Abstract
Biological cells estimate concentration gradients of signaling molecules with a precision that is limited not only by sensing noise, but additionally by the cell’s own stochastic motion. We ...ask for the theoretical limits of gradient estimation in the presence of both motility and sensing noise. We introduce a minimal model of a stationary chemotactic agent in the plane subject to rotational diffusion with rotational diffusion coefficient
D
. The agent uses Bayesian estimation to optimally infer the gradient direction relative to itself from noisy concentration measurements. Meanwhile, this direction changes on a time-scale 1/
D
. We show that the optimal effective measurement time, which characterizes the time interval over which past gradient measurements should be averaged to reduce sensing noise, does not scale with the rotational diffusion time 1/
D
, but with the square root (
rD
)
−1/2
, where
r
is a rate of information gain defined as a signal-to-noise ratio normalized per unit time. This result for gradient sensing parallels a recent result by Mora
et al
(2019
Phys. Rev. Lett.
) for sensing absolute concentration in time-varying environments.
Though foreign language anxiety (FLA) has long been recognized as an important affective factor in second language learning, its impact is worth studying in new educational contexts of emergency ...remote teaching in response to the COVID-19 outbreak. The present study examines the key factors behind FLA in online teaching of English for Specific Purposes (ESP). The research was conducted among a sample of 171 first-year undergraduate university students of Economics & Business economics and Informatics at the Juraj Dobrila University of Pula, Croatia, during the winter semester of 2020/2021. The research instrument used was a 33-item questionnaire adapted from the FLCAS scale (Horwitz et al., 1986) to reflect the online ESP classroom environment. The main results indicate that various background factors, such as gender, self-assessed levels of proficiency, length of learning English and frequency of English language use, significantly influence the reported levels of language anxiety. Furthermore, the study establishes the underlying structure of FLA, with five factors positively correlated with overall language anxiety at the .01 level of statistical significance: speech anxiety, evaluation and comprehension anxiety, online ESP classroom environment, anxiety of talking to native speakers, and lack of motivation for online class attendance. Finally, multiple regression analysis shows that the five aspects of FLA, alongside the variables of gender and self-assessed pronunciation proficiency, represent statistically significant predictors of the total level of FLA among online ESP learners. The other independent variables are confirmed to be unreliable in predicting the overall level of language anxiety in an online ESP classroom.
Abstract
STUDY QUESTION
Can cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) alone or in combination with cancer antigen 125 (CA-125) be ...considered as potential blood biomarkers of endometriosis?
SUMMARY ANSWER
The results of this study indicate that COMP has no diagnostic value. TGFBI has potential as a non-invasive biomarker of the early stages of endometriosis, while TGFBI together with CA-125 has similar diagnostic characteristics as CA-125 alone for all stages of endometriosis.
WHAT IS KNOWN ALREADY
Endometriosis is a common, chronic gynecological disease that significantly affects patient quality of life by causing pain and infertility. The gold standard for diagnosis is visual inspection of pelvic organs by laparoscopy, therefore there is an urgent need for discovery of non-invasive biomarkers for endometriosis to reduce diagnostic delays and allow earlier treatment of patients. The potential biomarkers for endometriosis evaluated in this study (COMP and TGFBI) were previously identified by our proteomic analysis of peritoneal fluid samples.
STUDY DESIGN, SIZE, DURATION
This is a case–control study divided into a discovery (n = 56 patients) and a validation phase (n = 237 patients). All patients were treated between 2008 and 2019 in a tertiary medical center.
PARTICIPANTS/MATERIALS, SETTING, METHOD
Patients were stratified based on the laparoscopic findings. The discovery phase included 32 endometriosis patients (cases) and 24 patients with confirmed absence of endometriosis (controls). The validation phase included 166 endometriosis and 71 control patients. Concentrations of COMP and TGFBI were measured by ELISA in plasma samples, whereas concentration of CA-125 was measured using a clinically validated assay for serum samples. Statistical and receiver operating characteristic (ROC) curve analyses were performed. The classification models were built using the linear support vector machine (SVM) method with the SVM built-in feature ranking method.
MAIN RESULTS AND THE ROLE OF CHANCE
The discovery phase revealed significantly increased concentration of TGFBI, but not COMP, in plasma samples of patients with endometriosis compared to controls. In this smaller cohort, univariate ROC analysis showed fair diagnostic potential of TGFBI, with an AUC value of 0.77, sensitivity of 58%, and specificity of 84%. The classification model built using linear SVM and combining TGFBI and CA-125 showed an AUC value of 0.91, sensitivity of 88% and specificity of 75% in distinguishing patients with endometriosis from controls. The validation phase results revealed similar diagnostic characteristics of the SVM model combining TGFBI and CA-125, with an AUC value of 0.83, sensitivity of 83% and specificity of 67% and CA-125 alone with AUC value of 0.83, sensitivity of 73% and specificity of 80%. TGFBI exhibited good diagnostic potential for early-stage endometriosis (revised American Society for Reproductive Medicine stage I–II), with an AUC value of 0.74, sensitivity of 61% and specificity of 83% compared to CA-125, which had an AUC value of 0.63, sensitivity of 60% and specificity of 67%. An SVM model combining TGFBI and CA-125 showed a high AUC value of 0.94 and sensitivity of 95% for diagnosing moderate-to-severe endometriosis.
LIMITATIONS, REASONS FOR CAUTION
The diagnostic models were built and validated from a single endometriosis center, and thus further validation and technical verification in a multicenter study with a larger cohort is needed. Additional limitation was lack of histological confirmation of disease for some patients in the validation phase.
WIDER IMPLICATIONS OF THE FINDINGS
This study revealed for the first time increased concentration of TGFBI in plasma samples of patients with endometriosis, particularly those with minimal-to-mild endometriosis, compared to controls. This is the first step in considering TGFBI as a potential non-invasive biomarker for the early stages of endometriosis. It also opens a path for new basic research to investigate the importance of TGFBI in the pathophysiology of endometriosis. Further studies are needed to confirm the diagnostic potential of a model based on TGFBI and CA-125 for the non-invasive diagnosis of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
The preparation of this manuscript was supported by grant J3-1755 from the Slovenian Research Agency to T.L.R and EU H2020-MSCA-RISE project TRENDO (grant 101008193). All authors declare that they have no conflicts of interest.
TRIAL REGISTRATION NUMBER
NCT0459154.
Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and ...their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated. Here we show that the spindle is chiral. Chirality is evident from the finding that microtubule bundles in human spindles follow a left-handed helical path, which cannot be explained by forces but rather by torques. Kinesin-5 (Kif11/Eg5) inactivation abolishes spindle chirality. Our theoretical model predicts that bending and twisting moments may generate curved shapes of bundles. We found that bundles turn by about -2 deg µm
around the spindle axis, which we explain by a twisting moment of roughly -10 pNµm. We conclude that torques, in addition to forces, exist in the spindle and determine its chiral architecture.
During metaphase, forces on kinetochores are exerted by k-fibres, bundles of microtubules that end at the kinetochore. Interestingly, non-kinetochore microtubules have been observed between sister ...kinetochores, but their function is unknown. Here we show by laser-cutting of a k-fibre in HeLa and PtK1 cells that a bundle of non-kinetochore microtubules, which we term 'bridging fibre', bridges sister k-fibres and balances the interkinetochore tension. We found PRC1 and EB3 in the bridging fibre, suggesting that it consists of antiparallel dynamic microtubules. By using a theoretical model that includes a bridging fibre, we show that the forces at the pole and at the kinetochore depend on the bridging fibre thickness. Moreover, our theory and experiments show larger relaxation of the interkinetochore distance for cuts closer to kinetochores. We conclude that the bridging fibre, by linking sister k-fibres, withstands the tension between sister kinetochores and enables the spindle to obtain a curved shape.
The objective of this paper was to analyse allelopathic effect of 3 different aqueous solutions from tree of heaven’s (Ailanthus altissima (Mill.) Swingle) root extract and their dilutions on common ...wheat (Triticum aestivum L.), pigweed (Amaranthus retroflexus L.) and red bristlegrass (Setaria pumila L.). Investigated aqueous solutions obtained from tree of heaven’s root extract were root aqueous solution, aqueous solution with isolated ailanthone and root aqueous solution without ailanthone. Each of these solutions was diluted with water in ratio 1:4 and 1:16 before application on seeds of 3 test-plant species. Concentrated root and ailanthone aqueous solution and dilutions were equivalent to concentration of 0.48 mg/mL ailanthone. High allelopathic effect on radicle and shoot length of all test-species was proven for all investigated aqueous solution and their dilutions. Inhibitory effect on initial growth of all test-species was proportional to the increase in concentration in all treatments. The effect on initial growth was stronger in relation to the effect on germination of test-species. Lower concentrations caused stimulation of red bristlegrass germination. Pigweed was the most sensitive and common wheat the least sensitive test-species. The least significant effect was measured in the aqueous solution of isolated ailanthone.
At the global level, the invasion of alien organisms is considered the second largest threat to biodiversity. The assumption is that the high allelopathic potential is one of the features that helps ...invasive plant species to spread to new areas. Allelopathic potential of 8 invasive plant species (donor species) and their impact on test-species was determined in the study. Donor species were velvetleaf (Abutilon theophrasti Med.), ragweed (Ambrosia elatior L.), jimsonweed (Datura stramonium L.), common cocklebur (Xanthium strumarium L.), tree of heaven (Ailanthus altissima (Mill.) Swingle), indigo bush (Amorpha fruticosa L.), Japanese knotweed (Reynoutria japonica Houtt.) and giant goldenrod (Solidago gigantea Aiton). Three cultivated plant species from 3 different plant families were used as test-species. Test-species were: oat (Avena sativa L.), oilseed rape (Brassica napus subsp. oleifera) and sunflower (Helianthus annuus L.). Water extracts made of whole plants of donor species were applied to the seeds of the test-species. High allelopathic potential was proven for all species included in experiment. Allelopathic effects were exclusively negative. Impact on germination for all species was much lower in relation to the impact on the radicle and shoot length of the test-species. Perennial donor species had a stronger allelopathic potential than annual donor species. Tree of heaven was the species with the strongest allelopathic potential. Its extracts inhibited germination, radicle and shoot length of oilseed rape by 19%, 94.88% and 98.91% respectively.
The mitotic spindle segregates chromosomes into two daughter cells during cell division. This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through ...mitosis. The forces in the spindle are difficult to directly measure using the available experimental techniques. Here, we review the ideas and recent advances of how forces can be determined from the spindle shape. By using these approaches, it has been shown that tension and compression coexist along a single kinetochore fiber, which are balanced by a bridging fiber between sister kinetochore fibers. An extension of this approach to three dimensions revealed that microtubule bundles have rich shapes, and extend not simply like meridians on the Earth's surface but, rather, twisted in a helical manner. Such complex shapes are due to rotational forces, which, in addition to linear forces, act in the spindle and may be generated by motor proteins such as kinesin-5. These findings open new questions for future studies, to understand the mechanisms of rotational forces and reveal their biological roles in cells.
To test the hypothesis that, in the initial evaluation of patients with suspected coronary artery disease (CAD), stress myocardial perfusion imaging (MPI) would result in less downstream testing than ...coronary computed tomographic angiography (CCTA).
In this international, randomized trial, mildly symptomatic patients with an intermediate likelihood of having CAD, and asymptomatic patients at intermediate risk of cardiac events, underwent either initial stress-rest MPI or CCTA. The primary outcome was downstream noninvasive or invasive testing at 6 months. Secondary outcomes included cumulative effective radiation dose (ERD) and costs at 12 months.
We recruited 303 patients (151 MPI and 152 CTA) from 6 centers in 6 countries. The initial MPI was abnormal in 29% (41/143) and CCTA in 56% (79/141) of patients. Fewer patients undergoing initial stress-rest MPI had further downstream testing at 6 months (adjusted OR 0.51, 95% CI 0.28-0.91, P = 0.023). There was a small increase in the median cumulative ERD with MPI (9.6 vs. 8.8 mSv, P = 0.04), but no difference in costs between the two strategies at 12 months.
In the management of patients with suspected CAD, a strategy of initial stress MPI is substantially less likely to require further downstream testing than initial testing with CCTA. Trial registration: clinicaltrials.gov identification number NCT01368770.
Croatia is a small but heterogeneous country with different pedo-climatic conditions in its parts. In the continental region, mountain region excluded, the climate is moderate continental and in the ...coastal region Mediterranean and sub-Mediterranean. The aim of this study was to explore the presence, prevalence and level of aggressiveness of some invasive alien plants between continental and coastal part of Croatia. Amorpha fruticosa L., Reynoutria japonica Houtt. and Solidago gigantea Ait. are widespread and very aggressive in the continental and rarely present in coastal part of Croatia. Ailanthus altissima (Mill.) Swingle is present in each Croatian county but it shows greater aggressiveness in the coastal region, including islands and some protected areas.
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