bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotype comparison among individuals with developmental delay/intellectual disability with or without genomic imbalances
Authors: de Souza L. C. , dos Santos A. P. , Sgardioli I. C. , Viguetti‐Campos N. L. , Marques Prota J. R. , de Oliveira‐Sobrinho R. P. , Vieira T. P. , Gil‐da‐Silva‐Lopes V. L.
Published: March 2019

Background

The chromosomal microarray analysis (CMA) is recommended as a first‐tier test for individuals with developmental delay (DD)/intellectual disability (ID) and/or multiple congenital anomalies. However, owing to high costs, this technique is not widely performed for diagnostic purposes in several countries. The aim of this study was to identify clinical features that could favour the hypothesis of genomic imbalances (GIs) in individuals with DD/ID.

Methods

The sample consisted of 63 individuals, and all of them underwent a detailed evaluation by a clinical geneticist and were investigated by the CMA. They were divided into two groups. Group A composed of 20 individuals with pathogenic copy number variants (CNVs); and group B composed of 43 individuals with normal CMA results or variants of uncertain clinical significance (VUS).

Results

Pathogenic GIs were found in 20 cases (32%), including 11 individuals with an abnormal karyotype, VUS was found in five individuals (8%) and the results were normal in 38 individuals (60%). Major anomalies were found in 15/20 (75%) individuals in group A against 35/43 (81%) in group B. Dysmorphisms (≥5) were found in 17/20 (85%) in group A and 41/43 (95%) in group B. The most frequent major anomalies detected in group A were congenital heart disease, epilepsy and renal malformation; and in group B, they were malformations of central nervous system, congenital heart disease, microcephaly, epilepsy and hearing impairment. There was no significant statistical difference among the frequencies in groups A and B.

Conclusions

Evidences point that every individual with DD/ID, with no specific clinical suspicion, should have screening for GIs as a first‐tier test, regardless of the presence or absence of additional major anomalies or dysmorphisms. Future studies with a similar design would be helpful, especially in countries where the access to new technologies is still limited.
The effect of automated landmark identification on morphometric analyses
Authors: Percival Christopher J. , Devine Jay , Darwin Benjamin C. , Liu Wei , van Eede Matthijs , Henkelman R. Mark , Hallgrimsson Benedikt
Published: March 2019

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time‐consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of ‘normal’ phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra‐ and inter‐strain variation. With this unique sample, we investigated how switching to a non‐linear image registration‐based automated landmarking method impacts estimated differences in genotype mean shape and shape variance‐covariance structure. In addition, we tested whether an initial registration of specimen images to genotype‐specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype‐specific registration step as part of a two‐level procedure did not substantially improve on the accuracy of one‐level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro‐computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra‐observer landmarking error. For appropriate samples and research questions, our image registration‐based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes.
Posture‐related stiffness mapping of paraspinal muscles
Authors: Creze Maud , Bedretdinova Dina , Soubeyrand Marc , Rocher Laurence , Gennisson Jean‐Luc , Gagey Olivier , Maître Xavier , Bellin Marie‐France
Published: March 2019

The paraspinal compartment acts as a bone–muscle composite beam of the spine. The elastic properties of the paraspinal muscles play a critical role in spine stabilization. These properties depend on the subjects’ posture, and they may be drastically altered by low back pain. Supersonic shear wave elastography can be used to provide quantitative stiffness maps (elastograms), which characterize the elastic properties of the probed tissue. The aim of this study was to challenge shear wave elastography sensitivity to postural stiffness changes in healthy paraspinal muscles. The stiffness of the main paraspinal muscles (longissimus, iliocostalis, multifidus) was measured by shear wave elastography at the lumbosacral level (L3 and S1) for six static postures performed by volunteers. Passive postures (rest, passive flexion, passive extension) were performed in a first shear wave elastography session, and active postures (upright, bending forward, bending backward) with rest posture for reference were performed in a second session. Measurements were repeated three times for each posture. Sixteen healthy young adults were enrolled in the study. Non‐parametric paired tests, multiple analyses of covariance, and intra‐class correlations were implemented for analysis. Shear wave elastography showed good to excellent reliability, except in the multifidus at S1, during bending forward, and in the multifidus at L3, during bending backward. Yet, during bending forward, only poor quality was recorded for nine volunteers in the longissimus. Significant intra‐ and inter‐muscular changes were observed with posture. Stiffness significantly increased for the upright position and bending forward with respect to the reference values recorded in passive postures. In conclusion, shear wave elastography allows reliable assessment of the stiffness of the paraspinal muscles except in the multifidus at S1 and longissimus, during bending forward, and in the multifidus at L3, during bending backward. It reveals a different biomechanical behaviour for the multifidus, the longissimus, and the iliocostalis.
Why Do Retailers Advertise Store Brands Differently Across Product Categories?
Authors: Griffith Rachel , Krol Michal , Smith Kate
Published: March 2019

We provide new evidence on retailers’ pricing and advertising of store brands in the U.K. grocery markets. We analyse a simple Hotelling model in which retailers and manufacturers endogenously advertise their respective brands; we account for the impact of advertising on retailer–manufacturer bargaining and downstream competition. The model predicts that retailers advertise their store brands less when advertising is more rivalrous. We present empirical evidence consistent with this prediction. According to our model, aggregate consumer surplus can be higher with store brands than when they are absent from the market.
Gasoline Price Dispersion and Consumer Search: Evidence from a Natural Experiment
Authors: Noel Michael D.
Published: March 2019

The vast majority of empirical studies examining the link between consumer search and price dispersion focus on how changes in consumer search impact price dispersion. This article does the reverse—it examines how a shock to price dispersion impacts consumer search. A direct measure of search is used and an exogenous shock to price dispersion is found in a refinery fire that caused decades‐old retail gasoline price cycles, and the nonlinear high‐frequency price dispersion pattern generated by them, to stop. Identifying effects from this shock, the results show a substantial response of consumer search to changes in price dispersion.
Regulation of the expression of key signalling molecules in mTOR pathway of skeletal muscle satellite cells in neonatal chicks: Effects of leucine and glycine–leucine peptide
Authors: She Yue , Deng Huiling , Cai Huiyi , Liu Guohua
Published: March 2019

This study was conducted to analyse the effects of leucine (Leu) and glycine (Gly)‐Leu peptide on expressions of key signalling molecules in mTOR pathway of skeletal muscle satellite cells in neonatal chicks. The 4‐day‐old male AA broilers with similar weight were selected to obtain the broiler skeletal muscle satellite cells with the two‐step method of collagenase‐I and trypsin digestion. The satellite cells were subjected to primary culture in vitro, and they were cultured in DMEM medium with the Leu concentration of 0.2 mM and 2 mM as well as with the Gly‐Leu peptide concentration of 0.2 mM and 2 mM. The experiment lasted for 5 days. The results showed that TOR, S6K1 and 4E‐BP1 mRNA expressions in the medium with Leu concentration of 2 mM were significantly higher than that in 0.2 mM group (p < 0.05). There was no difference between the medium with Gly‐Leu concentration of 2 mM and 0.2 mM on the TOR, S6K1 and 4E‐BP1 mRNA expressions (p > 0.05). In conclusion, Leu significantly increases TOR, S6K1 and 4E‐BP1 mRNA expressions of skeletal muscle satellite cells, but Gly‐Leu peptide has no effect on them.
Implementing Government Policy in Supply Chains: An International Coproduction Study of Public Procurement
Authors: Harland Christine , Telgen Jan , Callender Guy , Grimm Rick , Patrucco Andrea
Published: March 2019

Public procurement is the commercial arm of governments, contracting for goods, and services to feed public sector service provision. However, mainstream operations and supply chain management journals have published little on supply chains to governments, public procurement, and the significance of engaging small businesses in government supply chains. Policy feedback theory and thirteen coproduced international case studies of public procurement and small business agency dyadic relationships are used to explore this space. The research highlights the importance of both public procurement and small business as areas of policy and supply chain management research. Policy feedback theory is introduced as a means to understand relationships and is applied to a coproduction study to understand how supply chain management research can both explore and change policy.
Resurge deposits associated with the shallow marine early Cambrian Vakkejokk impact, north Sweden
Authors: Ormö J. , Minde P. , Nielsen A. T. , Alwmark C.
Published: March 2019

The lower Cambrian Vakkejokk Breccia is a proximal ejecta layer from a shallow marine impact. It is exposed for ~7 km along a steep mountainside in Lapland, northernmost Sweden. In its central parts, the layer is up to ~27 m thick. Here the breccia shows a vertical differentiation into (1) a lower subunit consisting of strongly deformed target sediments mixed with up to decameter size, mainly crystalline basement clasts (i.e., lower polymict breccia [LPB]); (2) a middle subunit consisting of a polymict, blocky to gravelly breccia, commonly graded (i.e., graded polymict breccia [GPB]), that, in turn, is sporadically overlain by (3) a few dm thick, sandy bed (i.e., top sandstone [TS]). Previous work interpreted the graded beds as deposited by resurging water during early crater modification. We made three short (<1.35 m) core drillings through the graded beds. The line‐logging technique previously used on cores from other marine‐target craters was complemented by logging of equal‐sized cells in photos made along the cores. Granulometry and clast lithology determinations provide further evidence for the top beds of the breccia being resurge deposits. However, the magnitude of this resurge can only be assessed by future deep core drilling of the infill of the crater hidden below the mountain.
The mystery of our mathematical universe
Authors: Paulson Steve , Gates S. James , Wertheim Margaret
Published: March 2019

Why is it that fundamental laws discovered through pure mathematics have been able to describe the behavior of our physical world with such precision? Given that the physical universe is composed of mathematical properties, some have posited that mathematics is the language of the universe, whose laws reveal what appears to be a hidden order in the natural world. Physicist S. James Gates, Jr. and science writer Margaret Wertheim explore the uncanny ability of mathematics to reveal the laws of nature.
Increasing plant diversity of experimental grasslands alters the age and growth of Plantago lanceolata from younger and faster to older and slower
Authors: Roeder Anna , Schweingruber Fritz H. , Fischer Markus , Roscher Christiane
Published: March 2019

The persistence of plant populations depends on the ability of individuals to cope with the conditions provided by the community. So far, it is not known whether differences in the diversity and composition of plant communities affect the age structure of plant populations or the expression of stem anatomical traits reflecting investment into plant growth and storage. We analyzed annual growth rings in the secondary xylem and measured stem anatomical traits in individuals from 18 populations of Plantago lanceolata growing in a 12‐year old grassland biodiversity experiment (Jena Experiment). Plant individuals of P. lanceolata were on average older and reproduced later with increasing species richness. Individuals of P. lanceolata were slightly younger and the age distribution within populations skewed to younger individuals in the presence of grasses. The presence of legumes did not affect mean age, but led to a more even age distribution within populations. The width of growth‐related tissues (xylem, phloem, phellem) decreased with increasing species richness. Plant diversity‐effects on storage‐related tissues (pith, cortex) were less consistent, as pith showed increasing width with species richness, while cortex did not change with plant diversity. Our results imply that plant diversity effects on population age structure and the expression of stem anatomical traits of P. lanceolata reflect a tradeoff: growth and turnover is fast at low diversity (younger age, higher allocation to growth‐related tissue, faster generative reproduction), while it is slow at high diversity (older age, higher allocation to storage‐related tissue, later generative reproduction).
Stochastic and deterministic processes drive wetland community assembly across a gradient of environmental filtering
Authors: Daniel Jody , Gleason Jennifer Erin , Cottenie Karl , Rooney Rebecca C.
Published: March 2019

The role of deterministic and stochastic processes in community assembly is a key question in community ecology. We evaluated the effect of an abiotic filter (hydroperiod) on the partitioned diversity of three taxonomic groups (birds, vegetation, macroinvertebrates) from prairie pothole wetlands in Alberta, Canada, which naturally vary in water permanence. We observed that alpha and gamma diversity were higher in permanent than temporary wetlands (16–25% and 34–47% respectively, depending on the taxon). This suggests an influence of deterministic constraints on the number of species a wetland can support. Taxa which cannot persist in shallow, temporary wetlands are excluded by the deterministic constraints that a shortened hydroperiod imposes. In contrast, we observed that beta diversity was significantly higher (2–12%) in temporary wetlands than permanent ones, and temporary wetlands supported more unique combinations of community composition than permanent wetlands, despite having a smaller regional species pool. This observation contradicts prior mesocosm studies that found beta diversity mirrored the pattern in gamma diversity along an environmental filtering gradient. We conclude that deterministic processes are more influential in more stable permanent wetlands, whereas stochastic processes play a more important role in assembly in dynamic temporary wetlands that must disassemble and re‐establish annually. Considering three distinct taxonomic groups differing in their relative mobility, our large‐scale field study demonstrates that both stochastic and deterministic processes act together to influence the assembly of multiple communities and that the relative importance of the two processes varies consistently along a gradient of environmental filtering.
Habitat‐driven life history variation in an amphibian metapopulation
Authors: Cayuela Hugo , Cruickshank Sam S. , Brandt Hannelore , Ozgul Arpat , Schmidt Benedikt R.
Published: March 2019

Life‐history theory states that, during the lifetime of an individual, resources are allocated to either somatic maintenance or reproduction. Resource allocation tradeoffs determine the evolution and ecology of life‐history strategies and determine an organisms’ position along the fast–slow continuum. Theory predicts that environmental stochasticity is an important driver of resource allocation and therefore life‐history evolution. Highly stochastic environments are expected to increase uncertainty in reproductive success and select for iteroparity and a slowing down of the life history. To date, most empirical studies have used comparisons among species to examine these theoretical predictions. By contrast, few have investigated how environmental stochasticity affects life‐history strategies at the intraspecific level. In this study, we examined how variation in breeding site stochasticity (among‐year variability in pond volume and hydroperiod) promotes the co‐occurrence of different life‐history strategies in a spatially structured population, and determines life‐history position along the fast–slow continuum in the yellow‐bellied toad Bombina variegata. We collected mark–recapture data from a metapopulation and used multievent capture–recapture models to estimate survival, recruitment and breeding probabilities. We found higher survival and longer lifespans in populations inhabiting variable sites compared to those breeding in stable ones. In addition, probabilities of recruitment and skipping a breeding event were higher in variable sites. The temporal variance of survival and recruitment probabilities, as well as the probability to skip breeding, was higher in variable sites. Taken together, these findings indicate that populations breeding in variable sites experienced a slowing down of the life‐history. Our study thus revealed similarities in the macroevolutionary and microevolutionary processes shaping life‐history evolution.
The impact of life form on the architecture of orchid mycorrhizal networks in tropical forest
Authors: Xing Xiaoke , Jacquemyn Hans , Gai Xuege , Gao Yue , Liu Qiang , Zhao Zeyu , Guo Shunxing
Published: March 2019

Understanding the processes that determine the architecture of interaction networks represents a major challenge in ecology and evolutionary biology. One of the most important interactions involving plants is the interaction between plants and mycorrhizal fungi. While there is a mounting body of research that has studied the architecture of plant–fungus interaction networks, less is known about the potential factors that drive network architecture. In this study, we described the architecture of the network of interactions between mycorrhizal fungi and 44 orchid species that represented different life forms and co‐occurred in tropical forest and assessed the relative importance of ecological, evolutionary and co‐evolutionary mechanisms determining network architecture. We found 87 different fungal operational taxonomic units (OTUs), most of which were members of the Tulasnellaceae. Most orchid species associated with multiple fungi simultaneously, indicating that extreme host selectivity was rare. However, an increasing specificity towards Tulasnellaceae fungal associates from terrestrial to epiphytic and lithophytic orchids was observed. The network of interactions showed an association pattern that was significantly modular (M = 0.7389, Mrandom = 0.6998) and nested (NODF = 5.53, p < 0.05). Terrestrial orchids had almost no links to modules containing epiphytic or lithophytic orchids, while modules containing epiphytic orchids also contained lithophytic orchids. Within each life form several modules were observed, suggesting that the processes that organize orchid–fungus interactions are independent of life form. The overall phylogenetic signal for both partners in the interaction network was very weak. Overall, these results indicate that tropical orchids associate with a wide number of mycorrhizal fungi and that ecological rather than phylogenetic constraints determine network architecture.
Reinventing heterosis phenomenon through deployment of alien introgression lines in rice (Oryza sativa L.)
Authors: Gaikwad Kiran B. , Singh Naveen , Bhatia Dharminder , Kaur Rupinder , Bains Navtej S. , Bharaj Tajinder S. , Singh Kuldeep
Published: March 2019

Introgression Lines (ILs) carrying alien genomic segments in the homozygous state may or may not be able to contribute positively to the phenotype on account of replacement of cultivated genome segment, however, the genetic elite in heterozygous condition can be attributed to the presence of both recipient and donor genome complements. Therefore, overdominance or pseudo‐overdominance effect at the heterozygous loci is anticipated. Set of 318 ILs, carrying several genomic segments from “A” genome donor wild species, were used for developing test hybrids with CMS line PMS17A. Of these, three hybrids observed significant yield advantage (>25%) over recurrent parents and checks. Parental ILs of these hybrids viz., IL326, IL901 and IL951 carried 5.62%, 2.52% introgression from Oryza rufipogon and 6.71% from Oryza nivara, respectively. These ILs were also crossed with their recurrent parent to develop introgression line hybrids (ILHs) to observe the contribution of the alien segment(s), in the homozygous and heterozygous state. The traits studied have higher mean value when genomic segments from wild species were in the heterozygous state as compared to the homozygous state.
Congenital hemangioma exhibiting postnatal growth
Authors: Knöpfel Nicole , Wälchli Regula , Luchsinger Isabelle , Theiler Martin , Weibel Lisa , Schwieger‐Briel Agnes
Published: March 2019

Congenital hemangiomas are vascular tumors that are fully formed at birth, typically without postnatal growth. Noninvoluting congenital hemangiomas (NICH) have a distinctive clinical, radiologic, and histopathological profile and lack of expansion or involution over time. Herein, we describe two cases of NICH with atypical postnatal growth.
Morphology‐controlled Fabrication of SnO2/ZnO Nanocomposites with Enhanced Photocatalytic Performance
Authors: Yu Yan , Yao Binghua , Cao Baoyue , Ma Wei
Published: March 2019

In this work, a series of novel SnO2/ZnO nanocomposites with different morphologies were fabricated via a facile hydrothermal technique followed by calcination in air. The morphological, structural and photocatalytic properties of the SnO2/ZnO nanocomposites were studied using different methods. The results showed that the synthesized nanocomposites possessed crystal phases of wurtzite hexagonal phase ZnO and tetragonal rutile phase SnO2. In addition, the morphologies of SnO2/ZnO nanocomposites strongly depended on the molar ratios of Sn and Zn. Compared with ZnO and SnO2, the SnO2/ZnO nanocomposites exhibited considerably higher degradation efficiency for the photodegradation of methylene blue and quinolone antibiotics under mercury lamp irradiation. The SZ‐2 nanospheres exhibited the highest degradation efficiency of 95.81%, which was about 2.63 times higher than that of ZnO nanoparticles. Moreover, the trapping experiments confirmed that ˙OH played the dominant role in MB degradation. Finally, the charge carriers potential transfer pathway and photocatalytic degradation mechanism were put forward. This study provides an economical way to prepare hybrid nanocomposites with controlled morphology for practical applications in the photocatalytic degradation of organic dyes and residual antibiotics.
Tiger Moms or Cat Dads: Parental Role in Bilingualism Among Asian and Latino Americans
Authors: Chen Jihui , Kang Hyun‐Sook
Published: March 2019

Objective

This study examines the differing roles of parents in producing bilingualism among second‐generation Asian and Latino Americans, the fastest growing immigrant groups in the United States.

Methods

We employ the probit model to estimate the likelihood of language maintenance for both ethnic groups using the Integrated Public Use Microdata Series (IPUMS) USA of 2005–2014.

Results

The estimation results show that mothers play a more significant role than fathers, especially for Latino Americans, and that heritage‐language retention increases with the parents’ age at arrival. We also find an increase in the rates of language maintenance across generations, presumably resulting from heightened awareness of the need to preserve cultural heritage among younger immigrants in recent decades.

Conclusion

These findings highlight the cultural and structural differences in gendered parenting between the two immigrant groups and suggest potential areas of gains through intervention programs for immigrant parents to promote parental investment in their children's development, including bilingualism.
Nonparametric identification and estimation of current status data in the presence of death
Authors: Mao Lu
Published: March 2019

We present a nonparametric study of current status data in the presence of death. Such data arise from biomedical investigations in which patients are examined for the onset of a certain disease, for example, tumor progression, but may die before the examination. A key difference between such studies on human subjects and the survival–sacrifice model in animal carcinogenicity experiments is that, due to ethical and perhaps technical reasons, deceased human subjects are not examined, so that the information on their disease status is lost. We show that, for current status data with death, only the overall and disease‐free survival functions can be identified, whereas the cumulative incidence of the disease is not identifiable. We describe a fast and stable algorithm to estimate the disease‐free survival function by maximizing a pseudo‐likelihood with plug‐in estimates for the overall survival rates. It is then proved that the global rate of convergence for the nonparametric maximum pseudo‐likelihood estimator is equal to Op(n−1/3) or the convergence rate of the estimated overall survival function, whichever is slower. Simulation studies show that the nonparametric maximum pseudo‐likelihood estimators are fairly accurate in small‐ to medium‐sized samples. Real data from breast cancer studies are analyzed as an illustration.
Efficient induction of heritable inversions in plant genomes using the CRISPR/Cas system
Authors: Schmidt Carla , Pacher Michael , Puchta Holger
Published: March 2019

During the evolution of plant genomes, sequence inversions occurred repeatedly making the respective regions inaccessible for meiotic recombination and thus for breeding. Therefore, it is important to develop technologies that allow the induction of inversions within chromosomes in a directed and efficient manner. Using the Cas9 nuclease from Staphylococcus aureus (SaCas9), we were able to obtain scarless heritable inversions with high efficiency in the model plant Arabidopsis thaliana. Via deep sequencing, we defined the patterns of junction formation in wild‐type and in the non‐homologous end‐joining (NHEJ) mutant ku70‐1. Surprisingly, in plants deficient of KU70, inversion induction is enhanced, indicating that KU70 is required for tethering the local broken ends together during repair. However, in contrast to wild‐type, most junctions are formed by microhomology‐mediated NHEJ and thus are imperfect with mainly deletions, making this approach unsuitable for practical applications. Using egg‐cell‐specific expression of Cas9, we were able to induce heritable inversions at different genomic loci and at intervals between 3 and 18 kb, in the percentage range, in the T1 generation. By screening individual lines, inversion frequencies of up to the 10% range were found in T2. Most of these inversions had scarless junctions and were without any sequence change within the inverted region, making the technology attractive for use in crop plants. Applying our approach, it should be possible to reverse natural inversions and induce artificial ones to break or fix linkages between traits at will.
The onset of embryo maturation in Arabidopsis is determined by its developmental stage and does not depend on endosperm cellularization
Authors: O'Neill John P. , Colon Kristen T. , Jenik Pablo D.
Published: March 2019

Seeds are dormant and desiccated structures, filled with storage products to be used after germination. These properties are determined by the maturation program, which starts, in Arabidopsis thaliana, mid‐embryogenesis, at about the same time and developmental stage in all the seeds in a fruit. The two factors, chronological and developmental time, are closely entangled during seed development, so their relative contribution to the transition to maturation is not well understood. It is also unclear whether that transition is determined autonomously by each seed or whether it depends on signals from the fruit. The onset of maturation follows the cellularization of the endosperm, and it has been proposed that there exists a causal relationship between both processes. We explored all these issues by analyzing markers for maturation in Arabidopsis mutant seeds that develop at a slower pace, or where endosperm cellularization happens too early, too late, or not at all. Our data show that the developmental stage of the embryo is the key determinant of the initiation of maturation, and that each seed makes that transition autonomously. We also found that, in contrast with previous models, endosperm cellularization is not required for the onset of maturation, suggesting that this transition is independent of the hexose/sucrose ratio in the seed. Our observations indicate that the mechanisms that control endosperm cellularization, embryo growth, and embryo maturation act independently of each other.
Phylogeography of West Indies Coral snakes (Micrurus): Island colonisation and banding patterns
Authors: Jowers Michael J. , Garcia Mudarra Juan Luis , Charles Stevland P. , Murphy John C.
Published: March 2019

In this study, we analyse New World coral snakes in a phylogenetic framework based upon an increased molecular data set, including novel sequences for the only two sympatric species known from an island (Trinidad, West Indies). Their presence in Trinidad and absence in Tobago offers a unique system to study the phylogeography of the region. We assess the tempo and mode of colonisation of Micrurus on the island, in addition to discussing the phylogenetic relationships for the genus Micrurus concerning two phenotypic traits, body and tail banding patterns. These relationships are analysed for the first time on statistical coalescent phylogeographic discrete ancestral reconstruction. We find a robust phylogenetic component in these characteristics, where strongly supported clades are recovered: prior to the onset of the Early Miocene, a triadal and tricolour tail clade composed of species from South America, and a second clade dating to the Middle‐Late‐ Miocene with monadal and bicolour tails widely distributed from North to South America. The divergence between clades dates to the Oligocene and suggests an ancient pre‐isthmus divergence supporting the arrival of the triadal clade into South America, before the connection between Central and South America was established. We find the two coral snakes present in the West Indies, M. diutius and M. circinalis, belong to the triadal and monadal clades, respectively. Guyana and Trinidad Micrurus diutius share the same haplotypes suggesting a Late Pleistocene–Holocene vicariance when sea level rises separated Trinidad from the mainland. A second lineage of diutius‐like snakes is present in Guyana and is confirmed as M. lemniscatus which is assigned as a voucher and restricts the type locality for M. lemniscatus.
A Model for Stall and Surge in Low-Speed Contra-Rotating Fans
Authors: Shahriyari Mohammad Javad , Khaleghi Hossein , Heinrich Martin
Published: March 2019

This paper reports on a theory for poststall transients in contra-rotating fans, which is developed from the basic Moore–Greitzer theory. A second-order hysteresis term is assumed for the fan pressure rise, which gives the theory more capabilities in predicting the fan instabilities. The effect of the rotational speed ratio of the two counter rotating rotors on the fan performance during the occurrence of surge and rotating stall are studied (the rotational speed of the front rotor is assumed to be kept constant whereas the speed of the rear rotor is variable). One of the new capabilities of the current model is the possibility of investigating the effect of the initial slope on the fan characteristic. Results reveal that unlike the conventional fans and compressors, in the current contra-rotating fan stall cannot be initiated from the negative slope portion of the fan pressure rise characteristic curve. One of the important advantages of the developed model is that it enables investigation of the effect of the rate of throttling on the instabilities. Results show that more the rotational speed of the rear rotor, the more robust to surge (caused by throttling) the fan is.
Cholesterol-Dependent Modulation of Stem Cell Biomechanics: Application to Adipogenesis
Authors: Sun Shan , Adyshev Djanybek , Dudek Steven , Paul Amit , McColloch Andrew , Cho Michael
Published: March 2019

Cell mechanics has been shown to regulate stem cell differentiation. We have previously reported that altered cell stiffness of mesenchymal stem cells can delay or facilitate biochemically directed differentiation. One of the factors that can affect the cell stiffness is cholesterol. However, the effect of cholesterol on differentiation of human mesenchymal stem cells remains elusive. In this paper, we demonstrate that cholesterol is involved in the modulation of the cell stiffness and subsequent adipogenic differentiation. Rapid cytoskeletal actin reorganization was evident and correlated with the cell's Young's modulus measured using atomic force microscopy. In addition, the level of membrane-bound cholesterol was found to increase during adipogenic differentiation and inversely varied with the cell stiffness. Furthermore, cholesterol played a key role in the regulation of the cell morphology and biomechanics, suggesting its crucial involvement in mechanotransduction. To better understand the underlying mechanisms, we investigated the effect of cholesterol on the membrane–cytoskeleton linker proteins (ezrin and moesin). Cholesterol depletion was found to upregulate the ezrin expression which promoted cell spreading, increased Young's modulus, and hindered adipogenesis. In contrast, cholesterol enrichment increased the moesin expression, decreased Young's modulus, and induced cell rounding and facilitated adipogenesis. Taken together, cholesterol appears to regulate the stem cell mechanics and adipogenesis through the membrane-associated linker proteins.
Online Diagnostics of Mechanical and Electrical Faults in Induction Motor Using Multiclass Support Vector Machine Algorithms Based on Frequency Domain Vibration and Current Signals
Authors: Gangsar Purushottam , Tiwari Rajiv
Published: March 2019

This paper demonstrates the development of a flexible fault diagnosis methodology that can detect up to ten different faults in the induction motor (IM), simultaneously. The major IM electrical faults, such as the broken rotor bar (BRB), phase unbalance (PUF), and stator winding fault (SWF), and mechanical faults, such as bearing fault (BF), unbalanced rotor (UR), bowed rotor (BR), and misaligned rotor (MR), are considered with different fault severities for the diagnosis. The experiments are conducted with three varying loads and seven different speeds, and the frequency domain vibration and current data are acquired at a relatively low sampling rate of 1 kHz. Several statistical features are extracted and then the best feature-set is selected using the wrapper model. Thereafter, a data classification tool based on the support vector machine (SVM) is used for the fault characterization. Initially, a multi-fault diagnosis is performed by training and testing the SVM at the same operating conditions (i.e., load and speed). The performance of the classifier is found to be very good at all IM operating conditions. The main focus of this study lies in overcoming the fault diagnosis, where the data are unavailable at required operating conditions. This is accomplished by employing interpolation and extrapolation strategies for different loads and speeds. The proposed methodology not only solves practical problem of unavailability of data at different operating conditions but also shows good performance and takes low computation time, which are vital requirements of an online intelligent condition monitoring system.
The architectural design of smart ventilation and drainage systems in termite nests
Authors: Singh Kamaljit , Muljadi Bagus P. , Raeini Ali Q. , Jost Christian , Vandeginste Veerle , Blunt Martin J. , Theraulaz Guy , Degond Pierre
Published: March 2019

Ventilation and drainage in termite nests are controlled by microscale morphological features of the outer walls.
Hydrogel 3D printing with the capacitor edge effect
Authors: Wang Jikun , Lu Tongqing , Yang Meng , Sun Danqi , Xia Yukun , Wang Tiejun
Published: March 2019

The capacitor edge effect can pattern liquids for 3D printing of various hydrogels.
Electronic structure at coarse-grained resolutions from supervised machine learning
Authors: Jackson Nicholas E. , Bowen Alec S. , Antony Lucas W. , Webb Michael A. , Vishwanath Venkatram , de Pablo Juan J.
Published: March 2019

Machine learning–enhanced molecular simulation opens a pathway to multiscale prediction for organic electronics.
Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells
Authors: Tamzalit Fella , Wang Mitchell S. , Jin Weiyang , Tello-Lafoz Maria , Boyko Vitaly , Heddleston John M. , Black Charles T. , Kam Lance C. , Huse Morgan
Published: March 2019

Cytotoxic T cells use actin-rich protrusions at the immunological synapse to enhance perforin-mediated target cell killing.
Characterization of
mcr-5
-Harboring
Salmonella enterica
subsp.
enterica
Serovar Typhimurium Isolates from Animal and Food Origin in Germany
Authors: Borowiak Maria , Hammerl Jens A. , Deneke Carlus , Fischer Jennie , Szabo Istvan , Malorny Burkhard
Published: March 2019

We characterized eight
mcr-5
-positive
Salmonella enterica
subsp.
enterica
serovar Typhimurium sequence type 34 (ST34) isolates obtained from pigs and meat in Germany.
A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti-
Staphylococcus aureus
Thiomab Antibody-Antibiotic Conjugate, in Healthy Volunteers
Authors: Peck Melicent , Rothenberg Michael E. , Deng Rong , Lewin-Koh Nicholas , She Gaohong , Kamath Amrita V. , Carrasco-Triguero Montserrat , Saad Ola , Castro Aide , Teufel Lisa , Dickerson Daniel S. , Leonardelli Marisa , Tavel Jorge A.
Published: March 2019

Staphylococcus aureus
causes serious bacterial infections with high morbidity and mortality, necessitating the discovery of new antibiotics. DSTA4637S is a novel antibody-antibiotic conjugate designed to target intracellular
S. aureus
that is not adequately eliminated by current standard-of-care antibiotics.
Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env
Authors: Anand Sai Priya , Grover Jonathan R. , Tolbert William D. , Prévost Jérémie , Richard Jonathan , Ding Shilei , Baril Sophie , Medjahed Halima , Evans David T. , Pazgier Marzena , Mothes Walther , Finzi Andrés
Published: March 2019

HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.
Mixed adenoneuroendocrine carcinoma of the urethra
Authors: Raison Nicholas , McGovern Ursula , Hines John , Volanis Dimitrios
Published: March 2019

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour found predominantly in the gastrointestinal tract. Comprising adenocarcinomatous and neuroendocrine components, MANEC have been reported in the bladder. We report the first case to our knowledge of a MANEC arising in the urethra. A 62-year-old woman presented with a suburethral mass. Initial excision of the mass revealed it to be a MANEC. Immunohistochemistry staining was positive for CK20 and synaptophysin associated with neuroendocrine tumours. Cross-sectional imaging ruled out metastases and the patient underwent radical urethrectomy, vaginal reconstruction and Mitrofanoff urinary diversion. The patient declined adjuvant chemotherapy and remained under regular surveillance. MANECs are uncommon tumours and treatment was therefore guided by expert opinion. A multidisciplinary approach is essential with the early involvement of surgeons, oncologists, histopathologist, radiologist and neuroendocrine specialists.
Hepatosplenic T cell lymphoma presenting as multiorgan failure
Authors: Pateria Puraskar , Martin Annalise , Khor Tze Sheng , Jayasekeran Vanoo
Published: March 2019

A 59-year-oldwoman presented with a 2-month history of malaise, abdominal distention and unintentional weight loss. She was initially managed as community acquired pneumonia with a suspicion of underlying chronic liver disease but she deteriorated rapidly into a multiorgan failure necessitating transfer to intensive care unit of a tertiary hospital. She was investigated with liver and bone marrow biopsy that confirmed the diagnosis of hepatosplenic T cell lymphoma. She was treated with cyclophosphamide, doxorubicin, vincristine, etoposide and prednisolone chemotherapy that was changed to salvage ifosfamide carboplatin etoposide (ICE) chemotherapy due to poor response with first-line chemotherapy and disease progression. Unfortunately, her disease progressed further and she opted for palliative management.
Correlation between aqueous flare and residual visual field area in retinitis pigmentosa
Authors: Nishiguchi Koji M , Yokoyama Yu , Kunikata Hiroshi , Abe Toshiaki , Nakazawa Toru
Published: March 2019

Background/aims

To investigate the relationship between aqueous flare, visual function and macular structures in retinitis pigmentosa (RP).

Methods

Clinical data from 123 patients with RP (227 eyes), 35 patients with macular dystrophy (68 eyes) and 148 controls (148 eyes) were analysed. The differences in aqueous flare between clinical entities and the correlation between aqueous flare (measured with a laser flare cell meter) versus visual acuity, visual field area (Goldmann perimetry) and macular thickness (optical coherence tomography) in patients with RP were determined. Influence of selected clinical data on flare was assessed using linear mixed-effects model.

Results

Aqueous flare was higher in patients with RP than patients with macular dystrophy or controls (p=7.49×E−13). Aqueous flare was correlated with visual field area (R=−0.379, p=3.72×E−9), but not with visual acuity (R=0.083, p=0.215). Macular thickness (R=0.234, p=3.74×E−4), but not foveal thickness (R=0.122, p=0.067), was positively correlated with flare. Flare was not affected by the presence of macular complications. All these associations were maintained when the right and the left eyes were assessed separately. Analysis by linear mixed-effects model revealed that age (p=8.58×E-5), visual field area (p=8.01×E-7) and average macular thickness (p=0.037) were correlated with flare.

Conclusion

Aqueous flare and visual field area were correlated in patients with RP. Aqueous flare may reflect the degree of overall retinal degeneration more closely than the local foveal impairment.
Immunotherapy-related hepatitis: real-world experience from a tertiary centre
Authors: Cheung Vincent , Gupta Tarun , Payne Miranda , Middleton Mark R , Collier Jane D , Simmons Alison , Klenerman Paul , Brain Oliver , Cobbold Jeremy F
Published: March 2019

Objective

Immune checkpoint inhibitors like anti-programmed cell death protein 1 (PD-1) drugs Nivolumab and Pembrolizumab and anti-cytotoxic T-lymphocyte associated (CTLA-4) drug Ipilimumab have become standard of care in many metastatic cancers. Immunotherapy-related hepatitis and cholangitis present a diagnostic and management challenge, being rare and incompletely characterised. We aim to report the incidence, features and treatments used for this in a real-world setting and to identify useful biomarkers, which can be used to predict effective use of steroids.

Design

Retrospective review of 453 patients started on immunotherapy over 7 years.

Setting

Tertiary hepatology and oncology centre.

Patients

21 patients identified with immunotherapy-related hepatotoxicity.

Results

Hepatitis was most common in those receiving dual therapy (incidence 20%), with 75% of Grade 4 hepatitis cases occurring with ipilimumab-containing regimens. Corticosteroid monotherapy is first line treatment, but doses above 60 mg OD prednisolone do not demonstrate any additional benefit in time to hepatitis resolution. The alanine transaminase (ALT) reduction in steroid-responsive hepatitis is typically rapid (with a halving of ALT within 11 days). The commencement of additional immunosuppression (typically mycophenolate) appears safe and prompts a more rapid fall in ALT than corticosteroid use alone. Infliximab was safely used twice as hepatitis treatment. We also describe one patient with rare immunotherapy-induced biliary disease.

Conclusions

Vigilance is required for detection of immunotherapy-associated liver disease as, other than dual immunotherapy, we can identify no predictive factors for its development. Our data suggest that corticosteroid response is not dependent on the higher dosing regimens. Early escalation of immunosuppression may be of benefit in the absence of a rapid response to corticosteroids.