bluuebunny/crossref_metadata_2025 huggingface dataset:
Debiasing the Measurement of Conditional Conservatism
Authors: BADIA MARC , DURO MIGUEL , PENALVA FERNANDO , RYAN STEPHEN G.
Published: April 2021

Basu's [“The Conservatism Principle and the Asymmetric Timeliness of Earnings.” Journal of Accounting and Economics 24 (1997): 3–37] measurement of conditional conservatism as the asymmetric timeliness of earnings underlies hundreds of studies. However, many subsequent studies cast doubt on the extent to which Basu's measure captures conditional conservatism versus statistical biases or alternative constructs (collectively, “biases”), thereby questioning the validity of the inferences that empirical researchers draw from analyses using the measure. We modify Basu's measure in four simple ways to remove these biases. Our key modification is the inclusion of interactive controls for return variance, a volatility proxy that captures Patatoukas and Thomas’ [“More Evidence of Bias in Differential Timeliness Estimates of Conditional Conservatism.” The Accounting Review 86 (2011): 1765–1794] return variance effect and various sources of economic optionality and adjustment costs. This inclusion captures volatility‐related effects on both the level of earnings and the sensitivity of earnings to returns, and it allows the magnitudes of these effects to vary with the sign of returns. We conduct validation analyses using placebo‐dependent variables, synthetic returns, and nonconditionally conservative earnings components that show our modified Basu measure is largely free of known biases. We further show that our measure is associated with contracting and other economic variables as predicted by theory. Our findings suggest that researchers can rely on our modified Basu measure to identify the determinants and effects of conditional conservatism.
Health effects of dietary sulfated polysaccharides from seafoods and their interaction with gut microbiota
Authors: Zhu Zhenjun , Han Yanhui , Ding Yu , Zhu Beiwei , Song Shuang , Xiao Hang
Published: April 2021

Various dietary sulfated polysaccharides (SPs) have been isolated from seafoods, including edible seaweeds and marine animals, and their health effects such as antiobesity and anti‐inflammatory activities have attracted remarkable interest. Sulfate groups have been shown to play important roles in the bioactivities of these polysaccharides. Recent in vitro and in vivo studies have suggested that the biological effects of dietary SPs are associated with the modulation of the gut microbiota. Dietary SPs could regulate the gut microbiota structure and, accordingly, affect the production of bioactive microbial metabolites. Because of their differential chemical structures, dietary SPs may specifically affect the growth of certain gut microbiota and associated metabolite production, which may contribute to variable health effects. This review summarizes the latest findings on the types and structural characteristics of SPs, the effects of different processing techniques on the structural characteristics and health effects of SPs, and the current understanding of the role of gut microbiota in the health effects of SPs. These findings might help in better understanding the mechanism of the health effects of SPs and provide a scientific basis for their application as functional food.
Exo‐inulinase production from Aspergillus fumigatus NFCCI 2426: purification, characterization, and immobilization for continuous fructose production
Authors: Rawat Hemant Kumar , Soni Hemant , Suryawanshi Rahul Kumar , Choukade Ritumbhara , Prajapati Bhanu Pratap , Kango Naveen
Published: April 2021

Aspergillus fumigatus was found to produce thermostable exo‐inulinase (EC 3.8.1.80; 38 U/ml) on inulin‐rich infusions. Exo‐inulinase (14.6 U/mg) was immobilized on glutaraldehyde activated Ca‐alginate beads for continuous generation of fructose by hydrolyzing sucrose, chicory, and dandelion substrates. Immobilization of enzyme was confirmed by microscopic and spectroscopic techniques. The exo‐inulinase was purified using ion‐exchange (1.30‐folds) and size‐exclusion chromatography (2.71‐folds). The purified exo‐inulinase showed 64 kDa band on gel and was optimally active at 60 °C and pH 6.0. Kinetic constants, Km and Vmax of purified exo‐inulinase, were 5.88 mM and 1.66 µM/min, respectively, and its relative activity was found to be enhanced (125.8%) in the presence of calcium ion. Immobilized preparation was utilized for continuous generation of fructose from chicory juice (26 to 70%) and dandelion root extracts (16 to 24%) by recycling upto five cycles, respectively. In comparison to other sweeteners, such as sucrose, fructose is considered as a healthy alternative. The present study demonstrated the use of immobilized exo‐inulinase in continuous generation of fructose from some underutilized plant sources that can be used in food industry.

Practical Application

Thermostable exo‐inulinase produced by A. fumigatus was immobilized on calcium alginate matrix and was employed for continuous hydrolysis of chicory juice and dandelion root extract for generation of fructose syrup.
Effectiveness of ultrasound‐assisted immersion thawing on the thawing rate and physicochemical properties of chicken breast muscle
Authors: Zhang Chao , Sun Qinxiu , Chen Qian , Liu Qian , Kong Baohua
Published: April 2021

This study evaluated the effect of air thawing (AT), water thawing (WT), and ultrasound‐assisted immersion thawing (UT) at different power levels (200, 300, 400, and 500 W) on the thawing rate, physicochemical properties, and protein structure of chicken breast muscle (pectoralis), and the weight of each sample was approximately 106 ± 3 g. UT shortened the total thawing time and decreased the cutting force with increasing ultrasound power. Additionally, UT at 300 W (UT‐300) remarkably reduced the thawing and cooking losses of the samples compared to AT, WT, and other UT powers (p < 0.05). Low‐field nuclear magnetic resonance spectroscopy showed that the T21 and T22 of the UT‐300 samples were shorter than those of the AT and WT samples (p < 0.05), which revealed that UT‐300 reduced the mobility and losses of both immobilized and free water. Moreover, UT‐300 remarkably reduced the damage to the myofibrillar protein (MP) structure. Overall, with appropriate ultrasonic power, the thawing rate increased and changes in the MP structure were reduced.

Practical Application

This study found that compared to that of AT samples, the thawing time of the UT‐300 samples markedly decreased by 57%. In addition, UT‐300 could reduce the damage to the myofibrillar protein structure, which was very beneficial for further processing of frozen foods.
Shifts in behavioral allocation patterns as a natural recovery mechanism: Postresolution expenditure patterns
Authors: Tucker Jalie A. , Cheong JeeWon , Chandler Susan D.
Published: April 2021

Background

Behavioral economics predicts that recovery from Alcohol Use Disorder involves shifts in resource allocation away from drinking, toward valuable nondrinking rewards that reinforce and stabilize recovery behavior patterns. Further, these shifts should distinguish nonproblem drinking (moderation) outcomes from outcomes involving abstinence or relapse. To evaluate these hypotheses, 5 prospective studies of recent natural recovery attempts were integrated to examine changes in monetary spending during the year following the initial cessation of heavy drinking as a function of 1‐year drinking outcomes.

Methods

Problem drinkers from Southeastern U.S. communities (N = 493, 67% male, 65% white, mean age = 46.5 years) were enrolled soon after stopping heavy drinking without treatment and followed prospectively for a year. An expanded Timeline Followback interview assessed daily drinking and monetary spending on alcohol and nondrinking commodities during the year before and after recovery initiation.

Results

Longitudinal associations between postresolution drinking and spending were evaluated using MPlus v.8. Initial models evaluated whether changes in spending at 4‐month intervals predicted drinking outcomes at 1 year and showed significant associations in 6 commodity categories (alcohol, consumable goods, gifts, entertainment, financial/legal affairs, housing/durable goods/insurance; ps < 0.05). Cross‐lagged models showed that the moderation outcome group shifted spending mid‐year to obtain large rewards with enduring benefits (e.g., housing), whereas the abstinent and relapsed groups spent less overall and purchased smaller rewards (e.g., consumable goods, entertainment, and gifts) throughout the year.

Conclusions

Dynamic changes in monetary allocation occurred during the postresolution year. As hypothesized, compared to the groups who abstained or relapsed, the moderation group shifted spending in ways that, overall, yielded higher value alcohol‐free reinforcement that should reinforce recovery while they enjoyed some limited nonproblem drinking below heavy drinking thresholds. These findings add to evidence that moderation entails different behavioral regulation processes than abstinent and relapse outcomes, which were more similar to one another.
Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors
Authors: Beard Emma , Jackson Sarah E. , Anthenelli Robert M. , Benowitz Neal L. , Aubin Lisa St. , McRae Thomas , Lawrence David , Russ Cristina , Krishen Alok , Evins A. Eden , West Robert
Published: April 2021

Background and Aims

Analysed using classical frequentist hypothesis testing with alpha set to 0.05, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events (NPSAEs) attributable to varenicline, bupropion, or nicotine patch compared with placebo. This might be because the null hypothesis was true or because the data were insensitive. The present study aimed to test the hypothesis more directly using Bayes factors.

Design

EAGLES was a randomised, double‐blind, triple‐dummy, controlled trial.

Setting

Global (16 countries across five continents), between November 2011 and January 2015.

Participants

Participants were smokers with (n = 4116) and without (n = 4028) psychiatric disorders.

Interventions

Varenicline (1 mg twice daily), bupropion (150 mg twice daily), nicotine patch (21 mg once daily with taper) and matched placebos.

Measurements

The outcomes included: (i) a composite measure of moderate/severe NPSAEs; and (ii) a composite measure of severe NPSAEs. The relative evidence for there being no difference in NPSAEs versus data insensitivity for the medications was calculated in the full and sub‐samples using Bayes factors and corresponding robustness regions.

Findings

For all but two comparisons, Bayes factors were <1/3, indicating moderate to strong evidence for no difference in risk of NPSAEs between active medications and placebo (Bayes factor = 0.02–0.23). In the psychiatric cohort versus placebo, the data were suggestive, but not conclusive of no increase in NPSAEs with varenicline (Bayes factor = 0.52) and bupropion (Bayes factor = 0.71). Here, the robustness regions ruled out a ≥7% and ≥8% risk increase with varenicline and bupropion, respectively.

Conclusions

Secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study trial using Bayes factors provides moderate to strong evidence that use of varenicline, bupropion or nicotine patches for smoking cessation does not increase the risk of neuropsychiatric adverse events relative to use of placebo in smokers without a history of psychiatric disorder. For smokers with a history of psychiatric disorder the evidence also points to no increased risk but with less confidence.
Effect of the use of earplugs and eye masks on the quality of sleep after major abdominal surgery: a randomised controlled trial
Authors: Leong R. W. , Davies L. J. , Fook‐Chong S. , Ng S. Y. , Lee Y. L.
Published: April 2021

Significant sleep disturbance can occur following major abdominal surgery. We aimed to evaluate the effectiveness of earplugs and eye masks in improving sleep quality and patient satisfaction, reducing nursing demands and in the incidence of delirium in patients after major abdominal surgery. We conducted a randomised controlled trial in 100 patients undergoing major abdominal surgery. We randomly allocated participants to sleep with or without earplugs and eye masks on postoperative days 1–3. The primary outcome measure was sleep quality as measured by the Richards‐Campbell Sleep Questionnaire. Secondary outcomes were patient satisfaction, frequency of nursing demand and incidence of delirium measured by the Neelon and Champagne Confusion Scale. Median (IQR [range]) sleep scores were 64 (38‐74 [0‐100] and 60 (44–82 [18–100]) for the control and intervention groups, respectively (p = 0.310). Age and Pittsburgh Sleep Quality Index scores were found to be significant factors affecting sleep quality. There were no differences in patient satisfaction, reduction in frequency of nursing demands or incidence of delirium on postoperative days 1–3 after major abdominal surgery. The compliance rate in the intervention group was 60–65%. This study has demonstrated that the use of earplugs and eye masks did not contribute to improvements in sleep quality. Of note, sleep quality was moderate, with higher age and worse baseline sleep quality contributing to worse sleep scores. More studies are needed to investigate interventions to improve sleep quality after major abdominal surgery.
Allogeneic haematopoietic cell transplantation for myelofibrosis: a real‐life perspective
Authors: Savani Malvi , Dulery Rémy , Bazarbachi Abdul Hamid , Mohty Razan , Brissot Eolia , Malard Florent , Bazarbachi Ali , Nagler Arnon , Mohty Mohamad
Published: April 2021

Myelofibrosis (MF) is a clonal stem cell neoplasm with heterogeneous clinical phenotypes and well‐established molecular drivers. Allogeneic haematopoietic stem cell transplantation (HSCT) offers an important curative treatment option for primary MF and post‐essential thrombocythaemia/polycythaemia vera MF or secondary MF. With a disease course that varies from indolent to highly progressive, we are now able to stratify risk of mortality through various tools including patient‐related clinical characteristics as well as molecular genetic profile. Owing to the high risk of mortality and morbidity associated with HSCT for patients with myelofibrosis, it is important to improve patient selection for transplant. Our primary goal is to comprehensively define our understanding of current practices including the role of Janus Kinase (JAK) inhibitors, to present the data behind transplantation before and after leukaemic transformation, and to introduce novel personalization of MF treatment with a proposed clinical‐molecular prognostic model to help elucidate a timepoint optimal for consideration of HSCT.
Scorpion venom heat‐resistant synthesized peptide ameliorates 6‐OHDA‐induced neurotoxicity and neuroinflammation: likely role of Nav1.6 inhibition in microglia
Authors: Li Xiujie , Wu Xuefei , Li Na , Li Donglai , Sui Aoran , Khan Khizar , Ge Biying , Li Sheng , Li Shao , Zhao Jie
Published: April 2021

Background and Purpose

Microglia‐related inflammation is associated with the pathology of Parkinson's disease. Functional voltage‐gated sodium channels (VGSCs) are involved in regulating microglial function. Here, we aim to investigate the effects of scorpion venom heat‐resistant synthesized peptide (SVHRSP) on 6‐hydroxydopamine (6‐OHDA)‐induced Parkinson's disease‐like mouse model and reveal its underlying mechanism.

Experimental Approach

Unilateral brain injection of 6‐OHDA was performed to establish Parkinson's disease mouse model. After behaviour test, brain tissues were collected for morphological analysis and protein/gene expression examination. Primary microglia culture was used to investigate the role of sodium channel Nav1.6 in the regulation of microglia inflammation by SVHRSP.

Key Results

SVHRSP treatment attenuated motor deficits, dopamine neuron degeneration, activation of glial cells and expression of pro‐inflammatory cytokines induced by 6‐OHDA lesion. Primary microglia activation and the production of pro‐inflammatory cytokines induced by lipopolysaccharide (LPS) were also suppressed by SVHRSP treatment. In addition, SVHRSP could inhibit mitogen‐activated protein kinases (MAPKs) pathway, which plays pivotal roles in the pro‐inflammatory response. Notably, SVHRSP treatment suppressed the overexpression of microglial Nav1.6 induced by 6‐OHDA and LPS. Finally, it was shown that the anti‐inflammatory effect of SVHRSP in microglia was Nav1.6 dependent and was related to suppression of sodium current and probably the consequent Na+/Ca2+ exchange.

Conclusions and Implications

SVHRSP might inhibit neuroinflammation and protect dopamine neurons via down‐regulating microglial Nav1.6 and subsequently suppressing intracellular Ca2+ accumulation to attenuate the activation of MAPKs signalling pathway in microglia.
Comorbidities and quality of life in children with intellectual disability
Authors: Reddihough Dinah , Leonard Helen , Jacoby Peter , Kim Rachel , Epstein Amy , Murphy Nada , Reid Sue , Whitehouse Andrew , Williams Katrina , Downs Jenny
Published: April 2021

Background

Many children with intellectual disability live with medical comorbidities. This study examined the impacts of comorbidities on quality of life (QOL) of children with intellectual disabilities and whether impacts varied with caregiver perceptions that medical needs had been met.

Methods

Primary caregivers of 447 children (aged 5–19 years) with an intellectual disability reported on their child's medical comorbidities and the extent to which they perceived their child's medical needs had been met in a cross‐sectional observational study. The Quality of Life Inventory‐Disability was used to measure QOL on a 100‐point scale. Linear regression models including interaction terms were used to evaluate their associations.

Results

Parent‐reported recurrent child pain (−4.97, 95% CI −8.21, −1.72), night‐time sleep disturbances (−4.98, 95% CI −7.23, −2.73), daytime somnolence (−8.71, 95% CI −11.30, −2.73), seizures that occurred at least weekly (−7.59, 95% CI −13.50, −1.68) and conservatively managed severe scoliosis (−7.39, 95% CI −12.97, −1.81) were negatively associated with child QOL. Despite the majority of parents (~70%) perceiving that their child's medical needs had been met to a great extent, this did not significantly moderate the association between any comorbidities and QOL.

Conclusions

Comorbidities were common and had marked associations with QOL. Evaluation and management of pain and sleep disturbance continue to be high priorities in improving QOL of young people with intellectual disabilities. Further research on the optimal methods of managing these comorbidities is warranted.
hCG is more effective than the GnRH agonist buserelin for inducing the first ovulation of the breeding season in mares
Authors: Fanelli Diana , Tesi Matteo , Rota Alessandra , Beltramo Massimiliano , Conte Giuseppe , Giorgi Mario , Barsotti Giovanni , Camillo Francesco , Panzani Duccio
Published: April 2021

Background

Human Chorionic Gonadotropin (hCG) and Gonadotropin Releasing Hormone agonists (GnRHa) are routinely used to induce ovulation in mares. However, GnRHa efficacy in transitional mares has been suggested to be low.

Objectives

The aims of this study were as follows: (a) to compare the efficacy of hCG and GnRHa in inducing the first ovulation of the breeding season and (b) to evaluate the correlation between ovulatory response, uterine oedema and teasing score at the time of treatment during the early or late transitional phase.

Study design

Randomised controlled superiority trial.

Methods

Mares in winter anoestrus were treated with sulpiride when at least two follicles reached a diameter of 25 mm. The day after the follicle reached 35 mm in diameter, mares in oestrus were treated with GnRHa buserelin (N = 29) or hCG (N = 33) and checked daily for ovulation.

Results

More mares (30/33, 90.1%) ovulated when the first ovulation after winter anoestrus was induced with hCG, than with GnRHa, (11/29, 38.0%) (P = .0001). Ovulation rate was lower in mares that did not show uterine oedema and full acceptance of the teaser stallion for at least three days before the treatment (32/41, 78% vs 9/21, 42.9%) P = .01.

Main limitations

Plasma LH and oestrogen concentrations were not performed.

Conclusions

These results demonstrate that hCG was more effective than GnRHa for inducing ovulation in the first cycle after winter anoestrus. Uterine oedema and behavioural signs of oestrus, for at least three days before the treatment, were predictors for a positive response to ovulation induction.
A plea for standardization of confocal microscopy and optical coherence tomography parameters to evaluate physiological and para‐physiological skin conditions in cosmetic science
Authors: Ciardo Silvana , Pezzini Claudia , Guida Stefania , Del Duca Ester , Ungar Jonathan , Guttman‐Yassky Emma , Manfredini Marco , Farnetani Francesca , Longo Caterina , Pellacani Giovanni
Published: April 2021

Non‐invasive reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have been extended to the dermo‐cosmetic field, for skin pathophysiology understanding and therapeutics monitoring. However, standardized methodology and parameters to interpret structures and changes in these settings are still lacking. Present study aimed to propose a validated standard methodology and a list of defined parameters for objective non‐pathological skin assessments in the cosmetically sensitive cheekbone area of the face. OCT and RCM quantitative, semi‐quantitative and qualitative features were considered for assessments. Validation process included 50 sets of images divided into two age groups. Inter‐rater reliability was explored to assess the influence of the proposed methodology. Quantitative OCT parameters of “epidermal thickness,” “density and attenuation coefficients” and “vascular density” were considered and calculated. Severity scales were developed for semi‐quantitative OCT features of “disruption of collagen” and “vascular asset,” while extent scales were produced for semi‐quantitative RCM “irregular honeycomb,” “mottled pigmentation” and “polycyclic papillary contours.” Qualitative assessment was obtained for RCM type of collagen, and comparison between age groups was performed for all features considered. Severity visual scales assistance proved excellent inter‐rater agreement across all semi‐quantitative and qualitative domains. The assistance of shareable software systems allows for objective OCT quantitative parameters measurement. The use of standard reference scales, within a defined assessment methodology, offers high inter‐rater reliability and thus reproducibility for semi‐quantitative and qualitative OCT and RCM parameters. Taken together, our results may represent a starting point for a standardized application of RCM and OCT in dermo‐cosmetic research and practice.
Disturbance type and species life history predict mammal responses to humans
Authors: Suraci Justin P. , Gaynor Kaitlyn M. , Allen Maximilian L. , Alexander Peter , Brashares Justin S. , Cendejas‐Zarelli Sara , Crooks Kevin , Elbroch L. Mark , Forrester Tavis , Green Austin M. , Haight Jeffrey , Harris Nyeema C. , Hebblewhite Mark , Isbell Forest , Johnston Barbara , Kays Roland , Lendrum Patrick E. , Lewis Jesse S. , McInturff Alex , McShea William , Murphy Thomas W. , Palmer Meredith S. , Parsons Arielle , Parsons Mitchell A. , Pendergast Mary E. , Pekins Charles , Prugh Laura R. , Sager‐Fradkin Kimberly A. , Schuttler Stephanie , Şekercioğlu Çağan H. , Shepherd Brenda , Whipple Laura , Whittington Jesse , Wittemyer George , Wilmers Christopher C.
Published: April 2021

Human activity and land use change impact every landscape on Earth, driving declines in many animal species while benefiting others. Species ecological and life history traits may predict success in human‐dominated landscapes such that only species with “winning” combinations of traits will persist in disturbed environments. However, this link between species traits and successful coexistence with humans remains obscured by the complexity of anthropogenic disturbances and variability among study systems. We compiled detection data for 24 mammal species from 61 populations across North America to quantify the effects of (1) the direct presence of people and (2) the human footprint (landscape modification) on mammal occurrence and activity levels. Thirty‐three percent of mammal species exhibited a net negative response (i.e., reduced occurrence or activity) to increasing human presence and/or footprint across populations, whereas 58% of species were positively associated with increasing disturbance. However, apparent benefits of human presence and footprint tended to decrease or disappear at higher disturbance levels, indicative of thresholds in mammal species’ capacity to tolerate disturbance or exploit human‐dominated landscapes. Species ecological and life history traits were strong predictors of their responses to human footprint, with increasing footprint favoring smaller, less carnivorous, faster‐reproducing species. The positive and negative effects of human presence were distributed more randomly with respect to species trait values, with apparent winners and losers across a range of body sizes and dietary guilds. Differential responses by some species to human presence and human footprint highlight the importance of considering these two forms of human disturbance separately when estimating anthropogenic impacts on wildlife. Our approach provides insights into the complex mechanisms through which human activities shape mammal communities globally, revealing the drivers of the loss of larger predators in human‐modified landscapes.
Effect of short carbon fiber content on the mechanical properties of TiB2‐based composites prepared by spark plasma sintering
Authors: Ghafuri Fateme , Emadi Rahmatollah , Ahmadian Mehdi , Zakeri Mohammad
Published: April 2021

In this study, TiB2‐30 vol% SiC composites containing 0, 5, 10, and 15 vol% short carbon fibers (Cf) were produced by spark plasma sintering (SPS). The effect of carbon fiber content on microstructure, density, and mechanical properties (micro‐hardness and flexural strength) of the fabricated composites was studied. Scanning electron microscopy (SEM) results indicated that the fibers were uniformly dispersed in the TiB2–SiC matrix using wet ball milling before SPS process. Fully dense TiB2–SiC–Cf composites were achieved by SPS process at 1900°C for 10 min under 30 MPa. With the addition of fibers, the relative density of the composites did not change considerably. Mechanical tests revealed that microhardness was reduced about 19% by the incorporation of carbon fibers, whereas the flexural strength improved significantly. However, the flexural strength diminished by adding carbon fibers above to critical value (5 vol%) due to residual thermal stresses, nonhomogeneous structure and graphitization of carbon fibers. It was found that the composite with 5 vol% Cf had the highest flexural strength (482 MPa), which was enhanced by 20% compared with the TiB2–SiC composite.
Post‐transcriptional control of T‐cell cytokine production: Implications for cancer therapy
Authors: Freen‐van Heeren Julian J.
Published: April 2021

As part of the adaptive immune system, T cells are vital for the eradication of infected and malignantly transformed cells. To perform their protective function, T cells produce effector molecules that are either directly cytotoxic, such as granzymes, perforin, interferon‐γ and tumour necrosis factor α, or attract and stimulate (immune) cells, such as interleukin‐2. As these molecules can also induce immunopathology, tight control of their production is required. Indeed, inflammatory cytokine production is regulated on multiple levels. Firstly, locus accessibility and transcription factor availability and activity determine the amount of mRNA produced. Secondly, post‐transcriptional mechanisms, influencing mRNA splicing/codon usage, stability, decay, localization and translation rate subsequently determine the amount of protein that is produced. In the immune suppressive environments of tumours, T cells gradually lose the capacity to produce effector molecules, resulting in tumour immune escape. Recently, the role of post‐transcriptional regulation in fine‐tuning T‐cell effector function has become more appreciated. Furthermore, several groups have shown that exhausted or dysfunctional T cells from cancer patients or murine models possess mRNA for inflammatory mediators, but fail to produce effector molecules, hinting that post‐transcriptional events also play a role in hampering tumour‐infiltrating lymphocyte effector function. Here, the post‐transcriptional regulatory events governing T‐cell cytokine production are reviewed, with a specific focus on the importance of post‐transcriptional regulation in anti‐tumour responses. Furthermore, potential approaches to circumvent tumour‐mediated dampening of T‐cell effector function through the (dis)engagement of post‐transcriptional events are explored, such as CRISPR/Cas9‐mediated genome editing or chimeric antigen receptors.
The kinetics of 14C-GR43175 in rat and dog
Authors: Dallas Falkner Aa , Dixon Christine M , Mcculloch Robert J , Saynor David A
Published: April 2021

GR43175 is a selective 5-HT1-like receptor agonist which is effective in the acute treatment of migraine. Rats and dogs were dosed intravenously (iv) and orally (po) with 1 mg 14C-GR43175 base (as succinate salt)/kg bodyweight. GR43175 is rapidly absorbed after oral dosing. In dog, 95–100% of the dose is absorbed, but less (25–30%) is absorbed by the rat. The bioavailability is >54% in dog, but lower in rat. Except for the CNS, drug-related material is widely distributed after iv dosing, but is mainly concentrated in the gastrointestinal tract and excretory organs after oral dosing. GR43175 is eliminated from plasma by a combination of renal and metabolic clearance. Some first-pass metabolism occurs in both species. In dog the major route of excretion is in urine (78–83% of the dose) after either route of administration. In rat, urine is also the major route of excretion (71%) after iv dosing. After oral dosing to the rat the major route of excretion is in the faeces (83%). GR43175 is extensively metabolized, after either route of administration, in both species. GR49336, the indole acetic acid derivative of GR43175, is the major metabolite in dog and a major metabolite in rat.
Effect of argon plasma on repair bond strength using nanofilled and microhybrid composites
Authors: Negreiros William Matthew , Ayres Ana Paula Almeida , Willers Amanda Endres , Hirata Ronaldo , Giannini Marcelo
Published: April 2021

Objectives

To evaluate the effect of atmospheric pressure plasma (PLA), sandblasting (SAN), silanization (SIL) and hydrophobic bonding resin (HBR) on the micro‐shear bond strength (MSBS) of fresh nanofilled (NF) or microhybrid (MH) composites to water‐aged nanofilled composite.

Materials and methods

NF plates were fabricated and stored in distilled water for 4 months. The aged plates were assigned to the groups (n = 6): 1‐ untreated; 2‐ SAN + SIL + HBR; 3‐ HBR; 4‐ PLA + HBR; 5‐ SAN + HBR; 6‐ SAN + PLA + HBR; and 7‐ PLA. Two fresh composite cylinders were constructed on each plate with NF or MH composites and tested after 24 h or 1 year of water‐storage, using the MSBS testing. Data were analyzed by three‐way ANOVA and Tukey test (α = 0.05).

Results

NF yielded better outcomes than MH at 24 h, which was not observed at 1 year. HBR showed the highest MSBS results, while untreated and PLA groups yielded the lowest one. MSBS reduced for all groups after 1 year.

Conclusions

Only HBR can obtain good MSBS results, while PLA alone was not beneficial. After 1 year, a reduction in repair MSBS was observed and the type of composite did not influence the results.

Clinical relevance

The repair technique can be simplified with the use of only an adhesive and macromechanical retentions in the old composite, regardless the type of fresh composite.
What can bryophyte diversity on Cangas (ironstone outcrops) teach us?
Authors: de Oliveira Bárbara Azevedo , de Oliveira Mateus Fernandes , Maciel‐Silva Adaíses S.
Published: April 2021

Questions

Bryophytes are a common plant component of the mining‐threatened ironstone outcrops called Cangas, although quite neglected. Aiming to improve conservation strategies for this Brazilian landscape, here we ask: (a) are there differences in species composition, richness and abundance and the role of reproduction (i.e., sexual and asexual expression, and reproductive success) among bryophyte communities of Cangas; and (b) do abiotic and geographic factors influence species composition on these outcrops?

Location

Eight Canga sites in the Quadrilátero Ferrífero (QF) of the state of Minas Gerais, southeast Brazil.

Methods

We sampled eight Canga sites for bryophyte species composition, richness, abundance, and reproduction (i.e., sexual and asexual expression, reproductive success) using 18 4‐m2 plots per site. Similarities in species composition among sites were assessed by cluster analysis; differences in richness, abundance, and reproduction parameters were tested by ANOVA; and the correlations between species composition and climatic variables, altitude, and geographical distance were tested by the Mantel test.

Results

The Canga sites had unique species compositions of bryophytes, with only liverwort richness and abundance differing significantly among sites. Nonetheless, there were floristic similarities among certain geographically close sites, and bryophyte composition was not completely explained by either environmental variables or geographical distance. Additionally, sexual, and asexual reproduction did not differ among Cangas.

Conclusions

Cangas of the Brazilian QF have unique bryophyte communities (i.e., high beta diversity), especially for liverworts. Liverwort composition was found to be strongly affected by threats to Cangas, especially in areas disturbed by intensive fire. We hypothesize that the local landscape and microclimate have a greater influence on bryophyte diversity than regional aspects. Therefore, future conservation efforts on Cangas must emphasize local diversity and the functionality of liverworts and mosses in different habitats, combined with enhanced protection of Conservation Units.
Clone worth? Genetic diversity in obligate apomictic Miconia albicans (Melastomataceae)
Authors: Dias A. C. C. , Marinho R. C. , Sampaio D. S. , Bonetti A. M. , Oliveira P. E.
Published: April 2021

Apomixis is the asexual production of seeds by plants and, in theory, would render low genetic diversity and even clonal lineages. However, recent studies have shown otherwise, although is not always clear where the genetic diversity of obligate apomicts comes from.

We evaluated the genetic diversity among sister seedlings of M. albicans, an obligate apomictic species in Cerrado, Neotropical Savannas in Central Brazil. A total of 50 seedlings from five individuals were analysed using ISSR primers. We obtained 107 fragments, all with good resolution, consistently observed and replicable.

The percentage of polymorphic loci ranged from 28.04% to 33.64% and Shannon’s information index (I) averaged 0.173. The expected heterozygosity (He) averaged 0.117, similar to the observed for populations of M. albicans and other selfed species. Only two seedlings showed the same genotype (possible clones), but most differed at least for five loci. Most of variance was among progenies (62%), but we found that 38% was within progenies. Genetic distances separated the progenies in two groups, and analogous analyses between individuals reconstructed the original progenies clustering.

The results confirmed a relatively high genetic diversity among sister seedling of this obligatory apomictic plant and clones were rare. This diversity can be generated during development, probably by restitutional meiosis or other recombination processes. These differences may accumulate into lineages and populations well adapted to heterogenous Cerrado environment.
Design principles of hybrid approaches in new product development: a systematic literature review
Authors: de Vasconcelos Gomes Leonardo Augusto , Seixas Reis de Paula Rafael Augusto , Figueiredo Facin Ana Lúcia , Chagas Brasil Vinicius , Sergio Salerno Mario
Published: April 2021

Setting the right approach for new product development (NPD) in the presence of uncertainty remains an ongoing debate in innovation management. Stage‐gate systems (SGS) and agile methodology (AM) are the dominant approaches. Recently, hybrid approaches (combining SGS and AM) have been proposed. Although these hybrid approaches represent a significant development in NPD, combining them without considering their design principles might lead to contradictory and competing conceptual formulations, thus increasing the difficulty of comparison among studies. Moreover, scholars and practitioners may struggle to understand when, why and how a certain configuration of the NPD process provides the right response to different manifestations of uncertainty. The current literature faces problems regarding the clarity of design principles (e.g. flexibility and adaptability), and this has led to research gaps concerning the uncertainty contingency and outcomes of hybrid approaches. This study combines bibliometric and content analyses to identify four design parameters and principles of NPD hybrid approaches: flexibility, adaptability, velocity and integration. Our findings might help advance the development and comparison of different hybrid approaches.
High‐resolution genotyping of HLA class I loci in children with type 1 diabetes and celiac disease
Authors: Alshiekh Shehab , Geraghty Daniel E. , Agardh Daniel
Published: April 2021

Objectives

HLA‐DQ2 and DQ8 contribute to the strongest risk haplotypes for type 1 diabetes (T1D) and celiac disease (CD). The variation in genetic risk association is likely linked to different HLA class II loci susceptibility, but association studies of HLA class I alleles are scarce. The aim was to investigate HLA class I A, B, and C alleles polymorphisms in children with only T1D, CD, and a subgroup with both T1D and CD (T1D w/CD).

Materials and methods

HLA class I A, B, and C genes were genotyped using next‐generation targeted sequencing. A conditional analysis was performed on 68 children with T1D, 219 children with CD and seven children with T1D w/CD enrolled from a birth cohort study at high genetic risk children from the South of Sweden.

Results

Among 1764 HLA class I allele variants, A*29:02:01 in T1D w/CD was associated with both T1D (OR = 21.42 [1.05, 1322.4], p = 0.0231) and CD (OR = 35 [2.36, 529.12], p = 0.0051) along with C*05:01:01 with both T1D (OR = 5.54 [1.06, 24.8], p = 0.02) and CD (OR = 6.84 [1.46, 26.01], p = 0.0077). No independent effects of HLA‐B allele associations were observed in T1D w/CD.

Conclusion

Although the distribution of HLA class I alleles differs between children with T1D and CD, the A*29:02:01 and C*05:01:01 alleles showed shared risk association of both diseases.
A Historical Review of Physical Education in China (1949-2020)
Authors: Yan Jin , Smith Jordan , Morgan Philip , Eather Narelle
Published: April 2021

With the drastic changes in the historical context, political and social reconstructions played a significant role in the formation of the contemporary education system in China as well as other countries around the world. Based on the chronicled outline of past revolutions in the Chinese society, this paper aims to provide a broad historical overview of the history and development of physical education (PE) in China since the founding of the People's Republic of China (PRC) in 1949. The process of PE reform in China occurred in four distinct stages, including the Initial Establishment Stage (1949 to 1956), the Exploration Period (1956 to 1966), the Regression Era (1966 to 1976), and the Era of Renaissance and Transformation (1979 to present). This historical review describes the development of PE as a curriculum area across these four critical periods and includes an analysis of historical contexts, policies, faculty training, curriculum settings, and pedagogical content in PE. This paper focuses mainly on PE within elementary and secondary schools in China, accompanied by a brief introduction to college PE in China. Through an examination of the four distinct stages of PE reform in China, a comprehensive understanding of the overall development of PE within these historical periods is presented. Inspired by the development of the educational system in China, a touch on the physical education concepts in countries around the world will also be included. The systematic review on international PE establishments serves to provide a general idea of how future improvements can be adapted to the trend of globalization and other potential public transformations.
Large-Eddy Simulations of High Rossby Number Flow in the High-Pressure Compressor Inter-Disk Cavity
Authors: Saini Deepak , Sandberg Richard D.
Published: April 2021

The focus of the present study is to understand the effect of Rayleigh number on a high Rossby number flow in a high-pressure compressor inter-disk cavity. These cavities form between the compressor disks of a gas turbine engine, and they are an integral part of the internal air cooling system. We perform highly resolved large-eddy simulations for two Rayleigh numbers of 0.76 × 108 and 1.54 × 108 at a fixed Rossby number of 4.5 by solving the compressible Navier–Stokes equations. The results show a flow structure dominated by a toroidal vortex in the inner region of the cavity. In the outer region, the flow is observed to move radially outwards by Ekman layers formed on the side disks and to move radially inwards through the central core region of the cavity. An enhancement in the intensity of the radial flares is observed in the outer region of the cavity for the high Rayleigh number case with no perceivable effect in the inner region. The near-shroud region is mostly dominated by the centrifugal buoyancy-induced flow and the wall Nusselt number calculated at the shroud is in close agreement with centrifugal buoyancy-induced flow without an axial bore flow.
Thermodynamic Assessment of Using Water as a Refrigerant in Cascade Refrigeration Systems With Other Environmentally Friendly Refrigerants
Authors: Alkhulaifi Yousif M. , Mokheimer Esmail M. A.
Published: April 2021

For current and future sustainability, refrigerants with high global warming potential (GWP) are being phased out and replaced with environmentally friendly refrigerants. To this end, research into the current and possible future low-GWP refrigerant alternatives in cascade refrigeration systems has caught much attention. In this paper, a mathematical model is developed to assess the optimum energetic, exergetic, and operational parameters of a cascade refrigeration system using water as a refrigerant in the upper cycle with R744, N2O, R41, R717, R290, and R1270 in the lower cycle for a cooling load of 10 TR (35.2 kW). Multiple studies have been conducted for evaporator temperatures between −25 and 5 °C. Results show that R41 and R717 as low- and intermediate-temperature refrigerants, respectively, are recommended for the bottom cycle. Furthermore, R717-water showed improved coefficient of performance (COP) compared to other top cycle refrigerants, with a COP improvement of 2.9% to 8.6%. This study demonstrates the thermal feasibility of using water as a refrigerant in low-temperature cascade systems. Using water as a refrigerant in the top cycle showed promising results in low-temperature applications without the risk of solidification. However, the drawbacks are the high volumetric flowrate and compressor discharge temperature, requiring high capacity water injected compressor.
Fluid Dynamics and Pressure Drop Prediction of Two-Phase Flow Through Sudden Contractions
Authors: Patra Saroj K. , Roul Manmatha K. , Satapathy Prasanta K. , Barik Ashok K.
Published: April 2021

The aim of the present study is to investigate fluid dynamics and pressure drop across sudden contractions in a two-dimensional, axisymmetric pipe carrying a two-phase mixture of air (secondary phase) and water (primary phase), using the Eulerian–Eulerian model of the multiphase flow physics to solve the mass, momentum, volume fraction and turbulent quantities with relevant boundary conditions in a finite volume framework. The realizable per-phase k-ε and Reynolds stress models have been used as the closure for turbulent quantities along with enhanced wall function for the near-wall treatment. The effects of various parameters such as mass flux, mass flow quality, area ratio (0.056–0.619), flow directions (horizontal/vertical), and system pressure on the two-phase pressure drops due to a contraction in the pipe have been quantified. For both the single and two-phase flows, it has been observed that the pressure drop decreases with area ratio, and increases with mass flux and mass flow quality of two-phase flow. The vena contracta for a single-phase flow was found. But for two-phase flow, neither the vena contracta nor the recirculation zone has been observed, as the mass quality exceeds above 50%. A higher pressure drop has been observed for vertical pipes as compared to horizontal pipes. The present numerical results have also been validated with published experimental results, believed to be one of the alternatives to the costly experimental methods for predicting the flow dynamics and pressure drop.
An Object-Oriented Knowledge-Based System for Assembly of Printed Circuit Boards
Authors: Padhy Sisir K. , Dwivedi S. N.
Published: April 2021

In this paper, Printed Circuit Board Assembly Advisor (PCAAD), an object-oriented knowledge-based system is described. The system aims to aid the designer by suggesting design modifications that will lead to a better design for assembly of the Printed Circuit Boards. To account for the new trends in the printed circuit board production, hybrid technology, i.e. combination of both the through-hole mounted technology and surface mounted technology, is taken into consideration in developing the knowledge base. The assembly constraints as well as various limitations of different techniques and processes are considered to formulate the rules and guidelines. Moreover, a hierarchical rule structure has been employed in creating the knowledge base. Smalltalk-80, the object-oriented language and Surface Percept Description Language (SPDL) are used for the creation of knowledge base.

The system provides a high-level user interface and reasoning capability to solve complex problems. It is capable of ranking different designs and suggesting design modifications to the designer during the design stage to eliminate assembly problems in the latter phase of board production.
In Support of Second Order Optimization
Authors: Cao Qiushi , Krishnaswami Prakash
Published: April 2021

The vast majority of applied optimization falls into the category of first order optimization. This paper attempts to make the case for increased use of second order optimization techniques. Some of the most serious criticisms against second order methods are discussed and are shown to have lost some of their validity in recent years. In addition, some positive advantages of second order methods are also presented. These advantages include computational efficiency, compatibility with new advances in hardware and spill-over benefits in areas such as minimum sensitivity design. A simple second order constrained optimization algorithm is developed and several examples are solved using this method. A comparison is made with first order methods in terms of the number of function evaluations. The results show that the second order method performs much better than the first order methods in this regard. The paper also suggests some directions for future research in second order optimization.