bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable Thermal Conductivity Metamaterials Applied to Passive Thermal Control of Satellites
Authors: Phoenix Austin A. 
Published: September 2023

Abstract
Active materials like the proposed variable thermal conductivity metamaterial enable new thermal designs and low-cost, low-power, passive thermal control. Thermal control of satellites conventionally requires active thermal control systems that are expensive, large, inefficient, energy-intensive, and unavailable for CubeSats. The high-temperature operation case is the thermal system’s primary design consideration for CubeSats. The thermal path is designed to reject as much heat as possible to ensure the system does not overheat. In other cases, such as during a power anomaly, the oversized thermal path results in rapid cooling, culminating in mission failure due to thermal limits on the electronics or batteries. Improving the thermal control of CubeSats can enable new thermally challenging missions, increase satellite longevity, and increase mission success rate by controlling the dynamic thermal environment. The materials available for thermal management are inherently limited, but new engineered materials provide unique opportunities to change how satellites adapt to thermal loads. This paper investigates using an adaptive metamaterial designed to passively change its thermal conductivity as a function of temperature to meet the needs of the satellite. The thermal performance of a CubeSat is evaluated with a variable thermal conductivity metamaterial located in the critical thermal path from the satellite to the radiator. The system’s performance using two metamaterial configurations is compared to a baseline copper thermal path. Multiple satellite thermal operation cases are investigated to determine the operation ranges, and the metamaterial’s performance in various conditions is quantified.
Kinetostatics of Deployable Concrete Formworks
Authors: Zhao Jing-Shan , Sun Xiao-Cheng , Wei Song-Tao , Lu Wen-Xiu 
Published: September 2023

Abstract
To reform the traditional concrete formwork, an overconstrained deployable frame is designed. It is composed of closed loop deployable units formed by scissor-form elements and orthogonal telescoping rods. Using the reciprocal screw theory, the mobility of the deployable frame is studied, and it has one degree-of-freedom (DoF). To analyze the kinematic performance of the frame in the deployment and folding processes and the static characteristics under external loads at different deployed states, a general approach to analyzing the kinematics and statics by modeling in screw form is proposed. The velocities of joints could be solved in screw coordinates, the position and acceleration of joints could be obtained via a first-order numerical integration and a first-order numerical differential interpolation, respectively. Then, the position information for each joint can be forwarded onto the static equilibrium equations. Through the static analysis at each deployed state, the inner forces in each rod and the active control forces are derived. Kinematics and statics are associated using velocities as the global variable, which allows a unified analysis of mechanisms. This method is computationally highly efficient and also fits for kinematic and static analysis of different kinds of multi-rigid-body mechanisms.
Transposon sequencing identifies genes impacting
Staphylococcus aureus
invasion in a human macrophage model
Authors: Lo Hsin-Yu , Long Dustin R. , Holmes Elizbeth A. , Penewit Kelsi , Hodgson Taylor , Lewis Janessa D. , Waalkes Adam , Salipante Stephen J. 
Published: September 2023

ABSTRACT

Staphylococcus aureus
is a facultative intracellular pathogen in many host cell types, facilitating its persistence in chronic infections. The genes contributing to intracellular pathogenesis have not yet been fully enumerated. Here, we cataloged genes influencing
S. aureus
invasion and survival within human THP-1 derived macrophages using two laboratory strains (ATCC2913 and JE2). We developed an
in vitro
transposition method to produce highly saturated transposon mutant libraries in
S. aureus
and performed transposon insertion sequencing (Tn-Seq) to identify candidate genes with significantly altered abundance following macrophage invasion. While some significant genes were strain-specific, 108 were identified as common across both
S. aureus
strains, with most (
n
= 106) being required for optimal macrophage infection. We used CRISPR interference (CRISPRi) to functionally validate phenotypic contributions for a subset of genes. Of the 20 genes passing validation, seven had previously identified roles in
S. aureus
virulence, and 13 were newly implicated. Validated genes frequently evidenced strain-specific effects, yielding opposing phenotypes when knocked down in the alternative strain. Genomic analysis of
de novo
mutations occurring in groups (
n
= 237) of clonally related
S. aureus
isolates from the airways of chronically infected individuals with cystic fibrosis (CF) revealed significantly greater
in vivo
purifying selection in conditionally essential candidate genes than those not associated with macrophage invasion. This study implicates a core set of genes necessary to support macrophage invasion by
S. aureus,
highlights strain-specific differences in phenotypic effects of effector genes, and provides evidence for selection of candidate genes identified by Tn-Seq analyses during chronic airway infection in CF patients
in vivo
.
Ribosome heterogeneity results in leader sequence-mediated regulation of protein synthesis in
Francisella tularensis
Authors: Trautmann Hannah S. , Schmidt Sierra S. , Gregory Steven T. , Ramsey Kathryn M. 
Published: September 2023

ABSTRACT

Although ribosomes are generally examined in aggregate, ribosomes can be heterogenous in composition. Evidence is accumulating that changes in ribosome composition may result in altered function, such that ribosome heterogeneity may provide a mechanism to regulate protein synthesis. Ribosome heterogeneity in the human pathogen
Francisella tularensis
results from incorporation of one of three homologs of bS21, a small ribosomal subunit protein demonstrated to regulate protein synthesis in other bacteria. Loss of one homolog, bS21-2, results in genome-wide post-transcriptional changes in protein abundance. This suggests that bS21-2 can, either directly or indirectly, lead to preferential translation of particular mRNAs. Here, we examine the potential of bS21-2 to function in a leader sequence-dependent manner and to function indirectly, via Hfq. We found that the 5´ untranslated region (UTR) of some bS21-2-responsive genes, including key virulence genes, is sufficient to alter translation in cells lacking bS21-2. We further identify features of a 5´ UTR that allow responsiveness to bS21-2. These include an imperfect Shine-Dalgarno sequence and a particular six nucleotide sequence. Our results are consistent with a model in which a bS21 homolog increases the efficiency of translation initiation through interactions with specific leader sequences. With respect to bS21-2 indirectly regulating translation via the RNA-binding protein Hfq, we found that Hfq controls transcript abundance rather than protein synthesis, impacting virulence gene expression via a distinct mechanism. Together, we determined that ribosome composition in
F. tularensis
regulates translation in a leader sequence-dependent manner, a regulatory mechanism which may be used in other bacteria.

IMPORTANCE

Ribosome heterogeneity is common in bacteria, and there is mounting evidence that ribosome composition plays a regulatory role in protein synthesis. However, mechanisms of ribosome-driven gene regulation are not well understood. In the human pathogen
Francisella tularensis
, which encodes multiple homologs for the ribosomal protein bS21, loss of one homolog impacts protein synthesis and virulence. Here, we explore the mechanism behind bS21-mediated changes in protein synthesis, finding that they can be linked to altered translation initiation and are dependent on specific sequences in the leaders of transcripts. Our data support a model in which ribosome composition regulates gene expression through translation, a strategy that may be conserved in diverse organisms with various sources of ribosome heterogeneity.
Structural basis of white-tailed deer,
Odocoileus virginianus
, ACE2 recognizing all the SARS-CoV-2 variants of concern with high affinity
Authors: Han Pu , Meng Yumin , Zhang Di , Xu Zepeng , Li Zhiyuan , Pan Xiaoqian , Zhao Zhennan , Li Linjie , Tang Lingfeng , Qi Jianxun , Liu Kefang , Gao George F. 
Published: September 2023

ABSTRACT

SARS-CoV-2 has been expanding its host range, among which the white-tailed deer (WTD),
Odocoileus virginianus,
became the first wildlife species infected on a large scale and might serve as a host reservoir for variants of concern (VOCs) in case no longer circulating in humans. In this study, we comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. We further determined the complex structures of WTD ACE2 with PT, Omicron BA.1, and BA.4/5 S trimer. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding. This study deepens our understanding of the interspecies transmission mechanisms of SARS-CoV-2 and further addresses the importance of constant monitoring on SARS-CoV-2 infections in wild animals.

IMPORTANCE
Even if we manage to eliminate the virus among humans, it will still circulate among wildlife and continuously be transmitted back to humans. A recent study indicated that WTD may serve as reservoir for nearly extinct SARS-CoV-2 strains. Therefore, it is critical to evaluate the binding abilities of SARS-CoV-2 variants to the WTD ACE2 receptor and elucidate the molecular mechanisms of binding of the RBDs to assess the risk of spillback events.
Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial
Authors: Deng Yihong , Polley Eric C , Wallach Joshua D , Herrin Jeph , Ross Joseph S , McCoy Rozalina G 
Published: September 2023

ObjectiveTo build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabetes.DesignEmulation of a target trial.SettingMedical and pharmacy claims data from the OptumLabs Data Warehouse, a de-identified US national dataset of beneficiaries of commercially insured and Medicare Advantage plans, 29 March 2013 to 30 June 2021.ParticipantsAdults (≥18 years) with type 2 diabetes who first started taking glimepiride, sitagliptin, liraglutide, insulin glargine, or canagliflozin between 29 March 2013 and 30 June 2021. Participants were treatment naive or were receiving metformin monotherapy at the time of starting the study drug.Main outcome measuresThe main outcomes were time to primary and secondary metabolic failure of the assigned treatment, calculated as days to haemoglobin A1clevels of ≥7.0% and >7.5%, respectively. Secondary metabolic, cardiovascular, and microvascular outcomes were analysed as specified in the GRADE statistical analysis plan. Propensity scores were estimated with the gradient boosting method, and inverse propensity score weighting was used to emulate randomisation to the treatment groups, which were then compared with Cox proportional hazards regression.(ResultsThe study cohort included participants starting treatment with glimepiride (n=20 511), liraglutide (n=5569), sitagliptin (n=13 039), insulin glargine (n=7262), and canagliflozin (n=5290). The insulin glargine arm was excluded because of insufficient control of confounding. Median times to primary metabolic failure were 439 (95% confidence interval 400 to 489) days in the canagliflozin arm, 439 (426 to 453) days in the glimepiride arm, 624 (567 to 731) days in the liraglutide arm, and 461 (442 to 482) days in the sitagliptin arm. Median time to secondary metabolic failure was also longest in the liraglutide arm. Adults receiving liraglutide had the lowest one year cumulative incidence rate of primary metabolic failure (0.37, 95% confidence interval 0.35 to 0.40) followed by sitagliptin (0.44, 0.43 to 0.45), glimepiride (0.45, 0.44 to 0.45), and canagliflozin (0.46, 0.44 to 0.48). Similarly, the one year cumulative incidence rate of secondary metabolic failure was 0.27 (0.25 to 0.29) in the canagliflozin arm, 0.28 (0.27 to 0.29) in the glimepiride arm, 0.23 (0.21 to 0.26) in the liraglutide arm, and 0.28 (0.27 to 0.29) in the sitagliptin arm. No differences were observed between the study arms in the rates of microvascular and macrovascular complications.ConclusionsIn this target trial emulation of an expanded GRADE study framework, liraglutide was more effective in achieving and maintaining glycaemic control as a second line glucose lowering drug than canagliflozin, sitagliptin, or glimepiride.
Assessing household financial burdens for preprimary education and associated socioeconomic inequalities: a case study in China
Authors: Wei Yi , Liu Kai , Kang Le , Behrman Jere R , Richter Linda M , Stein Alan , Song Yingquan , Lu Chunling 
Published: September 2023

BackgroundProviding young children with universal access to preprimary education (PPE) is considered a powerful tool for human capital development and eliminating the intergenerational transmission of poverty. To remove household financial barrier for achieving universal PPE, this study proposed a measure to identify households incurring ‘heavy financial burdens from paying for PPE’ (HBPPE) and conducted a case study in China.MethodsUsing nationally representative data in 2019, we estimated the percentage of households with HBPPE (spent 7% or more of their total annual expenditure) and associated socioeconomic inequalities. We also applied a three-level logit regression model to investigate the factors associated with the probabilities of households incurring HBPPE.ResultsHalf of the sampled households spent 7% or more of their expenditures on PPE. Households in the lowest wealth quintile (54%) or households with children attending private PPE (55%) had higher percentages of HBPPE than households in other wealth quintiles (eg, 51% in the highest wealth quintile) or households with children attending public kindergartens (41%). Logit regression analysis shows that the poorest households and households with children attending private kindergarten were more likely to incur HBPPE than their counterparts.ConclusionTo ensuring universal access to PPE in China, future policy should consider increasing the enrolment of children from low-income families in public kindergartens and increasing governmental investments in low-income households by subsidising children attending PPE.
Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis
Authors: Liu Nian , Yan Mingjie , Tao Qian , Wu Jie , Chen Jing , Chen Xiang , Peng Cong 
Published: September 2023

Backgroundanti-Programmed Death-1 (anti-PD-1) immunotherapy has shown promising manifestation in improving the survival rate of patients with advanced melanoma, with its efficacy closely linked to Programmed cell death-Ligand 1 (PD-L1) expression. However, low clinical efficacy and drug resistance remain major challenges. Although the metabolic alterations from tricarboxylic acid (TCA) cycle to glycolysis is a hallmark in cancer cells, accumulating evidence demonstrating TCA cycle plays critical roles in both tumorigenesis and treatment.MethodsThe plasma levels of metabolites in patients with melanoma were measured by nuclear magnetic resonance (NMR) spectroscopy. The effect of pyruvate dehydrogenase subunit 1 (PDHA1) and oxoglutarate dehydrogenase (OGDH) on immunotherapy was performed by B16F10 tumor-bearing mice. Flow cytometry analyzed the immune microenvironment. RNA sequencing analyzed the global transcriptome alterations in CPI613-treated melanoma cells. The regulation of PD-L1 and glycolysis by PDHA1/OGDH-ATF3 signaling were confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, dual-luciferase reporter gene, Chromatin immunoprecipitation (ChIP)-quantitative PCR and Seahorse assay. The relationship between PDHA1/OGDH-ATF3-glycolysis and the efficacy of melanoma anti-PD-1 immunotherapy was verified in the clinical database and single-cell RNA-seq (ScRNA-Seq).ResultsIn our study, the results showed that significant alterations in metabolites associated with glycolysis and the TCA cycle in plasma of patients with melanoma through NMR technique, and then, PDHA1 and OGDH, key enzymes for regulation TCA cycle, were remarkable raised in melanoma and negatively related to anti-PD-1 efficacy through clinical database analysis as well as ScRNA-Seq. Inhibition of PDHA1 and OGDH by either shRNA or pharmacological inhibitor by CPI613 dramatically attenuated melanoma progression as well as improved the therapeutic efficacy of anti-PD-1 against melanoma. Most importantly, suppression of TCA cycle remarkably raises PD-L1 expression and glycolysis flux through AMPK-CREB-ATF3 signaling.ConclusionsTaken together, our results demonstrated the role of TCA cycle in immune checkpoint blockade and provided a novel combination strategy for anti-PD-1 immunotherapy in melanoma treatment.
Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project
Authors: Moore A Rachel , Yu Jing , Pei Yang , Cheng Emily W Y , Taylor Tavares Ana Lisa , Walker Woolf T , Thomas N Simon , Kamath Arveen , Ibitoye Rita , Josifova Dragana , Wilsdon Anna , Ross Alison , Calder Alistair D , Offiah Amaka C , Wilkie Andrew O M ,   Genomics England Research Consortium, Taylor Jenny C , Pagnamenta Alistair T 
Published: September 2023

BackgroundCurrent clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication ‘single autosomal recessive mutation in rare disease’. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic ‘second-hit’ variants.MethodsTo investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity.ResultsUsing these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion inCFTRand a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2–6 ofENPP1. Although ambiguous by short-read WGS, theENPP1variant structure was resolved using optical genome mapping and RNA analysis.ConclusionSystematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.
Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation
Authors: Holewijn Rozemarije A , Zoon Thomas J C , Verbaan Dagmar , Bergfeld Isidoor O , Verwijk Esmée , Geurtsen Gert J , van Rooijen Geeske , van den Munckhof Pepijn , Bot Maarten , Denys Damiaan A J P , De Bie Rob M A , Schuurman P Rick 
Published: September 2023

BackgroundThis study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline.Methods110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life.ResultsThere were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson’s Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02).ConclusionsThis study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms.Trial registration numberNTR5809.