moral María B. , Berdonces-Gonzalez Pilar , Lopez de Goikoetxea María J. , Oliver Antonio
Published: May 2023

Objective:

To describe IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreaks at Galdakao University Hospital between March 2021 to December 2021.

Design:

Outbreak report.

Setting:

Galdakao University Hospital is a tertiary-care hospital in the Basque Country (northern Spain).

Patients:

All patients with a positive IMP-type carbapenemase producing Pseudomonas aeruginosa (IMP-PA) culture were included in this study, both colonization and infection cases.

Methods:

An outbreak investigation was conducted, in which molecular epidemiology analysis [pulsed-field gel electrophoresis and whole-genome sequencing (WGS)] and environmental screenings were performed.

Results:

Between March and December 2021, 21 cases of IMP-PA were detected in Galdakao University Hospital: 18 infection cases and 3 colonization cases. In total, 4 different pulsotypes were detected belonging to 4 clones according to WGS: ST175 (n = 14), ST633 (n = 3), ST179 (n = 3), and ST348 (n = 1). IMP-13 was detected in most isolates belonging to the ST175 clone and in all ST179 and ST348 clones, whereas IMP-29 was detected in isolates belonging to the ST633 clone. Clinical isolates belonging to the ST175 clone were isolated mainly from patients admitted to the respiratory ward, and isolates belonging to the ST633 clone from patients admitted to the ICU. Two environmental isolates belonging to the ST175 clone were detected in the respiratory ward.

Conclusions:

Molecular and genomic epidemiology revealed that there had been 2 independent IMP-PA outbreaks, one of long duration in the respiratory ward and the other more limited in the ICU.
Contribution of folic acid to human health and challenges of translating the science into effective policy: a call to action for the implementation of food fortification in Ireland
Authors: McNulty Helene , Ward Mary , Caffrey Aoife , Pentieva Kristina
Published: May 2023

Over 30 years ago it was proven beyond doubt that folic acid supplementation of mothers in early pregnancy protects against neural tube defects (NTD) in their babies. Such conclusive scientific evidence led to clear recommendations for women worldwide to take 0⋅4 mg/d folic acid before conceiving and in early pregnancy, but implementing these into effective policy has been problematic. As a result, there has been no change in the incidence of NTD in Ireland, the UK or any other European country over the 25-year period that the current strategy, recommending periconceptional folic acid supplements to women, has been in place. Thus preventable NTD are not being prevented. Notably, in September 2021, the UK government announced that starch is to be fortified with folic acid on a mandatory basis. A similar decision is now urgently needed in Ireland, where rates of NTD are among the highest in the world. A policy of mandatory folic acid fortification of food would be highly effective in preventing NTD because it reaches all women, including those who have not planned their pregnancy. International evidence shows that wherever such a policy has been introduced, it has proved to be effective in reducing rates of NTD in that country. Apart from preventing NTD, the driver of policy in the area, other potential health benefits across the lifecycle can be anticipated from folic acid fortification. Urgent action is needed on implementation of mandatory food fortification with folic acid in Ireland so that mothers and their babies can benefit.
Frequency effects in Spanish phonological speech errors: Weak sources in the context of weak syllables and words
Authors: Santiago Julio , Pérez Elvira , Palma Alfonso , Stemberger Joseph Paul
Published: May 2023

The present study examines the effects of the frequency of phoneme, syllable, and word units in the Granada corpus of Spanish phonological speech errors. We computed several measures of phoneme and syllable frequency and selected the most sensitive ones, along with word (lexeme) frequency to compare the frequencies of source, target, and error units at the phoneme, syllable, and word levels. Results showed that phoneme targets have equivalent frequency to matched controls, whereas source phonemes are lower in frequency than chance (the Weak Source effect) and target phonemes (the Davideffect). Target, source, and error syllables and words also were of lower frequency than chance, and error words (when they occur) were lowest in frequency. Contrary to most current theories, which focus on faulty processing of the target units, present results suggest that faulty processing of the source units (phonemes, syllables, and words) is an important factor contributing to phonological speech errors. Low-frequency words and syllables have more difficulty ensuring that their phonemes, especially those of low frequency, are output only in their correct locations.
Direct and indirect vaccination effects on SARS-CoV-2 infection in day-care centres: Evaluating the policy for early vaccination of day-care staff in Germany, 2021
Authors: Schoeps Anja , Walter Jan , Vogt Manfred , Bent Stefan , Zanger Philipp ,   the Palatina Public Health Study Group
Published: May 2023

To mitigate the known high transmission risk in day-care facilities for children aged 0–6 years, day-care staff were given priority for SARS-CoV-2 vaccination in Rhineland-Palatinate, Germany, in March 2021. This study assessed direct and indirect effects of early vaccination of day-care staff on SARS-CoV-2 transmission in daycares with the aim to provide a basis for the prioritisation of scarce vaccines in the future. Data came from statutory infectious disease notifications in educational institutions and from in-depth investigations by the district public health authorities. Using interrupted time series analyses, we measured the effect of mRNA-based vaccination of day-care staff on SARS-CoV-2 infections and transmission. Among 566 index cases from day-care centres, the mean number of secondary SARS-CoV-2 infections per index case dropped by −0.60 case per month after March 2021. The proportion of staff among all cases reported from daycares was around 60% in the pre-interruption phase and significantly decreased by 27 percentage points immediately in March 2021 and by further 6 percentage points each month in the post-interruption phase. Early vaccination of day-care staff reduced SARS-CoV-2 cases in the overall day-care setting and thus also protected unvaccinated children. This should inform future decisions on vaccination prioritisation.
Which Potential Evapotranspiration Formula to Use in Hydrological Modeling World‐Wide?
Authors: Pimentel R. , Arheimer B. , Crochemore L. , Andersson J. C. M. , Pechlivanidis I. G. , Gustafsson D.
Published: May 2023

Although many potential evapotranspiration (PET) formulas are available, there is still a lack of knowledge on when and where to use them in catchment modeling world‐wide. Here we experimented with three different formulas in a global hydrological model (the World‐wide HYPE), using 15 years of observations from 5,338 streamflow gauges and global evapotranspiration from Earth‐observations (MOD16). We tested model performance in a multi‐process approach to select the best formula for catchments covering the global landmass. From comparing the results with land‐cover, climate classification, water‐energy limitations, we found that climate is the main driver behind the spatial patterns in model performance. Hargreaves was the best PET formula in 50% of the catchments, most of them located in the Amazonas, central Europe, and Oceania; Jensen‐Haise was better for catchments in northern latitudes (36%). Finally, Priestley‐Taylor was the best formula for India and latitudes above 65° North. The selection of a PET formula seems to be more critical in tropical regions close to the equator, where the differences in performance are above 50%. This is also where PET is highest. We found a strong connection between the five main Köppen regions and the PET formulas, further supported by landcover analysis. Hence, the PET formulas differed in their capacity to provide useful input to the water balance modeling, with complex formulas only giving improved predictions in temperate and polar regions; however, for the rest of the globe simpler formulas were better. We thus recommend to apply different PET formulas based on climatic regions world‐wide.
TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer
Authors: Guenther Michael , Surendran Sai Agash , Haas Michael , Heinemann Volker , von Bergwelt-Baildon Michael , Engel Jutta , Werner Jens , Boeck Stefan , Ormanns Steffen
Published: May 2023

Background

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) overexpression in human tumours is associated with increased malignancy. Its effect on gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) has not been studied yet.

Methods

The prognostic impact of TPX2 expression was examined in the tumour tissue of 139 patients with advanced PDAC (aPDAC) treated within the AIO-PK0104 trial or translational trials and of 400 resected PDAC (rPDAC) patients. The findings were validated using RNAseq data of 149 resected PDAC patients.

Results

In the aPDAC cohorts, 13.7% of all samples showed high TPX2 expression, conferring significantly shorter progression-free survival (PFS, HR 5.25, P < 0.001) and overall survival times (OS, HR 4.36, P < 0.001) restricted to gemcitabine-based treated patients (n = 99). In the rPDAC cohort, 14.5% of all samples showed high TPX2 expression, conferring significantly shorter disease-free survival times (DFS, HR 2.56, P < 0.001) and OS times (HR 1.56, P = 0.04) restricted to patients treated with adjuvant gemcitabine. RNAseq data from the validation cohort confirmed the findings.

Conclusions

High TPX2 expression may serve as a negative predictor of gemcitabine-based palliative and adjuvant chemotherapy in PDAC and could be used to inform clinical therapy decisions.

Clinical trial registry

The clinical trial registry identifier is NCT00440167.
Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET
Authors: Kanellis Dimitris C. , Zisi Asimina , Skrott Zdenek , Lemmens Bennie , Espinoza Jaime A. , Kosar Martin , Björkman Andrea , Li Xuexin , Arampatzis Stefanos , Bartkova Jirina , Andújar-Sánchez Miguel , Fernandez-Capetillo Oscar , Mistrik Martin , Lindström Mikael S. , Bartek Jiri
Published: May 2023

Drug repurposing is a versatile strategy to improve current therapies. Disulfiram has long been used in the treatment of alcohol dependency and multiple clinical trials to evaluate its clinical value in oncology are ongoing. We have recently reported that the disulfiram metabolite diethyldithiocarbamate, when combined with copper (CuET), targets the NPL4 adapter of the p97VCP segregase to suppress the growth of a spectrum of cancer cell lines and xenograft models in vivo. CuET induces proteotoxic stress and genotoxic effects, however important issues concerning the full range of the CuET-evoked tumor cell phenotypes, their temporal order, and mechanistic basis have remained largely unexplored. Here, we have addressed these outstanding questions and show that in diverse human cancer cell models, CuET causes a very early translational arrest through the integrated stress response (ISR), later followed by features of nucleolar stress. Furthermore, we report that CuET entraps p53 in NPL4-rich aggregates leading to elevated p53 protein and its functional inhibition, consistent with the possibility of CuET-triggered cell death being p53-independent. Our transcriptomics profiling revealed activation of pro-survival adaptive pathways of ribosomal biogenesis (RiBi) and autophagy upon prolonged exposure to CuET, indicating potential feedback responses to CuET treatment. The latter concept was validated here by simultaneous pharmacological inhibition of RiBi and/or autophagy that further enhanced CuET’s tumor cytotoxicity, using both cell culture and zebrafish in vivo preclinical models. Overall, these findings expand the mechanistic repertoire of CuET’s anti-cancer activity, inform about the temporal order of responses and identify an unorthodox new mechanism of targeting p53. Our results are discussed in light of cancer-associated endogenous stresses as exploitable tumor vulnerabilities and may inspire future clinical applications of CuET in oncology, including combinatorial treatments and focus on potential advantages of using certain validated drug metabolites, rather than old, approved drugs with their, often complex, metabolic profiles.
Radiation therapy improves CAR T cell activity in acute lymphoblastic leukemia
Authors: Sugita Mayumi , Yamazaki Takahiro , Alhomoud Mohammad , Martinet Jérémie , Latouche Jean-Baptiste , Golden Encouse , Boyer Olivier , Van Besien Koen , Formenti Silvia C. , Galluzzi Lorenzo , Guzman Monica L.
Published: May 2023

Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19+ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19+ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose total body irradiation (LD-TBI) delivered to ALL-bearing mice prior to CAR T cell infusion considerably extended the overall survival benefit afforded by CAR T cells alone. Such an improved therapeutic activity was accompanied by a superior expansion of CAR T cells in vivo. These data encourage the initiation of clinical trials combining LD-TBI with CAR T cells in patients with hematological malignancies.
Dynamic changes of the Prf/Pto tomato resistance complex following effector recognition
Authors: Sheikh Arsheed H. , Zacharia Iosif , Pardal Alonso J. , Dominguez-Ferreras Ana , Sueldo Daniela J. , Kim Jung-Gun , Balmuth Alexi , Gutierrez Jose R. , Conlan Brendon F. , Ullah Najeeb , Nippe Olivia M. , Girija Anil M. , Wu Chih-Hang , Sessa Guido , Jones Alexandra M. E. , Grant Murray R. , Gifford Miriam L. , Mudgett Mary Beth , Rathjen John P. , Ntoukakis Vardis
Published: May 2023

In both plants and animals, nucleotide-binding leucine-rich repeat (NLR) immune receptors play critical roles in pathogen recognition and activation of innate immunity. In plants, NLRs recognise pathogen-derived effector proteins and initiate effector-triggered immunity (ETI). However, the molecular mechanisms that link NLR-mediated effector recognition and downstream signalling are not fully understood. By exploiting the well-characterised tomato Prf/Pto NLR resistance complex, we identified the 14-3-3 proteins TFT1 and TFT3 as interacting partners of both the NLR complex and the protein kinase MAPKKKα. Moreover, we identified the helper NRC proteins (NLR-required for cell death) as integral components of the Prf /Pto NLR recognition complex. Notably our studies revealed that TFTs and NRCs interact with distinct modules of the NLR complex and, following effector recognition, dissociate facilitating downstream signalling. Thus, our data provide a mechanistic link between activation of immune receptors and initiation of downstream signalling cascades.
Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling
Authors: Bian Fenghua , Lan Ying-Wei , Zhao Shuyang , Deng Zicheng , Shukla Samriddhi , Acharya Anusha , Donovan Johnny , Le Tien , Milewski David , Bacchetta Matthew , Hozain Ahmed Emad , Tipograf Yuliya , Chen Ya-Wen , Xu Yan , Shi Donglu , Kalinichenko Vladimir V. , Kalin Tanya V.
Published: May 2023

Pulmonary fibrosis results from dysregulated lung repair and involves multiple cell types. The role of endothelial cells (EC) in lung fibrosis is poorly understood. Using single cell RNA-sequencing we identified endothelial transcription factors involved in lung fibrogenesis, including FOXF1, SMAD6, ETV6 and LEF1. Focusing on FOXF1, we found that FOXF1 is decreased in EC within human idiopathic pulmonary fibrosis (IPF) and mouse bleomycin-injured lungs. Endothelial-specific Foxf1 inhibition in mice increased collagen depositions, promoted lung inflammation, and impaired R-Ras signaling. In vitro, FOXF1-deficient EC increased proliferation, invasion and activation of human lung fibroblasts, and stimulated macrophage migration by secreting IL-6, TNFα, CCL2 and CXCL1. FOXF1 inhibited TNFα and CCL2 through direct transcriptional activation of Rras gene promoter. Transgenic overexpression or endothelial-specific nanoparticle delivery of Foxf1 cDNA decreased pulmonary fibrosis in bleomycin-injured mice. Nanoparticle delivery of FOXF1 cDNA can be considered for future therapies in IPF.
Confining donor conformation distributions for efficient thermally activated delayed fluorescence with fast spin-flipping
Authors: Qiu Weidong , Liu Denghui , Li Mengke , Cai Xinyi , Chen Zijian , He Yanmei , Liang Baoyan , Peng Xiaomei , Qiao Zhenyang , Chen Jiting , Li Wei , Pu Junrong , Xie Wentao , Wang Zhiheng , Li Deli , Gan Yiyang , Jiao Yihang , Gu Qing , Su Shi-Jian
Published: May 2023

Fast spin-flipping is the key to exploit the triplet excitons in thermally activated delayed fluorescence based organic light-emitting diodes toward high efficiency, low efficiency roll-off and long operating lifetime. In common donor-acceptor type thermally activated delayed fluorescence molecules, the distribution of dihedral angles in the film state would have significant influence on the photo-physical properties, which are usually neglected by researches. Herein, we find that the excited state lifetimes of thermally activated delayed fluorescence emitters are subjected to conformation distributions in the host-guest system. Acridine-type flexible donors have a broad conformation distribution or bimodal distribution, in which some conformers feature large singlet-triplet energy gap, leading to long excited state lifetime. Utilization of rigid donors with steric hindrance can restrict the conformation distributions in the film to achieve degenerate singlet and triplet states, which is beneficial to efficient reverse intersystem crossing. Based on this principle, three prototype thermally activated delayed fluorescence emitters with confined conformation distributions are developed, achieving high reverse intersystem crossing rate constants greater than 106s−1, which enable highly efficient solution-processed organic light-emitting diodes with suppressed efficiency roll-off.
Contributions of replicative and translesion DNA polymerases to mutagenic bypass of canonical and atypical UV photoproducts
Authors: Vandenberg Brittany N. , Laughery Marian F. , Cordero Cameron , Plummer Dalton , Mitchell Debra , Kreyenhagen Jordan , Albaqshi Fatimah , Brown Alexander J. , Mieczkowski Piotr A. , Wyrick John J. , Roberts Steven A.
Published: May 2023

UV exposure induces a mutation signature of C > T substitutions at dipyrimidines in skin cancers. We recently identified additional UV-induced AC > TT and A > T substitutions that could respectively cause BRAF V600K and V600E oncogenic mutations. The mutagenic bypass mechanism past these atypical lesions, however, is unknown. Here, we whole genome sequenced UV-irradiated yeast and used reversion reporters to delineate the roles of replicative and translesion DNA polymerases in mutagenic bypass of UV-lesions. Our data indicates that yeast DNA polymerase eta (pol η) has varied impact on UV-induced mutations: protecting against C > T substitutions, promoting T > C and AC > TT substitutions, and not impacting A > T substitutions. Surprisingly, deletion rad30Δ increased novel UV-induced C > A substitutions at CA dinucleotides. In contrast, DNA polymerases zeta (pol ζ) and epsilon (pol ε) participated in AC > TT and A > T mutations. These results uncover lesion-specific accurate and mutagenic bypass of UV lesions, which likely contribute to key driver mutations in melanoma.
Extensive characterization and implementation of a family of three-qubit gates at the coherence limit
Authors: Warren Christopher W. , Fernández-Pendás Jorge , Ahmed Shahnawaz , Abad Tahereh , Bengtsson Andreas , Biznárová Janka , Debnath Kamanasish , Gu Xiu , Križan Christian , Osman Amr , Fadavi Roudsari Anita , Delsing Per , Johansson Göran , Frisk Kockum Anton , Tancredi Giovanna , Bylander Jonas
Published: May 2023

While all quantum algorithms can be expressed in terms of single-qubit and two-qubit gates, more expressive gate sets can help reduce the algorithmic depth. This is important in the presence of gate errors, especially those due to decoherence. Using superconducting qubits, we have implemented a three-qubit gate by simultaneously applying two-qubit operations, thereby realizing a three-body interaction. This method straightforwardly extends to other quantum hardware architectures, requires only a firmware upgrade to implement, and is faster than its constituent two-qubit gates. The three-qubit gate represents an entire family of operations, creating flexibility in the quantum-circuit compilation. We demonstrate a process fidelity of 97.90%, which is near the coherence limit of our device. We then generate two classes of entangled states, the Greenberger–Horne–Zeilinger and Dicke states, by applying the new gate only once; in comparison, decompositions into the standard gate set would have a two-qubit gate depth of two and three, respectively. Finally, we combine characterization methods and analyze the experimental and statistical errors in the fidelity of the gates and of the target states.
Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice
Authors: Gencay Yilmaz Emre , Jasinskytė Džiuginta , Robert Camille , Semsey Szabolcs , Martínez Virginia , Petersen Anders Østergaard , Brunner Katja , de Santiago Torio Ana , Salazar Alex , Turcu Iszabela Cristiana , Eriksen Melissa Kviesgaard , Koval Lev , Takos Adam , Pascal Ricardo , Schou Thea Staffeldt , Bayer Lone , Bryde Tina , Johansen Katja Chandelle , Bak Emilie Glad , Smrekar Frenk , Doyle Timothy B. , Satlin Michael J. , Gram Aurelie , Carvalho Joana , Jessen Lene , Hallström Björn , Hink Jonas , Damholt Birgitte , Troy Alice , Grove Mette , Clube Jasper , Grøndahl Christian , Haaber Jakob Krause , van der Helm Eric , Zdravkovic Milan , Sommer Morten Otto Alexander
Published: May 2023

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR–Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients.
Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials
Authors: Yosipovitch Gil , Mollanazar Nicholas , Ständer Sonja , Kwatra Shawn G. , Kim Brian S. , Laws Elizabeth , Mannent Leda P. , Amin Nikhil , Akinlade Bolanle , Staudinger Heribert W. , Patel Naimish , Yancopoulos George D. , Weinreich David M. , Wang Sheldon , Shi Genming , Bansal Ashish , O’Malley John T.
Published: May 2023

Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8–57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3–31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.

ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679.
Design of electromagnetic metasurface using two dimensional crystal nets
Authors: Hou Jie , Zhang Xiaohong , Guo Ying , Zhang Rui-Zhi , Guo Meng
Published: May 2023

Metasurfaces are of great interest as they exhibit unique electromagnetic properties. Currently, metasurface design focuses on generating new meta-atoms and their combinations. Here a topological database, reticular chemistry structure resource (RCSR), is introduced to bring a new dimension and more possibilities for metasurface design. RCSR has over 200 two-dimensional crystal nets, among which 72 are identified as suitable for metasurface design. Using a simple metallic cross as the metaatom, 72 metasurfaces are constructed from the atom positions and lattice vectors of the crystal nets templates. The transmission curves of all the metasurfaces are calculated using the finite-difference time-domain method. The calculated transmission curves have good diversity, showing that the crystal nets approach is a new engineering dimension for metasurface design. Three clusters are found for the calculated curves using the K-means algorithm and principal component analysis. The structure–property relationship between metasurface topology and transmission curve is investigated, but no simple descriptor has been found, indicating that further work is still needed. The crystal net design approach developed in this work can be extended to three-dimensional design and other types of metamaterials like mechanical materials.
Continued fractions and the Thomson problem
Authors: Moscato Pablo , Haque Mohammad Nazmul , Moscato Anna
Published: May 2023

We introduce new analytical approximations of the minimum electrostatic energy configuration of n electrons, E(n), when they are constrained to be on the surface of a unit sphere. Using 453 putative optimal configurations, we searched for approximations of the form $$E(n) = (n^2/2) \, e^{g(n)}$$

E

(
n
)

=

(

n
2

/
2
)

e

g
(
n
)

where g(n) was obtained via a memetic algorithm that searched for truncated analytic continued fractions finally obtaining one with Mean Squared Error equal to $${5.5549 \times 10^{-8}}$$

5.5549
×

10

-
8

for the model of the normalized energy ($$E_n(n) \equiv e^{g(n)} \equiv 2E(n)/n^2$$

E
n

(
n
)

≡

e

g
(
n
)

≡
2
E

(
n
)

/

n
2

). Using the Online Encyclopedia of Integer Sequences, we searched over 350,000 sequences and, for small values of n, we identified a strong correlation of the highest residual of our best approximations with the sequence of integers n defined by the condition that $$n^2+12$$

n
2

+
12

is a prime. We also observed an interesting correlation with the behavior of the smallest angle $$\alpha (n)$$

α
(
n
)

, measured in radians, subtended by the vectors associated with the nearest pair of electrons in the optimal configuration. When using both $$\sqrt{n}$$

n

and $$\alpha (n)$$

α
(
n
)

as variables a very simple approximation formula for $$E_n(n)$$

E
n

(
n
)

was obtained with MSE= $$7.9963 \times 10^{-8}$$

7.9963
×

10

-
8

and MSE= 73.2349 for E(n). When expanded as a power series in infinity, we observe that an unknown constant of an expansion as a function of $$n^{-1/2}$$

n

-
1
/
2

of E(n) first proposed by Glasser and Every in 1992 as $$-1.1039$$

-
1.1039

, and later refined by Morris, Deaven and Ho as $$-1.104616$$

-
1.104616

in 1996, may actually be very close to −1.10462553440167 when the assumed optima for $$n\le 200$$

n
≤
200

are used.
Efficient MIR crosstalk reduction based on silicon-on-calcium fluoride platform with Ge/Si strip arrays
Authors: Elgammal Nayira M. , Younis B. M. , Gaafar Mahmoud A. , Elkholy M. M. , Hameed Mohamed Farhat O. , Obayya S. S. A.
Published: May 2023

Reduction of the crosstalk (CT) between contiguous photonic components is still a big challenge in fabricating high packing density photonic integrated circuits (PICs). Few techniques to accomplish that goal have been offered in recent years but all in the near-IR region. In this paper, we report a design for realizing a highly efficient CT reduction in the MIR regime, for the first time to the best of our knowledge. The reported structure is based on the silicon-on-calcium-fluoride (SOCF) platform with uniform Ge/Si strip arrays. Using Ge strips shows better CT reduction and longer coupling length (Lc) than the conventional Si based devices over a wide bandwidth in the MIR region. The effect of adding a different number of Ge and Si strips with different dimensions between two adjacent Si waveguides on the Lc and hence on the CT is analyzed using both full vectorial finite element method and 3D finite difference time domain method. An increase in the Lc by 4 orders of magnitude and 6.5 times are obtained using Ge and Si strips, respectively, compared to strips-free Si waveguides. Consequently, crosstalk suppression of − 35 dB and − 10 dB for the Ge and Si strips, respectively, is shown. The proposed structure is beneficial for high packing density nanophotonic devices in the MIR regime, such as switches, modulators, splitters, and wavelength division (de)multiplexers, which are important for MIR communication integrated circuits, spectrometers, and sensors.
A data-driven approach to quantify disparities in power outages
Authors: Bhattacharyya Arkaprabha , Hastak Makarand
Published: May 2023

This research proposes a data-driven approach to identify possible disparities in a utility’s outage management practices. The approach has been illustrated for an Investor-Owned Utility located in the Midwest region in the U.S. Power outage data for approximately 5 years between March 2017 and January 2022 was collected for 36 ZIP/postal codes located within the utility’s service territory. The collected data was used to calculate the total number of outages, customers affected, and the duration of outages during those 5 years for each ZIP code. Next, each variable was normalized with respect to the population density of the ZIP code. After normalizing, a K-means clustering algorithm was implemented that created five clusters out of those 36 ZIP codes. The difference in the outage parameters was found to be statistically significant. This indicated differential experience with power outages in different ZIP codes. Next, three Generalized Linear Models were developed to test if the presence of critical facilities such as hospitals, 911 centers, and fire stations, as socioeconomic and demographic characteristics of the ZIP codes, can explain their differential experience with the power outage. It was found that the annual duration of outages is lower in the ZIP codes where critical facilities are located. On the other hand, ZIP codes with lower median household income have experienced more power outages, i.e., higher outage counts in those 5 years. Lastly, the ZIP codes with a higher percentage of the White population have experienced more severe outages that have affected more customers.
Morphodynamical cell state description via live-cell imaging trajectory embedding
Authors: Copperman Jeremy , Gross Sean M. , Chang Young Hwan , Heiser Laura M. , Zuckerman Daniel M.
Published: May 2023

Time-lapse imaging is a powerful approach to gain insight into the dynamic responses of cells, but the quantitative analysis of morphological changes over time remains challenging. Here, we exploit the concept of “trajectory embedding” to analyze cellular behavior using morphological feature trajectory histories—that is, multiple time points simultaneously, rather than the more common practice of examining morphological feature time courses in single timepoint (snapshot) morphological features. We apply this approach to analyze live-cell images of MCF10A mammary epithelial cells after treatment with a panel of microenvironmental perturbagens that strongly modulate cell motility, morphology, and cell cycle behavior. Our morphodynamical trajectory embedding analysis constructs a shared cell state landscape revealing ligand-specific regulation of cell state transitions and enables quantitative and descriptive models of single-cell trajectories. Additionally, we show that incorporation of trajectories into single-cell morphological analysis enables (i) systematic characterization of cell state trajectories, (ii) better separation of phenotypes, and (iii) more descriptive models of ligand-induced differences as compared to snapshot-based analysis. This morphodynamical trajectory embedding is broadly applicable to the quantitative analysis of cell responses via live-cell imaging across many biological and biomedical applications.
Cells sorted off hiPSC-derived kidney organoids coupled with immortalized cells reliably model the proximal tubule
Authors: Banan Sadeghian Ramin , Ueno Ryohei , Takata Yuji , Kawakami Akihiko , Ma Cheng , Araoka Toshikazu , Takasato Minoru , Yokokawa Ryuji
Published: May 2023

Of late, numerous microphysiological systems have been employed to model the renal proximal tubule. Yet there is lack of research on refining the functions of the proximal tubule epithelial layer—selective filtration and reabsorption. In this report, pseudo proximal tubule cells extracted from human-induced pluripotent stem cell-derived kidney organoids are combined and cultured with immortalized proximal tubule cells. It is shown that the cocultured tissue is an impervious epithelium that offers improved levels of certain transporters, extracellular matrix proteins collagen and laminin, and superior glucose transport and P-glycoprotein activity. mRNA expression levels higher than those obtained from each cell type were detected, suggesting an anomalous synergistic crosstalk between the two. Alongside, the improvements in morphological characteristics and performance of the immortalized proximal tubule tissue layer exposed, upon maturation, to human umbilical vein endothelial cells are thoroughly quantified and compared. Glucose and albumin reabsorption, as well as xenobiotic efflux rates through P-glycoprotein were all improved. The data presented abreast highlight the advantages of the cocultured epithelial layer and the non-iPSC-based bilayer. The in vitro models presented herein can be helpful in personalized nephrotoxicity studies.