bluuebunny/crossref_metadata_2025 huggingface dataset:
Expected Genotype Quality and Diploidized Marker Data from Genotyping-by-Sequencing of Urochloa spp. Tetraploids
Authors: Matias Filipe Inácio , Xavier Meireles Karem Guimarães , Nagamatsu Sheila Tiemi , Lima Barrios Sanzio Carvalho , do Valle Cacilda Borges , Carazzolle Marcelo Falsarella , Fritsche-Neto Roberto , Endelman Jeffrey B
Published: January 2019

Although genotyping-by-sequencing (GBS) is a well-established marker technology in diploids, the development of best practices for tetraploid species is a topic of current research. We determined the theoretical relationship between read depth and expected genotype quality (EGQ) for tetraploid vs. diploidized genotype calls. If the GBS method has 1% error, then 17 reads are needed to classify tetraploid samples as heterozygous vs. homozygous with 95% accuracy, compared with 63 reads to determine allele dosage. We developed an R script to convert tetraploid GBS data in Variant Call Format (VCF) into diploidized genotype calls and applied it to 267 interspecific hybrids of the tetraploid forage grass Urochloa (syn. Brachiaria). When reads were aligned to a mock reference genome created from GBS data of the U. brizantha cultivar ‘Marandu’, 25,678 bi-allelic SNPs were discovered, compared to approximately 3000 SNPs when aligning to the closest true reference genomes, Setaria viridis and S. italica. Crossvalidation revealed that missing genotypes were imputed by the Random Forest method with a median accuracy of 0.85, regardless of heterozygote frequency. Using the Urochloa spp. hybrids, we illustrated how filtering samples based only on GQ creates genotype bias; a depth threshold with corresponding EGQ equal to the GQ threshold is also needed, regardless of whether genotypes are called using a diploidized or allele dosage model.
Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin
Authors: Lee Yuh Chwen G. , Ogiyama Yuki , Martins Nuno M. C. , Beliveau Brian J. , Acevedo David , Wu C.-ting , Cavalli Giacomo , Karpen Gary H.
Published: January 2019

Membraneless pericentromeric heterochromatin (PCH) domains play vital roles in chromosome dynamics and genome stability. However, our current understanding of 3D genome organization does not include PCH domains because of technical challenges associated with repetitive sequences enriched in PCH genomic regions. We investigated the 3D architecture ofDrosophila melanogasterPCH domains and their spatial associations with euchromatic genome by developing a novel analysis method that incorporates genome-wide Hi-C reads originating from PCH DNA. Combined with cytogenetic analysis, we reveal a hierarchical organization of the PCH domains into distinct “territories.” Strikingly, H3K9me2/3-enriched regions embedded in the euchromatic genome show prevalent 3D interactions with the PCH domain. These spatial contacts require H3K9me2/3 enrichment, are likely mediated by liquid-liquid phase separation, and may influence organismal fitness. Our findings have important implications for how PCH architecture influences the function and evolution of both repetitive heterochromatin and the gene-rich euchromatin.

Author summary

The three dimensional (3D) organization of genomes in cell nuclei can influence a wide variety of genome functions. However, most of our understanding of this critical architecture has been limited to the gene-rich euchromatin, and largely ignores the gene-poor and repeat-rich pericentromeric heterochromatin, or PCH. PCH comprises large part of most eukaryotic genomes, forms 3D PCH domains in nuclei, and plays vital role in chromosome dynamics and genome stability. In this study, we developed a new method that overcomes the technical challenges imposed by the highly repetitive PCH DNA, and generated a comprehensive picture of its 3D organization. Combined with image analyses, we revealed a hierarchical organization of the PCH domains. Surprisingly, we showed that distant euchromatic regions enriched for repressive epigenetic marks also dynamically interact with the main PCH domains. These 3D interactions are mediated by liquid-liquid phase separation mechanisms, similar to how oil and vinegar separate in salad dressing, and can influence the fitness of individuals. Our discoveries have strong implications for how seemingly “junk” DNA could impact functions in the gene-rich euchromatin.
Simplified Molecular Classification of Lung Adenocarcinomas Based on EGFR, KRAS, and TP53 Mutations
Authors: Ruiz-Cordero Roberto , Ma Junsheng , Khanna Abha , Lyons Genevieve , Rinsurongkawong Waree , Bassett Roland , Guo Ming , Routbort Mark J. , Zhang Jianjun , Skoulidis Ferdinandos , Heymach John , Roarty Emily B. , Tang Zhenya , Medeiros L. Jeffrey , Patel Keyur P. , Luthra Rajyalakshmi , Chowdhuri Sinchita Roy
Published: January 2019

Introduction

Gene expression profiling has consistently identified three molecular subtypes of lung adenocarcinoma that have prognostic implications. To facilitate stratification of patients with this disease into similar molecular subtypes, we developed and validated a simple, mutually exclusive classification.

Methods

Mutational status of EGFR, KRAS, and TP53 was used to define six mutually exclusive molecular subtypes. A development cohort of 283 cytology specimens of lung adenocarcinoma was used to evaluate the associations between the proposed classification and clinicopathologic variables including demographic characteristics, smoking history, fluorescence in situ hybridization and molecular results. For validation and prognostic assessment, 63 of the 283 cytology specimens with available survival data were combined with a separate cohort of 428 surgical pathology specimens of lung adenocarcinoma.

Results

The proposed classification yielded significant associations between these molecular subtypes and clinical and prognostic features. We found better overall survival in patients who underwent surgery and had tumors enriched for EGFR mutations. Worse overall survival was associated with older age, stage IV disease, and tumors with comutations in KRAS and TP53. Interestingly, neither chemotherapy nor radiation therapy showed benefit to overall survival.

Conclusions

The mutational status of EGFR, KRAS, and TP53 can be used to easily classify lung adenocarcinoma patients into six subtypes that show a relationship with prognosis, especially in patients who underwent surgery, and these subtypes are similar to classifications based on more complex genomic methods reported previously.
Intrinsic spine dynamics are critical for recurrent network learning in models with and without autism spectrum disorder
Authors: Humble James , Hiratsuka Kazuhiro , Kasai Haruo , Toyoizum Taro
Published: January 2019

It is often assumed that Hebbian synaptic plasticity forms a cell assembly, a mutually interacting group of neurons that encodes memory. However, in recurrently connected networks with pure Hebbian plasticity, cell assemblies typically diverge or fade under ongoing changes of synaptic strength. Previously assumed mechanisms that stabilize cell assemblies do not robustly reproduce the experimentally reported unimodal and long-tailed distribution of synaptic strengths. Here, we show that augmenting Hebbian plasticity with experimentally observed intrinsic spine dynamics can stabilize cell assemblies and reproduce the distribution of synaptic strengths. Moreover, we posit that strong intrinsic spine dynamics impair learning performance. Our theory explains how excessively strong spine dynamics, experimentally observed in several animal models of autism spectrum disorder, impair learning associations in the brain.
Tad pili play a dynamic role in Caulobacter crescentus surface colonization
Authors: Sangermani Matteo , Hug Isabelle , Sauter Nora , Pfohl Thomas , Jenal Urs
Published: January 2019

Bacterial surface attachment is mediated by rotary flagella and filamentous appendages called pili. Here, we describe the role of Tad pili during surface colonization of Caulobacter crescentus. Using an optical trap and microfluidic controlled flow conditions as a mimic of natural environments, we demonstrate that Tad pili undergo repeated cycles of extension and retraction. Within seconds after establishing surface contact, pili reorient cells into an upright position promoting walking-like movements against the medium flow. Pili-mediated positioning of the flagellated pole close to the surface facilitates motor-mediated mechanical sensing and promotes anchoring of the holdfast, an adhesive substance that affords long-term attachment. We present evidence that the second messenger c-di-GMP regulates pili dynamics during surface encounter in distinct ways, promoting increased activity at intermediate levels and retraction of pili at peak concentrations. We propose a model, in which flagellum and Tad pili functionally interact and together impose a ratchet-like mechanism that progressively drives C. crescentus cells towards permanent surface attachment.
Targeted sequencing of candidate genes of dyslipidemia in Punjabi Sikhs: Population-specific rare variants inGCKRpromote ectopic fat deposition
Authors: Sanghera Dharambir K. , Hopkins Ruth , Malone-Perez Megan W. , Bejar Cynthia , Tan Chengcheng , Mussa Huda , Whitby Paul , Rao Chinthapally V. , Fung KarMing A. , Lightfoot Stan , Frazer J Kimble
Published: January 2019

Dyslipidemia is a well-established risk factor for cardiovascular diseases. Although, advances in genome-wide technologies have enabled the discovery of hundreds of genes associated with blood lipid phenotypes, most of the heritability remains unexplained. Here we performed targeted resequencing of 13 bona fide candidate genes of dyslipidemia to identify the underlying biological functions. We sequenced 940 Sikh subjects with extreme serum levels of hypertriglyceridemia (HTG) and 2,355 subjects were used for replication studies; all 3,295 participants were part of the Asian Indians Diabetic Heart Study. Gene-centric analysis revealed a burden of variants for increasing HTG risk inGCKR(p=2.1×10−5),LPL(p=1.6×10−3) andMLXIPL(p=1.6×10−2) genes. Of these, three missense and damaging variants withinGCKRwere further examined for functional consequencesin vivousing a transgenic zebrafish model. All three mutations were South Asian population-specific and were largely absent in other multiethnic populations of the Exome Aggregation Consortium. We built different transgenic models of humanGCKRwith and without mutations and analyzed the effects of dietary changesin vivo. Despite the short-term feeding, profound phenotypic changes were apparent in hepatocyte histology and fat deposition associated with increased expression of GCKR in response to a high fat diet (HFD). Liver histology of theGCKRmutshowed severe fatty metamorphosis which correlated with ~7 fold increase in the mRNA expression in theGCKRmutfish even in the absence of a high fat diet. These findings suggest that functionally disruptiveGCKRvariants not only increase the risk of HTG but may enhance ectopic lipid/fat storage defects in the absence of obesity and HFD. To our knowledge, this is the first transgenic zebrafish model of a putative human disease gene built to accurately assess the influence of rare genetic changes and their phenotypic consequencesin vivo.
Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2C342Y/+ mouse models of Crouzon syndrome
Authors: Nam Hwa Kyung , Vesela Iva , Schutte Sara Dean , Hatch Nan E.
Published: January 2019

Craniosynostosis is the premature fusion of cranial bones. The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in a C57BL/6 FGFR2C342Y/+ model of neonatal onset craniosynostosis or a BALB/c FGFR2C342Y/+ model of postnatal onset craniosynostosis. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro computed tomography. Craniofacial shape was measured with calipers. Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2C342Y/+ mice. In contrast, treatment with TNAP improved cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2C342Y/+ mice. These results indicate that perinatal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2C342Y/+ neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent.
Why Pacing Frequency Affects the Production of Early Afterdepolarizations in Cardiomyocytes: An Explanation Revealed by Slow/Fast Analysis of a Minimal Model
Authors: Vo Theodore , Bertram Richard
Published: January 2019

Early afterdepolarizations (EADs) are pathological voltage oscillations in cardiomyocytes that have been observed in response to a number of pharmacological agents and disease conditions. Phase-2 EADs consist of small voltage fluctuations that occur during the plateau of an action potential, typically under conditions in which the action potential is elongated. Although a single-cell behavior, EADs can lead to tissue-level arrhythmias, including ventricular tachycardia. Much is currently known about the biophysical mechanisms (i.e., the roles of ion channels and intracellular Ca2+ stores) for the various forms of EADs, due partially to the development and analysis of mathematical models. This includes the application of slow/fast analysis, which takes advantage of timescale separation inherent in the system to simplify its analysis. We take this further, using a minimal 3D model to demonstrate that the phase-2 EADs are canards that are formed in the neighborhood of a folded node singularity. This knowledge allows us to determine the number of EADs that can be produced for a given parameter set without performing computer simulations, and provides guidance on parameter changes that can facilitate or inhibit EAD production. With this approach, we demonstrate why periodic stimulation, as would occur in an intact heart, preferentially facilitates EAD production when applied at low frequencies,. We also explain the origin of complex alternan dynamics that can occur with intermediate-frequency stimulation, in which varying numbers of EADs are produced with each stimulation. These revelations fall out naturally from an understanding of folded node singularities, but are hard or impossible to glean from a knowledge of the biophysical mechanism for EADs alone. Therefore, an understanding of the canard mechanism is a useful complement to an understanding of the biophysical mechanism that has been developed over years of experimental and computational investigations.
Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams
Authors: Zippo Antonio G. , Bertoli Gloria , Riccardi Maria Pia , Valente Maurizio , Bräuer-Krisch Elke , Caramenti Gian Carlo , Requardt Herwig , Grosso Veronica del , Coan Paola , Bravin Alberto , Biella Gabriele E. M.
Published: January 2019

Chronic pain (CP) is a condition characterized by a wide spectrum of clinical signs and symptoms, missing a sound modelling at the neuronal network scale. Recently, we presented a general theory showing common electrophysiological traits in different CP rat models, i.e. a collapse of relevant functional connectivity network properties, such as modularity, in the somatosensory thalamo-cortical (TC) network. In this work, we preliminary investigated by anin silicoaccurate simulator of the six-layer mammalian cortical networks that evidenced the crucial collapse of network modularity in CP simulated conditions and the consequent reduction of network adaptive processes. On this track, in studies on CP experimental animals affected by sciatic nerve multiple ligature (Bennett-Xie model), by synchrotron-generated X-ray microbeam (MB) irradiations (7 parallel beams, 100um width), we targetedin vivothe CP involved hindlimb somatosensory projection cortex that, because of the doses radiation (360 Gy, peak at each beam), non-invasively produced fast and precise tissue destruction along the 7 beam projections. These parcellated the cortical tissue and restored the cortical network statistics related to modularity and information processing efficiency as evidenced from post irradiationin vivoelectrophysiological recordings. In addition, by MB treatment there was an ensuing removal of behavioral signs of allodynia and hyperalgesia accompanied by recovered normal gait schemes yet preserving the normal sensory thresholds of the experimental rats up to three months after the MB irradiation. Finally, novel and unprecedented therapeutic appraisals for CP are devised.

Significance Statement

Chronic pain (CP) is an excruciating condition with severe effects on patients’ life. Apart from many clinical and experimental studies no current theory on CP is generally accepted. Recently, we proposed a general theory of CP in experimental animals as characterized by strong alteration of the connections among neurons in different brain regions. We show here onin silicosimulations that specific connectivity changes in the somatosensory cortex recover the lost functional integrity. Concurrently, in experimental animals, we re-modulated,in vivo, some anatomical connections of the somatosensory cortex by extremely thin synchrotron generated X-ray microbeam irradiations. The resulting behavioral and electrophysiological signs of CP disappeared yet maintaining normal sensory responses. No adverse or pathological effects on blank animals were observable.
VX-809/661 Correction of F508del-CFTR Rescue Nrf2 Dysfunction In CF Airway Epithelia: Supplemental Figures
Authors: Borcherding Dana C , Lin Songbai , Siefert Matthew , Brewington John , Plafker Scott , Ziady Assem
Published: January 2019

Cystic Fibrosis (CF) is a multi-organ progressive genetic disease caused by loss of functional cystic fibrosis transmembrane conductance regulator (CFTR) channel, including in airway epithelia. Previously, we identified a significant dysfunction in CF cells of the transcription factor nuclear-factor-E2-related factor-2 (Nrf2), a major regulator of redox balance and inflammatory signaling. Here we report the discovery of an interaction and colocalization of Nrf2 and CFTR in non-CF human primary bronchial epithelia by Proximity Ligation Assay, immunoprecipitation, and immunofluorescence, which is diminished in CF human primary bronchial epithelia, and rescued with VX-809 or VX-661 treatment for 48-72 hr. In primary CF cells, F508del-CFTR correctors induce Nrf2 nuclear localization, Nrf2-dependent luciferase activity, and transcriptional activation of target genes. Diminished Nrf2 activity and colocalization with F508del-CFTR is also exhibited in mutant mice. Correction of Nrf2 by VX-809/VX-661 is dependent on sufficient correction of F508del and is blocked by inhibition of corrected channel function, or high-level shRNA knockdown of F508del-CFTR. Finally, partial CFTR knockdown, insufficient to decrease channel function, does not inhibit Nrf2 activity, further establishing the importance of CFTR function. Our findings demonstrate, for the first time, that CFTR and Nrf2 interact, and that VX-809/VX-661 correction of CFTR can correct Nrf2 dysfunction in CF.
Bacterial and Archaeal Communities in Recycling Effluents from a Bauxite Flotation Plant
Authors: Liu Xinxing , Wu Yong-Hong , Liu Xi , Han-yan Wu , Xie Jianping , Wang Guohua , Qiu Guan-zhou , Huo Qiang
Published: January 2019

Recycling effluent has become a bottleneck and an environmental risk associated with the regular production of bauxite via flotation and the sustainable development of the aluminum industry in China. To find a practical direction for biotreatment, the bacterial and archaeal communities in recycling effluents containing concentrate and tailings from bauxite flotation plants were investigated by a metagenomic sequencing method in association with the evaluated geochemical properties. The results showed that Paracoccus, Desulfomicrobium, Exiguobacterium, Tindallia, Ercella and Anoxynatronum were the primary bacterial genera and Methanothrix, Methanobacterium, Nitrososphaera and Methanosarcina were the dominant archaeal genera. Upon combining the microbial diversity and the geochemical properties of the two sample types, the microbial community containing Desulfomicrobium, Paracoccus, Tindallia, Methanobacterium, Methanothrix and Nitrososphaera was better adapted to the biodegradation of flotation collectors, and the microbial community consisting of Paracoccus, Exiguobacterium, Methanothrix and Methanobacterium was more efficient at hydrolyzed polyacrylamide (HPAM) biodegradation. In addition, a large proportion of unclassified OTUs has indicated that recycling effluent is a worthy resource for isolating new strains from the Firmicutes phylum.
Oriented Gaussian beams for high-accuracy computation with accuracy control of X-ray propagation through a multi-lens system
Authors: Wojda P. , Kshevetskii S.
Published: January 2019

A highly accurate method for calculating X-ray propagation is developed. Within this approach, the propagating wave is represented as a superposition of oriented Gaussian beams. The direction of wave propagation in each Gaussian beam agrees with the local direction of propagation of the X-ray wavefront. When calculating the propagation of X-ray waves through lenses, the thin lens approximation is applied. In this approximation, the wave parameters change discontinuously when the wave passes through a lens; the corresponding explicit formulae are derived. The theory is applied to highly accurate calculation of the focusing of X-rays by a system of many beryllium lenses. Fine structure of the wave electric field on the focal plane is revealed and studied. The fine structure is formed due to the diffraction of waves at the edges of the lens apertures. Tools for controlling the calculation accuracy are proposed. The amplitude of the electric field on the focal plane and the focal spot width are shown to be very sensitive to the quality of the calculation, while the best focus position can be obtained even from simple calculations.
Study of stacking interactions between two neutral tetrathiafulvalene molecules in Cambridge Structural Database crystal structures and by quantum chemical calculations
Authors: Antonijević Ivana S. , Malenov Dušan P. , Hall Michael B. , Zarić Snežana D.
Published: January 2019

Tetrathiafulvalene (TTF) and its derivatives are very well known as electron donors with widespread use in the field of organic conductors and superconductors. Stacking interactions between two neutral TTF fragments were studied by analysing data from Cambridge Structural Database crystal structures and by quantum chemical calculations. Analysis of the contacts found in crystal structures shows high occurrence of parallel displaced orientations of TTF molecules. In the majority of the contacts, two TTF molecules are displaced along their longer C
2 axis. The most frequent geometry has the strongest TTF–TTF stacking interaction, with CCSD(T)/CBS energy of −9.96 kcal mol−1. All the other frequent geometries in crystal structures are similar to geometries of the minima on the calculated potential energy surface.
Complex internationalization strategies and firm export performance during the great trade collapse
Authors: Córcoles David , Díaz-Mora Carmen , Gandoy Rosario
Published: January 2019

Purpose

Focusing on the global trade collapse and the subsequent recovery period, the purpose of this paper is to examine the export performance of firms that are involved in complex internationalization strategies.

Design/methodology/approach

The authors use a random-effects probit model with panel data and a dynamic panel data model (GMM system) for Spanish manufacturing firms from 2006 to 2013 period.

Findings

It is found that, once firm characteristics are controlled for, complex internationalization plays an important role in continuing to export and, additionally, positively influences the level of exports. Firms active in a complex mix of internationalization strategies have an added advantage, which enables them to confront the uncertainty of foreign markets in better conditions and translates to a lower likelihood of ceasing exporting and to higher export values.

Practical implications

The present paper throws light on this question by showing that the negative impact of trade collapse in 2009 on the export level was lower for firms inserted in complex internationalization strategies and the subsequent recovery was more intense.

Originality/value

The analysis goes one step further and investigates whether the impact is different during the trade collapse in 2009 and the following recovery. Here, previous empirical research at firm level on the role of complex internationalization strategies in trade is contradictory.
Harm-focused offender triage and prioritization: a Philadelphia case study
Authors: Ratcliffe Jerry H. , Kikuchi George
Published: January 2019

Purpose

The purpose of this paper is to describe and test a quantitative harm-focused approach to offender selection for investigation and surveillance. The approach incorporates a measure of crime harm as well as a time-decay function that adjusts the score downward for offenders who desist from crime.

Design/methodology/approach

Across 10 of 21 high-crime police districts in the city of Philadelphia, the authors compare the mean harm scores of 60 prolific offenders selected by district analysts, 60 prolific offenders selected citywide by detectives assigned to the Gun Violence Reduction Task Force and the top 60 prolific offenders chosen from a harm-score generated list of known offenders in the ten high-crime districts.

Findings

The offenders on the harm-focused list have significantly greater mean harm scores than the offenders identified by the crime analysts or task force personnel. They have a significantly greater mean number of gun crime episodes in their offending history as well.

Research limitations/implications

The harm-focused approach uses arrest data that may not accurately reflect convictions and which miss undetected criminal activity. A leader of a criminal organization who orchestrates criminal activities but does not engage directly may have a low harm score. Arrest data may also suffer from some inherent bias. The approach also requires the creation of a crime harm index. Determining the operational impact on overall crime reduction by focusing on offenders with higher harm scores will require further research.

Practical implications

Clinical methods of target selection based on officer intuition, opinion and experience may have limitations in terms of effectiveness and accuracy. They also lack transparency and may incorporate bias, a critical consideration given the current crisis in police-community trust and legitimacy. The actuarial method of weighing the harm of past offending with a crime harm score may be more acceptable and defendable to the community. It also identifies offenders with a higher frequency of involvement in gun crimes. Until methodological limitations are better understood, a compromise may be to start with the harm-score method (data-driven) and supplement this initial list through intelligence and investigative information.

Originality/value

The paper expands crime harm indices to quantify offender triage lists. The authors also empirically demonstrate through a case study that the approach is more effective at identifying harmful offenders than methods that solely rely on the experience or intuition of either crime analysts or detectives.
Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands, extraocular sebaceous carcinoma and benign sebaceous tumors
Authors: Boecker Werner , Reusch Michael , Mielke Volker , Reusch Ursula , Loening Thomas , Tiemann Markus , Buchwalow Igor
Published: January 2019

The histogenesis of extraocular sebaceous carcinomas is – in contrast to ocular sebaceous carcinomas – unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki‐67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63+ K5+ progenitors which generate the K10+ luminal cells of sebaceous ducts; and (ii) p63+ K5+ K7+ progenitors which finally generate K7+ adipophilin+ EMA+ sebocytes. Without exception, all types of sebaceous tumors contained p63+ K5+ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin+ and/or EMA+ mature sebocytes and to K10+ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63+ K5+ cells play a major role.
The phenology of migration in an unpredictable world
Authors: Schindler Daniel E.
Published: January 2019

In Focus: Freshwater, C., Trudel, M., Beacham, T. D., Gauthier, S., Johnson, S. C., Neville, C. & Juanes, F. (2016) . Journal of Animal Ecology, 88, 67–78. https://doi.org/10.1111/1365-2656.12852

Pacific salmon undertake arduous and risky migrations from their freshwater nursery grounds to the coastal ocean, northwards to their feeding grounds, and then back to their freshwater natal habitats to spawn. Understanding the phenology of such migrations has largely been viewed through the lens of microevolution producing optimal strategies that reflect local selection pressures; less emphasis has been placed on quantifying how variation in migration patterns can spread the risks associated with life in variable and unpredictable ecosystems. In this issue, Freshwater et al. use the information contained in ear stones (otoliths) and DNA of migrating juvenile sockeye salmon from the Fraser River of western Canada to quantify variation in the timing of their marine migrations. Not only were there population‐specific differences in migration phenology of fish from the same river, but there was substantial variation among individuals from specific populations. These patterns also varied from year to year. Data like these emphasize the risks involved in such migrations and suggest that variation in key migration traits are maintained because of the inherent unpredictability of ecosystems. Management and conservation efforts would be well‐served to consider actions that maintain such ecological variation to facilitate meta‐population persistence in a rapidly changing world.
Bullet Caliber and Type Categorization from Gunshot Wounds inSus Scrofa(Linnaeus) Long Bone
Authors: Henwood Bailey J. , Oost Tracy S. , Fairgrieve Scott I.
Published: January 2019

Studies on ballistic trauma to the ribs and thorax, cranium, and long bones demonstrate the potential of obtaining a bullet caliber from an entrance wound. In order to validate prior research on caliber estimation in bone tissue and assess the viability of bullet type determination based on the macroscopic evidence at the entrance wound, thirty fleshed pork (Sus scrofa) shoulders (humeri) were shot with either lead or copper jacketed bullets in one of three calibers; 0.22, 9 mm, or 0.38. Overall, our findings are consistent with previous research indicating that calibers can be grouped into “small” and “large” categories. Bullet type, lead or copper jacket, can be ascertained based on cortical flaking and the analysis of materials deposited around the entry wound. The addition of this evidence holds value in cases where no firearm or ballistic evidence is recovered from a crime scene.
Doing Ethnography in AirSpace: The Promise and Danger of ‘Frictionless’ Global Research
Authors: HOY TOM
Published: January 2019

'AirSpace', according to Kyle Chayka, is the increasingly homogenized experience of the western(ized) business traveller, driven by major tech platforms (including Google, Airbnb and Uber.) As international travellers, ethnographers must account for the impact of AirSpace on their research practice. After delineating the concept of AirSpace the paper posits three dangers ethnographers must negotiate: (1) The cost of control: AirSpace offers researchers control, but can narrow the scope of research (2) The risk of superficiality: AirSpace provides shortcuts to cultural understanding, but can limit deeper comprehension (3) The assumption of equivalence: AirSpace provides shared reference points, but can create the illusion of equivelance with research subjects. By exploring these three dangers the paper invites readers to reflect on their own research practice and consider how to utilize the benefits of these platforms while mitigating the issues outlined.
Empathy Is not Evidence: 4 Traps of Commodified Empathy
Authors: ROBERTSON RACHEL , ALLEN PENNY
Published: January 2019

Product teams, including our own, often interpret empathy as evidence. However, in practice, empathy is actually something that drives us to seek evidence. By observing and evaluating various examples within Shopify, we have identified 4 traps that are common in the way empathy is manifested. We modelled the relationship between empathy, problems, evidence, and decisions to provide strategies for how to use empathy effectively while being sympathetic to its limitations. Since empathy drives us to seek evidence, and thus cannot be considered evidence itself, empathy must be used at an appropriate level of abstraction throughout the product decision‐making process in order to influence good decisions.
Humans Can Be Cranky and Data Is Naive: Using Subjective Evidence to Drive Automated Decisions at Airbnb
Authors: CARTER STEPHANIE , DEAR RICHARD
Published: January 2019

How can we build fairness into automated systems, and what evidence is needed to do so? Recently, Airbnb grappled with this question to brainstorm ways to re‐envision the way hosts review guests who stay with them. Reviews are key to how Airbnb builds trust between strangers. In 2018 we started to think about new ways to leverage host reviews for decision making at scale, such as identifying exceptional guests for a potential loyalty program or notifying guests that need to be warned about poor behavior. The challenge is that the evidence available to use for automated decisions, star ratings and reviews left by hosts, are inherently subjective and sensitive to the cross‐cultural contexts in which they were created. This case study explores how the collaboration between research and data science revealed that the underlying constraint for Airbnb to leverage subjective evidence is a fundamental difference between ‘public’ and ‘private’ feedback. The outcome of this integrated, cross‐disciplinary approach was a proposed re‐envisioned review flow that clearly separates public and private‐to‐Airbnb feedback with a single binary question. If implemented, it should allow Airbnb to collect additional evidence from hosts that can be utilized to make automatic decisions about whether guests need warnings or whether they have met an exceptional quality bar for a potential loyalty program.
Designing for Interactions with Automated Vehicles: Ethnography at the Boundary of Quantitative‐Data‐Driven Disciplines
Authors: ROTHMÜLLER MARKUS , RASMUSSEN PERNILLE HOLM , VENDELBO‐LARSEN SIGNE ALEXANDRA
Published: January 2019

This case study presents ethnographic work in the midst of two fields of technological innovation: automated vehicles (AV) and virtual reality (VR). It showcases the work of three MSc. Techno‐Anthropology students and their collaboration with the EU H2020 project ‘interACT', sharing the goal to develop external human‐machine interfaces (e‐HMI) for AVs to cooperate with human road users in urban traffic in the future. The authors reflect on their collaboration with human factor researchers, data scientists, engineers, experimental researchers, VR‐developers and HMI‐designers, and on experienced challenges between the paradigms of qualitative and quantitative research. Despite the immense value of ethnography and other disciplines to collectively create holistic representations of reality, this case study reveals several tensions and struggles to align multi‐disciplinary worldviews. Results show the value of including ethnographers: 1) in the design and piloting of a digital observation app for the creation of large datasets; 2) in the analysis of large amounts of data; 3) in finding the potential of and designing e‐HMI concepts; 4) in the representation of real‐world context and complexity in VR; 5) in the evaluation of e‐HMI prototypes in VR; and finally 6) in critically reflecting on the construction of evidence from multiple disciplines, including ethnography itself.
Revitalising Openness at Mozilla: A Mixed Method Research Approach
Authors: JENSEN RINA TAMBO
Published: January 2019

This is a case about how Mozilla, the open source browser company, set out to reconnect with ‘collaborating in the open’ to regain its competitive advantage. This case describes how a multi‐disciplinary research team used ethnographic, market, and data analysis to articulate and clarify the problem, and build a strategy towards revitalizing Openness at Mozilla. It will aim to prove that the subsequent change achieved could only have been accomplished by a mixed method research approach. And importantly show, how the team used data to prove the distribution of findings, coupled with ethnography to shine light on the why and how of those findings. The case study will do this by discussing the key insights and how these fueled recommendation and subsequent change in the organisation.

The project presented many problems: from convincing stakeholders of the need to fully explore the problem, to connecting widely different research methods and gleaning insights that built strongly on all strands of research. Overcoming these issues together, the team managed to outlay the key problems and opportunities for Mozilla and build a strategy which has affected real change in the company and is now being implemented by a team of 20 employees. We call this strategy Open by Design. Which, to us, means being open, purposefully.
Diagnosing the World Pulse
Authors: GOLIAS CHRISTOPHER A.
Published: January 2019

This Pecha Kucha explores the ethics of interpreting data by employing an extended metaphor of data as the lifeblood of the connected world. It begins by exploring two distinct viewpoints on medical pulse diagnosis, starting from the perspective of the acupuncturist diagnosing a patient's pulse and continuing through differences between Eastern pulse diagnosis and biomedical pulse diagnosis. I explore data as lifeblood, and imagine more visceral ways to read data (e.g., auguring data) and the ethical implications of such a reading. I envision data as a flowing river filling a lake, in which diagnostic specialists observe society's reflection. In the process, I contrast utopian visions of a data driven world with dystopian ones before resolving tension by returning to the central comparison of data scientist and medical doctor. The presentation concludes by recalling medicine's Hippocratic Oath, an ethical charter binding practitioners to a code of conduct, and implying that data science consider a similar injunction.
Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management
Authors: Back Michael , Jayamanne Dasantha T , Brazier David , Newey Alison , Bailey Dale , Schembri Geoffrey P , Hsiao Edward , Khasraw Mustafa , Wong Matthew , Kastelan Marina , Guo Linxin , Clarke Stephen , Wheeler Helen
Published: January 2019

Introduction

Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype.

Methods

Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse‐free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan‐Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log‐rank test used to determine associated factors.

Results

One hundred and fifty‐six patients were included with median follow‐up for survivors of 4.7 years. Fifty‐six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy‐three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis.

Conclusion

Within AG, molecular classification predicts for survival, and should influence current decision‐making.
The micro elasticity of substitution and non‐neutral technology
Authors: Raval Devesh R.
Published: January 2019

This article provides evidence on the micro capital‐labor elasticity of substitution and the bias of technology. Using data on US manufacturing plants, I find several facts inconsistent with a Cobb‐Douglas production function, including large, persistent variation in capital shares. I then estimate the elasticity using variation in local wages, and several instruments for them, for identification. Estimates of the substitution elasticity using all plants range between 0.3 and 0.5, with similar estimates across industries. I use these elasticity estimates to measure labor augmenting productivity, and find that labor augmenting productivity is highly persistent, and correlated with exports, size, and growth.
What should clinicians do as fentanyl replaces heroin?
Authors: Bisaga Adam
Published: January 2019

Commentary to: Illicit fentanyls in the opioid street market: desired or imposed?
Chronic obstructive pulmonary disease (COPD) among opioid‐dependent patients in agonist treatment. A diagnostic study
Authors: Grischott Thomas , Falcato Luis , Senn Oliver , Puhan Milo Alan , Bruggmann Philip
Published: January 2019

Aims

To estimate the prevalence of chronic obstructive pulmonary disease (COPD) and related risk factors in people in opioid agonist treatment (OAT), to compare airflow limitation severity and age‐specific COPD prevalence rates with those in the general population, and to assess the OAT patients’ willingness to adopt life‐style changes and to use therapeutic offers for COPD management.

Design

Cross‐sectional study in a random sample of OAT patients.

Setting

Out‐patient centres for substance addiction medicine in Zurich, Switzerland.

Participants

A total of 125 participants, recruited from November 2016 to April 2017 through invitation letters followed by phone or personal contact.

Measurements

Standardized questionnaires about drug use, smoking habits and medical history, completed during face‐to‐face interviews or from medical records. Spirometry without and—depending on the result—with bronchodilation.

Findings

Almost one‐third [30.3%; 95% confidence interval (CI) = 22.6–39.0%] of the 119 participants with valid spirometry tests were diagnosed with COPD. Among males aged 30–59 years, the age‐adjusted prevalence of at least moderate airflow limitation (GOLD grade ≥ 2) was 2.4 (95% CI = 1.3–4.4) times as high as in the ever‐smoking Swiss population in the same age group. Smoking tobacco (92.0%) and substance inhalation (cannabis = 97.6%, cocaine = 69.6%, heroin = 68.0%) were highly prevalent among all participants. The participants expressed considerable interest in life‐style changes and use of therapeutic offers for COPD management, with smoking cessation being least (20.2% of tobacco smokers interested) and pharmacological treatment to alleviate COPD symptoms most popular.

Conclusions

In Switzerland, COPD prevalence and multiple risk factors for COPD appear to be high among people in OAT compared with the general population. Individuals in OAT appear to develop COPD at a younger average age compared with the general population and are open to life‐style changes and other COPD management approaches.
Conductive electrospun scaffolds with electrical stimulation for neural differentiation of conjunctiva mesenchymal stem cells
Authors: Rahmani Ali , Nadri Samad , Kazemi Habib Sayed , Mortazavi Yousef , Sojoodi Mahdi
Published: January 2019

An electrical stimulus is a new approach to neural differentiation of stem cells. In this work, the neural differentiation of conjunctiva mesenchymal stem cells (CJMSCs) on a new 3D conductive fibrous scaffold of silk fibroin (SF) and reduced graphene oxide (rGo) were examined. rGo (3.5% w/w) was dispersed in SF‐acid formic solution (10% w/v) and conductive nanofibrous scaffold was fabricated using the electrospinning method. SEM and TEM microscopies were used for fibrous scaffold characterization. CJMSCs were cultured on the scaffold and 2 electrical impulse models (Current 1:115 V/m, 100‐Hz frequency and current 2:115 v/m voltages, 0.1‐Hz frequency) were applied for 7 days. Also, the effect of the fibrous scaffold and electrical impulses on cell viability and neural gene expression were examined using MTT assay and qPCR analysis. Fibrous scaffold with the 220 ± 20 nm diameter and good dispersion of graphene nanosheets at the surface of nanofibers were fabricated. The MTT result showed the viability of cells on the scaffold, with current 2 lower than current 1. qPCR analysis confirmed that the expression of β‐tubulin (2.4‐fold P ≤ 0.026), MAP‐2 (1.48‐fold; P ≤ 0.03), and nestin (1.5‐fold; P ≤ 0.03) genes were higher in CJMSCs on conductive scaffold with 100‐Hz frequency compared to 0.1‐Hz frequency. Collectively, we proposed that SF‐rGo fibrous scaffolds, as a new conductive fibrous scaffold with electrical stimulation are good strategies for neural differentiation of stem cells and the type of electrical pulses has an influence on neural differentiation and proliferation of CJMSCs.