bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid generation of monocyte‐derived antigen‐presenting cells with dendritic cell‐like properties
Authors: Cunningham Sarah , Hackstein Holger
Published: March 2021

Background

One of the major challenges in cellular therapy is the establishment and validation of simple and fast production protocols meeting good manufacturing practice (GMP) requirements. Dendritic cells (DCs) are of particular therapeutic interest, due to their critical role in T cell response initiation and regulation. Conventional wisdom states that DC generation from monocytes is a time‐consuming protocol, taking up to 7–9 days.

Study Design and Methods

This study systematically screened and validated numerous culture components and conditions to identify the minimal requirements, which can give rise to functional monocyte‐derived antigen‐presenting cells (MoAPCs) in less than 48 h (36 h MoAPC). A total of 36 h MoAPCs were evaluated in terms of surface marker expression, endocytic capability, and induction of antigen‐specific T cell expansion via flow cytometry.

Results

Screening of media compositions, glucose concentrations, and surface marker kinetics, particularly DC‐SIGN as a DC‐specific marker, allowed the generation of DC‐like APCs in 36 h (36 h MoAPCs). A total of 36 h MoAPCs displayed a similar phenotype to 48 h MoAPC and standard 7 d MoDCs in terms of HLA‐DP,DQ,DR, CD83, and DC‐SIGN expression, while CD1a was preferentially expressed in standard MoDCs. Functional evaluation revealed that 36 h MoAPCs displayed reduced endocytosis capabilities and IL‐12p70 production. However, 36 h MoAPCs were able to induce T cell expansion both in an allogenic and antigen‐specific setting.

Conclusion

Our results indicate that mature 36 h MoAPCs possess DC‐like capabilities by inducing antigen‐specific T cell responses. This study has important implications for the generation of DC‐based cellular therapies, allowing a more cost and time‐efficient generation of APCs.
A mitogenomic phylogeny of the Entomobryoidea (Collembola): A comparative perspective
Authors: Godeiro Nerivânia Nunes , Bellini Bruno Cavalcante , Ding Nifeng , Xu Cong , Ding Yinhuan , Zhang Feng
Published: March 2021

Mitogenomes have been widely used as markers to reconstruct phylogenies of various groups of arthropods, but specifically for Collembola they have not been useful to resolve the relationships between some families, such as Paronellidae and Entomobryidae. Here, we present a phylogenetic study integrating previously published data and 20 new mitogenomes, totalling 54 species of Entomobryoidea and two external groups. Eight of the nine subfamilies were included, with species from the most representative genera. The new mitogenomes were sequenced, assembled and annotated, resulting in sequences with a length of approximately 14,000 bp. Phylogenetic analyses were conducted based on the 13 protein‐ and 2 rRNAs‐encoding genes of the 56 mitogenomes. Both maximum likelihood (with six different datasets/models) and Bayesian inference analyses were performed. Orchesellidae, Seirinae and Lepidocyrtinae were reaffirmed as monophyletic groups, while the phylogenetic relationships between Paronellidae and Entomobryidae remain confused. A complete resolution of the Entomobryoidea phylogeny will require a comprehensive genomic sampling of the most informative nuclear and mitochondrial markers to finally overcome traditional systematic problems.
An Efficient Multi-Scale Modeling Method that Reveals Coupled Effects Between Surface Roughness and Roll-Stack Deformation in Cold Sheet Rolling
Authors: Zhang Feng , Malik Arif S.
Published: March 2021

In thin-gauge cold rolling of metal sheet, the surface roughness of work rolls (WRs) is known to affect the rolled sheet surface morphology, the required rolling load, and the roll wear. While modeling of rough surfaces using statistical asperity theory has been widely applied to problems involving semi-infinite solids, the application of asperity distributions and their elastic-plastic behavior has not been considered in roll-stack models for cold sheet rolling. In this work, a simplified-mixed finite element method (SM-FEM) is combined with statistical elastic-plastic asperity theory to study contact interference and coupling effects between a rough work roll (WR) surface and the roll-stack mechanics in cold sheet rolling. By mixing equivalent rough surface contact foundations, Hertz foundations, and Timoshenko beam stiffness, an approach is created to efficiently model interactions between the micro-scale asperities and the macro-scale roll-stack deformation. Nonlinearities from elastic-plastic material behavior of the asperities and the sheet, as well as changing contact conditions along the roll length, are also accommodated. Performance of the multi-scale SM-FEM approach is made by comparison with a continuum finite element virtual material model. 3D studies for a 4-high mill reveal new multi-scale coupling behaviors, including nonuniform roughness transfer, and perturbations to the sheet thickness “crown” and contact force profiles. The described multi-scale SM-FEM approach is general and applies to rough surface contact problems involving plates and shear-deformable beams having multiple contact interfaces and arbitrary surface profiles.
Stop-Motion Animation to Model the Analemma
Authors: Elliott Leslie Atkins , Hunter Amanda , Krutz Carl , Moran ShaKayla , Sherrow Elliot
Published: March 2021

The Sun does not return to the same position in the sky every 24 hours. At local noon, for example, the Sun will appear higher in the sky as we move from winter to summer solstice. In addition, and perhaps more surprisingly, solar days (the roughly 24 hours between subsequent local noons) vary in length, causing the Sun to be east or west of its location 24 hours prior. Over a year, this variation traces out a figure 8, known as an analemma, as shown in Fig.1. It can also be seen in the sundial in Fig. 2, where the gnomon incorporates the analemma to produce an accurate reading of local time.
A Rotational Dynamics Laboratory Upgrade
Authors: Bierman J. , Buckley D. , Kemper J. , Greer A.
Published: March 2021

In our first-semester introductory physics laboratory, we have an exercise on rotational dynamics. We have recently upgraded the equipment that we use in that exercise without changing the actual exercise. The new equipment has performed well so far, and we wanted to share what we did with others who may be looking for a relatively inexpensive way to outfit a laboratory on rotational dynamics. We will describe the physics of the exercise and what we ask our students to do. We will describe the components we purchased, what they cost, and how we assembled the apparatus. Finally, we will present some results from the exercise using the apparatus we built.
Bringing the Welcome Home: One Section’s Efforts at Incorporating AAPT’s Diversity and Inclusion Practices
Authors: Dreyfuss Bree Barnett , Marasco David
Published: March 2021

While AAPT and many other physics organizations have been introducing a series of effective practices around diversity and inclusion at the national level in recent years, it was wondered if these were being adopted at the local level. It is hoped that section members and section representatives will decide to further expand the actions of national leadership to make their own section meetings more inclusive. In order to assess if this was in fact the case, a survey on diversity practices that have been used at the national level and can be implemented at the section level was sent to AAPT’s section reps’ mailing list in the spring of 2018, with a follow-up survey in winter 2020. Feedback in both cycles suggested that a guide for section leadership would be useful. The Northern California/Nevada Section has made progress in implementing some of the effective practices from the national meetings into our local section meetings, and we share these efforts in the hope that they assist our fellow sections.
The Pedagogical Power of Wonder Questions
Authors: Lindstrøm Christine
Published: March 2021

There is no shortage of great pedagogical tools available, but many require considerable investment of time and effort (and oftentimes money and equipment), which can be a significant barrier for already time-poor teachers. Wonder Questions is a pedagogical tool that is simple, flexible, and pedagogically powerful in three ways: 1) it supports and stimulates student learning, 2) it models scientists’ behavior, and 3) it can be a powerful motivator for students and teachers alike. In short, Wonder Questions is a task that requires students to produce a question as opposed to an answer. It can be posed in the following way: “Write a Wonder Question. A Wonder Question is something you wonder about after having done the pre-work that is related to it but not necessarily covered by it.” Note that “Wonder Questions” refers to the pedagogical tool, whereas “Wonder Questions” refers to a set of actual student questions.
Converting Physlets and Other Java Programs to JavaScript
Authors: Christian Wolfgang , Belloni Mario , Hanson Robert M. , Mason Bruce , Barbato Lyle
Published: March 2021

Physlets, educational applets developed at Davidson College, are a widely used teaching resource designed to simulate a variety of physical phenomena. Originally, each Physlet was a Java simulation that was embedded in an HTML page as an applet and then customized using JavaScript to simulate a specific physics concept. The use of Java to simulate the physics and HTML + JavaScript to add narrative and to customize the web page allowed teachers to create thousands of Physlet-based illustrations, explorations, and problems. Unfortunately, changes in technology standards have required a drastic change in how these learning resources can be delivered.
Observing Solar Limb Darkening in the Classroom
Authors: Inbanathan S.S.R. , Moorthy K. , S Ashok Kumar
Published: March 2021

The falling temperature of the photosphere with height is responsible for the effect known as limb darkening. The Sun is not equally bright all over the disc. When we observe the Sun towards the limbs, it appears to get darker. Light from the photosphere travels through an absorptive medium. Therefore, one can see only so far into the photosphere. This is the optical depth (Fig. 1). The line of sight at the center sees deeper into the Sun to an optical depth of about 2/3 into the photosphere. In other words, photons that escape from a smaller radius of the photosphere have originated in a hotter region; therefore, they will have a higher intensity. Photons that originate from a larger radius come from a cooler part of the photosphere; therefore, this results in lower intensity. This effect is known as solar limb darkening. In addition, the solar photosphere displays various phenomena that can easily be observed in images obtained with small telescopes, such as sunspots, faculae, and granulation. Limb darkening results from the fact that we are looking into hot gas when we look at the Sun and, as a consequence of this, the brightness of the Sun decreases as one looks from the center of the disc (where we see deeper inside the Sun) towards the limb (where we will not see as deeply into the solar atmosphere because we are looking at a slant through the photospheric material).
Two Differential Mechanisms
Authors: Greenslade Thomas B.
Published: March 2021

About 30 years ago I taught a series of summer enrichment programs for high school physics teachers, using funding from the Howard Hughes Medical Institutes. I deliberately chose teachers from smaller cities and towns who were unlikely to have contact with other physics teachers. One of my more interesting teachers came from a rural area in a far Midwestern state. He was teaching all of the sciences, including physics, and had never had a college course in physics. His technique was to have the students disassemble devices and analyze their operation.
Using Submaximal Exercise Heart Rate for Monitoring Cardiorespiratory Fitness Changes in Professional Soccer Players: A Replication Study
Authors: Altmann Stefan , Neumann Rainer , Härtel Sascha , Woll Alexander , Buchheit Martin
Published: March 2021

Purpose: To assess the value of monitoring changes in fitness in professional soccer players, using changes in heart rate at submaximal intensity (HR12km/h) over the velocity at a lactate concentration of 4 mmol/L (v4mmol/L). The authors reexamined (1) a range of threshold magnitudes, which may improve detecting substantial individual changes and (2) the agreement between changes in these 2 variables. Methods: On at least 2 occasions during different moments of the season, 97 professional soccer players from Germany (first, second, and fourth division) completed an incremental test to determine HR12km/h and v4mmol/L. Optimal thresholds for changes in HR12km/h and v4mmol/L were assessed, using various methods (eg, smallest worthwhile change + typical error [TE], successive reiterations approach). Agreement between both variable changes was examined for the whole sample (225 comparisons), 4 different subgroups (depending on the moment of the season), and in an individual over 6 years (n = 23 tests). Results: Changes of 4.5% and 6.0% for HR12km/h and v4mmol/L, respectively, were rated as optimal to indicate substantial changes in fitness. Depending on the (sub)groups analyzed, these thresholds yielded 0% to 2% full mismatches, 22% to 38% partial agreements, and 60% to 78% full agreements in terms of fitness change interpretation between both variables. Conclusions: When lactate sampling during incremental tests is not possible, practitioners willing to monitor adult professional soccer players’ (Germany; first, second, and fourth division) training status can confidently implement short, 3-minute submaximal runs, with 4.5% changes in HR12km/h being indicative of true substantial fitness changes, with 60% to 78% accuracy. Future studies should investigate the potential role of confounding factors of HR12km/h to improve changes in fitness prediction.
Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy
Authors: Liu Xia , Hartman Celine L. , Li Lingyun , Albert Carolyn J. , Si Fusheng , Gao Aiqin , Huang Lan , Zhao Yangjing , Lin Wenli , Hsueh Eddy C. , Shen Lizong , Shao Qixiang , Hoft Daniel F. , Ford David A. , Peng Guangyong
Published: March 2021

Reprogramming lipid metabolism reverses effector T cell senescence and enhances antitumor immunity in mouse models.
Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection
Authors: Nishio Akira , Bolte Fabian J. , Takeda Kazuyo , Park Nana , Yu Zu-Xi , Park Heiyoung , Valdez Kristin , Ghany Marc G. , Rehermann Barbara
Published: March 2021

The innate immune response of patients with HBV infection to pegylated interferon therapy is reduced by sequestration of PEG–IFN-α/anti-PEG complexes.
Increasing breast milk betaine modulates
Akkermansia
abundance in mammalian neonates and improves long-term metabolic health
Authors: Ribo Silvia , Sánchez-Infantes David , Martinez-Guino Laura , García-Mantrana Izaskun , Ramon-Krauel Marta , Tondo Mireia , Arning Erland , Nofrarías Miquel , Osorio-Conles Óscar , Fernández-Pérez Antonio , González-Torres Pedro , Cebrià Judith , Gavaldà-Navarro Aleix , Chenoll Empar , Isganaitis Elvira , Villarroya Francesc , Vallejo Mario , Segalés Joaquim , Jiménez-Chillarón Josep C. , Bottiglieri Teodoro , Demerath Ellen W. , Fields David A. , Collado María Carmen , Lerin Carles
Published: March 2021

Maternal betaine supplementation during lactation increases breast milk betaine content with beneficial metabolic effects on mouse offspring.
Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor
Authors: Roux Blandine , Vaganay Camille , Vargas Jesse D. , Alexe Gabriela , Benaksas Chaima , Pardieu Bryann , Fenouille Nina , Ellegast Jana M. , Malolepsza Edyta , Ling Frank , Sodaro Gaetano , Ross Linda , Pikman Yana , Conway Amy S. , Tang Yangzhong , Wu Tony , Anderson Daniel J. , Le Moigne Ronan , Zhou Han-Jie , Luciano Frédéric , Hartigan Christina R. , Galinsky Ilene , DeAngelo Daniel J. , Stone Richard M. , Auberger Patrick , Schenone Monica , Carr Steven A. , Guirouilh-Barbat Josée , Lopez Bernard , Khaled Mehdi , Lage Kasper , Hermine Olivier , Hemann Michael T. , Puissant Alexandre , Stegmaier Kimberly , Benajiba Lina
Published: March 2021

Acute myeloid leukemia cells are dependent on the DNA repair function of valosin-containing protein, opening up an avenue for disease treatment.
Knowns and Unknowns of Vitamin B
6
Metabolism in Escherichia coli
Authors: Tramonti Angela , Nardella Caterina , di Salvo Martino L. , Barile Anna , D’Alessio Federico , de Crécy-Lagard Valérie , Contestabile Roberto
Published: March 2021

Vitamin B6 is an ensemble of six interconvertible vitamers: pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL), and their 5′-phosphate derivatives, PNP, PMP, and PLP. Pyridoxal 5′-phosphate is a coenzyme in a variety of enzyme reactions concerning transformations of amino and amino acid compounds.
Stability of SARS-CoV-2 Spike G614 Variant Surpasses That of the D614 Variant after Cold Storage
Authors: Huang Sheng-Yu , Kung Yu-An , Huang Peng-Nien , Chang Sheng-Yun , Gong Yu-Nong , Han Yi-Ju , Chiang Huan-Jung , Liu Kuan-Ting , Lee Kuo-Ming , Chang Chia-Yu , Chang Chia-Ching , Huang Chung-Guei , Shih Shin-Ru
Published: March 2021

It has been observed that variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more stable and infectious after storage at −20°C than at 4°C. A SARS-CoV-2 S-D614G variant is currently the most dominant variant in circulation and is associated with enhanced infectivity.
Supplemental Material: Mud in sandy riverbed deposits as a proxy for ancient fine-sediment supply
Authors: Wysocki Nathaniel , Hajek Elizabeth
Published: March 2021

Details of experimental conditions and analyses.
Osteopathic manipulative treatment to improve exclusive breast feeding at 1 month
Authors: Danielo Jouhier Marie , Boscher Cécile , Roze Jean-Christophe , Cailleau Nicolas , Chaligne Frédéric , Legrand Arnaud , Flamant Cyril , Muller Jean-Baptiste
Published: March 2021

Objective

Previous studies have assessed breastfeeding-support programmes. Among these, osteopathic manipulative treatment (OMT) is a frequently used approach, although without strong evidence of efficacy.

Methods

A double-blind randomised controlled trial was conducted between July 2013 and March 2016. Breastfed term infants were eligible if one of the following criteria was met: suboptimal breastfeeding behaviour, maternal cracked nipples or maternal pain. The infants were randomly assigned to the intervention or the control group. The intervention consisted of two sessions of early OMT, while in the control group, the manipulations were performed on a doll behind a screen. The primary outcome was the exclusive breastfeeding rate at 1 month, which was assessed in an intention-to-treat analysis. Randomisation was computer generated and only accessible to the osteopath practitioner. The parents, research assistants and paediatricians were masked to group assignment.

Results

One hundred twenty-eight mother–infant dyads were randomised, with 64 assigned to each group. In each group, five infants were lost to follow-up. In the intervention group, 31 of 59 (53%) of infants were still exclusively breast fed at 1 month vs 39 of 59 (66%) in the control group, (OR 0.55, 95% CI 0.26 to 1.17; p=0.12). After adjustment for suboptimal breastfeeding behaviour, caesarean section, use of supplements and breast shields, the adjusted OR was 0.44 (95% CI 0.17 to 1.11; p=0.08). No adverse effects were reported in either group.

Conclusion

OMT did not improve exclusive breast feeding at 1 month.

Trial registration number

NCT01890668.
Association between serum fibroblast growth factor 21 level and sight-threatening diabetic retinopathy in Chinese patients with type 2 diabetes
Authors: Jin Shi , Xia Ning , Han Lingling
Published: March 2021

Introduction

We conducted this cross-sectional study to explore the relationship between serum fibroblast growth factor 21 (FGF21) level and sight-threatening diabetic retinopathy (STDR).

Research design and methods

A total of 654 patients with type 2 diabetes were recruited. Diabetic retinopathy (DR) was evaluated by the bilateral retinal photography, and patients were assigned into groups of no DR (NDR) (n=345, 52.75%), non-sight-threatening diabetic retinopathy (NSTDR) (n=207, 31.65%), involving patients with mild or moderate non-proliferative retinopathy (NPDR) and STDR (n=102, 15.60%), including those with severe NPDR or proliferative diabetic retinopathy (PDR). Serum FGF21 levels were quantified by a sandwich ELISA. Patients were divided into quartiles according to their serum FGF21 level.

Results

There was a significant difference in serum FGF21 level among the three groups of patients (p<0.01). Compared with other quartiles (Q1–Q3), the patients in Q4 had a higher prevalence of DR and STDR (p<0.05). Compared with Q1, a positive association was observed between serum FGF21 level and DR in Q3 and Q4 (p<0.01). After adjusting for age, gender and other risk factors, serum FGF21 level in Q4 was found to be associated with increased risk of DR and STDR (p<0.01). Serum FGF21 level was noted as an independent risk factor for DR and STDR (p<0.01). Serum FGF21 level >478.76 pg/mL suggested the occurrence of DR and that level >554.69 pg/mL indicated STDR (p<0.01).

Conclusions

Serum FGF21 level was a biomarker for the risk of developing DR or STDR. The risk of STDR increased when the serum FGF21 level of patients with type 2 diabetes was >554.69 pg/mL.
Vietnam and innovation in COVID-19 testing
Authors: Klingler-Vidra Robyn , Tran Berlin , Uusikyla Ida
Published: March 2021

Vietnam made global headlines for its effective management of the first wave of COVID-19. Now, at the time of writing in Spring 2021, although there are occasional instances of imported cases in the headlines, in Vietnam the country’s battle with the virus is often spoke of in past tense. After all, the country has responded effectively to each wave, by implementing localised, targeted lockdowns in an effort to quell outbreaks, and through a combination of government, business sector and grassroots innovation that lessened the spread of the virus and ameliorated the impact of the lockdown. To give context to the scale of Vietnam’s tremendous response, through June 2020 the country had fewer than 400 cases and 0 deaths. While the ultimate outcome from the pandemic remains to be seen, we believe there are important lessons to be learnt by analysing the determinants of Vietnam’s innovative actions to flatten the curve. In this review, we distil five lessons: (1) a shared purpose is an essential motivator, (2) grassroots and small business entrepreneurs are important innovators, (3) multistakeholder collaboration is a powerful force, (4) contextual innovation is essential, and (5) the state is a key enabler of timely innovation. We focus, in particular, on the case of innovation occurring in affordable COVID-19 test kit development in Vietnam.
Ageing and heterogeneity regarding autism spectrum conditions: a protocol paper of an accelerated longitudinal study
Authors: Geurts Hilde M , Agelink van Rentergem Joost A , Radhoe Tulsi , Torenvliet Carolien , Van der Putten Wikke J , Groenman Annabeth P
Published: March 2021

Introduction

Autism spectrum conditions (ASC) develop early in life and are thought to last a lifetime. However, ASC research has two major knowledge gaps that hinder progression in understanding the concept of ASC and in providing proper support for autistic adults: (1) the majority of knowledge about ASC mainly stems from childhood studies so little is known about older autistic adults and (2) while it is broadly recognised that ASC is a heterogeneous condition, we do not yet understand the differences in trajectories leading to their future outcome. We aim to fill both knowledge gaps.

Methods and analysis

A multistage overlapping cohort design assessing (cognitive) ageing in ASC is designed to obtain an accelerated longitudinal data set. Data, including a multitude of questionnaires, diagnostics and cognitive tests, are collected over four waves within a 10-year time frame. This will provide information regarding actual changes in quality of life, co-occurring health conditions and cognition as well as the possibility to test external validity and temporal stability in newly formed behavioural subtypes. Participants consist of three groups of adults aged 20–90 years: (1) with a clinical diagnosis of ASC, (2) with a clinical diagnosis of attention deficit hyperactivity disorder (ADHD) but no ASC, (3) no ASC/ADHD (ie, comparison group). The sample size differs between waves and instruments. Detailed analysis plans will be preregistered in AsPredicted or at the Open Science Framework.

Ethics and dissemination

Ethical approval for this study was obtained from the ethical review board of the Department of Psychology of the University of Amsterdam (wave 1 2011-PN-1952 and 2013-PN-2668, wave 2 2015-BC-4270, waves 3 and 4 2018-BC-9285). In line with the funding policies of the grant organisation funding this study, future papers will be published open access.
Telomere length is independently associated with all-cause mortality in chronic heart failure
Authors: Romaine Simon P R , Denniff Matthew , Codd Veryan , Nath Mintu , Koekemoer Andrea , Anker Stefan D , Cleland John G , Filippatos Gerasimos , Levin Daniel , Metra Marco , Mordi Ify R , Ouwerkerk Wouter , ter Maaten Jozine M , van Veldhuisen Dirk J , Zannad Faiez , Ng Leong L , van der Harst Pim , Lang Chim C , Voors Adriaan A , Nelson Christopher P , Samani Nilesh J
Published: March 2021

Objective

Patients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance. We therefore sought to determine whether LTL is associated with outcomes in patients with heart failure.

Methods

We measured LTL in patients with heart failure from the BIOSTAT-CHF Index (n=2260) and BIOSTAT-CHF Tayside (n=1413) cohorts. Cox proportional hazards analyses were performed individually in each cohort and the estimates combined using meta-analysis. Our co-primary endpoints were all-cause mortality and heart failure hospitalisation.

Results

In age-adjusted and sex-adjusted analyses, shorter LTL was associated with higher all-cause mortality in both cohorts individually and when combined (meta-analysis HR (per SD decrease in LTL)=1.16 (95% CI 1.08 to 1.24); p=2.66×10−5), an effect equivalent to that of being four years older. The association remained significant after adjustment for the BIOSTAT-CHF clinical risk score to account for known prognostic factors (HR=1.12 (95% CI 1.05 to 1.20); p=1.04×10−3). Shorter LTL was associated with both cardiovascular (HR=1.09 (95% CI 1.00 to 1.19); p=0.047) and non-cardiovascular deaths (HR=1.18 (95% CI 1.05 to 1.32); p=4.80×10−3). There was no association between LTL and heart failure hospitalisation (HR=0.99 (95% CI 0.92 to 1.07); p=0.855).

Conclusion

In patients with heart failure, shorter mean LTL is independently associated with all-cause mortality.
Complete metabolic response in patients with advanced non-small cell lung cancer with prolonged response to immune checkpoint inhibitor therapy
Authors: Ferdinandus Justin , Metzenmacher Martin , Kessler Lukas , Umutlu Lale , Aigner Clemens , Kambartel Karl-Otto , Grünwald Viktor , Eberhardt Wilfried Ernst Erich , Fendler Wolfgang Peter , Herrmann Ken , Faehling Martin , Christoph Daniel Christian
Published: March 2021

Introduction

Immunotherapy is the new standard of care in advanced non-small cell lung cancer (NSCLC). Recently published data show that treatment discontinuation after 12 months of nivolumab treatment is associated with shorter survival. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcomes is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients who have not progressed after 24 months of immunotherapy.

Methods

This is a retrospective analysis of 45 patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose imaging for assessment of residual metabolic activity after at least 24 months. CMR was defined as uptake in tumor lesions below background levels, using mediastinum as a reference.

Results

Out of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first-line patients. Patients with CMR were younger (median 65.7 vs 75.5, p=0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however, median follow-up was only 5.6 (range 0.8–17.0) months.

Conclusion

After a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.
WHO guidance on ethics in outbreaks and the COVID-19 pandemic: a critical appraisal
Authors: Saxena Abha , Bouvier Paul André , Shamsi-Gooshki Ehsan , Köhler Johannes , Schwartz Lisa J
Published: March 2021

In 2016, following pandemic influenza threats and the 2014–2016 Ebola virus disease outbreaks, the WHO developed a guidance document for managing ethical issues in infectious disease outbreaks. In this article, we analyse some ethical issues that have had a predominant role in decision making in response to the current COVID-19 pandemic but were absent or not addressed in the same ways in the 2016 guidance document. A pandemic results in a health crisis and social and political crises both nationally and globally. The ethical implications of these global effects should be properly identified so that appropriate actions can be taken globally and not just in national isolation. Our analysis, which is a starting point to test the broader relevance of the 2016 WHO document that remains the only available guidance document applicable globally, concludes that the WHO guidance should be updated to provide reasoned and thoughtful comprehensive ethics advice for the sound management of the current and future pandemics.
The calibration challenge when inferring longitudinal track profile from the inertial response of an in-service train
Authors: Quirke Paraic , OBrien Eugene J. , Bowe Cathal , Cantero Daniel , Malekjafarian Abdollah
Published: March 2021

An Irish Rail intercity train was instrumented for a period of one month with inertial sensors. In this paper, a novel calibration algorithm is proposed to determine, with reasonable accuracy, vehicle model parameters from the measured vehicle response data. Frequency domain decomposition (FDD) is used to find the dominant frequencies in the captured data. Randomly chosen 2 km data segments are chosen from a number of datasets, thereby averaging out the effects of variations in track longitudinal profile, track stiffness, signal noise and other unknowns. The remaining dominant peaks are taken to be vehicle frequencies. An optimization technique known as Cross Entropy is used to find vehicle mass and stiffness properties that best match modal vehicle eigenfrequencies identified in the frequency analysis. Finally, the calibrated vehicle is run over a measured track profile and the resulting model output is compared to measured data to validate the results.
Superintegrability of Kontsevich matrix model
Authors: Mironov Andrei , Morozov Alexei
Published: March 2021

Many eigenvalue matrix models possess a peculiar basis of observables that have explicitly calculable averages. This explicit calculability is a stronger feature than ordinary integrability, just like the cases of quadratic and Coulomb potentials are distinguished among other central potentials, and we call itsuperintegrability. As a peculiarity of matrix models, the relevant basis is formed by the Schur polynomials (characters) and their generalizations, and superintegrability looks like a property$$\langle character\rangle \,\sim character$$⟨character⟩∼character. This is already known to happen in the most important cases of Hermitian, unitary, and complex matrix models. Here we add two more examples of principal importance, where the model depends onexternal fields: a special version of complex model and the cubic Kontsevich model. In the former case, straightforward is a generalization to the complex tensor model. In the latter case, the relevant characters are the celebratedQSchur functions appearing in the description of spin Hurwitz numbers and other related contexts.
Dynamics of charged particles and magnetic dipoles around magnetized quasi-Schwarzschild black holes
Authors: Narzilloev Bakhtiyor , Rayimbaev Javlon , Abdujabbarov Ahmadjon , Ahmedov Bobomurat , Bambi Cosimo
Published: March 2021

In the present paper, we have investigated the motion of charged particles together with magnetic dipoles to determine how well the spacetime deviation parameter $$\epsilon $$
ϵ
and external uniform magnetic field can mimic the spin of a rotating Kerr black hole. Investigation of charged particle motion has shown that the deviation parameter $$\epsilon $$
ϵ
in the absence of an external magnetic fields can mimic the rotation parameter of the Kerr spacetime up to $$a/M \approx 0.5$$

a
/
M
≈
0.5

. The combination of an external magnetic field and deviation parameter can do even a better job mimicking the rotation parameter up to $$a/M\simeq 0.93$$

a
/
M
≃
0.93

, which corresponds to the rapidly rotating case. Study of the dynamics of the magnetic dipoles around quasi-Schwarzschild black holes in the external magnetic field has shown that there are degeneracy values of the ISCO radius of test particles at $$\epsilon _{cr}>\epsilon \ge 0.35$$

ϵ

cr

>
ϵ
≥
0.35

which may lead to two different values of the innermost stable circular orbit (ISCO) radius. When the deviation parameter is in the range of $$\epsilon \in (-1,\ 1)$$

ϵ
∈
(
-
1
,

1
)

, it can mimic the spin of a rotating Kerr black hole in the range $$a/M \in (0.0537, \ 0.3952)$$

a
/
M
∈
(
0.0537
,

0.3952
)

for magnetic dipoles with values of the magnetic coupling parameter $$\beta \in [-0.25,\ 0.25]$$

β
∈
[
-
0.25
,

0.25
]

in corotating orbits.
A Deep Fourier Neural Network for Seizure Prediction Using Convolutional Neural Network and Ratios of Spectral Power
Authors: Peng Peizhen , Xie Liping , Wei Haikun
Published: March 2021

Epileptic seizure prediction is one of the most used therapeutic adjuvant strategies for drug-resistant epilepsy. Conventional methods usually adopt handcrafted features and manual parameter setting. The over-reliance on the expertise of specialists may lead to weak exploitation of features and low popularization of clinical application. This paper proposes a novel parameterless patient-specific method based on Fourier Neural Network (FNN), where the Fourier transform and backpropagation learning are synthesized to make the predictor more efficient and practical. The employment of FNN is the first attempt in the field of seizure prediction due to its automatic extraction of immanent spectra in epileptic signals. Despite the self-adaptive superiority of FNN, we introduce Convolutional Neural Network (CNN) to further improve its search capability in high-dimensional feature spaces. The study also develops a multi-layer module to estimate spectral power ratios of raw recordings, which optimizes the prediction by enhancing feature diversity. Based on these modules, this paper proposes a two-channel deep neural network: Fourier Ratio Convolutional Neural Network (FRCNN). To demonstrate the reliability of the model, we explain the mathematical meaning of hidden-layer neurons in FRCNN theoretically. This approach is evaluated on both intracranial and scalp EEG datasets. It shows that the predictor achieved a sensitivity of 91.2% and a false prediction rate (FPR) of 0.06[Formula: see text]h[Formula: see text] across intracranial subjects and a sensitivity of 85.4% and an FPR of 0.14[Formula: see text]h[Formula: see text] over scalp subjects. The results indicate that FRCNN enables the convenience of epilepsy treatments while preserving a high degree of precision. In the end, a detailed comparison with the previous methods demonstrates that FRCNN has achieved higher performance and generalization ability.
Design and Development of N-Level Symmetrical Multilevel Inverter Topology with Reduced Switches
Authors: Premkumar K. , Shyam D.
Published: March 2021

In this paper, 11-level multilevel inverter with reduced power switch configuration is developed and investigated. This proposed configuration can be extended for [Formula: see text] levels with the required number of power switches. Comparative analysis between the proposed multilevel inverter topology and well-known existing multilevel inverter topologies is carried out. Fundamental switching angle calculation for the power switches of the proposed topology has been optimized using black widow optimization algorithm technique and also the proposed topology has been tested with the classical multicarrier alternative phase opposition disposition PWM technique. To test the effectiveness of the proposed topology, different tests have been conducted such as testing with different modulation indexes, DC input voltages, load settings and voltage ride-through capabilities. This paper presents various simulation and experimental results under various operating conditions to prove the performance of the proposed multilevel inverter topology.
Gradings allowing wild automorphisms
Authors: Trushin Anton
Published: March 2021

In 2004, Shestakov and Umirbaev proved that the Nagata automorphism of the polynomial algebra in three variables is wild. We fix a [Formula: see text]-grading on this algebra and consider graded-wild automorphisms, i.e. such automorphisms that cannot be decomposed onto elementary automorphisms respecting the grading. We describe all gradings allowing graded-wild automorphisms.
Semirigid GCD domains II
Authors: Zafrullah M.
Published: March 2021

Let [Formula: see text] be an integral domain with quotient field [Formula: see text] throughout[Formula: see text] Call two elements [Formula: see text][Formula: see text]-coprime if [Formula: see text] Call a nonzero non-unit [Formula: see text] of an integral domain [Formula: see text] rigid if for all [Formula: see text] we have [Formula: see text] or [Formula: see text] Also, call [Formula: see text] semirigid if every nonzero non-unit of [Formula: see text] is expressible as a finite product of rigid elements. We show that a semirigid domain [Formula: see text] is a GCD domain if and only if [Formula: see text] satisfies [Formula: see text] product of every pair of non-[Formula: see text]-coprime rigid elements is again rigid. Next, call [Formula: see text] a valuation element if [Formula: see text] for some valuation ring [Formula: see text] with [Formula: see text] and call [Formula: see text] a VFD if every nonzero non-unit of [Formula: see text] is a finite product of valuation elements. It turns out that a valuation element is what we call a packed element: a rigid element [Formula: see text] all of whose powers are rigid and [Formula: see text] is a prime ideal. Calling [Formula: see text] a semi-packed domain (SPD) if every nonzero non-unit of [Formula: see text] is a finite product of packed elements, we study SPDs and explore situations in which a variant of an SPD is a semirigid GCD domain.
Joins of paths and cycles of equal order with sigma chromatic number 2
Authors: Garciano Agnes D. , Lagura Maria Czarina T. , Marcelo Reginaldo M.
Published: March 2021

For a simple connected graph [Formula: see text] let [Formula: see text] be a coloring of [Formula: see text] where two adjacent vertices may be assigned the same color. Let [Formula: see text] be the sum of colors of neighbors of any vertex [Formula: see text] The coloring [Formula: see text] is a sigma coloring of [Formula: see text] if for any two adjacent vertices [Formula: see text] [Formula: see text] The least number of colors required in a sigma coloring of [Formula: see text] is the sigma chromatic number of [Formula: see text] and is denoted by [Formula: see text] A sigma coloring of a graph is a neighbor-distinguishing type of coloring and it is known that the sigma chromatic number of a graph is bounded above by its chromatic number. It is also known that for a path [Formula: see text] and a cycle [Formula: see text] where [Formula: see text] [Formula: see text] and [Formula: see text] if [Formula: see text] is even. Let [Formula: see text] the join of the graphs [Formula: see text], where [Formula: see text] or [Formula: see text] [Formula: see text] and [Formula: see text] is not an odd cycle for any [Formula: see text]. It has been shown that if [Formula: see text] for [Formula: see text] and [Formula: see text] then [Formula: see text]. In this study, we give necessary and sufficient conditions under which [Formula: see text] where [Formula: see text] is the join of copies of [Formula: see text] and/or [Formula: see text] for the same value of [Formula: see text]. Let [Formula: see text] and [Formula: see text] be positive integers with [Formula: see text] and [Formula: see text] In this paper, we show that [Formula: see text] if and only if [Formula: see text] or [Formula: see text] is odd, [Formula: see text] is even and [Formula: see text]; and [Formula: see text] if and only if [Formula: see text] is even and [Formula: see text] We also obtain necessary and sufficient conditions on [Formula: see text] and [Formula: see text], so that [Formula: see text] for [Formula: see text] where [Formula: see text] or [Formula: see text] other than the cases [Formula: see text] and [Formula: see text]
Fast discharge–charge properties of FePS3 electrode for all-solid-state batteries using sulfide electrolytes and its stable diffusion path
Authors: Fujii Yuta , Ito Hiroaki , Miura Akira , Rosero-Navarro Nataly Carolina , Tadanaga Kiyoharu , Lu Li
Published: March 2021

We report the fast discharge–charge cycle of micro-sized FePS3 electrode particles in all-solid-state batteries (ASSBs) using sulfide electrolytes at 80∘C. At a current density of 2.04 mA cm[Formula: see text], corresponding to approximately 1 C, the capacity of the FePS3 electrodes reached [Formula: see text]180 mAh g[Formula: see text] without any electron or lithium-ion conductive additives. Galvanostatic intermittent titration technique (GITT) measurements showed a stable diffusion path of FePS3 represented by the product of the diffusion coefficient and square of the surface area. These electrochemical properties were compared with those of FeS, whose capacity was lower because of its unstable diffusion path.
Fault-Tolerant Formation Tracking Control for Heterogeneous Multiagent Systems with Directed Topology
Authors: Gong Jianye , Ma Yajie , Jiang Bin , Mao Zehui
Published: March 2021

In this paper, the adaptive fault-tolerant formation tracking control problem for a set of heterogeneous unmanned aerial vehicle (UAV) and unmanned ground vehicle (UGV) systems with actuator loss of effectiveness faults is investigated. The cooperative fault-tolerant formation control strategy for UAV and UGV collaborative systems is classified into the altitude consensus control scheme for follower UAVs and the position cooperative formation control scheme for all followers. The altitude consensus control algorithm is designed by utilizing backstepping control technique to drive all UAVs to a desired predefined height. Then, based on synchronization formation error information, the position cooperative formation control algorithm is proposed for all followers to reach the expected position and perform the desired formation configuration. The adaptive fault estimation term is adopted in the designed fault-tolerant formation control algorithm to compensate for the actuator loss of effectiveness fault. Finally, a simulation example is proposed to reveal the validity of the designed cooperative formation tracking control scheme.
Introduction: subsurface sand remobilization and injection
Authors: Hurst Andrew , Grippa Antonio , Silcock Simone Y. , Huuse Mads , Bowman Mike , Cobain Sarah L.
Published: March 2021

Observation of basin-scale networks of sandstone intrusions are described from subsurface studies and outcrop locations. Regional scale studies are prevalent in the volume and two new regionally significant subsurface sand injection complexes are described. Higher resolution studies, both outcrop and subsurface, show the small-scale complexity but high level of connectedness of sandstone intrusions. Discordance with bedding at all scales is diagnostic of sandstone intrusions. The propensity of hydraulic fractures to develop and fill with fluidized sand in a broad range of host rocks is demonstrated by examples from metamorphic and magmatic basement, and lignite. Terminology used to describe sandstone intrusions and other elements of sand injection complexes is diverse.
Hardground, gap and thin black shale: spatial heterogeneity of arrested carbonate sedimentation during the Jenkyns Event (T-OAE) in a Tethyan pelagic Basin (Gerecse Mts, Hungary)
Authors: Müller Tamás , Price Gregory D. , Mattioli Emanuela , Leskó Máté Zs. , Kristály Ferenc , Pálfy József
Published: March 2021

The Jenkyns Event or Toarcian Oceanic Anoxic Event was an episode of severe environmental perturbations reflected in carbon isotope and other geochemical anomalies. Although well studied in the epicontinental basins in NW Europe, its effects are less understood in open marine environments. Here we present new geochemical (carbon isotope, CaCO
3
, [Mn]) and nannofossil biostratigraphic data from the Tölgyhát and Kisgerecse sections in the Gerecse Hills (Hungary). These sections record pelagic carbonate sedimentation near the margin of the Tethys Ocean. A negative carbon isotope excursion of
c.
6‰ is observed in the Tölgyhát section, in a condensed clay and black shale layer where the CaCO
3
content drops in association with the Jenkyns Event. At Kisgerecse, bio- and chemostratigraphic data suggest a gap in the lower Toarcian. The presence of an uppermost Pliensbachian hardground, the absence of the lowermost Toarcian Tenuicostatum ammonite zone and the condensed record of the Jenkyns Event at Tölgyhát, together with a condensed Tenuicostatum Zone and the missing negative carbon isotope anomaly at Kisgerecse, imply arrested carbonate sedimentation. A calcification crisis and sea-level rise together led to a decrease in carbonate production and terrigenous input, suggesting that volcanogenic CO
2
-driven global warming may have been their common cause.