bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of rate of change of parameter on early warning signals for critical transitions
Authors: Pavithran Induja , Sujith R. I.
Published: January 2021

Many dynamical systems exhibit abrupt transitions or tipping as the control parameter is varied. In scenarios where the parameter is varied continuously, the rate of change of the control parameter greatly affects the performance of early warning signals (EWS) for such critical transitions. We study the impact of variation of the control parameter with a finite rate on the performance of EWS for critical transitions in a thermoacoustic system (a horizontal Rijke tube) exhibiting subcritical Hopf bifurcation. There is a growing interest in developing early warning signals for tipping in real systems. First, we explore the efficacy of early warning signals based on critical slowing down and fractal characteristics. From this study, lag-1 autocorrelation (AC) and Hurst exponent (H) are found to be good measures to predict the transition well before the tipping point. The warning time, obtained using AC and H, reduces with an increase in the rate of change of the control parameter following an inverse power law relation. Hence, for very fast rates, the warning time may be too short to perform any control action. Furthermore, we report the observation of a hyperexponential scaling relation between the AC and the variance of fluctuations during such a dynamic Hopf bifurcation. We construct a theoretical model for noisy Hopf bifurcation wherein the control parameter is continuously varied at different rates to study the effect of rate of change of the parameter on EWS. Similar results, including the hyperexponential scaling, are observed in the model as well.
Detection of the liquid–liquid transitions in superalloys melts upon overheating and relaxation by the electromagnetic method
Authors: Tyagunov Andrey , Tyagunov Gennady , Milder Oleg , Tarasov Dmitry
Published: January 2021

Among numerous melt structure model representations, the most relevant for liquid heat-resistant nickel alloys description is the quasicrystalline model of a microinhomogeneous structure, in which it is assumed that multicomponent nickel melts consist of clusters and intercluster space. Clusters inherit the short-range order of the atomic structure from various phases of the initial solid metal crystalline structure. Heating the melt to a certain temperature and/or increasing a period of its isothermal holding at constant pressure led to a second-order phase liquid–liquid phase transition (LLT). As a result, atomic associations that are more balanced and uniformly distributed over the melt volume are formed. Structural changes in nickel superalloy melts are irreversible and have a significant effect on the formation of the structure and properties of a solid metal during crystallization. Structural LLT changes in multicomponent nickel melts are the basis for a scientific substantiation of the technological modes of smelting, which contributes to an improvement in the technological properties of melts, a reduction of metallurgical defects, a rational use of expensive elements and foundry waste, as well as a significant improvement in the quality of metal products. This work is devoted to the experimental determination of the LLT transition in superalloy melts by the noninvasive electromagnetic method.
Tertiary alkyl halides as growth activator and inhibitor for novel atomic layer deposition of low resistive titanium nitride
Authors: Yeon Changbong , Jung Jaesun , Byun Hyeran , Tan Kok Chew , Song Taeho , kim Sojung , Kim Jin Hee , Lee Seok Jong , Park Young-Soo
Published: January 2021

A novel atomic layer deposition (ALD) that utilizes tertiary alkyl (tert-alkyl) halides as both growth activator and inhibitor is introduced and demonstrated for the deposition of a low resistive TiN film using TiCl4 and NH3. Among the alkyl halides, tert-butyl iodide is identified as a suitable material for both growth inhibition and growth activation without any incorporation of C impurity in the film. The electrical resistivity values of TiN thin films in activator-type and inhibitor-type ALD were significantly improved by 55% and 49%, respectively. The mechanism of the reduction in electrical resistivity is elucidated by means of theoretical approach and characterizations of TiN films. For activator-type ALD, tert-butyl iodide induces in situ ligand exchange with an adsorbed Ti precursor to form Ti–I bonds, leading to an increase in the reactivity with a NH3 reactant. For inhibitor-type ALD, the improvement of film conformality in a high aspect ratio (>22:1) substrate is exhibited. This study demonstrates that the effectiveness on the use of tert-alkyl halides in ALD deposition can serve as an important guideline for future studies of the growth activator and growth inhibitor to improve film properties, making the method widely applicable.
Design and analysis of magnetostrictive sensors for wireless temperature sensing
Authors: Rajagopal Manjunath C. , Sinha Sanjiv
Published: January 2021

Magnetostrictive transducers are commonly used as actuators and sonar transducers, and in remote non-destructive evaluation. Their use in wireless thermometry is relatively unexplored. Since magnetostriction-based sensors are passive, they could potentially enable long-term near-field thermometry. While the temperature sensitivity of resonance frequency in magnetostrictive transducers has been reported in previous studies, the origin of the temperature sensitivity has, however, not been elucidated. Here, we identify material properties that determine temperature sensitivity and identify ways to improve sensitivity as well as the detection technique. Using a combination of analytical and computational methods, we systematically identify the material properties that directly influence the temperature coefficient of resonance frequency (TCF). We first experimentally measure the shift in resonance frequency due to temperature changes in a Metglas strip to be 0.03% K−1. Using insights from theory, we then experimentally demonstrate a fivefold improvement to the TCF by using Terfenol in place of Metglas as the magnetostrictive sensor material. We further demonstrate an alternate temperature sensing technique that does not require measuring the resonance frequency, consequently reducing instrument complexity. This work provides a general framework to analyze magnetostrictive materials and the sensing scheme for near-field wireless thermometry.
Principal strain rate evolution within turbulent premixed flames for different combustion regimes
Authors: Kasten Christian , Ahmed Umair , Klein Markus , Chakraborty Nilanjan
Published: January 2021

The statistical behaviors of the principal strain rates and its evolution in turbulent premixed flames have been analyzed using a three-dimensional direct numerical simulations dataset of statistically planar turbulent premixed flames with different turbulence intensities spanning from the corrugated flamelet regime to the thin reaction zone regime. It has been found that the scalar gradient predominantly aligns collinearly with the most extensive principal strain rate eigendirection within the flame for large values of Damköhler numbers and small values of turbulence intensities and Karlovitz numbers. However, this tendency weakens with the increasing turbulence intensity, which, for a given integral length scale, amounts to a decrease (an increase) in the Damköhler (Karlovitz) number. Moreover, it has been observed that the terms due to molecular diffusion, pressure Hessian, and the correlation between pressure and density gradients play key roles in the evolution of principal strain rates for flames with large values of Damköhler numbers and small values of Karlovitz numbers. However, the relative importance of the terms arising from the correlation between pressure and density gradients and the pressure Hessian relative to the strain rate and vorticity contributions of the principal strain rate transport diminishes with the increasing Karlovitz number and decreasing Damköhler number. The statistical behaviors of the mean values of the terms of the transport equation of the principal strain rate have been explained based on the relative alignments of principal strain rate eigenvectors with vorticity, pressure gradient, and the eigenvectors of the pressure Hessian tensor. The findings of the current analysis suggest that the pressure gradient and pressure Hessian tensor play key roles in the evolution of principal strain rates within premixed turbulent flames, and their influence needs to be accounted for high fidelity modeling of the tangential strain rate and scalar–turbulence interaction terms of the flame surface density and scalar dissipation rate transport equations, respectively. This provides possible explanations for the modification in the alignment of the reactive scalar gradient with local principal strain rates in premixed flames in comparison to that in non-reacting turbulent flows.
Local coercivity at X-ray nanobeam irradiated regions in amorphous Fe80B20 stripes
Authors: Urdiroz U. , Navarro E. , Sánchez-Agudo M. , Cebollada F. , Palomares F. J. , Criado G. Martínez , González J. M.
Published: January 2021

We report on the effect, on the local magnetization reversal taking place in amorphous Fe80B20 stripes, of the irradiation with nanobeam synchrotron X-ray. That irradiation preserves the amorphous structure and results on the increase of the local coercivity with respect to that measured in a non-irradiated sample, in which the coercivity is mediated by the nucleation-propagation of a single wall. The local coercivity increases in a non-linear way with the width of the irradiated regions when that width is smaller than that of the wall mediating the magnetization switching in the non-irradiated stripe and gets saturated when the irradiated regions dimension is larger than the propagating wall width. We correlate this behavior with the induction at the irradiated regions of a reduction of the local effective anisotropy with respect to the stripe as-lithographed value. From the relationship between the coercivity and the width of the irradiated regions we estimate the local anisotropy reduction in a 25% of that measured in the non-irradiated stripe.
Translocation of black foot pāua (
Authors: Bennett-Jones Louise , Gnanalingam Gaya , Flack Brendan , Scott Nigel , Pritchard Daniel , Moller Henrik , Hepburn Christopher
Published: January 2021

Loss of access to cultural keystone species is a familiar story across the Pacific. Serial depletion of pāua (abalone, Haliotis iris), a cultural keystone for Māori in Aotearoa New Zealand, threatens Indigenous practices and values. Kāti Huirapa Rūnaka ki Puketeraki, a hapū (subtribe) of Ngāi Tahu, have struggled for over 30 years to address loss of local pāua populations. Regulations introduced by the East Otago Taiāpure, a customary fishery management area established in 1999, recognise Indigenous rights to access and manage marine resources. Despite concerted efforts to rebuild pāua populations while allowing fishing, pāua have continued to decline and the fishery was closed in 2019. A wealth of mātauranga (Māori knowledge) surrounds enhancement practices for pāua. Here, mātauranga relating to translocation was collated through interviews and applied, in conjunction with additional knowledge bases, to translocate pāua from reefs threatened by sand inundation to more accessible but historically overexploited bays. In total, 420 pāua, translocated across 21 sites, were monitored for a 2-week period, after which aggregations returned to pretranslocation densities. Total mortality reached 8.8% over this time, attributed primarily to predation by the sea star Astrostole scabra. Results suggest that translocation may not be suitable for creating artificial aggregations using the methods applied; however, it could address other management concerns, hence suggestions are made for methodological improvements. The interaction between pāua and A. scabra demonstrates the need for continued transformation in management to allow for the application of a multispecies integrated approach in the restoration of pāua.
Mapping the intermedia agenda setting (IAS) literature
Authors: Su Yan , Xiao Xizhu
Published: January 2021

This study systematically reviewed empirical intermedia agenda setting (IAS) research published between 1997 and 2019, in terms of the level of agenda-setting, the methodologies – including the coding strategies and time-series analytical techniques – the types of media, and the flow of IAS effects. According to our results, previous IAS studies exhibited the following trends: (1) an overwhelming majority of the IAS studies was anchored by the first agenda-setting level, whilst examinations of the NAS model and multiple levels have increased in recent years; (2) excessive IAS studies performed content analyses, (3) applied manual coding strategies, (4) conducted cross-lagged correlation analyses to examine time-series effects, (5) and focused on newspapers and Twitter; (6) most IAS research confirmed the flow from one traditional media to another traditional media, whereas more recent studies also revealed the flow from traditional to emerging media, and their reciprocal relationship; (7) the majority of IAS studies confirmed the elite-to-non-elite flow of IAS effects. Based on these findings, this study encourages futures IAS researchers to attach more importance to (1) contextual diversity, (2) balanced examinations of each agenda-setting level, (3) methodological innovations, (4) technological pluralism, and (5) providing more evidence for the flow of IAS effects across different types of media.
Invited Commentary: Medicaid Policy and Pregnancy Outcomes—Toward a Reproductive Autonomy Framework
Authors: Jarlenski Marian
Published: January 2021

The Medicaid program covers more than 70 million people and is the largest single health insurance payer for pregnancy and delivery in the United States. In this issue of the Journal, Margerison et al. (Am J Epidemiol. 2021;190(8):1488–1498) investigate the extent to which expansion of Medicaid coverage to nonpregnant low-income adults under the Affordable Care Act may have improved prepregnancy or birth outcomes. They found that Medicaid expansions by states were not associated with changes in prepregnancy health, including smoking and obesity. Similarly, there were no changes in preterm birth or small or large size for gestational age attributable to Medicaid expansion. Results were consistent across a range of model specifications and with allowance for different lag times between Medicaid expansion and pregnancy. The results are consistent with prior research finding that pregnancy-specific Medicaid expansions did not uniformly translate to improved pregnancy and birth outcomes. Results should be interpreted in light of the limited contribution that medical services make to overall health and well-being. To reduce the high rates of adverse pregnancy and child health outcomes in the United States, Medicaid policy must move toward a reproductive autonomy framework that shifts the focus away from pregnancy-specific benefits and toward a comprehensive and patient-empowering reproductive health paradigm.
The Role of Mitochondrial Dysfunction in Preeclampsia: Causative Factor or Collateral Damage?
Authors: Smith Alex N , Wang Xi , Thomas Daniel G , Tatum Robert E , Booz George W , Cunningham Mark W
Published: January 2021

Preeclampsia, new onset hypertension in pregnancy, affects ~5%–10% of the world’s population. Preeclampsia is the leading cause of morbidity and mortality for both the mother and fetus. As of today, there is no cure for this disease except for delivery of the fetal–placental unit. The exact causation and onset of the disease are unknown. However, recent studies have shown a strong correlation between mitochondrial dysfunction and preeclampsia. Circulating mitochondrial DNA, elevated reactive oxygen species, angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA), activated natural killer cells, and upregulated inflammatory responses all contribute to mitochondrial dysfunction and the pathophysiology of preeclampsia. This review summarizes the current literature of both experimental and clinical observations that support the hypothesis that mitochondrial dysfunction contributes to the pathophysiology of preeclampsia and may be a precursor to the disease onset. This review will also address the use of therapies to improve mitochondrial dysfunction in preeclampsia.
Rapid local adaptation in both sexual and asexual invasive populations of monkeyflowers (Mimulusspp.)
Authors: Simón-Porcar Violeta I , Silva Jose L , Vallejo-Marín Mario
Published: January 2021

Background and Aims

Traditionally, local adaptation has been seen as the outcome of a long evolutionary history, particularly with regard to sexual lineages. By contrast, phenotypic plasticity has been thought to be most important during the initial stages of population establishment and in asexual species. We evaluated the roles of adaptive evolution and phenotypic plasticity in the invasive success of two closely related species of invasive monkeyflowers (Mimulus) in the UK that have contrasting reproductive strategies: M. guttatus combines sexual (seeds) and asexual (clonal growth) reproduction while M. × robertsii is entirely asexual.

Methods

We compared the clonality (number of stolons), floral and vegetative phenotype, and phenotypic plasticity of native (M. guttatus) and invasive (M. guttatus and M. × robertsii) populations grown in controlled environment chambers under the environmental conditions at each latitudinal extreme of the UK. The goal was to discern the roles of temperature and photoperiod on the expression of phenotypic traits. Next, we tested the existence of local adaptation in the two species within the invasive range with a reciprocal transplant experiment at two field sites in the latitudinal extremes of the UK, and analysed which phenotypic traits underlie potential local fitness advantages in each species.

Key Results

Populations of M. guttatus in the UK showed local adaptation through sexual function (fruit production), while M. × robertsii showed local adaptation via asexual function (stolon production). Phenotypic selection analyses revealed that different traits are associated with fitness in each species. Invasive and native populations of M. guttatus had similar phenotypic plasticity and clonality. M. × robertsii presents greater plasticity and clonality than native M. guttatus, but most populations have restricted clonality under the warm conditions of the south of the UK.

Conclusions

This study provides experimental evidence of local adaptation in a strictly asexual invasive species with high clonality and phenotypic plasticity. This indicates that even asexual taxa can rapidly (<200 years) adapt to novel environmental conditions in which alternative strategies may not ensure the persistence of populations.
Characterization of ω3 fatty acid desaturases from oomycetes and their application toward eicosapentaenoic acid production in Mortierella alpina
Authors: Mo Brian K H , Ando Akinori , Nakatsuji Ryohei , Okuda Tomoyo , Takemoto Yuki , Ikemoto Hiroyuki , Kikukawa Hiroshi , Sakamoto Takaiku , Sakuradani Eiji , Ogawa Jun
Published: January 2021

ω3 Polyunsaturated fatty acids are currently obtained mainly from fisheries; thus, sustainable alternative sources such as oleaginous microorganisms are required. Here, we describe the isolation, characterization, and application of 3 novel ω3 desaturases with ω3 polyunsaturated fatty acid–producing activity at ordinary temperatures (28 °C). First, we selected Pythium sulcatum and Plectospira myriandra after screening for oomycetes with high eicosapentaenoic acid/arachidonic acid ratios and isolated the genes psulω3 and pmd17, respectively, which encode ω3 desaturases. Subsequent characterization showed that PSULω3 exhibited ω3 desaturase activity on both C18 and C20 ω6 polyunsaturated fatty acids while PMD17 exhibited ω3 desaturase activity exclusively on C20 ω6 polyunsaturated fatty acids. Expression of psulω3 and pmd17 in the arachidonic acid–producer Mortierella alpina resulted in transformants that produced eicosapentaenoic acid/total fatty acid values of 38% and 40%, respectively, at ordinary temperatures. These ω3 desaturases should facilitate the construction of sustainable ω3 polyunsaturated fatty acid sources.
Competition, price dispersion and capacity constraints: the case of the U.S. corn seed industry
Authors: Ilin Cornelia , Shi Guanming
Published: January 2021

abstract

In this paper we examine the effect of competition on price dispersion and argue that the effect is contingent on the ability of firms to meet market demand. Our comparative static results show that competition among symmetrically capacity-unconstrained firms, or among firms with asymmetric capacities leads to an overall price increase along the distribution function. To investigate these findings empirically, we use a novel data set from the U.S. corn seed industry with firm and farm level sales information for conventional and genetically modified corn seeds between 2004 and 2009. We estimate the empirical model using the Fixed Effect Instrumental Variable Quantile Regression and find evidence consistent with the theory. The analysis also shows that capacity-unconstrained seed firms charge a price premium, confirming the positive relationship between product availability and pricing found in our theoretical model.
Local catheter impedance drop during pulmonary vein isolation predicts acute conduction block in patients with paroxysmal atrial fibrillation: initial results of the LOCALIZE clinical trial
Authors: Das Moloy , Luik Armin , Shepherd Ewen , Sulkin Matthew , Laughner Jacob , Oesterlein Tobias , Duffy Elizabeth , Meyer Christian , Jais Pierre , Duchateau Josselin , Yue Arthur , Ullah Waqas , Ramos Pablo , García-Bolao Ignacio
Published: January 2021

Aims

Radiofrequency ablation creates irreversible cardiac damage through resistive heating and this temperature change results in a generator impedance drop. Evaluation of a novel local impedance (LI) technology measured exclusively at the tip of the ablation catheter found that larger LI drops were indicative of more effective lesion formation. We aimed to evaluate whether LI drop is associated with conduction block in patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI).

Methods and results

Sixty patients underwent LI-blinded de novo PVI using a point-by-point ablation workflow. Pulmonary vein rings were divided into 16 anatomical segments. After a 20-min waiting period, gaps were identified on electroanatomic maps. Median LI drop within segments with inter-lesion distance ≤6 mm was calculated offline. The diagnostic accuracy of LI drop for predicting segment block was assessed using receiver operating characteristic analysis.

For segments with inter-lesion distance ≤6 mm, acutely blocked segments had a significantly larger LI drop [19.8 (14.1–27.1) Ω] compared with segments with gaps [10.6 (7.8–14.7) Ω, P < 0.001). In view of left atrial wall thickness differences, the association between LI drop and block was further evaluated for anterior/roof and posterior/inferior segments. The optimal LI cut-off value for anterior/roof segments was 16.1 Ω (positive predictive value for block: 96.3%) and for posterior/inferior segments was 12.3 Ω (positive predictive value for block: 98.1%) where inter-lesion distances were ≤6 mm.

Conclusion

The magnitude of LI drop was predictive of acute PVI segment conduction block in patients with paroxysmal AF. The thinner posterior wall required smaller LI drops for block compared with the thicker anterior wall.
The Relationship between the Misfolding Avoidance Hypothesis and Protein Evolutionary Rates in the Light of Empirical Evidence
Authors: Usmanova Dinara R , Plata Germán , Vitkup Dennis
Published: January 2021

For more than a decade, the misfolding avoidance hypothesis (MAH) and related theories have dominated evolutionary discussions aimed at explaining the variance of the molecular clock across cellular proteins. In this study, we use various experimental data to further investigate the consistency of the MAH predictions with empirical evidence. We also critically discuss experimental results that motivated the MAH development and that are often viewed as evidence of its major contribution to the variability of protein evolutionary rates. We demonstrate, in Escherichia coli and Homo sapiens, the lack of a substantial negative correlation between protein evolutionary rates and Gibbs free energies of unfolding, a direct measure of protein stability. We then analyze multiple new genome-scale data sets characterizing protein aggregation and interaction propensities, the properties that are likely optimized in evolution to alleviate deleterious effects associated with toxic protein misfolding and misinteractions. Our results demonstrate that the propensity of proteins to aggregate, the fraction of charged amino acids, and protein stickiness do correlate with protein abundances. Nevertheless, across multiple organisms and various data sets we do not observe substantial correlations between proteins’ aggregation- and stability-related properties and evolutionary rates. Therefore, diverse empirical data support the conclusion that the MAH and similar hypotheses do not play a major role in mediating a strong negative correlation between protein expression and the molecular clock, and thus in explaining the variability of evolutionary rates across cellular proteins.
Diazinon resistance, fluctuating asymmetry and fitness in the Australian sheep blowfly, lucilia cuprina.
Authors: McKenzie J A , Clarke G M
Published: January 2021

Genetic evidence suggests that the evolution of resistance to the insecticide diazinon in Lucilia cuprina initially produced an increase in asymmetry. At that time resistant flies were presumed to be at a selective disadvantage in the absence of diazinon. Subsequent evolution in natural populations selected modifiers to ameliorate these effects. The fitness and fluctuating asymmetry levels of resistant flies are currently similar to those of susceptibles. Previous genetic analyses have shown the fitness modifier to co-segregate with the region of chromosome III marked by the white eyes, w, locus, unlinked to the diazinon resistance locus, Rop-1, on chromosome IV. This study maps the asymmetry modifier to the same region, shows, as in the case of the fitness modifier, its effect to be dominant and presents data consistent with the fitness/asymmetry modifier being the same gene (gene complex). These results suggest changes in fluctuating asymmetry reflect changes in fitness.
Genetic applications of an inverse polymerase chain reaction.
Authors: Ochman H , Gerber A S , Hartl D L
Published: January 2021

A method is presented for the rapid in vitro amplification of DNA sequences that flank a region of known sequence. The method uses the polymerase chain reaction (PCR), but it has the primers oriented in the reverse direction of the usual orientation. The template for the reverse primers is a restriction fragment that has been ligated upon itself to form a circle. This procedure of inverse PCR (IPCR) has many applications in molecular genetics, for example, the amplification and identification of sequences flanking transposable elements. In this paper we show the feasibility of IPCR by amplifying the sequences that flank an IS1 element in the genome of a natural isolate of Escherichia coli.
Effects of amino acid substitutions at the active site in Escherichia coli beta-galactosidase.
Authors: Cupples C G , Miller J H
Published: January 2021

Forty-nine amino acid substitutions were made at four positions in the Escherichia coli enzyme beta-galactosidase; three of the four targeted amino acids are thought to be part of the active site. Many of the substitutions were made by converting the appropriate codon in lacZ to an amber codon, and using one of 12 suppressor strains to introduce the replacement amino acid. Glu-461 and Tyr-503 were replaced, independently, with 13 amino acids. All 26 of the strains containing mutant enzymes are Lac-. Enzyme activity is reduced to less than 10% of wild type by substitutions at Glu-461 and to less than 1% of wild type by substitutions at Tyr-503. Many of the mutant enzymes have less than 0.1% wild-type activity. His-464 and Met-3 were replaced with 11 and 12 amino acids, respectively. Strains containing any one of these mutant proteins are Lac+. The results support previous evidence that Glu-461 and Tyr-503 are essential for catalysis, and suggest that His-464 is not part of the active site. Site-directed mutagenesis was facilitated by construction of an f1 bacteriophage containing the complete lacZ gene on a single EcoRI fragment.
Transposon Tn5 target specificity: preference for insertion at G/C pairs.
Authors: Lodge J K , Weston-Hafer K , Berg D E
Published: January 2021

The procaryotic transposon Tn5 inserts into many different sites within a single gene, but some sites (hotspots) are targeted repeatedly. Hotspots are not closely related in sequence, but most have G/C pairs at the ends of the nine base pairs duplicated by Tn5 insertion. In pBR322, the major hotspot coincides with the "-10 region" of the tet promoter. We mutated the G/C pairs at this hotspot and assayed for insertion into hotspot I, resistance to tetracycline, and plasmid supercoiling. We found that changing the G/C pairs to A/T pairs reduced the frequency of insertion into the hotspot by at least fivefold. The reduction in hotspot use caused by these G/C to A/T changes was not attributable to changes in plasmid supercoiling or tet promoter strength.
Isolation and characterization of conditional-lethal mutations in the TUB1 alpha-tubulin gene of the yeast Saccharomyces cerevisiae.
Authors: Schatz P J , Solomon F , Botstein D
Published: January 2021

Microtubules in yeast are functional components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. We have isolated 70 conditional-lethal mutations in the TUB1 alpha-tubulin gene of the yeast Saccharomyces cerevisiae using a plasmid replacement technique. Of the 70 mutations isolated, 67 resulted in cold-sensitivity, one resulted in temperature-sensitivity, and two resulted in both. Fine-structure mapping revealed that the mutations were located throughout the TUB1 gene. We characterized the phenotypes caused by 38 of the mutations after shifts of mutants to the nonpermissive temperature. Populations of temperature-shifted mutant cells contained an excess of large-budded cells with undivided nuclei, consistent with the previously determined role of microtubules in yeast mitosis. Several of the mutants arrested growth with a sufficiently uniform morphology to indicate that TUB1 has at least one specific role in the progression of the yeast cell cycle. A number of the mutants had gross defects in microtubule assembly at the restrictive temperature, some with no microtubules and some with excess microtubules. Other mutants contained disorganized microtubules and nuclei. There were no obvious correlations between these phenotypes and the map positions of the mutations. Greater than 90% of the mutants examined were hypersensitive to the antimicrotubule drug benomyl. Mutations that suppressed the cold-sensitive phenotypes of two of the TUB1 alleles occurred in TUB2, the single structural gene specifying beta-tubulin.
A conditional mutant having paralyzed cilia and a block in cytokinesis is rescued by cytoplasmic exchange in Tetrahymena thermophila.
Authors: Pennock D G , Thatcher T , Bowen J , Bruns P J , Gorovsky M A
Published: January 2021

Nineteen mutants that are conditional for both the ability to regain motility following deciliation and the ability to grow were isolated. The mutations causing slow growth were placed into five complementation groups. None of the mutations appears to affect energy production as all mutants remained motile at the restrictive temperature. In three complementation groups protein synthesis and the levels of mRNA encoding alpha-tubulin or actin were largely unaffected at the restrictive temperature, consistent with the hypothesis that mutations in these three groups directly affect the assembly of functional cilia and growth. Complementation group 1 was chosen for further characterization. Both phenotypes were shown to be linked, suggesting they are caused by a single mutation. Group 1 mutants regenerated cilia at the restrictive temperature, but the cilia were nonmotile. This mutation also caused a block in cytokinesis at the restrictive temperature but did not affect nuclear divisions or DNA synthesis. The block in cell division was transiently rescued by wild-type cytoplasm exchanged when mutants were paired with wild-type cells during conjugation (round 1 of genomic exclusion). Thus, at least one mutation has been isolated that affects assembly of some microtubule-based structures in Tetrahymena (cilia during regeneration) but not others (nuclei divide at 38 degrees), and the product of this gene is likely to play a role in both ciliary function and in cytokinesis.
Linkage disequilibrium in natural and experimental populations of Drosophila melanogaster.
Authors: Smit-McBride Z , Moya A , Ayala F J
Published: January 2021

We have studied linkage disequilibrium in Drosophila melanogaster in two samples from a wild population and in four large laboratory populations derived from the wild samples. We have assayed four polymorphic enzyme loci, fairly closely linked in the third chromosome: Sod Est-6, Pgm, and Odh. The assay method used allows us to identify the allele associations separately in each of the two homologous chromosomes from each male sampled. We have detected significant linkage disequilibrium between two loci in 16.7% of the cases in the wild samples and in 27.8% of the cases in the experimental populations, considerably more than would be expected by chance alone. We have also found three-locus disequilibria in more instances than would be expected by chance. Some disequilibria present in the wild samples disappear in the experimental populations derived from them, but new ones appear over the generations. The effective population sizes required to generate the observed disequilibria by randomness range from 40 to more than 60,000 individuals in the natural population, depending on which locus pair is considered, and from 100 to more than 60,000 in the experimental populations. These population sizes are unrealistic; the fact that different locus-pairs yield disparate estimates within the same population argues against the likelihood that the disequilibria may have arisen as a consequence of population bottlenecks. Migration, or population mixing, cannot be excluded as the process generating the disequilibria in the wild samples, but can in the experimental populations. We conclude that linkage disequilibrium in these populations is most likely due to natural selection acting on the allozymes, or on loci very tightly linked to them.
Requirements for hedgehog, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila.
Authors: Mohler J
Published: January 2021

Mutations of the hedgehog gene are generally embryonic lethal, resulting in a lawn of denticles on the ventral surface. In strong alleles, no segmentation is obvious and the anteroposterior polarity of ventral denticles is lost. Temperature shift analysis of a temperature-sensitive allele indicates an embryonic activity period for hedgehog between 2.5 and 6 hr of embryonic development (at 25 degrees) and a larval/pupal period from 4 to 7 days of development (at 25 degrees). Mosaic analysis of hedgehog mutations in the adult cuticle indicates a series of defined defects associated with the failure of appropriate hedgehog expression. In particular, defects in the distal portions of the legs and antenna occur in association with homozygous hedgehog clones in the posterior compartment of those structures. Because the defects are associated with homozygous clones, but are not co-extensive, a type of "domineering" nonautonomy is proposed for the activity of the hedgehog gene.
A linkage map of mouse chromosome 12: localization of Igh and effects of sex and interference on recombination.
Authors: Blank R D , Campbell G R , Calabro A , D'Eustachio P
Published: January 2021

Inheritance of restriction fragment length polymorphisms associated with four anonymous DNA markers (D12Nyu1, 2, 3 and 4), the Fos proto-oncogene, the Mtv-9 viral integration site, and the alpha 1-antitrypsin (Aat-1) and immunoglobulin heavy chain (Igh) gene families in the mouse has been followed in a backcross experiment. A Bayesian multilocus map-building strategy yielded the map: centromere-D12Nyu2-10 cM-D12Nyu1-2 cM-D12Nyu3-15 cM-Fos-1 cM-D12Nyu4-2 cM-Mtv-9-8 cM-Aat-1-17 cM-Igh-C. A map constructed from male meiotic data was substantially shorter than one constructed from female meiotic data. Significant interference was observed for the linkage group. Two groups of markers studied in recombinant inbred strains of mice could be interpolated into the map: Es-25, D12Nyu10, D12Nyu7 and Apob form a cluster proximal to D12Nyu2, and Ly-18, Ah, and D12Nyu5 form a cluster between D12Nyu2 and D12Nyu1. These data establish an unambiguously ordered linkage group including Igh and Aat-1 that spans most of chromosome 12.
A NOTE ON THE VARIANCE OF THE NUMBER OF LOCI HAVING A GIVEN GENE FREQUENCY
Authors: Ewens W J , Maruyama T
Published: January 2021

In a recent note in this journal (Maruyama 1973), one of us has considered, for a certain genetic model, the variance of the distribution of the number of loci having a given gene frequency. The formula given is incorrect. This brief note considers this problem and notes the correct solution in one particular case.
ON NEI AND ROYCHOUDHURY'S SAMPLING VARIANCES OF HETEROZYGOSITY AND GENETIC DISTANCE
Authors: Mitra S
Published: January 2021

Nei and Roychoudhury have developed an inequality relationship between the expected values of (jx- g)  2 and (ĝ—)  2 where jx is a biased and ĝ is an unbiased estimate of population homozygosity g. Their inequality is somewhat weak and can be improved, as is demonstrated in this paper.
GENETIC RECOMBINATION IN SEXUAL CROSSES OF PHYCOMYCES
Authors: Eslava A P , Alvarez M I , Burke Patricia V , Delbrück M
Published: January 2021

Sexual crosses between strains of Phycomyces blakesleeanus, involving three auxotrophic and one color marker and yielding a high proportion of zygospore germination, are described. Samples of 20-40 germ spores from 311 individual fertile germ sporangia originating from five two-factor and three three-factor crosses were characterized. The results show: (1) absence of any contribution of apogamic nuclei to the progeny, (2) confirmation of Burgeff's conjecture that the germ spores of any germ sporangium in most cases derive from one meiosis. In a cross involving two allelic markers the analysis of 175 pooled germ sporangia suggests an intragenic recombination frequency of 0.6%. All other factor combinations tested are unlinked. The bulk of the germ spores are homokaryotic. However, a small portion (4%) are heterokaryotic with respect to mating type.
GENES AFFECTING PRODUCTIVITY IN NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER
Authors: Watanabe Takao K , Ohnishi Seido
Published: January 2021

Two hundred second chromosomes were extracted from a Japanese population in October of 1972, and the viabilities and productivities of homozygotes and heterozygotes from them were examined. Viability was measured by the Cy method and productivity by the number of progeny produced per female. The frequency of lethal-carrying chromosomes was 0.315. When the average heterozygote viability was standardized as 1.000, the average homozygote viability was 0.595 including the lethal lines, and 0.866 excluding them. The frequency of recessive sterile chromosomes among 131 non-lethal lines was 0.092 in females and 0.183 in males. There were two instances in which homozygosis for the second chromosome caused sterility in both sexes, which was close to the number expected (2.2) on a random basis of 0.092 × 0.183 × 131. When the average heterozygote productivity of 200 lines was standardized as 1.000, the average homozygote productivity was 0.532 including female steriles, and 0.584 excluding them. The ratio of detrimental load to lethal load was 0.383, while the ratio of partial sterility load to complete sterility load was 5.767. The average viability of lethal heterozygotes was slightly, but not significantly, lower than that of lethal-free heterozygotes, while the average productivity of lethal heterozygotes was significantly lower than that of lethal-free heterozygotes. There was a significant association of sterility in either sex with low viability of homozygotes. However, no statistically significant differences in viability and productivity were detected between sterile heterozygotes and non-sterile heterozygotes. The heterozygous effects of viability and productivity polygenes were examined by regressions of the heterozygotes on the sum of corresponding homozygotes. The regression coefficients were slightly positive for both viability and productivity if lethal and sterile chromosomes were excluded. The correlation between viability and productivity in homozygotes was significantly positive when sterile chromosomes were included, but the significance disappeared when the sterile chromosomes were excluded. In the heterozygotes there were no detectable correlations between them.
Adaptive learning algorithms to optimize mobile applications for behavioral health: guidelines for design decisions
Authors: Figueroa Caroline A , Aguilera Adrian , Chakraborty Bibhas , Modiri Arghavan , Aggarwal Jai , Deliu Nina , Sarkar Urmimala , Jay Williams Joseph , Lyles Courtney R
Published: January 2021

Objective

Providing behavioral health interventions via smartphones allows these interventions to be adapted to the changing behavior, preferences, and needs of individuals. This can be achieved through reinforcement learning (RL), a sub-area of machine learning. However, many challenges could affect the effectiveness of these algorithms in the real world. We provide guidelines for decision-making.

Materials and Methods

Using thematic analysis, we describe challenges, considerations, and solutions for algorithm design decisions in a collaboration between health services researchers, clinicians, and data scientists. We use the design process of an RL algorithm for a mobile health study “DIAMANTE” for increasing physical activity in underserved patients with diabetes and depression. Over the 1.5-year project, we kept track of the research process using collaborative cloud Google Documents, Whatsapp messenger, and video teleconferencing. We discussed, categorized, and coded critical challenges. We grouped challenges to create thematic topic process domains.

Results

Nine challenges emerged, which we divided into 3 major themes: 1. Choosing the model for decision-making, including appropriate contextual and reward variables; 2. Data handling/collection, such as how to deal with missing or incorrect data in real-time; 3. Weighing the algorithm performance vs effectiveness/implementation in real-world settings.

Conclusion

The creation of effective behavioral health interventions does not depend only on final algorithm performance. Many decisions in the real world are necessary to formulate the design of problem parameters to which an algorithm is applied. Researchers must document and evaulate these considerations and decisions before and during the intervention period, to increase transparency, accountability, and reproducibility.

Trial Registration

clinicaltrials.gov, NCT03490253.
Multivariable Manipulation of Spectrophotometric Data with Genetic Algorithm Selection for Novel Quantitative Resolution of Five Antiviral Drugs in Their Pharmaceutical Products
Authors: Essam Hebatallah M , Morsi Amani M , El-Zeiny Mohammed B
Published: January 2021

Background

In many real-world situations there are many components in a mixture that produce an enormous amount of information.

Objective

The main task is to build up balanced models that convert these data into meaningful information to deal with. Hence, different chemometric models were applied for the analysis of data obtained from a mixture containing sofosbuvir, ledipasvir, velpatasvir, daclatasvir, and valacyclovir that were recently used internationally for their antiviral activity.

Methods

Partial Least Squares, Spectral Residual Augmented Classical Least Squares, and Concentration Residual Augmented Classical Least Squares designs were applied with and without variable selection procedure [Genetic Algorithm (GA)]. The methods were used for the quantitative analysis of the drugs in laboratory prepared mixtures and real market sample through handling the UV spectral data.

Results

Robust models were obtained by applying GA. The proposed methods were found to be rapid, simple, and required no preliminary separation steps.

Conclusion

These models can be used on a routine basis in quality control laboratories or factories giving competitor results to those obtained by the reported methods.

Highlights

The proposed models offer a powerful analytical alternative for laboratories that consider economic strategies in their requirements.
Fast autooxidation of a bis-histidyl-ligated globin from the anhydrobiotic tardigrade, Ramazzottius varieornatus, by molecular oxygen
Authors: Kobayashi Kazuo , Kim JeeEun , Fukuda Yohta , Kozawa Takahiro , Inoue Tsuyoshi
Published: January 2021

Tardigrades, a phylum of meiofaunal organisms, exhibit extraordinary tolerance to various environmental conditions, including extreme temperatures (−273 to 151°C) and exposure to ionizing radiation. Proteins from anhydrobiotic tardigrades with homology to known proteins from other organisms are new potential targets for structural genomics. Recently, we reported spectroscopic and structural characterization of a hexacoordinated haemoglobin (Kumaglobin [Kgb]) found in an anhydrobiotic tardigrade. In the absence of its exogenous ligand, Kgb displays hexacoordination with distal and proximal histidines. In this work, we analysed binding of the molecular oxygen ligand following reduction of haem in Kgb using a pulse radiolysis technique. Radiolytically generated hydrated electrons (eaq−) reduced the haem iron of Kgb within 20 µs. Subsequently, ferrous haem reacted with O2 to form a ferrous-dioxygen intermediate with a second-order rate constant of 3.0 × 106 M−1 s−1. The intermediate was rapidly (within 0.1 s) autooxidized to the ferric form. Redox potential measurements revealed an Eʹ0 of −400 mV (vs. standard hydrogen electrode) in the ferric/ferrous couple. Our results suggest that Kgb may serve as a physiological generator of O2▪− via redox signalling and/or electron transfer.