bluuebunny/crossref_metadata_2025 huggingface dataset:
Aligning classroom assessment with engineering practice: A design‐based research study of a two‐stage exam with authentic assessment
Authors: Koretsky Milo D. , McColley Campbell J. , Gugel James L. , Ekstedt Thomas W.
Published: October 2021

Background

Authentic assessment and two‐stage exams have recently received attention; however, they are rarely used together. We reimagine assessment by integrating an authentic, computer‐based assessment into the structure of a two‐stage exam in a large engineering class.

Purpose

We seek to identify ways that such assessment extends classroom testing to better align with engineering practice by examining the ways teams negotiate uncertainty to make engineering decisions. We also identify differing students' reactions to increased uncertainty during tests.

Design/Method

Using the methodical framework of design‐based research, we analyze performance and reflection data for 117 student teams through two design iterations to explore four design and theoretical conjectures.

Results

Teams chose multiple solution paths to this authentic task, an aspect that aligns with the characteristics of engineering practice that we seek to assess. In addition, the technology tool allows the evaluation of procedural accuracy for many of the teams' chosen paths. The teams' decision‐making performances correlate; however, decision‐making and traditional assessments do not correlate, suggesting they measure different competencies. The computer‐based second stage provides a holistic assessment that shifts the messages that students implicitly receive about valued practices in the classroom. However, not all students took up the authentic group assessment in desired ways.

Conclusions

Technology‐based two‐stage exams with authentic assessment show promise to shift testing practices in large engineering classes to include decision‐making. Such assessments better align with engineering practices that are valued in the profession, but more work is needed to develop systems for widespread implementation.
Th1 cytokine gene polymorphism and the corresponding plasma cytokine levels: A comparative study in HIV‐1 positive and exposed uninfected infants
Authors: R. Chavan Vijay , Ahir Swati , Kerkar Shilpa , Ansari Zakia , Samant‐Mavani Padmaja , Nanavati Ruchi , Mehta Preeti , Mania‐Pramanik Jayanti
Published: October 2021

The pro‐inflammatory (Th1) cytokines namely interleukin (IL)‐2, IL‐6, IL‐12, interferon (IFN)‐γ, tumor necrosis factor‐α (TNF‐α) are vital in the clearance of HIV infection. This prospective cohort study aimed to evaluate the polymorphisms of Th1 cytokine genes and their corresponding plasma cytokine levels in HIV‐1 positive and exposed uninfected (EU) infants born to HIV‐1 positive mothers. CD4 count, viral load of HIV‐1 positive mothers was done using commercially available reagents. Cytokine genotyping analysis and levels were done in 20 HIV‐1 positive and 54 EU infants. The polymorphisms of Th1 cytokines were done using the PCR‐SSP method. Plasma cytokine levels were estimated using Bio‐Plex‐Pro cytokine assay (BIO‐RAD; USA). Results revealed treatment status of the mothers and viral load were the two confounding factors having a significant effect on HIV status of the infant. TNF‐α GG genotype is significantly higher in EU infants as compared with HIV‐1 positive infants. GG genotype was associated with high TNF‐ α levels in HIV‐1 positive infants but the difference was not statistically significant. HIV‐1 positive infants with ‐IFN‐γ (+874) TT genotype was significantly associated with high IFN‐γ levels. To the best of our knowledge, this is the first study reporting the role of Th1 cytokine gene polymorphisms and their corresponding plasma cytokine levels in HIV‐1 positive and EU infants from India.
Differential expression of circulating microRNAs in serum: Potential biomarkers to track Japanese encephalitis virus infection
Authors: Baluni Manjari , Ghildiyal Sneha , Fatima Tanzeem , Tiwari Rashmi , Upadhyay Shivbrat , Dhole Tapan N. , Reddy D. Himanshu , Singh Dharamveer
Published: October 2021

Japanese encephalitis is one of the serious vector‐borne viral encephalitis diseases found worldwide and poses a major threat to public health. Most Japanese encephalitis virus (JEV) infections are subclinical; only 1: 250 to 1:1000 infected persons develop clinical presentations. Delay in proper diagnosis of JE affects the timeliness of treatment initiation and increases the mortality rate in patients. Therefore, there is an extreme need to develop potential biomarkers, which might improve the diagnosis and can become the basis for development of new therapeutics. The microRNAs (miRNAs/or miRs) are small noncoding RNAs of 17–24 nucleotides that are known to regulate about 60% of human genes. Although miRNAs have been found to regulate various aspects of innate and adaptive immune responses, less information on circulating miRNAs in JE is known. The study of JEV infected human serum miRNAs will provide novel information for the diagnosis of JE as well as for the improvement of disease outcome.

Total RNA, including miRNA, was extracted from serum followed by the complementary DNA (cDNA) synthesis by using sequence‐specific primers. cDNA was amplified using target‐specific TaqMan MicroRNA Assay. Real‐time polymerase chain reaction data was normalized using both exogenous (cel‐miR‐39) and endogenous (hsa‐miR‐93) controls.

We have found significantly altered expression of miR‐155 and miR‐21 in serum of JEV infected patients as compared to healthy controls, revealing their role as a a noninvasive biomarker in JE. A significant correlation between miRNAs and JE was observed that offers the basis for miRNAs to serve as a new component to develop possible therapeutic strategies for JE in near future.
The high‐frequency variability of Antarctic sea ice and polar cold air incursions over Amazonia
Authors: Carpenedo Camila Bertoletti , Campos José Leandro Pereira Silveira , Ambrizzi Tércio , Braga Ricardo Burgo
Published: October 2021

The cold air incursion over South America is associated with the frontal systems generated in the Antarctic region, and sea ice cover plays an important role in its formation. Little is known about how the high‐frequency variability of the coupled ocean–cryosphere‐atmosphere system affects weather conditions in South America, especially in the Amazon region ‐ in tandem with the largest tropical forest on the planet and a key region of the global climate system. The results presented here suggest that the high‐frequency variability of the expansion of Antarctic sea ice extent (SIE) extremes, in the Ross Sea and Indian Ocean, modulate the cold air incursion over the Amazon in the southern winter 4 and 2 days after the expansion of SIE extremes, respectively. The SIE extremes can couple with the atmosphere, inducing Rossby waves that propagate and undergo amplification downstream from the Ross Sea and Indian Ocean during such extremes. In this way, the atmospheric wave train acquires a more southern spread over South America, reaching tropical latitudes after the SIE extremes. In non‐SIE extreme periods, the atmospheric wave train has a more zonal spread and reaches only the extratropical latitudes of the continent.
The effects of non‐stationarity on SPI for operational drought monitoring in Europe
Authors: Cammalleri Carmelo , Spinoni Jonathan , Barbosa Paulo , Toreti Andrea , Vogt Jürgen V.
Published: October 2021

It is a good practice to follow common guidelines in the computation of Standardized Precipitation Index (SPI) data sets as part of operational drought monitoring systems. In the European Drought Observatory (https://edo.jrc.ec.europa.eu/), reference statistics are computed following the World Meteorological Organization Guidelines on the Calculation of Climate Normals, where a definition of the reference period for monitoring applications is introduced as the most recent 30‐year period finishing in a year ending with 0. In this study, the temporal consistency of the SPI time series computed using the fifth‐generation European Centre for Medium‐range Weather Forecast reanalyses model precipitation data set is tested over Europe to quantify the effect of the transition from one baseline period (1981–2010) to another (1991–2020) and to evaluate the capability of these static baselines to reproduce the behaviour of non‐stationary SPIs (nSPIs). The results of the comparison suggest that the threshold commonly used to identify droughts (SPI = −1) is only marginally affected by the change in reference period (mean absolute deviation, MAD = 0.15 ± 0.1) for short‐term SPI, whereas larger differences (MAD up to 0.6) can be observed over certain areas (i.e., Southern Italy and Eastern Europe) for longer accumulation periods (i.e., SPI‐9 or SPI‐12). Examples show that changes in drought classification from extremely dry (SPI < −2) to moderately dry (SPI < −1) are not uncommon, which may lead to misinterpretation by users. Finally, analyses against nSPI highlight an overall good correspondence between stationary and nSPIs, even if both static baselines displayed difficulties in reliably capturing the magnitude of nSPI for the entire 10‐year period for which they should be used. In this regard, it has been demonstrated that more spatially uniform results can be achieved with 5‐year updates, with a good matching (MAD <0.25) for SPI‐1 and an acceptable matching (MAD < 0.50) for SPI‐12 over more than 80% of Europe.
Heatwaves in Southern Armenia in the context of climate change
Authors: Galstyan Hrachuhi , Shiri Babak , Safaryan Tatevik
Published: October 2021

The quantitative and qualitative evaluations of long‐term trends and spatial distribution of heatwaves (HW) are carried out in Southern Armenia (Syunik province). For this purpose, the daily average maximum air temperature data (𝑇max) from four meteorological stations (Sisian, Goris, Kapan, and Meghri) are studied for the 1936–2019 period. The HW catchment algorithm and a new concept of HW (which is called potential HWs [PHWs]) are developed. The presence of trends and their significance for different HW measures are assessed utilizing linear and exponential trends, Sen's slope, and Mann–Kendall (MK) trend test. The results show that HWs become increasingly frequent and intense. Moreover, they have extended duration, as they emerge earlier and fade later in Syunik province. Significant variation trends of HW are observed (e.g., the frequency of HWs increased up to five times), especially after the 1990s in southern and central parts of the province. Contrary to this, relatively weaker or no trends occurred in the northern parts. Our methodological approach successfully determines the HW measures' trends in the province based on the relief features and altitude differences. The outcomes highlight their notable impact on the progression of HW. Overall, this study provides significant insights into understanding HW's variations and their transformation in the mountainous areas.
Influence of Polymer Gate Dielectric on Organic Field‐Effect Transistors: Interdependence of Molecular Weight, Solvent Polarity, and Surface Energy—A Case Study with PMMA and Pentacene
Authors: V. R. Rajeev , Pillai Sradha , Nunzi Jean‐Michel , Unni K. N. Narayanan
Published: October 2021

The semiconductor/dielectric interface controls the performance of organic field‐effect transistors (OFETs). Herein, the influence of both the molecular weight and the polarity of the solvent of a poly(methyl methacrylate) (PMMA)‐based gate dielectric on the performance of pentacene OFETs is systematically investigated, by studying surface energy, surface roughness, morphology, leakage current, and capacitance of the dielectric. Various existing views on the role of the surface energy are considered while deriving a correlation. Larger pentacene grains are observed when the film is grown on high molecular weight‐PMMA films cast from high dipole moment‐solvent. The electrical properties of the corresponding OFETs show great improvement compared to those of OFETs fabricated with low molecular weight‐PMMA film as the gate dielectric, irrespective of the solvent. The authors attribute this enhanced performance to the increased surface energy of the polymeric dielectric which turns out to be a strong function of its molecular weight and the dipole moment of the solvent. Bias‐stress measurements on the OFETs confirm this correlation.
Smart city policy in developing countries: Case study of the new administrative capital in Egypt
Authors: Ali Mohamed Abouelhassan
Published: October 2021

Smart city policy has been employed through the last two decades to accommodate the urban modifications, which utilize information technology, innovation, and smart management for urban governance. The study aims to discuss the case study for the Egyptian condition's smart city model and policy, using policy narrative analysis for the fourth‐generation cities and the pioneer model. From a policy perspective, the Egyptian smart city model's contribution has received little attention from previous studies dealing with the smart city in the Egyptian context. Therefore, the present research explores presenting and discuss the Egyptian smart city model as an innovation development policy perspective. The analysis employs The new administrative capital as a case study. The policy documents and the online interview with Administrative Capital for Urban Development Company officials have been used. Our findings found that the NAC might be the successful path for the smart city model inside the Egyptian context, considering some implementation policy recommendations. The NAC's innovative components deem a prompt to invigorate the regional and national levels' innovation process. The Egyptian case study's smart city model uses a holistic strategy with a quadruple helix to develop the urban system to attract knowledge and innovation.
Fire retarded polyurethane foam composites based on steel slag/ammonium polyphosphate system: A novel strategy for utilization of metallurgical solid waste
Authors: Yang Sujie , Liu Xiuyu , Tang Gang , Long Hongming , Wang Bibo , Zhang Hao , Ji Yilong , Yang Yadong
Published: October 2021

A series of FR‐RPUF composites were prepared by a one‐step water foaming process with ammonium polyphosphate (APP) and steel slag (SS) as flame retardants. Thermogravimetric analysis (TG), limiting oxygen index (LOI), UL‐94 vertical combustion test, microscale combustion calorimetry (MCC), TG‐Fourier transform infrared spectrometry (TG‐FTIR), scanning electron microscopy (SEM), Raman spectra and FTIR were used to investigate the thermal stability, flame retardancy, combustion performance, gas phase products, and char residue morphology of FR‐RPUF composites. TG test results showed that the initial decomposition temperature (T‐5wt%) and char residue rate at 700°C of RPUF/APP/SS composites were significantly enhanced by the addition of APP and SS, and the thermal stability of the composites was improved. Flame retardant test results confirmed the significantly increased LOI values of RPUF/APP/SS composites with V‐0 rating. TG‐FTIR also confirmed the obviously decreased release of toxic gases and flammable gases in the combustion of RPUF/APP/SS composites. SEM and Raman spectra of char residues for the composites suggested that APP/SS system improved the compactness and graphitization degree of char layer for RPUF/APP/SS composite. The above researches provide a new strategy for the utilization of SS in fire safety engineering.
Mitochondria govern histone acetylation in colorectal cancer
Authors: Ohshima Kenji , Oi Ryo , Nojima Satoshi , Morii Eiichi
Published: October 2021

Cancer cells have an altered metabolic state that supports their growth, for example, aerobic glycolysis, known as the Warburg effect. Colorectal cancer cells have been reported to exhibit the Warburg effect and mainly rely on glycolysis for progression and have dysfunctional mitochondria. So far, how mitochondrial function influences the properties of colorectal cancer cells is unclear. Here, we demonstrated that mitochondria maintain histone acetylation, in particular acetylated histone H3 lysine 27 (H3K27ac), a surrogate epigenomic marker of active super‐enhancers, in colorectal cancer cells. Immunohistochemistry was used on human colorectal adenocarcinoma specimens and showed that mitochondrial mass and H3K27ac marks were increased in adenocarcinoma lesions compared with adjacent non‐neoplastic mucosa. Immunoblotting after using inhibitors of the mitochondrial respiratory complex or mitochondrial DNA‐depleted human colorectal cancer cells revealed that mitochondria maintained pan‐histone acetylation and H3K27ac marks. Notably, anchorage‐independent growth, a feature of cancer, increased mitochondrial mass and H3K27ac marks in human colorectal cancer cells. These findings indicate that mitochondria in human colorectal cancer cells are not dysfunctional, as formerly believed, but function as inducers of histone acetylation. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Perinatal outcomes after selective feticide via umbilical cord occlusion in complicated monochorionic pregnancies: A systematic review and meta‐analysis
Authors: Wu Tianchen , Chen Ziyi , Yin Xiaohan , Shi Huifeng , Niu Jieqiong , Xie Jialei , Wei Yuan , Wang Xiaoli
Published: October 2021

Objective

We aimed to compare perinatal outcomes between umbilical cord occlusion techniques in monochorionic pregnancies, including umbilical cord ligation, fetoscopic laser coagulation, interstitial laser coagulation, bipolar cord occlusion, radiofrequency ablation, and microwave ablation.

Methods

This study was registered with PROSPERO (CRD42020158861). PubMed, Web of Science, Cochrane Library, and Embase were searched for studies published up to May 2020. The DerSimonian‐Laird random‐effects model was used for the meta‐analysis. Subgroup analyses were performed to compare the outcomes among the six techniques. Meta‐regression was used to adjust for confounders.

Results

Thirty‐four studies with 1646 participants were included. The overall survival was 76.5% after umbilical cord ligation, 78.8% after fetoscopic laser coagulation, 60.3% after interstitial laser coagulation, 79.2% after bipolar cord occlusion, 77.5% after radiofrequency ablation, and 75.0% after microwave ablation. Subgroup comparison showed the rates of overall survival and preterm premature rupture of membranes were not significant different among six techniques. However, rates of fetal loss, premature birth, live birth, and neonatal death differed significantly among the six groups.

Conclusions

The choice of umbilical cord occlusion techniques will affect perinatal outcomes. We suggested that the choice of umbilical cord occlusion techniques should fully consider these differences among techniques.
What would I do? Perspectives on the factors underlying Lynch syndrome genetic testing and results sharing decisions for high‐risk colorectal cancer patients
Authors: Tiernan Gabriella , Freeman Victoria , Morrow April , Hogden Emily , Canfell Karen , Kang Yoon‐Jung , Taylor Natalie
Published: October 2021

Objective

Universal tumour testing for Lynch syndrome (LS) in all incident colorectal cancers (CRCs) and sequential diagnostic genetic testing is cost‐effective in Australia. Because of this, our study aimed to understand factors underlying possible decisions faced by tumour test‐positive CRC patients and their at‐risk relatives throughout the LS diagnosis pathway.

Methods

Semi‐structured telephone interviews were conducted with 23 participants, using four hypothetical scenarios. Vignette‐guided closed‐ and open‐ended questions asked about LS genetic testing uptake, discussing diagnosis with at‐risk relatives, and risk‐reducing interventions. Personal perspectives on genetic testing were collected pre‐post vignette discussion. Inductive thematic analysis was performed on open‐ended questions. Decisional pathway diagrams were developed to convey factors influencing complex decision‐making processes.

Results

Participant responses incorporated unfolding scenario information, resulting in three decision themes: (1) wanting to know one's LS status; (2) informing family about LS; (3) navigating risk‐reducing interventions. Across all themes, ‘knowledge’ emerged as a facilitator, and ‘negative emotional experience’ as a barrier. Personal supportive views toward genetic testing increased post‐interview.

Conclusions

When communicating with tumour test‐positive CRC patients or their relatives about LS genetic testing, providing guidance/resources to inform decisions around risk‐reducing interventions and informing family members is critical. Scenario‐driven interviews provide insight into what individuals might do when facing complex healthcare decisions and could aid informed decision‐making. This approach may be applicable in other conditions, particularly with mainstreaming being increasingly introduced into the genetic context.
Effects of Ga on Mechanical Properties and Microstructure of Cu–Sn–Ti Filler
Authors: Li Hailing , Chen Ji , Cui Bing , Fu Yucan , Zhao Dan , Li Yujia , Xu Dong
Published: October 2021

To solve a series of problems of Cu–Sn–Ti fillers, Ga is added to the fillers to promote its mechanical properties and microstructure. The metallographic structure of Cu–Sn–Ti–xGa filler metals is detected by optical microscope. Energy dispersive spectroscopy (EDS) areal, X‐ray diffraction (XRD), and differential thermal analysis (DSC) are used to analyze the morphology and microstructure of the fillers. The results show that doped Ga can significantly decrease the melting point and increase mechanical properties of the fillers. The shear strength of the filler metals with 1% Ga content is 160% higher than without Ga. In addition, it is also observed that a small amount of Ga refine the CuSnTi filler metals matrix structure. The diffusion of elements in the filler metals is detected. Compared with Sn solid solution, Ga tends to form a solid solution with Cu. When the Ga content is 2 wt%, the shear strength of the filler metal decreases due to the appearance of coarse crystals at the bottom of the dimple. Through the study of the reaction layer between diamond and filler metal, it is found that Ga can increase the thickness of the interface reaction layer.
Directly Confirming the Z1/2 Center as the Electron Trap in SiC Through Accessing the Nonradiative Recombination
Authors: Gu Yuxiang , Shi Lin , Luo Jun-Wei , Li Shu-Shen , Wang Lin-Wang
Published: October 2021

SiC is an important wide‐bandgap semiconductor for high‐power electronics and high‐temperature applications. Its Z
1/2 center, recognized as a carrier lifetime killer, has been extensively studied as it is a key issue impeding many applications of SiC. It is well established that the Z
1/2 center originates from carbon vacancies (VC), but direct access to the microscopic mechanism underlying its nonradiative recombination process is lacking. Herein, to consolidate such identification, the multiphonon‐assisted nonradiative recombination rates of previously proposed different candidates of the Z
1/2 center are evaluated by performing first‐principles calculations. The calculated electron transition cross sections of the VC ( at the k‐site and at the h‐site) are in accordance with the experimental values [from to ] for the Z
1/2 center. However, all of the other candidates are orders of magnitudes smaller in transition cross sections. This provides further evidence that the carbon vacancy (VC) is the Z
1/2 center from the electron transition cross sections. However, it is also found that the hole transition cross sections of the VC are very small. Various hypotheses are provided to consolidate this fact with the conclusion that Z
1/2 is the carrier lifetime killer.
Garcinia kola and garcinoic acid suppress SARS‐CoV‐2 spike glycoprotein S1‐induced hyper‐inflammation in human PBMCs through inhibition of NF‐κB activation
Authors: Olajide Olumayokun A , Iwuanyanwu Victoria U , Lepiarz‐Raba Izabela , Al‐Hindawi Alaa A , Aderogba Mutalib A , Sharp Hazel L , Nash Robert J
Published: October 2021

Symptoms and complications associated with severe SARS‐CoV‐2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS‐CoV‐2 spike protein S1‐induced increased production of pro‐inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS‐CoV‐2 spike protein S1‐stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 μg/ml) and garcinoic acid (1.25, 2.5, and 5 μM) significantly reduced SARS‐CoV‐2 spike protein S1‐induced secretion of TNFα, IL‐6, IL‐1β, and IL‐8 in PBMCs. In‐cell western assays showed that pre‐treatment with Garcinia kola extract and garcinoic acid reduced expressions of both phospho‐p65 and phospho‐IκBα proteins, as well as NF‐κB DNA binding capacity and NF‐κB‐driven luciferase expression following stimulation of PBMCs with spike protein S1. Furthermore, pre‐treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS‐CoV‐2 spike protein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm in severe SARS‐CoV‐2 and other coronavirus infections.
Contributions of downstream baroclinic development to strong Southern Hemisphere cut‐off lows
Authors: Pinheiro Henri R. , Hodges Kevin I. , Gan Manoel A. , Ferreira Sergio H. S. , Andrade Kelen M.
Published: October 2021

Cut‐Off Lows (COLs) in the Southern Hemisphere and the mechanisms involved in their development are investigated in detail using the eddy kinetic energy (EKE) budget applied to data from the ERA‐Interim reanalysis. This approach considers the most important processes that are typical for the evolution of midlatitude disturbances such as the baroclinic (BRC) and barotropic (BRT) conversions, and the ageostrophic flux convergence (AFC), known as downstream development. Composites of the volume‐integrated EKE and its components are evaluated based on the 200 most intense SH COLs (>98th percentile) observed in a 36‐year period. Results show that the AFC together with the BRC conversion are the most important contributors to the EKE growth for the COLs, characterizing the downstream baroclinic development. The AFC plays an important role in genesis and intensification phases of the COLs, while the BRC conversion is important for the system maintenance. The dissipation of the COLs occurs due to dispersive fluxes (ageostrophic flux divergence) together with other processes not directly computed in the EKE equation, such as friction and latent heat release which are problematic in reanalysis datasets. The BRT conversion contributes negatively to the COL development by transferring EKE to the zonal flow kinetic energy, though this is not enough to dampen the intensification. Regional differences were found in the energetics, indicating that COLs originating upstream of the continents are clearly dominated by ageostrophic fluxes, while the systems over the Australian region are mostly driven by baroclinic processes.
Constrained hierarchical Bayesian model for latent subgroups in basket trials with two classifiers
Authors: Takeda Kentaro , Liu Shufang , Rong Alan
Published: October 2021

The basket trial in oncology is a novel clinical trial design that enables the simultaneous assessment of one treatment in multiple cancer types. In addition to the usual basket classifier of the cancer types, many recent basket trials further contain other classifiers like biomarkers that potentially affect the clinical outcomes. In other words, the treatment effects in those baskets are often categorized by not only the cancer types but also the levels of other classifiers. Therefore, the assumption of exchangeability is often violated when some baskets are more sensitive to the targeted treatment, whereas others are less. In this article, we propose a constrained hierarchical Bayesian model for latent subgroups (CHBM‐LS) to deal with potential heterogeneity of treatment effects due to both the cancer type (first classifier) and another classifier (second classifier) in basket trials. Different baskets defined by multiple cancer types and multiple levels of the second classifier are aggregated into subgroups using a latent subgroup modeling approach. Within each latent subgroup, the treatment effects are similar and approximately exchangeable to borrow information. The CHBM‐LS approach evaluates the treatment effect for each basket while allowing adaptive information borrowing across the baskets by identifying latent subgroups. The simulation study shows that the CHBM‐LS approach outperforms other approaches with higher statistical power and better‐controlled type I error rates under various scenarios with heterogeneous treatment effects across baskets.
Torsional design method used in Eurasia region: A comparative study
Authors: Ju Hyunjin , Lee Deuckhang , Kim Kil‐Hee , Yerzhanov Meirzhan , Zhang Dichuan , Kim Jong R.
Published: October 2021

This study conducted an extensive review and evaluation of torsional design methods specified in SNiP and other international building codes. Unlike thin‐walled tube approach utilized as a key basis of design expressions in ACI 318, CSA, and Eurocode 2, skew‐bending theory is still adopted as torsional design methods specified in SNiP code used through Eurasia region. This comparative study is timely required since there are radical code changes in leading Eurasia countries, such as Russia, Kazakhstan, and Uzbekistan, toward Eurocode from SNiP code. To this end, a total of 253 reinforced concrete (RC) specimens that failed in pure torsion were collected from the literature to compare the analytical accuracy of the torsional design methods specified in various design codes. It was found that the torsional design methods specified in SNiP and CSA codes can estimate the torsional strengths of RC members with good level of accuracy, while Eurocode 2 provided quite conservative results. In addition, the maximum limitations stipulated in each design code on the compressive strength of concrete and yield strength of reinforcements are of importance for the safe and efficient torsional design due to interrelation between reinforcement ratios considering materials strengths and inclination angle of compressive concrete strut.
Pooled Testing and Its Applications in the COVID-19 Pandemic
Authors: Aldridge Matthew , Ellis David
Published: October 2021

When testing for a disease such as COVID-19, the standard method is individual testing: we take a sample from each individual and test these samples separately. An alternative is pooled testing (or ‘group testing’), where samples are mixed together in different pools, and those pooled samples are tested. When the prevalence of the disease is low and the accuracy of the test is fairly high, pooled testing strategies can be more efficient than individual testing. In this chapter, we discuss the mathematics of pooled testing and its uses during pandemics, in particular the COVID-19 pandemic. We analyse some one- and two-stage pooling strategies under perfect and imperfect tests, and consider the practical issues in the application of such protocols.
Epidemic Compartmental Models and Their Insurance Applications
Authors: Feng Runhuan , Garrido José , Jin Longhao , Loke Sooie-Hoe , Zhang Linfeng
Published: October 2021

Our society’s efforts to fight pandemics rely heavily on our ability to understand, model and predict the transmission dynamics of infectious diseases. Compartmental models are among the most commonly used mathematical tools to explain reported infections and deaths. This chapter offers a brief overview of basic compartmental models as well as several actuarial applications, ranging from product design and reserving of epidemic insurance, to the projection of healthcare demand and the allocation of scarce resources. The intent is to bridge classical epidemiological models with actuarial and financial applications that provide healthcare coverage and utilise limited healthcare resources during pandemics.
Searching for leptoquarks at future muon colliders
Authors: Asadi Pouya , Capdevilla Rodolfo , Cesarotti Cari , Homiller Samuel
Published: October 2021

Abstract

A high energy muon collider can provide new and complementary discovery potential to the LHC or future hadron colliders. Leptoquarks are a motivated class of exotic new physics models, with distinct production channels at hadron and lepton machines. We study a vector leptoquark model at a muon collider with$$ \sqrt{s} $$s= 3,14 TeV within a set of both UV and phenomenologically motivated flavor scenarios. We compute which production mechanism has the greatest reach for various values of the leptoquark mass and the coupling between leptoquark and Standard Model fermions. We find that we can probe leptoquark masses up to an order of magnitude beyond$$ \sqrt{s} $$swith perturbative couplings. Additionally, we can also probe regions of parameter space unavailable to flavor experiments. In particular, all of the parameter space of interest to explain recent low-energy anomalies inBmeson decays would be covered even by a$$ \sqrt{s} $$s= 3 TeV collider.
Comments on the holographic description of Narain theories
Authors: Dymarsky Anatoly , Shapere Alfred
Published: October 2021

Abstract

We discuss the holographic description of Narain U(1)c× U(1)c conformal field theories, and their potential similarity to conventional weakly coupled gravitational theories in the bulk, in the sense that the effective IR bulk description includes “U(1) gravity” amended with additional light degrees of freedom. Starting from this picture, we formulate the hypothesis that in the large central charge limit the density of states of any Narain theory is bounded by below by the density of states of U(1) gravity. This immediately implies that the maximal value of the spectral gap for primary fields is ∆1 = c/(2πe). To test the self-consistency of this proposal, we study its implications using chiral lattice CFTs and CFTs based on quantum stabilizer codes. First we notice that the conjecture yields a new bound on quantum stabilizer codes, which is compatible with previously known bounds in the literature. We proceed to discuss the variance of the density of states, which for consistency must be vanishingly small in the large-c limit. We consider ensembles of code and chiral theories and show that in both cases the density variance is exponentially small in the central charge.
A new branch of inflationary speed limits
Authors: Mathis Dayshon , Mousatov Alexandros , Panagopoulos George , Silverstein Eva
Published: October 2021

Abstract

We present a new mechanism for inflation which exhibits a speed limit on scalar motion, generating accelerated expansion even on a steep potential. This arises from explicitly integrating out the short modes of additional fields coupled to the inflaton ϕ via a dimension six operator, yielding an expression for the effective action which includes a nontrivial (logarithmic) function of (∂ϕ)2. The speed limit appears at the branch cut of this logarithm arising in a large flavor expansion, similarly to the square root branch cut in DBI inflation arising in a large color expansion. Finally, we describe observational constraints on the parameters of this model.
Primitive normalisers in quasipolynomial time
Authors: Chang Mun See , Roney-Dougal Colva M.
Published: October 2021

The normaliser problem has as input two subgroups H and K of the symmetric group $$\mathrm {S}_n$$

S
n

, and asks for a generating set for $$N_K(H)$$

N
K

(
H
)

: it is not known to have a subexponential time solution. It is proved in Roney-Dougal and Siccha (Bull Lond Math Soc 52(2):358–366, 2020) that if H is primitive, then the normaliser problem can be solved in quasipolynomial time. We show that for all subgroups H and K of $$\mathrm {S}_n$$

S
n

, in quasipolynomial time, we can decide whether $$N_{\mathrm {S}_n}(H)$$

N

S
n

(
H
)

is primitive, and if so, compute $$N_K(H)$$

N
K

(
H
)

. Hence we reduce the question of whether one can solve the normaliser problem in quasipolynomial time to the case where the normaliser in $$\mathrm {S}_n$$

S
n

is known not to be primitive.
MicroRNA-34a: the bad guy in age-related vascular diseases
Authors: Raucci Angela , Macrì Federica , Castiglione Stefania , Badi Ileana , Vinci Maria Cristina , Zuccolo Estella
Published: October 2021

The age-related vasculature alteration is the prominent risk factor for vascular diseases (VD), namely, atherosclerosis, abdominal aortic aneurysm, vascular calcification (VC) and pulmonary arterial hypertension (PAH). The chronic sterile low-grade inflammation state, aliasinflammaging, characterizes elderly people and participates in VD development. MicroRNA34-a (miR-34a) is emerging as an important mediator ofinflammagingand VD. miR-34a increases with aging in vessels and induces senescence and the acquisition of the senescence-associated secretory phenotype (SASP) in vascular smooth muscle (VSMCs) and endothelial (ECs) cells. Similarly, other VD risk factors, including dyslipidemia, hyperglycemia and hypertension, modify miR-34a expression to promote vascular senescence and inflammation. miR-34a upregulation causes endothelial dysfunction by affecting ECs nitric oxide bioavailability, adhesion molecules expression and inflammatory cells recruitment. miR-34a-induced senescence facilitates VSMCs osteoblastic switch and VC development in hyperphosphatemia conditions. Conversely, atherogenic and hypoxic stimuli downregulate miR-34a levels and promote VSMCs proliferation and migration during atherosclerosis and PAH.MiR34agenetic ablation or miR-34a inhibition by anti-miR-34a molecules in different experimental models of VD reduce vascular inflammation, senescence and apoptosis through sirtuin 1 Notch1, and B-cell lymphoma 2 modulation. Notably, pleiotropic drugs, like statins, liraglutide and metformin, affect miR-34a expression. Finally, human studies report that miR-34a levels associate to atherosclerosis and diabetes and correlate with inflammatory factors during aging. Herein, we comprehensively review the current knowledge about miR-34a-dependent molecular and cellular mechanisms activated by VD risk factors and highlight the diagnostic and therapeutic potential of modulating its expression in order to reduceinflammagingand VD burn and extend healthy lifespan.
A higher non-severe hypoglycaemia rate is associated with an increased risk of subsequent severe hypoglycaemia and major adverse cardiovascular events in individuals with type 2 diabetes in the LEADER study
Authors: Heller Simon R. , Geybels Milan S. , Iqbal Ahmed , Liu Lei , Wagner Lily , Chow Elaine
Published: October 2021

Aims/hypothesis

Hypoglycaemia is a common side effect of insulin and some other antihyperglycaemic agents used to treat diabetes. Severe hypoglycaemia has been associated with adverse cardiovascular events in trials of intensive glycaemic control in type 2 diabetes. The relationship between non-severe hypoglycaemic episodes (NSHEs) and severe hypoglycaemia in type 2 diabetes has been documented. However, an association between more frequent NSHEs and cardiovascular events has not been verified. This post hoc analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial aimed to confirm whether there is an association between NSHEs and severe hypoglycaemic episodes in individuals with type 2 diabetes. In addition, the possible association between NSHEs and major adverse cardiac events (MACE), cardiovascular death and all-cause mortality was investigated.

Methods

LEADER was a double-blind, multicentre, placebo-controlled trial that found that liraglutide significantly reduced the risk of MACE compared with the placebo. In this post hoc analysis, we explored, in all LEADER participants, whether the annual rate of NSHEs (defined as self-measured plasma glucose <3.1 mmol/l [56 mg/dl]) was associated with time to first severe hypoglycaemic episode (defined as an episode requiring the assistance of another person), time to first MACE, time to cardiovascular death and time to all-cause mortality. Participants with <2 NSHEs per year were used as reference for HR estimates. Cox regression with a time-varying covariate was used.

Results

We demonstrate that there is an association between NSHEs (2–11 NSHEs per year and ≥12 NSHEs per year) and severe hypoglycaemic episodes (unadjusted HRs 1.98 [95% CI 1.43, 2.75] and 5.01 [95% CI 2.84, 8.84], respectively), which was consistent when baseline characteristics were accounted for. Additionally, while no association was found between participants with 2–11 NSHEs per year and adverse cardiovascular outcomes, higher rates of NSHEs (≥12 episodes per year) were associated with higher risk of MACE (HR 1.50 [95% CI 1.01, 2.23]), cardiovascular death (HR 2.08 [95% CI 1.17, 3.70]) and overall death (HR 1.80 [95% CI 1.11, 2.92]).

Conclusions/interpretation

The analysis of data from the LEADER trial demonstrated that higher rates of NSHEs were associated with both a higher risk of severe hypoglycaemia and adverse cardiovascular outcomes in individuals with type 2 diabetes. Therefore, irrespective of the cause of this association, it is important that individuals with high rates of hypoglycaemia are identified so that the potentially increased risk of cardiovascular events can be managed and steps can be taken to reduce NSHEs.

Trial registration

ClinicalTrials.gov (NCT01179048).

Graphical abstract
Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle
Authors: Sarabhai Theresia , Koliaki Chrysi , Mastrototaro Lucia , Kahl Sabine , Pesta Dominik , Apostolopoulou Maria , Wolkersdorfer Martin , Bönner Anna C. , Bobrov Pavel , Markgraf Daniel F. , Herder Christian , Roden Michael
Published: October 2021

Aims/hypothesis

Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling.

Methods

In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals.

Results

SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05).

Conclusions/interpretation

Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling.

Trial registration

ClinicalTrials.gov.NCT01736202.

Funding

German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.

Graphical abstract
A non-cooperative game theory approach to cost sharing in networks
Authors: Hinojosa M. A. , Caro A.
Published: October 2021

This paper considers networks in which nodes have communication needs between them. The cost of building or maintaining an edge with a given capacity is the same across any pair of agents. It is known that feasibility is reached by any maximal-capacity spanning tree. A multi-stage non-cooperative game is considered in which, at each stage, every agent simultaneously decides either to propose building a connection to another agent or to wait for a better opportunity. The required capacity between any pair of agents can be seen as being to their benefit if and only if, in the resulting tree, there exists a path between them such that every edge provides at least this required capacity. On the other hand, the agents who decide to connect have to pay for the link by equally splitting the cost. The problem is analyzed in a context in which the preferences of the agents regarding benefits and costs are lexicographic. The concepts of capacity synthesis equilibrium (CSE) and strong capacity synthesis equilibrium (strong CSE) are introduced and a mechanism to reach some of these equilibria is presented. We also analyze CSEs and strong CSEs in relation to the Nash equilibria of the benefit capacity synthesis game.
Luteirhabdus pelagi gen. nov., sp. nov., a novel member of the family Flavobacteriaceae, isolated from the West Pacific Ocean
Authors: Ren Wen-Ting , Meng Fan-Xu , Guo Li-Li , Sun Li , Xu Xue-Wei , Zhou Peng , Wu Yue-Hong
Published: October 2021

A Gram-stain-negative, aerobic, and yellow-pigmented bacterium, designated A3-108T, was isolated from seawater of the West Pacific Ocean. Cells were non-motile and rod-shaped, with carotenoid-type pigments. Strain A3-108Tgrew at pH 6.0–8.5 (optimum 6.5) and 15–40 °C (optimum 28 °C), in the presence of 0.5–10% (w/v) NaCl (optimum 1.0%). It possessed the ability to produce H2S. Based on the 16S rRNA gene analysis, strain A3-108Texhibited highest similarity withAureisphaera salinaA6D-50T(90.6%). Phylogenetic analysis shown that strain A3-108Taffiliated with members of the familyFlavobacteriaceaeand represented an independent lineage. The principal fatty acids were iso-C15:0, iso-C17:03-OH, iso-C15:1G, and summed feature 3 (C16:1ω7cand/or C16:1ω6c). The sole isoprenoid quinone was MK-6. The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified aminolipid and one unidentified lipid. The ANIb, in silico DDH and AAI values among the genomes of strain A3-108Tand three reference strains were 67.3–71.1%, 18.7–22.1%, and 58.8–71.4%, respectively. The G + C content was 41.0%. Distinctness of the phylogenetic position as well as differentiating chemotaxonomic and other phenotypic traits revealed that strain A3-108Trepresented a novel genus and species of the familyFlavobacteriaceae, for which the nameLuteirhabdus pelagigen. nov., sp. nov. is proposed (type strain, A3-108T = CGMCC 1.18821T = KCTC 82563T).