bluuebunny/crossref_metadata_2025 huggingface dataset:
The bare necessities of plant K+ channel regulation
Authors: Lefoulon Cécile
Published: June 2021

Potassium (K+) channels serve a wide range of functions in plants from mineral nutrition and osmotic balance to turgor generation for cell expansion and guard cell aperture control. Plant K+ channels are members of the superfamily of voltage-dependent K+ channels, or Kv channels, that include the Shaker channels first identified in fruit flies (Drosophila melanogaster). Kv channels have been studied in depth over the past half century and are the best-known of the voltage-dependent channels in plants. Like the Kv channels of animals, the plant Kv channels are regulated over timescales of milliseconds by conformational mechanisms that are commonly referred to as gating. Many aspects of gating are now well established, but these channels still hold some secrets, especially when it comes to the control of gating. How this control is achieved is especially important, as it holds substantial prospects for solutions to plant breeding with improved growth and water use efficiencies. Resolution of the structure for the KAT1 K+ channel, the first channel from plants to be crystallized, shows that many previous assumptions about how the channels function need now to be revisited. Here, I strip the plant Kv channels bare to understand how they work, how they are gated by voltage and, in some cases, by K+ itself, and how the gating of these channels can be regulated by the binding with other protein partners. Each of these features of plant Kv channels has important implications for plant physiology.
Fractional Parts of Non-Integer Powers of Primes. II
Authors: Shubin Andrei
Published: June 2021

We continue to study the distribution of prime numbers p, satisfying the condition $\{p^{\alpha} \} \in I \subset [0; 1)$, in arithmetic progressions. In this paper, we prove an analogue of Bombieri–Vinogradov theorem for 0 < α < 1/9 with the level of distribution $\theta = 2/5 - (3/5) \alpha$, which improves the previous result corresponding to $\theta \leqslant 1/3$.
Persistent thrombocytopenia predicts poor long-term survival in patients with antiphospholipid syndrome: a 38-year follow-up study
Authors: Pardos-Gea José , Marques-Soares Joana R , Buján Segundo , Ordi-Ros José , Alijotas-Reig Jaume
Published: June 2021

Objectives

To investigate the impact of thrombocytopenia on survival in patients with APS.

Methods

Thrombocytopenia and other predictors of outcome were retrospectively evaluated in an aPL-positive and APS cohort with 38-year follow-up (1980–2018). Thrombocytopenia was defined as <150 × 109 platelets/l. Hazard ratios (HR) of mortality were calculated using Cox-regression models.

Results

Among 114 patients, 64% had primary APS, 25% secondary APS and 10% asymptomatic aPL. Mean follow-up was 19 (range 5–38) years. ANA [hazard ratio (HR) 1.8, 95% CI 0.8, 3.6, P = 0.10], arterial thrombotic events (HR 7.0, 95% CI 1.4, 3.5, P = 0.016), myocardial infarction (HR 8.3, 95% CI 1.1, 59, P = 0.03), intracardiac thrombosis (HR 17, 95% CI 1, 279, P = 0.04) and thrombocytopenia (HR 2.9, 95% CI 1.4, 6.1, P = 0.004) were risk factors for all-cause mortality, but in multivariate analysis only thrombocytopenia (HR 2.7, 95% CI 1.3, 6.0, P = 0.01) remained significant. Persistent (HR 4.4, 95% CI 2.1, 9.2, P = 0.001) and low–moderate thrombocytopenia (HR 2.8, 95% CI 1.2, 6.4, P = 0.01) were associated with a significant increase in mortality compared with acute (HR 1.6, 95% CI 0.5, 5.3, P = 0.40) and severe (HR 2.1, 95% CI 0.5, 9.2, P = 0.30) forms. APS patients with vs without thrombocytopenia were more frequently male (58 vs 24%, P = 0.001) with arterial thrombosis (55 vs 32%, P = 0.04), LA positivity (100 vs 87%, P = 0.04), type I aPL profile (89% vs 71%, P = 0.05) and anticoagulant treatment (89 vs 63%, P = 0.01). Thrombosis caused 13% of deaths in thrombocytopenic patients and 1% in those without (P = 0.01).

Conclusion

Thrombocytopenia is an aPL-related manifestation that identifies patients with severe disease phenotype and high thrombotic risk. Persistent low–moderate thrombocytopenia is associated with a reduced long-term survival.
SKY PLC v SKYKICK UK LTD
Authors:   Court of Justice of the European Union (Fourth Chamber)
Published: June 2021

H1 Trade Marks – European trade marks – SKY – Validity – Specification of goods and services – Broad specifications – “Computer software” – Requirement of clarity and precision – Whether a ground of invalidity – Whether amounting to failure to satisfy requirement of graphical representability – Whether contrary to the public interest – Bad faith – Effect of lack of intention to use in whole or in part – Vires of s. 32(3) of the Trade Marks Act 1994 – Reference to Court of Justice
Empirical and Methodological Challenges to the Model-Based Inference of Diversification Rates in Extinct Clades
Authors: Černý David , Madzia Daniel , Slater Graham J
Published: June 2021

Changes in speciation and extinction rates are key to the dynamics of clade diversification, but attempts to infer them from phylogenies of extant species face challenges. Methods capable of synthesizing information from extant and fossil species have yielded novel insights into diversification rate variation through time, but little is known about their behavior when analyzing entirely extinct clades. Here, we use empirical and simulated data to assess how two popular methods, PyRate and Fossil BAMM, perform in this setting. We inferred the first tip-dated trees for ornithischian dinosaurs and combined them with fossil occurrence data to test whether the clade underwent an end-Cretaceous decline. We then simulated phylogenies and fossil records under empirical constraints to determine whether macroevolutionary and preservation rates can be teased apart under paleobiologically realistic conditions. We obtained discordant inferences about ornithischian macroevolution including a long-term speciation rate decline (BAMM), mostly flat rates with a steep diversification drop (PyRate) or without one (BAMM), and episodes of implausibly accelerated speciation and extinction (PyRate). Simulations revealed little to no conflation between speciation and preservation, but yielded spuriously correlated speciation and extinction estimates while time-smearing tree-wide shifts (BAMM) or overestimating their number (PyRate). Our results indicate that the small phylogenetic data sets available to vertebrate paleontologists and the assumptions made by current model-based methods combine to yield potentially unreliable inferences about the diversification of extinct clades. We provide guidelines for interpreting the results of the existing approaches in light of their limitations and suggest how the latter may be mitigated. [BAMM; diversification; fossils; macroevolutionary rates; Ornithischia; PyRate.]
Commercial beef farms excelling in terminal and maternal genetic merit generate more gross profit
Authors: Kelly David N , Connolly K , Kelly P , Cromie A R , Murphy C P , Sleator R D , Berry D P
Published: June 2021

Validation of beef total merit breeding indexes for improving performance and profitability has previously been undertaken at the individual animal level; however, no herd-level validation of beef genetic merit and profit has been previously investigated. The objective of the present study was to quantify the relationship between herd profitability and both herd-average terminal and maternal genetic merit across 1,311 commercial Irish beef herds. Herd-level physical and financial performance data were available from a financial benchmarking tool used by Irish farmers and their extension advisors. Animal genetic merit data originated from the Irish Cattle Breeding Federation who undertake the national beef and dairy genetic evaluations. Herd-average genetic merit variables included the terminal index of young animals, the maternal index of dams, and the terminal index of service sires. The herds represented three production systems: 1) cow-calf to beef, 2) cow-calf to weanling/yearling, and 3) weanling/yearling to beef. Associations between herd financial performance metrics and herd average genetic merit variables were quantified using a series of linear mixed models with year, production system, herd size, stocking rate, concentrate input, and the two-way interactions between production system and herd size, stocking rate, and concentrate input included as nuisance factors. Herd nested within the county of Ireland (n = 26) was included as a repeated effect. Herds with young cattle excelling in terminal index enjoyed greater gross and net profit per hectare (ha), per livestock unit (LU), and per kg net live-weight output. The change in gross profit per LU per unit change in the terminal index of young animals was €1.41 (SE = 0.23), while the respective regression coefficient for net profit per LU was €1.37 (SE = 0.30); the standard deviation of the terminal index is €37. Herd-average dam maternal index and sire terminal index were both independently positively associated with gross profit per ha and gross profit per LU. Each one unit increase in dam maternal index (standard deviation of €38) was associated with a €1.40 (SE = 0.48) and €0.76 (SE = 0.29) greater gross profit per ha and per LU, respectively. Results from the present study at the herd-level concur with previous validation studies at the individual animal level thus instilling further confidence among stakeholders as to the expected improvement in herd profitability with improving genetic merit.
Risk factors, outcomes and time to detect positive blood culture among cases with acute brucellosis
Authors: Gaifer Zied , Ali Mohammed E Mohammed , AlJehani Basmah H , Shaikh Hawazin A , Hussein Sheikheldin B
Published: June 2021

Background

Brucellosis causes a disabling human disease and loss of animals' lives. The clinical significance of Brucella bacteremia is still unclear and Brucella identification in blood culture is suboptimal.

Methods

This was a retrospective study conducted in Medina in Saudi Arabia from August 2016 to May 2019. We included cases with brucellosis symptoms and a positive culture or serological evidence for brucellosis, comparing bacteremic with non-bacteremic brucellosis cases for the rates of complications, infection relapses and brucellosis development. Also, we estimated blood culture positivity rates and the time to detect Brucella in an automatic blood culture instrument.

Results

Of the total number of 147 cases, 62 (42%) had a positive blood culture for Brucella, and the blood culture instrument (BACT/ALERT 3D) detected all positive blood cultures within 3 d of incubation. We found higher rates of chronic brucellosis in bacteremia than non-bacteremia cases (OR 7.25, 95% CI 1.41 to 37.23; p=0.018). Patients aged <15 y developed a higher rate of bacteremia than those aged ≥15 yr (OR 11.93 95% CI 1.37 to 103.75; p=0.025).

Conclusion

Brucella bacteremia is an independent predictor for the development of chronic infection. Brucella bacteremia cases may need long follow-up periods and a more thorough evaluation to exclude deep-seated infection.
Difficult Conversations in Palliative Care: Innovations in Learning
Authors: Halliday Deborah A. , Dorney Paulette , Landis Jennifer
Published: June 2021

Accelerated nursing students have a short time frame in which to assimilate knowledge as postbaccalaureate nursing programs are approximately 16 months in length. Research has demonstrated limited innovative evidence-based teaching strategies when developing palliative care curricula in accelerated nursing programs. The authors addressed this gap by using student-centered learning activities and simulation within the context of an end-of-life course. This novel approach allowed students the opportunity to practice important therapeutic communication skills while enhancing their knowledge of palliative nursing care.
Extraocular Sebaceous Carcinoma Treated With Mohs Micrographic Surgery—A 24-Year Retrospective Review of Tumor Characteristics and Treatment Outcomes
Authors: Seago Meghan , Hosking Anna-Marie , Greenway Hubert T. , Kelley Benjamin
Published: June 2021

BACKGROUND

Extraocular sebaceous carcinoma (SC) is rare, with distinct features from its ocular counterpart. These neoplasms have been associated with Muir-Torre syndrome (MTS). Associated internal malignancies include gastrointestinal and genitourinary.

OBJECTIVE

Assess for local recurrence, metastasis, disease-specific death, and additional malignancies in patients with extraocular SC treated with Mohs micrographic surgery (MMS) at a single referral center.

METHODS

Review of patients with extraocular SC treated with MMS between 1995 and 2019. Follow-up was obtained by chart review.

RESULTS

Thirty-eight patients with 41 tumors were identified (25, 66% male). During a mean follow-up of 5.9 ± 5 years, one case of metastasis was identified in an incompletely treated case. No recurrence was identified in the remaining 40 tumors. Five of 41 (12%) tumors had aggressive histologic features. Seven of 38 (18%) patients had a diagnosis of MTS or associated risk factors. There was no association between MTS or its risk factors and high-risk tumors.

CONCLUSION

There were no incidences of local recurrence, metastasis, or disease-specific death in cases treated completely with MMS. Metastasis and disease-specific death occurred in an incompletely treated case, highlighting the risk associated with aggressive tumors.
Geranylgeraniol prevents zoledronic acid-mediated reduction of viable mesenchymal stem cells via induction of Rho-dependent YAP activation
Authors: Singhatanadgit Weerachai , Hankamolsiri Weerawan , Janvikul Wanida
Published: June 2021

Long-term use of zoledronic acid (ZA) increases the risk of medication-related osteonecrosis of the jaw (MRONJ). This may be attributed to ZA-mediated reduction of viable mesenchymal stem cells (MSCs). ZA inhibits protein geranylgeranylation, thus suppressing cell viability and proliferation. Geranylgeraniol (GGOH), which is a naturally found intermediate compound in the mevalonate pathway, has positive effects against ZA. However, precise mechanisms by which GGOH may help preserve stem cell viability against ZA are not fully understood. The objective of this study was to investigate the cytoprotective mechanisms of GGOH against ZA. The results showed that while ZA dramatically decreased the number of viable MSCs, GGOH prevented this negative effect. GGOH-rescued ZA-exposed MSCs formed mineralization comparable to that produced by normal MSCs. Mechanistically, GGOH preserved the number of viable MSCs by its reversal of ZA-mediated Ki67+MSC number reduction, cell cycle arrest and apoptosis. Moreover, GGOH prevented ZA-suppressed RhoA activity and YAP activation. The results also established the involvement of Rho-dependent YAP and YAP-mediated CDK6 in the cytoprotective ability of GGOH against ZA. In conclusion, GGOH preserves a pool of viable MSCs with osteogenic potency against ZA by rescuing the activity of Rho-dependent YAP activation, suggesting GGOH as a promising agent and YAP as a potential therapeutic target for MRONJ.
Existence of Chandrasekhar’s limit in generalized uncertainty white dwarfs
Authors: Mathew Arun , Nandy Malay K.
Published: June 2021

The existence of Chandrasekhar’s limit has played various decisive roles in astronomical observations for many decades. However, various recent theoretical investigations suggest that gravitational collapse of white dwarfs is withheld for arbitrarily high masses beyond Chandrasekhar’s limit if the equation of state incorporates the effect of quantum gravity via the generalized uncertainty principle. There have been a few attempts to restore the Chandrasekhar limit but they are found to be inadequate. In this paper, we rigorously resolve this problem by analysing the dynamical instability in general relativity. We confirm the existence of Chandrasekhar’s limit as well as stable mass–radius curves that behave consistently with astronomical observations. Moreover, this stability analysis suggests gravitational collapse beyond the Chandrasekhar limit signifying the possibility of compact objects denser than white dwarfs.
Asperity level characterization of abrasive wear using atomic force microscopy
Authors: Walker Jack , Umer Jamal , Mohammadpour Mahdi , Theodossiades Stephanos , Bewsher Stephen R. , Offner Guenter , Bansal Hemant , Leighton Michael , Braunstingl Michael , Flesch Heinz-Georg
Published: June 2021

Using an atomic force microscope, a nanoscale wear characterization method has been applied to a commercial steel substrate AISI 52100, a common bearing material. Two wear mechanisms were observed by the presented method: atom attrition and elastoplastic ploughing. It is shown that not only friction can be used to classify the difference between these two mechanisms, but also the ‘degree of wear’. Archard's Law of adhesion shows good conformity to experimental data at the nanoscale for the elastoplastic ploughing mechanism. However, there is a distinct discontinuity between the two identified mechanisms of wear and their relation to the load and the removed volume. The length-scale effect of the material's hardness property plays an integral role in the relationship between the ‘degree of wear’ and load. The transition between wear mechanisms is hardness-dependent, as below a load threshold limited plastic deformation in the form of pile up is exhibited. It is revealed that the presented method can be used as a rapid wear characterization technique, but additional work is necessary to project individual asperity interaction observations to macroscale contacts.
Profile likelihood analysis for a stochastic model of diffusion in heterogeneous media
Authors: Simpson Matthew J. , Browning Alexander P. , Drovandi Christopher , Carr Elliot J. , Maclaren Oliver J. , Baker Ruth E.
Published: June 2021

We compute profile likelihoods for a stochastic model of diffusive transport motivated by experimental observations of heat conduction in layered skin tissues. This process is modelled as a random walk in a layered one-dimensional material, where each layer has a distinct particle hopping rate. Particles are released at some location, and the duration of time taken for each particle to reach an absorbing boundary is recorded. To explore whether these data can be used to identify the hopping rates in each layer, we compute various profile likelihoods using two methods: first, an exact likelihood is evaluated using a relatively expensive Markov chain approach; and, second, we form an approximate likelihood by assuming the distribution of exit times is given by a Gamma distribution whose first two moments match the moments from the continuum limit description of the stochastic model. Using the exact and approximate likelihoods, we construct various profile likelihoods for a range of problems. In cases where parameter values are not identifiable, we make progress by re-interpreting those data with a reduced model with a smaller number of layers.
Perspectives on the formation of peakons in the stochastic Camassa–Holm equation
Authors: Bendall Thomas M. , Cotter Colin J. , Holm Darryl D.
Published: June 2021

A famous feature of the Camassa–Holm equation is its admission of peaked soliton solutions known as peakons. We investigate this equation under the influence of stochastic transport. Noting that peakons are weak solutions of the equation, we present a finite-element discretization for it, which we use to explore the formation of peakons. Our simulations using this discretization reveal that peakons can still form in the presence of stochastic perturbations. Peakons can emerge both through wave breaking, as the slope turns vertical, and without wave breaking as the inflection points of the velocity profile rise to reach the summit.
Dynamics of one-dimensional spin models under the line-graph operator
Authors: Javarone Marco Alberto , O’Connor Josh A.
Published: June 2021

We investigate the application of the line-graph operator to one-dimensional spin models with periodic boundary conditions. The spins (or interactions) in the original spin structure become the interactions (or spins) in the resulting spin structure. We identify conditions which ensure that each new spin structure is stable, that is, its spin configuration minimizes its internal energy. Then, making a correspondence between spin configurations and binary sequences, we propose a model of information growth and evolution based on the line-graph operator. Since this operator can generate frustrations in newly formed spin chains, in the proposed model such frustrations are immediately removed. Also, in some cases, the previously frustrated chains are allowed to recombine into new stable chains. As a result, we obtain a population of spin chains whose dynamics is studied using Monte Carlo simulations. Lastly, we discuss potential applications to areas of research such as combinatorics and theoretical biology.
Genomic signatures of spatially divergent selection at clownfish range margins
Authors: Clark René D. , Aardema Matthew L. , Andolfatto Peter , Barber Paul H. , Hattori Akihisa , Hoey Jennifer A. , Montes Humberto R. , Pinsky Malin L.
Published: June 2021

Understanding how evolutionary forces interact to drive patterns of selection and distribute genetic variation across a species' range is of great interest in ecology and evolution, especially in an era of global change. While theory predicts how and when populations at range margins are likely to undergo local adaptation, empirical evidence testing these models remains sparse. Here, we address this knowledge gap by investigating the relationship between selection, gene flow and genetic drift in the yellowtail clownfish,
Amphiprion clarkii,
from the core to the northern periphery of the species range. Analyses reveal low genetic diversity at the range edge, gene flow from the core to the edge and genomic signatures of local adaptation at 56 single nucleotide polymorphisms in 25 candidate genes, most of which are significantly correlated with minimum annual sea surface temperature. Several of these candidate genes play a role in functions that are upregulated during cold stress, including protein turnover, metabolism and translation. Our results illustrate how spatially divergent selection spanning the range core to the periphery can occur despite the potential for strong genetic drift at the range edge and moderate gene flow from the core populations.
Adaptive, caste-specific changes to recombination rates in a thelytokous honeybee population
Authors: Oldroyd Benjamin P. , Yagound Boris , Allsopp Michael H. , Holmes Michael J. , Buchmann Gabrielle , Zayed Amro , Beekman Madeleine
Published: June 2021

The ability to clone oneself has clear benefits—no need for mate hunting or dilution of one's genome in offspring. It is therefore unsurprising that some populations of haplo-diploid social insects have evolved thelytokous parthenogenesis—the virgin birth of a female. But thelytokous parthenogenesis has a downside: the loss of heterozygosity (LoH) as a consequence of genetic recombination. LoH in haplo-diploid insects can be highly deleterious because female sex determination often relies on heterozygosity at sex-determining loci. The two female castes of the Cape honeybee,Apis mellifera capensis, differ in their mode of reproduction. While workers always reproduce thelytokously, queens always mate and reproduce sexually. For workers, it is important to reduce the frequency of recombination so as to not produce offspring that are homozygous. Here, we ask whether recombination rates differ between Cape workers and Cape queens that we experimentally manipulated to reproduce thelytokously. We tested our hypothesis that Cape workers have evolved mechanisms that restrain genetic recombination, whereas queens have no need for such mechanisms because they reproduce sexually. Using a combination of microsatellite genotyping and whole-genome sequencing we find that a reduction in recombination is confined to workers only.
Intensive human contact correlates with smaller brains: differential brain size reduction in cattle types
Authors: Balcarcel A. M. , Veitschegger K. , Clauss M. , Sánchez-Villagra M. R.
Published: June 2021

Cattle are one of the most intensively bred domestic animals, providing humans with a multitude of products and uses. Using data from the fossil record, we test if their domestication, as for other taxa, has resulted in a reduction of their brain size. We not only conclude thatBos taurus(domestic cattle) have smaller brains than their wild ancestor,Bos primigenius(aurochs), but that brain size varies significantly by breed, with some having much smaller brains than others. Differences in husbandry practices between several breed categories align with a range of human engagement, which also aligns with the degree of selection for docility. Sampling 317 domestics from 71 breeds, we investigate if differences in brain size correlate with the intensity of human contact. A clear pattern emerges whereby a brain reduction gradient parallels a gradient in behavioural selection. Bullfighting cattle, which are bred for fighting and aggressive temperament, have much larger brains than dairy breeds, which are intensively selected for docility. Our results add to a fundamental aspect of animal domestication theory: the interplay between basic features of the domestic environment—selection for docility, absence of predators and human provision of resources—seems to explain differences in brain size.
Mimicry in motion and morphology: do information limitation, trade-offs or compensation relax selection for mimetic accuracy?
Authors: McLean Donald James , Herberstein Marie E.
Published: June 2021

Many animals mimic dangerous or undesirable prey as a defence from predators. We would expect predators to reliably avoid animals that closely resemble dangerous prey, yet imperfect mimics are common across a wide taxonomic range. There have been many hypotheses suggested to explain imperfect mimicry, but comparative tests across multiple mimicry systems are needed to determine which are applicable, and which—if any—represent general principles governing imperfect mimicry. We tested four hypotheses on Australian ant mimics and found support for only one of them: the information limitation hypothesis. A predator with incomplete information will be unable to discriminate some poor mimics from their models. We further present a simple model to show that predators are likely to operate with incomplete information because they forage and make decisions while they are learning, so might never learn to properly discriminate poor mimics from their models. We found no evidence that one accurate mimetic trait can compensate for, or constrain, another, or that rapid movement reduces selection pressure for good mimicry. We argue that information limitation may be a general principle behind imperfect mimicry of complex traits, while interactions between components of mimicry are unlikely to provide a general explanation for imperfect mimicry.
Anticipation of common buzzard population patterns in the changing UK landscape
Authors: Arraut Eduardo M. , Walls Sean W. , Macdonald David W. , Kenward Robert E.
Published: June 2021

Harmonious coexistence between humans, other animals and ecosystem services they support is a complex issue, typically impacted by landscape change, which affects animal distribution and abundance. In the last 30 years, afforestation on grasslands across Great Britain has been increasing, motivated by socio-economic reasons and climate change mitigation. Beyond expected benefits, an obvious question is what are the consequences for wider biodiversity of this scale of landscape change. Here, we explore the impact of such change on the expanding population of common buzzardsButeo buteo, a raptor with a history of human-induced setbacks. Using Resource-Area-Dependence Analysis (RADA), with which we estimated individuals' resource needs using 10-day radio-tracking sessions and the 1990s Land Cover Map of GB, and agent-based modelling, we predict that buzzards in our study area in lowland UK had fully recovered (to 2.2 ind km−2) by 1995. We also anticipate that the conversion of 30%, 60% and 90% of economically viable meadow into woodland would reduce buzzard abundance nonlinearly by 15%, 38% and 74%, respectively. The same approach used here could allow for cost-effective anticipation of other animals' population patterns in changing landscapes, thus helping to harmonize economy, landscape change and biodiversity.
Cellular Activities of SARS-CoV-2 Main Protease Inhibitors Reveal Their Unique Characteristics
Authors: Cao Wenyue , Cho Chia-Chuan Dean , Geng Zhi Zachary , Ma Xinyu R. , Allen Robert , Shaabani Namir , Vatansever Erol C. , Alugubelli Yugendar R. , Ma Yuying , Ellenburg William H. , Yang Kai S. , Qiao Yuchen , Ji Henry , Xu Shiqing , Liu Wenshe Ray
Published: June 2021

As an essential enzyme of SARS-CoV-2, the pathogen of COVID-19, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor with cellular potency. By coupling this toxicity alleviation with the expression of an MPro-eGFP fusion protein in a human cell host for straightforward characterization with fluorescent flow cytometry, we developed an effective method that allows bulk analysis of cellular potency of MPro inhibitors. In comparison to an antiviral assay in which MPro inhibitors may target host proteases or other processes in the SARS-CoV-2 life cycle to convene strong antiviral effects, this novel assay is more advantageous in providing precise cellular MPro inhibition information for assessment and optimization of MPro inhibitors. We used this assay to analyze 30 literature reported MPro inhibitors including MPI1-9 that were newly developed aldehyde-based reversible covalent inhibitors of MPro, GC376 and 11a that are two investigational drugs undergoing clinical trials for the treatment of COVID-19 patients in United States, boceprevir, calpain inhibitor II, calpain inhibitor XII, ebselen, bepridil that is an antianginal drug with potent anti-SARS-CoV-2 activity, and chloroquine and hydroxychloroquine that were previously shown to inhibit MPro. Our results showed that most inhibitors displayed cellular potency much weaker than their potency in direct inhibition of the enzyme. Many inhibitors exhibited weak or undetectable cellular potency up to 10 μM. On contrary to their strong antiviral effects, 11a, calpain inhibitor II, calpain XII, ebselen, and bepridil showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle to convene potent antiviral effects. characterization of these molecules on their antiviral mechanisms will likely reveal novel drug targets for COVID-19. Chloroquine and hydroxychloroquine showed close to undetectable cellular potency to inhibit MPro. Kinetic recharacterization of these two compounds rules out their possibility as MPro inhibitors. Our results also revealed that MPI5, 6, 7, and 8 have high cellular and antiviral potency with both IC50 and EC50 values respectively below 1 μM. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Given its strong cellular and antiviral potency, we cautiously suggest that MPI8 is ready for preclinical and clinical investigations for the treatment of COVID-19.
Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants
Authors: Logue James , Johnson Robert , Patel Nita , Zhou Bin , Maciejewski Sonia , Zhou Haixia , Portnoff Alyse , Tian Jing-Hui , McGrath Marisa , Haupt Robert , Weston Stuart , Hammond Holly , Guebre-Xabier Mimi , Dillen Carly , Plested Joyce , Cloney-Clark Shane , Greene Ann M , Massare Mike , Glenn Greg , Smith Gale , Frieman Matthew
Published: June 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally. As SARS-CoV-2 has transmitted from person to person, variant viruses have emerged with elevated transmission rates and higher risk of infection for vaccinees. We present data showing that a recombinant prefusion-stabilized Spike (rS) protein based on the B.1.351 sequence (rS-B.1.351) was highly immunogenic in mice and produced neutralizing antibodies against SARS-CoV-2/WA1, B.1.1.7, and B.1.351. Mice vaccinated with our prototype vaccine NVX-CoV2373 (rS-WU1) or rS-B.1.351 alone, in combination, or as a heterologous prime boost, were protected when challenged with live SARS-CoV-2/B.1.1.7 or SARS-CoV-2/B.1.351. Virus titer was reduced to undetectable levels in the lungs post-challenge in all vaccinated mice, and Th1-skewed cellular responses were observed. A strong anamnestic response was demonstrated in baboons boosted with rS-B.1.351 approximately one year after immunization with NVX-CoV2373 (rS-WU1). An rS-B.1.351 vaccine alone or in combination with prototype rS-WU1 induced protective antibody- and cell-mediated responses that were protective against challenge with SARS-CoV-2 variant viruses.
Alkali metal salts of 4-hydroxybenzoic acid: a structural and educational study
Authors: Abrahams Brendan F. , Commons Christopher J. , Hudson Timothy A. , Sanchez Arlt Robin , White Keith F. , Chang Michael , Jackowski John J. , Lee Matthew , Lee Shang X. , Liu Harrison D. , Mei Bill M. , Meng Joshua E. , Poon Lincoln , Xu Xiaolin , Yu Zekai
Published: June 2021

As part of an educational exercise designed to introduce school students to the technique of single-crystal X-ray diffraction and enhance their understanding of primary and secondary bonding, a group of nine secondary school students was given the opportunity to prepare new compounds and to solve and refine data collected on the crystalline materials they had prepared. Their investigation of the alkali metal salts of 4-hydroxybenzoic acid (H2hba) yielded nine new compounds and their structures are described in this article. Whilst the salts might be expected to have similar atomic arrangements, there are significant differences in their structures. Although H2hba is a relatively simple organic molecule, it displays remarkable coordinative flexibility, forming ionic solids containing the uncharged molecule, the monoanion Hhba− or the dianion hba2−. A common feature of the structures is their layered arrangement: alternating hydrophilic layers made up of closely packed metal–oxygen polyhedra separated by the hydrophobic component of the hydroxybenzoate linking units. Close packing of these units seems to be a dominant influence in determining the overall structure. The hydroxybenzoate units are usually both parallel and antiparallel with their immediate neighbours, with packing that can be edge-to-face, face-to-face or a mixture of the two. Hydrogen bonding plays a key role in the structure of most compounds and a short strong hydrogen bond (SSHB) is observed in two of the networks. The compounds of 4-hydroxybenzoic acid, C7H6O3, described here are: poly[di-μ-aqua-μ-4-oxidobenzoato-dilithium], [Li2(C7H4O3)(H2O)2]
n
, 1, poly[triaqua-μ-4-oxidobenzoato-dilithium], [Li2(C7H4O3)(H2O)3]
n
, 2, poly[μ-4-hydroxybenzoato-lithium], [Li(C7H5O3)]
n
, 3, catena-poly[4-hydroxybenzoate [[diaquasodium]-di-μ-aqua]], {[Na(H2O)4](C7H5O3)}
n
, 4, poly[di-μ-aqua-aqua-μ-4-hydroxybenzoato-potassium], [K(C7H5O3)(H2O)3]
n
, 5, poly[μ-aqua-μ-4-hydroxybenzoato-potassium], [K(C7H5O3)(H2O)]
n
, 6, poly[aqua-μ-4-hydroxybenzoato-rubidium], [Rb(C7H5O3)(H2O)]
n
, 7, poly[aqua-μ-4-hydroxybenzoato-caesium], [Cs(C7H5O3)(H2O)]
n
, 8, poly[[μ-aqua-aqua(μ-4-hydroxybenzoato)(4-hydroxybenzoic acid)sodium] monohydrate], {[Na(C7H5O3)(C7H6O3)(H2O)2]·H2O}
n
, 9, poly[[(μ-4-hydroxybenzoato)(μ-4-hydroxybenzoic acid)rubidium] monohydrate], {[K(C7H5O3)(C7H6O3)]·H2O}
n
, 10, and poly[[(μ-4-hydroxybenzoato)(μ-4-hydroxybenzoic acid)rubidium] monohydrate], {[Rb(C7H5O3)(C7H6O3)]·H2O}
n
, 11.
Planning to repose long and heavy objects considering a combination of regrasp and constrained drooping
Authors: Raessa Mohamed , Wan Weiwei , Harada Kensuke
Published: June 2021

Purpose

This paper aims to present a hierarchical motion planner for planning the manipulation motion to repose long and heavy objects considering external support surfaces.

Design/methodology/approach

The planner includes a task-level layer and a motion-level layer. This paper formulates the manipulation planning problem at the task level by considering grasp poses as nodes and object poses for edges. This paper considers regrasping and constrained in-hand slip (drooping) during building graphs and find mixed regrasping and drooping sequences by searching the graph. The generated sequences autonomously divide the object weight between the arm and the support surface and avoid configuration obstacles. Cartesian planning is used at the robot motion level to generate motions between adjacent critical grasp poses of the sequence found by the task-level layer.

Findings

Various experiments are carried out to examine the performance of the proposed planner. The results show improved capability of robot arms to manipulate long and heavy objects using the proposed planner.

Originality/value

The authors’ contribution is that they initially develop a graph-based planning system that reasons both in-hand and regrasp manipulation motion considering external supports. On one hand, the planner integrates regrasping and drooping to realize in-hand manipulation with external support. On the other hand, it switches states by releasing and regrasping objects when the object is in stably placed. The search graphs' nodes could be retrieved from remote cloud servers that provide a large amount of pre-annotated data to implement cyber intelligence.
Embracing the employee orientation: does customer relationship matter in brand building?
Authors: Jhamb Deepika , Kampani Nidhi , Arya Vikas
Published: June 2021

Purpose

The study aims to explore the themes responsible for employee orientation and further their role in building strong customer relationships in telecom and organized retail outlets in emerging markets.

Design/methodology/approach

Employing the qualitative approach, a total of 31 in-depth interviews with customer relationship management (CRM) officers of telecom and organized outlets were carried out. Data were analysed using NVIVO-12 plus and ATLAS tools.

Findings

The analysis extracted 13 unique themes namely training and development, communication skills, convincing skills, interpersonal skills, knowledge management, grievance handling, organisation's culture development, service climate, adaptive behaviour, customer retention skills, customer profiling, trust and commitment, and suitability of employees. The results claimed that these themes can assist in building strong customer relationships. However, the extent of the significance of themes may vary for telecom and organized retail outlets.

Research limitations/implications

The findings have vital implications for frontline employees to drive customer value as they directly involve with customers. Findings further suggest that hiring of employees according to their location and catchment area of outlets are utmost important.

Originality/value

Employee orientation is an indispensable determinant in building a sustainable relationship with customers through uniqueness and consistency in meeting customers' expectations. This is a first attempt to explore the various unique themes responsible for employee orientation and the imperative role of such themes in maintaining long-lasting customer relationships.
Brushless direct current motor with MV-PID controller management system based on arm microcontroller
Authors: Kanagaraj Prathibanandhi , Ramadoss Ramesh , Calpakkam Yaashuwanth , Basha Adam Raja
Published: June 2021

Purpose

The brushless direct current motor (BLDCM) is widely accepted and adopted by many industries instead of direct current motors due to high reliability during operation. Brushless direct current (BLDC) has outstanding efficiency as losses that arise out of voltage drops at brushes and friction losses are eliminated. The main factor that affects the performance is temperature introduced in the internal copper core windings. The control of motor speed generates high temperature in BLDC operation. The high temperature is due to presence of ripples in the operational current. The purpose is to present an effective controlling mechanism for speed management and to improve the performance of BLDCM to activate effective management of speed.

Design/methodology/approach

The purpose is to present an optimal algorithm based on modified moth-flame optimization algorithm over recurrent neural network (MMFO-RNN) for speed management to improve the performance. The core objective of the presented work is to achieve improvement in performance without affecting the design of the system with no additional circuitry. The management of speed in BLDCM has been achieved through reduction or minimization of ripples encircled with torque of the motor. The implementation ends in two stages, namely, controlling the loop of torque and controlling the loop of speed. The MMFO-RNN starts with error optimization, which arises from both the loops, and most effective values have been achieved through MMFO-RNN protocol.

Findings

The parameters are enriched with Multi Resolution Proportional Integral and Derivative (MRPID) controller operation to achieve minimal ripples for the torque of BLDC and manage the speed of the motor. The performance is increased by adopting this technique approximately 12% in comparison with the existing methodology, which is the main contributions of the presented work. The outcomes are analyzed with the existing methodologies through MATLAB Simulink tool, and the comparative analyses suggest that better performance of the proposed system produces over existing techniques, and proto type model is developed and cross verifies the proposed system.

Originality/value

The MMFO-RNN starts with error optimization, which arises from both the loops, and most effective values have been achieved through MMFO-RNN protocol. The parameters are enriched with MRPID controller operation to achieve nil or minimal ripples and to encircle the torque of Brushless Direct Current and manage the speed.
Optimized DA-reconfigurable FIR filters for software defined radio channelizer applications
Authors: Murthy C. Srinivasa , Sridevi K.
Published: June 2021

Purpose

In this paper, the authors present different methods for reconfigurable finite impulse response (RFIR) filter design. Distributed arithmetic (DA)-based reconfigurable FIR filter design is suitable for software-defined radio (SDR) applications. The main contribution of reconfiguration is reuse of registers, multipliers, adders and to optimize various parameters such as area, power dissipation, speed, throughput, latency and hardware utilizations of flip-flops and slices. Therefore, effective design of building blocks will be optimized for RFIR filter with all the above parameters.

Design/methodology/approach

The modified, direct form register structure of FIR filter contributes the reuse concept and allows utilization of less number of registers and parallel computation operations. The disadvantage of DA and other conventional methods is delay increases proportionally with filter length. This is due to different partial products generated by adders. The usage of adder and multipliers in DA-FIR filter restricts the area and power dissipation because of their complexity of generation of sum and carry bits. The hardware implementation time of an adder can be reduced by parallel prefix adder (PPA) usage based on Ling equation. PPA uses shift-add multiplication, which is a repetitive process of addition, and this process is known as Bypass Zero feed multiplicand in direct multiplication, and the proposed technique optimizes area-power product efficiently. The modified DA (MDA)-based RFIR filter is designed for 64 taps filter length (N). The design is developed by using Verilog hardware description language and implemented on field-programmable gate array. Also, this design validates SDR channel equalizer.

Findings

Both RFIR and SDR are integrated as single system and implemented on Artix-7 development board of XC7A100tCSG324 and exploited the advantages in area-delay, power-speed products and energy efficiency. The theoretical and practical comparisons have been carried out, and the results are compared with existing DA-RFIR designs in terms of throughput, latency, area-delay, power-speed products and energy efficiency, which are improved by 14.5%, 23%, 6.5%, 34.2% and 21%, respectively.

Originality/value

The DA-based RFIR filter is validated using Chipscope Pro software tool on Artix-7 FPGA in Xilinx ISE design suite and compared constraint parameters with existing state-of-art results. It is also tested the filtering operation by applying the RFIR filter on Audio signals for removal of noisy signals and it is found that 95% of noise signals are filtered effectively.
Participatory child-centered disaster risk reduction education: an innovative Chinese NGO program
Authors: Lu Yi , Wei Lai , Cao Binxin , Li Jianqiang
Published: June 2021

Purpose

Disaster risk reduction (DRR) researchers and practitioners have found that schools can play a critical role in DRR education, with many Non-Governmental Organizations (NGOs) developing initiatives to actively involve children in DRR education programs. This paper reports on a case study on an innovative Chinese NGO school-based program focused on participatory child-centered DRR (PCC-DRR) education, from which a PCC-DRR education framework was developed so that similar programs could be replicated, especially in developing countries.

Design/methodology/approach

After nearly a year of research involving follow-up interviews, fieldwork and secondary data collection from annual reports, news reports and official websites, a case study was conducted on the PCC-DRR education program developed by the One Foundation (OF), a resource-rich NGO in China, that focused on its education strategies and project practice in Ya'an following the 2013 Lushan earthquake.

Findings

Based on constructivist theory, the OF developed a PCC-DRR education program that had four specific branches: teacher capacity building, child DRR education, campus risk management and campus safety culture, which was then implemented in 115 schools and consequently evaluated as being highly effective.

Originality/value

The innovative OF PCC-DRR education program adds to theoretical and practical DRR education research as a “best practice” case. Because the proposed framework is child-centered, participatory and collaborative, it provides excellent guidance and reference for countries seeking to develop school-based DRR education programs.