bluuebunny/crossref_metadata_2025 huggingface dataset:
The coding and long noncoding single-cell atlas of the developing human fetal striatum
Authors: Bocchi Vittoria Dickinson , Conforti Paola , Vezzoli Elena , Besusso Dario , Cappadona Claudio , Lischetti Tiziana , Galimberti Maura , Ranzani Valeria , Bonnal Raoul J. P. , De Simone Marco , Rossetti Grazisa , He Xiaoling , Kamimoto Kenji , Espuny-Camacho Ira , Faedo Andrea , Gervasoni Federica , Vuono Romina , Morris Samantha A. , Chen Jian , Felsenfeld Dan , Pavesi Giulio , Barker Roger A. , Pagani Massimiliano , Cattaneo Elena
Published: May 2021

Development of the human striatum revealed

Deep in the brain, the striatum receives and coordinates inputs from other parts of the brain. Bocchi
et al.
surveyed molecular features as the striatum develops in the human brain. Single-cell surveys of long intergenic noncoding RNAs revealed a progenitor for medium spiny neurons and provide insight into evolutionary divergence of this critical part of the brain.

Science
, this issue p.
eabf5759
Reversible fusion-fission fibers
Authors: Cruz-Silva Rodolfo , Elías Ana Laura
Published: May 2021

Reversible assembly of graphene oxide fibers creates a pathway for practical applications
Illuminating the first bacteria
Authors: Katz Laura A.
Published: May 2021

A new analysis aims to uncover the root of the bacterial tree of life
Role of the ionic environment in enhancing the activity of reacting molecules in zeolite pores
Authors: Pfriem Niklas , Hintermeier Peter H. , Eckstein Sebastian , Kim Sungmin , Liu Qiang , Shi Hui , Milakovic Lara , Liu Yuanshuai , Haller Gary L. , Baráth Eszter , Liu Yue , Lercher Johannes A.
Published: May 2021

Speeding reactions through ionic strength

Brønsted acidity is introduced into microporous zeolites through the addition of framework aluminum. Pfriem
et al.
show that in the presence of water, the limited volume in the microchannels of zeolite H-MFI leads to a high concentration of hydrated hydronium ions at aluminum sites. The resulting high charge density creates a highly non-ideal solvation environment and, for cyclohexanol dehydrogenation, the charged carbenium-ion transition state was stabilized. A higher rate was maintained with lower-acidity sodium ion–exchanged zeolites that had the same high ionic strength.

Science
, abh3418, this issue p.
952
Epidemiology of Carbapenem Resistance Determinants Identified in Meropenem-Nonsusceptible
Enterobacterales
Collected as Part of a Global Surveillance Program, 2012 to 2017
Authors: Kazmierczak Krystyna M. , Karlowsky James A. , de Jonge Boudewijn L. M. , Stone Gregory G. , Sahm Daniel F.
Published: May 2021

To estimate the incidence of carbapenem-resistant
Enterobacterales
(CRE), a global collection of 81,781 surveillance isolates of
Enterobacterales
collected from patients in 39 countries in five geographic regions from 2012 to 2017 was studied. Overall, 3.3% of isolates were meropenem-nonsusceptible (MIC ≥2 μg/ml), ranging from 1.4% (North America) to 5.3% (Latin America) of isolates by region.
Klebsiella pneumoniae
accounted for the largest number of meropenem-nonsusceptible isolates (76.7%).
Pharmacokinetics and Antifungal Activity of Echinocandins in Ascites Fluid of Critically Ill Patients
Authors: Welte René , Oberacher Herbert , Gasperetti Tiziana , Pfisterer Hartwig , Griesmacher Andrea , Santner Tobias , Lass-Flörl Cornelia , Hörtnagl Caroline , Leitner-Rupprich Sandra , Aigner Maria , Lorenz Ingo , Schmid Stefan , Edlinger Michael , Eller Philipp , Dankl Daniel , Joannidis Michael , Bellmann Romuald
Published: May 2021

The pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis.
Ferret Interferon (IFN)-Inducible Transmembrane Proteins Are Upregulated by both IFN-α and Influenza Virus Infection
Authors: Horman William S. J. , Kedzierska Katherine , Rootes Christina L. , Bean Andrew G. D. , Nguyen Thi H. O. , Layton Daniel S.
Published: May 2021

IFITM proteins can prevent the entry of several pH-dependent viruses, including high-consequence viruses such as HIV, influenza viruses, and SARS-coronaviruses. Mutations in these genes have been associated with worsened disease outcomes with mutations in their IFITM genes, highlighting these genes as potential disease risk factors.
SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses
Authors: Carnell George W. , Ciazynska Katarzyna A. , Wells David A. , Xiong Xiaoli , Aguinam Ernest T. , McLaughlin Stephen H. , Mallery Donna , Ebrahimi Soraya , Ceron-Gutierrez Lourdes , Asbach Benedikt , Einhauser Sebastian , Wagner Ralf , James Leo C. , Doffinger Rainer , Heeney Jonathan L. , Briggs John A. G.
Published: May 2021

Vaccines in use against SARS-CoV-2 induce immune responses against the spike protein. There is intense interest in whether the antibody response induced by vaccines will be robust against new variants, as well as in next-generation vaccines for use in previously infected or immunized individuals.
CCR2 Regulates Vaccine-Induced Mucosal T-Cell Memory to Influenza A Virus
Authors: Lee Woojong , Kingstad-Bakke Brock , Kedl Ross M. , Kawaoka Yoshihiro , Suresh M.
Published: May 2021

While antibody-based immunity to influenza A virus (IAV) is type and subtype specific, lung- and airway-resident memory T cells that recognize conserved epitopes in the internal viral proteins are known to provide heterosubtypic immunity. Hence, broadly protective IAV vaccines need to elicit robust T cell memory in the respiratory tract.
Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome
Authors: Lulla Valeria , Wandel Michal P. , Bandyra Katarzyna J. , Ulferts Rachel , Wu Mary , Dendooven Tom , Yang Xiaofei , Doyle Nicole , Oerum Stephanie , Beale Rupert , O’Rourke Sara M. , Randow Felix , Maier Helena J. , Scott William , Ding Yiliang , Firth Andrew E. , Bloznelyte Kotryna , Luisi Ben F.
Published: May 2021

The highly conserved stem-loop 2 motif (s2m) is found in the genomes of many RNA viruses, including SARS-CoV-2. Our findings indicate that the s2m element can be targeted by antisense oligonucleotides. The antiviral potential of this conserved element represents a promising start for further research into targeting conserved elements in RNA viruses.
Inflammatory myofibroblastic tumours of the duodenopancreaticobiliary tract
Authors: Shah Pritik A , Babu Raghavendra , Ramaswamy Veena , G Subash K
Published: May 2021

Inflammatory myofibroblastic tumours (IMTs) are rare benign neoplasms of intermediate malignant potential that are found in the lungs and rarely at extrapulmonary sites common in children and young adults. IMTs tend to be locally invasive and have some amount of metastatic potential as well. We present two cases of IMTs involving the duodenum, pancreas and distal bile duct. The first case presented with extensive involvement of the first three parts of the duodenum and head of the pancreas, while the second presented with a pancreatic and biliary tree involvement. Upon examinations and investigations, these tumours mimicked malignant neoplasms. A Whipple procedure for surgical resection was undertaken in both cases. The histological findings showed fascicles of spindle cells with infiltration of lymphocytes and plasma cells. The inflammatory myofibroblastic tumour was diagnosed based on pathological grounds with immunohistochemistry. Preoperative diagnosis of IMTs is difficult and complete surgical resection is the primary treatment.
Flucloxacillin-induced liver injury in elderly patient
Authors: Angheleanu Roberta , Swart Johnny N
Published: May 2021

Flucloxacillin is a penicillin antibiotic used as first-line treatment for soft tissue infections caused byStaphylococcus aureus. It is used frequently in the elderly and is an established cause of cholestatic liver injury. Risk factors for cholestasis include prolonged duration of treatment, female sex and older age. Elderly patients are also more likely to suffer from comorbidities and polypharmacy, which increases the incidence of drug-induced liver injury and hospitalisation, which in turn can lead to irreversible deterioration in functional baseline. Our case report aims to raise awareness of flucloxacillin-induced liver injury in elderly patients and to encourage the use of alternative treatments and/or limited duration. We advocate for further research into individualised treatments and new diagnostic techniques in patients with painless jaundice based on their genotype.
Challenges in reported COVID-19 data: best practices and recommendations for future epidemics
Authors: Badker Rinette , Miller Kierste , Pardee Chris , Oppenheim Ben , Stephenson Nicole , Ash Benjamin , Philippsen Tanya , Ngoon Christopher , Savage Partrick , Lam Cathine , Madhav Nita
Published: May 2021

The proliferation of composite data sources tracking the COVID-19 pandemic emphasises the need for such databases during large-scale infectious disease events as well as the potential pitfalls due to the challenges of combining disparate data sources. Multiple organisations have attempted to standardise the compilation of disparate data from multiple sources during the COVID-19 pandemic. However, each composite data source can use a different approach to compile data and address data issues with varying results.

We discuss some best practices for researchers endeavouring to create such compilations while discussing three key categories of challenges: (1) data dissemination, which includes discrepant estimates and varying data structures due to multiple agencies and reporting sources generating public health statistics on the same event; (2) data elements, such as date formats and location names, lack standardisation, and differing spatial and temporal resolutions often create challenges when combining sources; and (3) epidemiological factors, including missing data, reporting lags, retrospective data corrections and changes to case definitions that cannot easily be addressed by the data compiler but must be kept in mind when reviewing the data.

Efforts to reform the global health data ecosystem should bear such challenges in mind. Standards and best practices should be developed and incorporated to yield more robust, transparent and interoperable data. Since no standards exist yet, we have highlighted key challenges in creating a comprehensive spatiotemporal view of outbreaks from multiple, often discrepant, reporting sources and provided guidelines to address them. In general, we caution against an over-reliance on fully automated systems for integrating surveillance data and strongly advise that epidemiological experts remain engaged in the process of data assessment, integration, validation and interpretation to identify, diagnose and resolve data challenges.
Diversity and inclusion in simulation: addressing ethical and psychological safety concerns when working with simulated participants
Authors: Picketts Leanne , Warren Marika Dawn , Bohnert Carrie
Published: May 2021

Healthcare learners can gain necessary experience working with diverse and priority communities through human simulation. In this context, simulated participants (SPs) may be recruited for specific roles because of their appearance, lived experience or identity. Although one of the benefits of simulation is providing learners with practice where the risk of causing harm to patients in the clinical setting is reduced, simulation shifts the potential harm from real patients to SPs. Negative effects of tokenism, misrepresentation, stereotyping or microaggressions may be amplified when SPs are recruited for personal characteristics or lived experience. Educators have an ethical obligation to promote diversity and inclusion; however, we are also obliged to mitigate harm to SPs.

The goals of simulation (fulfilling learning objectives safely, authentically and effectively) and curricular obligations to address diverse and priority communities can be in tension with one another; valuing educational benefits might cause educators to deprioritise safety concerns. We explore this tension using a framework of diversity practices, ethics and values and simulation standards of best practice. Through the lens of healthcare ethics, we draw on the ways clinical research can provide a model for how ethical concerns can be approached in simulation, and suggest strategies to uphold authenticity and safety while representing diverse and priority communities. Our objective is not to provide a conclusive statement about how values should be weighed relative to each other, but to offer a framework to guide the complex process of weighing potential risks and benefits when working with diverse and priority communities.
Oral nicotine marketing claims in direct-mail advertising
Authors: Czaplicki Lauren , Patel Minal , Rahman Basmah , Yoon Stephanie , Schillo Barbara , Rose Shyanika W
Published: May 2021

Background

Little is known regarding how oral nicotine products (eg, nicotine pouches, lozenges) are marketed to consumers, including whether potential implicit reduced harm claims are used. In the current study, we explored the marketing claims present in a sample of direct-mail oral nicotine advertisements sent to US consumers (March 2018–August 2020).

Methods

Direct-mail ads (n=50) were acquired from Mintel and dual-coded for the following claims: alternative to other tobacco products, ability to use anywhere, spit-free, smoke-free and product does not contain tobacco leaf. We merged the coded data with Mintel’s volume estimate (number of mail pieces sent to consumers) and calculated the proportion of oral nicotine advertisements containing claims by category.

Results

Of the 38 million pieces of oral nicotine direct-mail sent to US consumers, most featured claims that the product could be used anywhere (84%, 31.8 million pieces); was an alternative to other tobacco products (69%, 26.1 million pieces); and did not contain tobacco leaf (eg, ‘tobacco leaf-free’, ‘simple’ approach of extracting nicotine from tobacco; 55%, 20.7 million pieces). A slightly smaller proportion contained claims that oral nicotine was ‘spit-free’ (52%, 19.8 million pieces) or ‘smoke-free’ (31%, 11.7 million pieces).

Conclusion

Our results provide an early indication of marketing claims used to promote oral nicotine. The strategies documented, particularly the use of language to highlight oral nicotine is tobacco-free, may covey these products as lower-risk to consumers despite the lack of evidence or proper federal authorisation that oral nicotine products are a modified-risk tobacco product. Future research is needed to examine consumer perceptions of such claims.
Developing SonReb models to predict the compressive strength of concrete using different percentage of recycled brick aggregate
Authors: Thapa Sheetal , Sharma Richi Prasad , Halder Lipika
Published: May 2021

This study was conducted to determine the relationship between nondestructive and destructive tests in concrete cubes using different ratios of normal stone and recycled brick as coarse aggregates. Variations in the grade of concrete, density, and age were considered to make the model prediction more efficient in places where the use of recycled brick aggregates is common. Normal concrete grades M20, M25, and M30 were considered having density variation by replacing stone with recycled brick aggregate, and age by testing concrete strength at 7, 28, and 84 days. A regression model was created using artificial neural networks and multiple regression analyses. The study showed that the regression model developed using an artificial neural network predicted better results. The models obtained from the experiment were compared with other models provided by different authors. The study also considered the effect of using recycled brick aggregate in nondestructive tests and the modulus of concrete.
Beam blow up due to beamstrahlung in circular e$$^+$$e$$^-$$ colliders
Authors: Valdivia Garcia M. A. , Zimmermann F.
Published: May 2021

After the discovery of the Higgs boson in 2012, several future circular colliders — Higgs factories — are proposed, such as FCC-ee and CEPC. At these e$$^+$$

+

e$$^-$$

-

colliders, beamstrahlung can greatly affect the equilibrium bunch length and energy spread. If the dispersion function at the collision point is not zero, beamstrahlung will also increase the transverse emittances. In this paper, we derive analytical formulae for the equilibrium beam parameters, considering the varying electromagnetic field during the collision, and taking into account hourglass effect, crossing angle, and crab waist. We illustrate the importance of beamstrahlung, including the increase of bunch length and the implied tolerance on the spurious dispersion function at the collision point, by considering a few examples.
CHAOTIC DYNAMICS OF A NOVEL 2D DISCRETE FRACTIONAL ORDER USHIKI MAP
Authors: HIGAZY M. , SELVAM GEORGE MARIA , JANAGARAJ R.
Published: May 2021

The aim of this paper is to analyze the chaotic dynamics of a novel 2D fractional order discrete Ushiki map using Caputo-like delta fractional difference operator. The dynamical nature of the proposed discrete fractional Ushiki map is examined with evolution of time states and bifurcation diagrams. In addition, control law aimed at stabilizing the proposed map and the synchronization of the discrete fractional order Ushiki map are also presented. Numerical examples are exhibited to demonstrate the validity of the theoretical findings of the study.
ONLINE ACTIVE ENSEMBLE LEARNING FOR ROBOT COLLISION DETECTION IN DYNAMIC ENVIRONMENTS
Authors: ZOU RUI , LIU YUBIN , CHU GUOQING , ZHAO JIE , CAI HEGAO
Published: May 2021

In order to improve the accuracy and precision of online learning-based collision detection methods, an online active ensemble learning for robot collision detection (OAELRCD) is proposed in this paper. The OAELRCD consists of two key components: (1) an ensemble learning method to combine several base classifiers in order to improve the accuracy and precision of collision detection, (2) an active learning algorithm to reduce the number of training samples in order to realize online training and learning when the environment changes. We evaluate the proposed OAELRCD on one robot arm in dynamic environments with moving workspace obstacles, showing that the proposed OAELRCD outperforms state-of-the-art online learning-based method and geometric collision checkers. Compared to the state-of-the-art online learning-based method for robot collision detection in dynamic environments, the proposed OAELRCD provides noticeable improvements in TPR, AUC, Accuracy and TNR. Compared to state-of-the-art geometric collision checkers, with the proposed OAELRCD, collision checks are faster.
Government Big Data Ecosystem: Definitions, Types of Data, Actors, and Roles and the Impact in Public Administrations
Authors: Shah Syed Iftikhar Hussain , Peristeras Vassilios , Magnisalis Ioannis
Published: May 2021

The public sector, private firms, business community, and civil society are generating data that are high in volume, veracity, and velocity and come from a diversity of sources. This type of data is today known as big data. Public administrations pursue big data as “new oil” and implement data-centric policies to collect, generate, process, share, exploit, and protect data for promoting good governance, transparency, innovative digital services, and citizens’ engagement in public policy. All of the above constitute the Government Big Data Ecosystem (GBDE). Despite the great interest in this ecosystem, there is a lack of clear definitions, the various important types of government data remain vague, the different actors and their roles are not well defined, while the impact in key public administration sectors is not yet deeply understood and assessed. Such research and literature gaps impose a crucial obstacle for a better understanding of the prospects and nascent issues in exploiting GBDE. With this study, we aim to start filling the above-mentioned gaps by organizing our findings from an extended Systematic Literature Review into a framework to organise and address the above-mentioned challenges. Our goal is to contribute in this fast-evolving area by bringing some clarity and establishing common understanding around key elements of the emerging GBDE.
The Effects of Negative Online Reviews on Consumer Perception, Attitude and Purchase Intention: Experimental Investigation of the Amount, Quality, and Presentation Order of eWOM
Authors: Liao Hsiu-Li , Huang Zhen-Yu , Liu Su-Houn
Published: May 2021

The quick growth and fast spread of electronic word-of-mouth (eWOM) have created a new threat to Internet merchants and marketers through paid online reviewers flooding sites with product and service reviews that could confuse and deter customers. This study examined the effects of the posts by paid reviewers—specifically, the negative reviews—on consumers’ risk perception, product attitude, and purchase intention. While extant research examined negative eWOM as an information source, little attention has been paid to the role of a hired reviewer's post aimed at destroying the reputation of certain targets (Internet Water Army Attack [IWAA]). To gain a better understanding of this phenomenon, three experiments were conducted to investigate the effects of the amount, quality, and presentation order of negative eWOM on consumers’ perception change and decision making. We tested the hypothesis using a test environment that mimicked a PTT online forum (
https://www.ptt.cc/
) in Taiwan. Three simulation cases (smartphone, digital camera, and tablet) based on real-world events were used. A total of 193 participants completed all three experiments and provided valid responses. The results of this study are mostly consistent with previous research findings that online marketing is greatly threatened by negative eWOM. Nevertheless, it was also found that the effects of the amount, quality, and presentation order of negative eWOM are more complicated than we have anticipated. The findings revealed that IWAA can effectively increase customers’ risk perception toward a product and change their attitude and purchase intention.
Repulsive Curves
Authors: Yu Chris , Schumacher Henrik , Crane Keenan
Published: May 2021

Curves play a fundamental role across computer graphics, physical simulation, and mathematical visualization, yet most tools for curve design do nothing to prevent crossings or self-intersections. This article develops efficient algorithms for (self-)repulsion of plane and space curves that are well-suited to problems in computational design. Our starting point is the so-called
tangent-point energy
, which provides an infinite barrier to self-intersection. In contrast to local collision detection strategies used in, e.g., physical simulation, this energy considers interactions between all pairs of points, and is hence useful for global shape optimization: local minima tend to be aesthetically pleasing, physically valid, and nicely distributed in space. A reformulation of gradient descent based on a
Sobolev-Slobodeckij inner product
enables us to make rapid progress toward local minima—independent of curve resolution. We also develop a hierarchical multigrid scheme that significantly reduces the per-step cost of optimization. The energy is easily integrated with a variety of constraints and penalties (e.g., inextensibility, or obstacle avoidance), which we use for applications including curve packing, knot untangling, graph embedding, non-crossing spline interpolation, flow visualization, and robotic path planning.
Reinforcement Learning–based Collective Entity Alignment with Adaptive Features
Authors: Zeng Weixin , Zhao Xiang , Tang Jiuyang , Lin Xuemin , Groth Paul
Published: May 2021

Entity alignment (EA) is the task of identifying the entities that refer to the same real-world object but are located in different knowledge graphs (KGs). For entities to be aligned, existing EA solutions treat them separately and generate alignment results as ranked lists of entities on the other side. Nevertheless, this decision-making paradigm fails to take into account the interdependence among entities. Although some recent efforts mitigate this issue by imposing the 1-to-1 constraint on the alignment process, they still cannot adequately model the underlying interdependence and the results tend to be sub-optimal.

To fill in this gap, in this work, we delve into the dynamics of the decision-making process, and offer a reinforcement learning (RL)–based model to align entities collectively. Under the RL framework, we devise the coherence and exclusiveness constraints to characterize the interdependence and restrict collective alignment. Additionally, to generate more precise inputs to the RL framework, we employ representative features to capture different aspects of the similarity between entities in heterogeneous KGs, which are integrated by an adaptive feature fusion strategy. Our proposal is evaluated on both cross-lingual and mono-lingual EA benchmarks and compared against state-of-the-art solutions. The empirical results verify its effectiveness and superiority.
HGAT: Heterogeneous Graph Attention Networks for Semi-supervised Short Text Classification
Authors: Yang Tianchi , Hu Linmei , Shi Chuan , Ji Houye , Li Xiaoli , Nie Liqiang
Published: May 2021

Short text classification has been widely explored in news tagging to provide more efficient search strategies and more effective search results for information retrieval. However, most existing studies, concentrating on long text classification, deliver unsatisfactory performance on short texts due to the sparsity issue and the insufficiency of labeled data. In this article, we propose a novel heterogeneous graph neural network-based method for semi-supervised short text classification, leveraging full advantage of limited labeled data and large unlabeled data through information propagation along the graph. Specifically, we first present a flexible heterogeneous information network (HIN) framework for modeling short texts, which can integrate any type of additional information and meanwhile capture their relations to address the semantic sparsity. Then, we propose Heterogeneous Graph Attention networks (HGAT) to embed the HIN for short text classification based on a dual-level attention mechanism, including node-level and type-level attentions. To efficiently classify new coming texts that do not previously exist in the HIN, we extend our model HGAT for inductive learning, avoiding re-training the model on the evolving HIN. Extensive experiments on single-/multi-label classification demonstrates that our proposed model HGAT significantly outperforms state-of-the-art methods across the benchmark datasets under both transductive and inductive learning.
Assessing Top- Preferences
Authors: Clarke Charles L. A. , Vtyurina Alexandra , Smucker Mark D.
Published: May 2021

Assessors make preference judgments faster and more consistently than graded judgments. Preference judgments can also recognize distinctions between items that appear equivalent under graded judgments. Unfortunately, preference judgments can require more than linear effort to fully order a pool of items, and evaluation measures for preference judgments are not as well established as those for graded judgments, such as NDCG. In this article, we explore the assessment process for partial preference judgments, with the aim of identifying and ordering the top items in the pool, rather than fully ordering the entire pool. To measure the performance of a ranker, we compare its output to this preferred ordering by applying a rank similarity measure. We demonstrate the practical feasibility of this approach by crowdsourcing partial preferences for the TREC 2019 Conversational Assistance Track, replacing NDCG with a new measure named
compatibility
. This new measure has its most striking impact when comparing modern neural rankers, where it is able to recognize significant improvements in quality that would otherwise be missed by NDCG.
From Bench to Keyboard and Back Again: A Brief History of Lambda Phage Modeling
Authors: Cortes Michael G. , Lin Yiruo , Zeng Lanying , Balázsi Gábor
Published: May 2021

Cellular decision making is the process whereby cells choose one developmental pathway from multiple possible ones, either spontaneously or due to environmental stimuli. Examples in various cell types suggest an almost inexhaustible plethora of underlying molecular mechanisms. In general, cellular decisions rely on the gene regulatory network, which integrates external signals to drive cell fate choice. The search for general principles of such a process benefits from appropriate biological model systems that reveal how and why certain gene regulatory mechanisms drive specific cellular decisions according to ecological context and evolutionary outcomes. In this article, we review the historical and ongoing development of the phage lambda lysis–lysogeny decision as a model system to investigate all aspects of cellular decision making. The unique generality, simplicity, and richness of phage lambda decision making render it a constant source ofmathematical modeling–aided inspiration across all of biology. We discuss the origins and progress of quantitative phage lambda modeling from the 1950s until today, as well as its possible future directions. We provide examples of how modeling enabled methods and theory development, leading to new biological insights by revealing gaps in the theory and pinpointing areas requiring further experimental investigation. Overall, we highlight the utility of theoretical approaches both as predictive tools, to forecast the outcome of novel experiments, and as explanatory tools, to elucidate the natural processes underlying experimental data.
Structure and Mechanics of Dynein Motors
Authors: Canty John T. , Tan Ruensern , Kusakci Emre , Fernandes Jonathan , Yildiz Ahmet
Published: May 2021

Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in interphase cells and mediating spindle assembly and chromosome positioning during cell division. Other dynein isoforms transport cargos in cilia and power ciliary beating. Dyneins were the least studied of the cytoskeletal motors due to challenges in the reconstitution of active dynein complexes in vitro and the scarcity of high-resolution methods for in-depth structural and biophysical characterization of these motors. These challenges have been recently addressed, and there have been major advances in our understanding of the activation, mechanism, and regulation of dyneins. This review synthesizes the results of structural and biophysical studies for each class of dynein motors. We highlight several outstanding questions about the regulation of bidirectional transport along microtubules and the mechanisms that sustain self-coordinated oscillations within motile cilia.
Exercise modality, but not exercise training, alters the acute effect of exercise on endothelial function in healthy men
Authors: Boidin Maxime , Erskine Robert M. , Thijssen Dick H. J. , Dawson Ellen Adele
Published: May 2021

We found that resistance and endurance exercise modalities lead to different endothelial function responses after a single bout of exercise. Endothelial function increased after an acute bout of resistance exercise, whereas it decreased after an acute bout of endurance exercise. Four weeks of chronic exercise training did not affect the acute endothelial function response.
Inspiratory muscle responses to sudden airway occlusion in chronic obstructive pulmonary disease
Authors: Epiu Isabella , Gandevia Simon C. , Boswell-Ruys Claire L. , Basha Chanelle , Archer Sean N. J. , Butler Jane E. , Hudson Anna L.
Published: May 2021

A potent short-latency reflex inhibition of inspiratory muscles produced by airway occlusion was tested in people with COPD and age-matched controls. The reflex was more prevalent in COPD, presumably due to an increased neural drive to breathe. When present, the reflex was similar in duration in the two groups, longer than historical data for younger control groups. The work reveals novel differences in reflex control of inspiratory muscles due to aging as well as COPD.
Comparison of survival of preterm newborn rabbits at 25–28 days of gestation with perinatal therapies at birth transition
Authors: Luo Siwei , Guo Xiaojing , Xu Yaling , Dong Ying , Rehan Virender K. , Sun Bo
Published: May 2021

An extremely preterm rabbit model with gestational age of 25–26 ( term 31) days was established by mechanical ventilation with individually adjusted tidal volume at lower ranges. The administration of antenatal glucocorticoids and/or postnatal surfactant achieved significantly longer duration to maintain 50% survival and facilitated lung maturation and protection at early saccular stage. The usefulness of this model should be validated in future investigation of perinatal and neonatal morbidity and mortality at extremely preterm birth transition.
Neural control of matched motor units during muscle shortening and lengthening at increasing velocities
Authors: Oliveira Anderson Souza , Negro Francesco
Published: May 2021

The control of movement velocity is accomplished by the modulation of the neural drive to muscle and its variation over time. In this study, we tracked motor units decomposed from HD-sEMG across shortening and lengthening contractions at increasing velocities in two submaximal load levels. We demonstrate that concentric and eccentric contractions of the tibialis anterior muscle at slow velocities are achieved by specific motor unit rate coding strategies rather than distinct recruitment schemes.
Nutritional considerations to counteract gastrointestinal permeability during exertional heat stress
Authors: King Michelle A. , Rollo Ian , Baker Lindsay B.
Published: May 2021

Intestinal barrier integrity and function are compromised during exertional heat stress (EHS) potentially leading to consequences that range from minor gastrointestinal (GI) disturbances to fatal outcomes in exertional heat stroke or septic shock. This mini-review provides a concise discussion of nutritional interventions that may protect against intestinal permeability during EHS and suggests physiological mechanisms responsible for this protection. Although diverse nutritional interventions have been suggested to be protective against EHS-induced GI permeability, the ingestion of certain amino acids, carbohydrates, and fluid per se is potentially effective strategy, whereas evidence for various polyphenols and pre/probiotics is developing. Plausible physiological mechanisms of protection include increased blood flow, epithelial cell proliferation, upregulation of intracellular heat shock proteins, modulation of inflammatory signaling, alteration of the GI microbiota, and increased expression of tight junction (TJ) proteins. Further clinical research is needed to propose specific nutritional candidates and recommendations for their application to prevent intestinal barrier disruption and elucidate mechanisms during EHS.
Dynamic cerebral autoregulation and cerebrovascular carbon dioxide reactivity in middle and posterior cerebral arteries in young endurance-trained women
Authors: Labrecque Lawrence , Drapeau Audrey , Rahimaly Kevan , Imhoff Sarah , Brassard Patrice
Published: May 2021

Herein, we describe responses from two major mechanisms regulating cerebral blood flow with a special attention on regional differences in young endurance-trained women. The novel findings are that dynamic cerebral autoregulation and absolute cerebrovascular reactivity to carbon dioxide appear similar between the middle and posterior cerebral arteries of these young women.
Tailored Therapy Based on Molecular Characteristics in Endometrial Cancer
Authors: Lee Suk-young
Published: May 2021

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.
A Systematic Approach for the Reliability Evaluation of Electric Connector
Authors: Wang Ruoyu , Xu Liangjun , Zhou Yilin
Published: May 2021

Under the trend of high density and miniaturization, the current that the connector transmits per unit volume is getting higher and higher, which makes the reliability design of the connector more challenging. Under the pressure of high performance and low cost requirements, the design has to be more accurate and more efficient. Thus, in the design process, a systematic approach for reliability evaluation is required. However, there is no valid enough approach that is integrated, well-organized, and quantitative. In this article, a systematic approach for the reliability evaluation of connector was proposed, and by applying it on a typical object named a blade-spring connector, the validity of this approach was verified. After the framework of this approach has been established, the methods and models needed were provided, including the method to build up material selection criterion and the assessment models of stress relaxation, thermal diffusion, and sliding wear, respectively. Then, the feasibility of a newly developed copper alloy on the connector and the reliability behaviors of this connector were determined through this approach. The unsatisfactory aspects of reliability were pointed out and some possible redesign choices were provided. Results and discussion revealed that the proposed approach is a helpful tool for designing electric connectors, especially on the reliability design.
Effect of Nd:YAG, Er,Cr:YSGG Laser Irradiation, and Adjunctive Photodynamic Therapy on Push‐Out Bond Strength of Zirconia Posts to Radicular Dentin
Authors: Alshammary Freah , Karobari Mohmed I. , Assiry Ali A. , Marya Anand , Shaikh Gul M. , Siddiqui Ammar A. , Alam Mohammad K.
Published: May 2021

This study is aimed at assessing the influence of Nd:YAG, Er,Cr:YSGG laser irradiation, and adjunctive photodynamic therapy (aPDT) on the bond strength of zirconia posts to radicular dentin. Eighty extracted anterior teeth were randomly categorized into 4 groups (n = 20) based on varying laser irradiation treatments, i.e., conventional cleaning and shaping (CCS), Nd:YAG, Er,Cr:YSGG, and aPDT group, respectively. Using a cutting machine, the samples were prepared for push‐out bond strength analysis; 4 sections (2 on each apical and cervical) of around 1 mm thickness were sectioned for all roots at a right angle to the long axis of the post. After making the space for the post, they were incorporated into the root system and were subjected to different laser treatments. The universal testing machine was utilized to assess the push‐out bond strength, which had a defined 1 mm/minute crosshead speed until the failure was encountered. Specimens in the aPDT group (8.20 ± 2.14 MPa) demonstrated the highest mean push‐out bond strength, whereas the lowest was shown by samples in the CCS group (7.08 ± 1.11 MPa). According to the independent t‐test, the mean push‐out bond strength scores of the cervical segments were higher as compared to the apical segments in research groups (p < 0.05). Overall, the adhesive type was the most frequently encountered failure mode in all of the experimental groups, with the least number of failures observed in aPDT treated teeth samples. In conclusion, the push‐out bond strength to radicular dentin was not much influenced by Nd:YAG, Er,Cr:YSGG laser, and aPDT in comparison with CCS. Although statistically not significant, however, the application of aPDT provided better outcomes as compared to other research groups.
Second-Order Semi-Discretized Schemes for Solving Stochastic Quenching Models on Arbitrary Spatial Grids
Authors: Garcia-Montoya Nina , Kabre Julienne , Macías-Díaz Jorge E. , Sheng Qin
Published: May 2021

Reaction-diffusion-advection equations provide precise interpretations for many important phenomena in complex interactions between natural and artificial systems. This paper studies second-order semi-discretizations for the numerical solution of reaction-diffusion-advection equations modeling quenching types of singularities occurring in numerous applications. Our investigations particularly focus at cases where nonuniform spatial grids are utilized. Detailed derivations and analysis are accomplished. Easy-to-use and highly effective second-order schemes are acquired. Computational experiments are presented to illustrate our results as well as to demonstrate the viability and capability of the new methods for solving singular quenching problems on arbitrary grid platforms.
Deformation Investigations on the Flexspline with the Conic Curve Combined Cam Wave Generator
Authors: Wang Shuyan , Guo Dongxiang , Mao Shiteng
Published: May 2021

The deformation of the flexspline and the meshing quality are largely determined by the profile of a wave generator. The wave generator with a combined profile can effectively reduce or improve the deformation stress and strain of the flexspline for improving the transmission efficiency and reducing wear or noise. In this paper, in view of the facts that conic is originally cut out of the cone and different conic curves are easy to transform, a design concept of the curve cam wave generator based on the conic curve is proposed. Firstly, the combined principle, constraint conditions, and mathematic model of the curve cam generator based on the conic curve are established. Secondly, the deformation theory of the flexspline acted by the curve cam wave generator with conic curves has been developed, and finite element analysis on stress and strain of the flexspline compared with a standard elliptic wave generator has been carried out. Finally, a cam wave generator combined with the circle and ellipse as a sample has been developed and manufactured. Circumferential strain test has been further carried out by a static strain gauge to verify the strain characteristics of the flexspline acted with the circle and ellipse combined cam wave generator. The FEM results show that, in the meshing area of the flexspline, the maximum equivalent stress of the flexspline under the action of the arc and the ellipse wave generator is about 93 MPa, which is 36.3% lower than the maximum equivalent stress of the flexspline under the action of the standard ellipse which is 143 MPa. The experimental results show that the fitting curve of the experimental results fits well with the finite element analysis curve.
The Downregulation of ADAM17 Exerts Protective Effects against Cardiac Fibrosis by Regulating Endoplasmic Reticulum Stress and Mitophagy
Authors: Guan Chang , Zhang Hai-Feng , Wang Ya-Jing , Chen Zhi-Teng , Deng Bing-Qing , Qiu Qiong , Chen Si-Xu , Wu Mao-Xiong , Chen Yang-Xin , Wang Jing-Feng
Published: May 2021

Background. A disintegrin and metalloproteinase 17 (ADAM17) is a transmembrane protein that is widely expressed in various tissues; it mediates the shedding of many membrane‐bound molecules, involving cell‐cell and cell‐matrix interactions. We investigated the role of ADAM17 within mouse cardiac fibroblasts (mCFs) in heart fibrosis. Methods. mCFs were isolated from the hearts of neonatal mice. Effects of ADAM17 on the differentiation of mCFs towards myofibroblasts and their fibrotic behaviors following induction with TGF‐β1 were examined. The expression levels of fibrotic proteins, such as collagen I and α‐SMA, were assessed by qRT‐PCR analysis and western blotting. Cell proliferation and migration were measured using the CCK‐8 and wound healing assay. To identify the target gene for ADAM17, the protein levels of the components of endoplasmic reticulum (ER) stress and the PINK1/Parkin pathway were assessed following ADAM17 silencing. The effects of ADAM17 silencing or treatment with thapsigargin, a key stimulator of acute ER stress, on mCFs proliferation, migration, and collagen secretion were also examined. In vivo, we used a mouse model of cardiac fibrosis established by left anterior descending artery ligation; the mice were administered oral gavage with a selective ADAM17 inhibitor (TMI‐005) for 4 weeks after the operation. Results. We found that the ADAM17 expression levels were higher in fibrosis heart tissues and TGF‐β1‐treated mCFs. The ADAM17‐specific siRNAs decreased TGF‐β1‐induced increase in the collagen secretion, proliferation, and migration of mCFs. Knockdown of ADAM17 reduces the activation of mCFs by inhibiting the ATF6 branch of ER stress and further activating mitophagy. Moreover, decreased ADAM17 expression also ameliorated cardiac fibrosis and improved heart function. Conclusions. This study highlights that mCF ADAM17 expression plays a key role in cardiac fibrosis by regulating ER stress and mitophagy, thereby limiting fibrosis and improving heart function. Therefore, ADAM17 downregulation, within the physiological range, could exert protective effects against cardiac fibrosis.
Research on Multiobjective Location of Urban Emergency Logistics under Major Emergencies
Authors: Wang Hongchun , Ma Xinying
Published: May 2021

After the outbreak of major emergencies, the scheduling of emergency supplies is the key to the emergency rescue work, and the establishment of appropriate emergency logistics centers plays a crucial supporting role. In order to deal with the problem of emergency facility location and material distribution in urban emergency logistics system, this paper establishes a dual objective mixed integer nonlinear programming (MINLP) model with the objective of minimizing the emergency rescue time and maximizing the satisfaction rate of emergency material demand, designs a genetic algorithm to solve the emergency logistics location and allocation model, and obtains the Pareto optimal solution set of the model. Finally, a case study of COVID-19 epidemic in Beijing-Tianjin-Hebei region was carried out to verify the feasibility and effectiveness of the model and algorithm in the actual application, which can provide reference and suggestions for the location and material distribution of urban emergency logistics centers.