bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a non-randomized, monocentric phase II clinical trial—PaCa-DD-041 (Eudra-CT 2009-011968-11)
Authors: Zimmermann Carolin , Distler Marius , Jentsch Christina , Blum Sophia , Folprecht Gunnar , Zöphel Klaus , Polster Heike , Troost Esther G. C. , Abolmaali Nasreddin , Weitz Jürgen , Baumann Michael , Saeger Hans-Detlev , Grützmann Robert
Published: July 2020

Background

Pancreatic cancer is a devastating disease with a 5-year survival rate of 20–25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy.

Methods

Patients with histologically proven resectable, borderline resectable or unresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the standardized uptake value (SUV) measured with FDG-PET. Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was performed using contrast-enhanced CT and contrast-enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen.

Results

A total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal SUV (SUVmax) during therapy (p < 0.001). Using the mean apparent diffusion coefficient (ADC), response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7–38 months).

Conclusion

Based on these limited patient numbers, it was possible to show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. FDG-PET/CT may be a reliable method to evaluate response to the combined therapy. In contrast, when evaluating the response using mean ADC, DW-MRI did not show conclusive results.
Inflammation shapes pathogenesis of murine arrhythmogenic cardiomyopathy
Authors: Lubos Nadine , van der Gaag Svenja , Gerçek Muhammed , Kant Sebastian , Leube Rudolf E. , Krusche Claudia A.
Published: July 2020

Arrhythmogenic cardiomyopathy (AC) is an incurable genetic disease, whose pathogenesis is poorly understood. AC is characterized by arrhythmia, fibrosis, and cardiodilation that may lead to sudden cardiac death or heart failure. To elucidate AC pathogenesis and to design possible treatment strategies of AC, multiple murine models have been established. Among them, mice carrying desmoglein 2 mutations are particularly valuable given the identification of desmoglein 2 mutations in human AC and the detection of desmoglein 2 auto-antibodies in AC patients. Using two mouse strains producing either a mutant desmoglein 2 or lacking desmoglein 2 in cardiomyocytes, we test the hypothesis that inflammation is a major component of disease pathogenesis. We show that multifocal cardiomyocyte necrosis initiates a neutrophil-dominated inflammatory response, which also involves macrophages and T cells. Increased expression of Ccl2/Ccr2, Ccl3/Ccr5, and Cxcl5/Cxcr2 mRNA reflects the observed immune cell recruitment. During the ensuing acute disease phase, Mmp12+ and Spp1+ macrophages and T cells accumulate in scars, which mature from cell- to collagen-rich. The expression of Cx3cl1/Cx3cr1, Ccl2/Ccr2, and Cxcl10/Cxcr3 dominates this disease phase. We furthermore find that during chronic disease progression macrophages and T cells persist within mature scars and are present in expanding interstitial fibrosis. Ccl12 and Cx3cl1 are predominant chemokines in this disease phase. Together, our observations provide strong evidence that specific immune cell populations and chemokine expression profiles modulate inflammatory and repair processes throughout AC progression.
Protozoan infections are under-recognized in Swedish patients with gastrointestinal symptoms
Authors: Ögren Jessica , Dienus Olaf , Beser Jessica , Henningsson Anna J. , Matussek Andreas
Published: July 2020

In acute gastroenteritis (GE), identification of the infectious agent is important for patient management and surveillance. The prevalence of GE caused by protozoa may be underestimated in Swedish patients. The purpose was to compare the prevalence of E. histolytica, Cryptosporidium spp., G. intestinalis, and C. cayetanensis in samples from patients where the clinician had requested testing for gastrointestinal parasites only (n = 758) to where testing for bacterial GE only (n = 803) or where both parasite and bacterial testing (n = 1259) was requested and a healthy control group (n = 197). This prospective cohort study was conducted in Region Jönköping County, Sweden (October 2018–March 2019). Fecal samples were analyzed with microscopy and real-time PCR. Cryptosporidium spp. was detected in 16 patients in the bacterial GE group and in 13 in the both bacterial and parasite group; no cases were detected in the group were only parasite infection was suspected. C. cayetanensis was detected in two patients in the bacterial GE group. One case of E. histolytica was detected in the bacterial group and one in the both bacterial and parasite group. G. intestinalis was detected in 14 patients in the parasite only group, 12 in the both parasite and bacterial group, three in the bacterial GE group, and one in the control group. Diarrhea caused by protozoa, especially Cryptosporidium was under–recognized by clinicians and is likely more common than hitherto estimated in Sweden. A more symptom-based diagnostic algorithm may increase detection and knowledge about protozoan infections.
A regionally-adaptable “scaled backbone” ground motion logic tree for shallow seismicity in Europe: application to the 2020 European seismic hazard model
Authors: Weatherill Graeme , Kotha Sreeram Reddy , Cotton Fabrice
Published: July 2020

The selection of ground motion models, and the representation of their epistemic uncertainty in the form of a logic tree, is one of the fundamental components of probabilistic seismic hazard and risk analysis. A new ground motion model (GMM) logic tree has been developed for the 2020 European seismic hazard model, which develops upon recently compiled ground motion data sets in Europe. In contrast to previous European seismic hazard models, the new ground model logic tree is built around the scaled backbone concept. Epistemic uncertainties are represented as calibrations to a reference model and aim to characterise the potential distributions of median ground motions resulting from variability in source scaling and attenuation. These scaled backbone logic trees are developed and presented for shallow crustal seismic sources in Europe. Using the new European strong motion flatfile, and capitalising on recent perspectives in ground motion modelling in the scientific literature, a general and transferable procedure is presented for the construction of a backbone model and the regionalisation of epistemic uncertainty. This innovative approach forms a general framework for revising and updating the GMM logic tree at national and European scale as new strong motion data emerge in the future.
Distinct microalgae species for food—part 1: a methodological (top-down) approach for the life cycle assessment of microalgae cultivation in tubular photobioreactors
Authors: Schade S. , Meier T.
Published: July 2020

Specific microalgae species are an adequate source of EPA and DHA and are able to provide a complete protein, which makes them highly interesting for human nutrition. However, microalgae cultivation has also been described to be energy intensive and environmentally unfavorable in pilot-scale reactors. Moreover, production in cold temperature zones has not been sufficiently investigated. In particular, the effects of tube materials and cultivation season length have rarely been previously investigated in the context of a comparative LCA of microalgae cultivation. A computational “top-down” model was conducted to calculate input flows for Nannochloropsis sp. and Phaeodactylum tricornutum cultivation in a hypothetical tubular photobioreactor. Cultivation processes were calculated according to detailed satellite climatic data for the chosen location in Central Germany. This model was applied to a set of different scenarios, including variations in photobioreactor material, tube diameter, microalgae species, and cultivation season length. Based on these data, a life cycle assessment (LCA) was performed following ISO standard 14040/44. The impact assessment comprised the global warming potential, acidification, eutrophication, cumulative energy demand, and water scarcity. The results showed that a long cultivation season in spring and fall was always preferable in terms of environmental impacts, although productivity decreased significantly due to the climatic preconditions. Acrylic glass as a tube material had higher environmental impacts than all other scenarios. The cultivation of an alternative microalgae species showed only marginal differences in the environmental impacts compared with the baseline scenario. Critical processes in all scenarios included the usage of hydrogen peroxide for the cleaning of the tubes, nitrogen fertilizer, and electricity for mixing, centrifugation, and drying. Microalgae cultivation in a tubular photobioreactor in a “cold-weather” climate for food is sustainable and could possibly be a complement to nutrients from other food groups. The added value of this study lies in the detailed description of a complex and flexible microalgae cultivation model. The new model introduced in this study can be applied to numerous other scenarios to evaluate photoautotrophic microalgae cultivation in tubular photobioreactors. Thus, it is possible to vary the facility location, seasons, scale, tube dimensions and material, microalgae species, nutrient inputs, and flow velocity. Moreover, single processes can easily be complemented or exchanged to further adjust the model individually, if, for instance, another downstream pathway is required.
Modeling multi-tier heterogeneous small cell networks: rate and coverage performance
Authors: Fadoul Moubachir Madani
Published: July 2020

The rapid growth of small cells is driving cellular network toward randomness and heterogeneity. The multi-tier heterogeneous network (HetNet) addresses the massive connectivity demands of the emerging cellular networks. Cellular networks are usually modeled by placing each tier (e.g macro, pico and relay nodes) deterministically on a grid which ignores the spatial randomness of the nodes. Several works were idealized for not capturing the interference which is a major performance bottleneck. Overcoming such limitation by realistic models is much appreciated. Multi-tier relay cellular network is studied in this paper, In particular, we consider $${\mathscr {K}}$$
K
-tier transmission modeled by factorial moment and stochastic geometry and compare it with a single-tier, traditional grid model and multi-antenna ultra-dense network (UDN) model to obtain tractable rate coverage and coverage probability. The locations of the relays, base stations, and users nodes are modeled as a Poisson Point Process. The results showed that the proposed model outperforms the traditional multi-antenna UDN model and its accuracy is confirmed to be similar to the traditional grid model. The obtained results from the proposed and comparable models demonstrate the effectiveness and analytical tractability to study the HetNet performance.
Genetic analysis of callus formation in a diversity panel of 96 rose genotypes
Authors: Nguyen Thi Hong Nhung , Winkelmann Traud , Debener Thomas
Published: July 2020

In a diversity panel of 96 rose genotypes, variation in the capacity to form calluses on leaf explants in vitro was investigated, and a genome-wide association study (GWAS) was performed to identify genetic factors associated with callus formation. Calluses were induced from wounded in vitro leaflets on two media differing in their plant growth regulator composition. Significant differences between genotypes were observed in callus size on the first callus-inducing medium (CIM1, containing 10.7 µM naphthylene acetic acid) using a 0–4 scale, as well as on a second callus-inducing medium (CIM2, containing 4.5 µM dichlorophenoxyacetic acid and 2 µM 6-(γ,γ-dimethylallylaminopurine)) with callus size scales of 0.82–4. GWAS utilizing the WagRhSNP 68K SNP array for callus size induced on either CIM1 or CIM2 enabled the identification of 26 and 13 significantly associated SNPs, respectively. Among these SNPs, we found the SNPs Rh12GR_12098_1092Q (uncharacterized gene) and RhMCRND_2903_1233Q in a gene encoding a pentatricopeptide repeat-containing protein were associated with callus size on CIM1, with large effects being observed between alleles. Two SNPs, RhK5_5473_763P (S-formylglutathione hydrolase) and Rh12GR_37799_568Q (polyglutamine binding protein, WW domain binding protein), were associated with callus size on CIM2 with large effect sizes. The markers associated with callus size on CIM1 form a large cluster on chromosome 3 and minor clusters on other chromosomes and provide the first preliminary indications of candidate genes responsible for the observed phenotypic variation.
Comparative study on analytical and computational aerodynamic models for flapping wings MAVs
Authors: Valdez M.F. , Balachandran B. , Preidikman S.
Published: July 2020

A range of quasi-steady and unsteady aerodynamic models are used to predict the aerodynamic forces experienced by a flapping wing and a detailed comparison amongst these predictions in provided. The complexity of the models ranges from the analytical potential flow model to the computational Unsteady Vortex Lattice Method (UVLM), which allows one to describe the motion of the wake and account for its influence on the fluid loads. The novelty of this effort lies in a modification of the predicted forces as a generalisation of the leading edge suction analogy. This modification is introduced to account for the delayed stall mechanism due to leading edge flow separation. The model predictions are compared with two sets of independent experimental data and with computational fluid dynamics (CFD) simulation data available in the literature. It is found that both, the modified analytical model and the UVLM model can be used to describe the time history of the lift force, in some cases with better results than a high-fidelity CFD model. The models presented here constitute a useful basis for the aerodynamic design of bioinspired flapping-wings micro-air vehicles.
The second season of excavations at Jebel Moya (south-central Sudan)
Authors: Brass Michael , Adam Ahmed , Vella Gregory Isabelle , Abdallah Rayan , Alawad Osman , Abdalla Ammar , Kozieradzka-Ogunmakin Iwona , Wellings Joss , Albadwi Anfal , Moyne Charles Le , Hassan Fakri , Abdelrahman Ali
Published: July 2020

This report presents the latest data from ongoing excavations at Jebel Moya, Sudan. This year saw the opening of five new trenches and continued excavation of an archaeologically rich trench. We have recovered four individual burials, a mud brick wall and a number of animal and archaeobotanical remains. The excavations also yielded a longer pottery sequence, showing clearly that the site was in use by at least the sixth millennium BC. This season confirms the long and complex history of Jebel Moya and provides the material for future studies on population health and subsistence. This season also saw an increase in community engagement and a more detailed study of the various historical trajectories that make up the biography of Jebel Moya.
Lady Qu's Inscriptions: Literacy and Sovereignty in a Native Domain, Southwest China
Authors: Mueggler Erik
Published: July 2020

In 1533, Lady Qu, native prefect of Wuding Prefecture in northern Yunnan, sponsored the inscription of two texts on a cliff face at the center of her domain. One was in Nasu, the language of the ruling lineage; the other was in Chinese. Both commemorated the long, powerful line of Né (or Yi) native chieftains to which Lady Qu was heir. Yet they gave contradictory accounts of the forms of chiefly succession, sources of political authority, and geopolitical position of the native domain. The inscriptions show that chiefly sovereignty was neither merely embodied in ancestral authority nor simply endowed by the emperor. Sovereignty—particularly that of a female chieftain—was the capacity to master both modes of self-description while embodying their incompatibility. While we often understand colonialism through power-laden projects of translation, Lady Qu's inscriptions give evidence that Ming colonization of the southwest might require a different approach. Native chieftains were often intermediaries in encounters between indigenous peoples and imperial agents, garrisoned soldiers, and other migrants. Rather than merely understanding these elites as translators and mediators of colonialism, we might also ask how they emphasized and strategically deployed cultural and linguistic differences to achieve ends of their own.
A History of Pigs in China: From Curious Omnivores to Industrial Pork
Authors: Lander Brian , Schneider Mindi , Brunson Katherine
Published: July 2020

Pigs have played a central role in the subsistence and culture of China for millennia. The close relationship between pigs and people began when humans gradually domesticated wild pigs over 8,000 years ago. While pigs initially foraged around settlements, population growth led people to pen their pigs, which made them household trash processors and fertilizer producers. Household pigs were in daily contact with people, who bred them to fatten quickly and produce larger litters. Early modern Europeans found Chinese pigs far superior to their own and bred the two to create the breeds now employed in industrial pork production around the world, including China. In recent decades, industrial farms that scientifically control every aspect of pigs’ lives have spread rapidly. Until recently, most Chinese people ate pork only on special occasions; their ability in recent decades to eat it regularly exemplifies China's increasing prosperity. Meanwhile, vast areas of North and South American farmland are now devoted to growing soybeans to feed hundreds of millions of pigs in China, and the methane, manure, and antibiotic resistance they produce creates environmental and health problems on a global scale.
Endometriose
Authors: Mathieu Svea-Vivica , Kobe Adrian , Pfammatter Thomas , Hötker Andreas
Published: July 2020

Zusammenfassung. Die Endometriose als Absiedlung funktionalen Endometriumgewebes ausserhalb der Gebärmutterhöhle zählt zu den häufigsten gynäkologischen Erkrankungen. Dennoch vergehen aufgrund der unspezifischen Symptome häufig mehr als 10 Jahre zwischen Symptombeginn und Diagnosestellung, was insbesondere an der variablen Ausprägung der Symp­tomatik in Abhängigkeit von der Lokalisation liegt. Zu den Manifestationsorten gehört neben den klassischen Endometriomen des Ovars vor allem auch die tiefe pelvine Endometriose, die zu narbigen Veränderungen und chronischen Unterbauchschmerzen führen kann. In der Diagnostik und insbesondere zum Staging der Erkrankung kommt zunehmend die MRI aufgrund ihres hervorragenden Weichteilkontrastes zum Einsatz. Hierfür wurden neben spezifischen Scoring-Systemen zur strukturierten Befundung (z. B. ENZIAN- Score) auch europäische Richtlinien erstellt. Therapeutisch kann, neben einer symptomorientierten Therapie, bei schwereren Fällen eine anti-hormonelle Therapie bzw. die chirurgische Exzision der Läsionen erfolgen. Im Falle einer Adenomyose, des Befalls des Myometriums des Uterus, hat sich neuerdings die Embolisation der Aae. uterinae als minimalinvasives Therapieverfahren mit guten Ergebnissen etabliert.
Personality Assessment Through the Situational and Behavioral	Features of Instagram Photos
Authors: Cooper A. Bell , Blake Andrew B. , Pauletti Rachel E. , Cooper Patrick J. , Sherman Ryne A. , Lee Daniel I.
Published: July 2020

Abstract. This study explores whether photos posted on online social networks can be used to assess personality. We have demonstrated that personality is connected to human- and machine-detected situational cues, characteristics, classes, behavior, and affect displayed in Instagram photos. Observations of individual relationships between normal or dark side personality characteristics and situational features of photos give insight into the various aspects of online portrayal of oneself and the personality behind the photos.
Autism in Aotearoa
Authors: Kember Sarah M. , Williams Matt N.
Published: July 2020

Abstract. Screening measures for autism spectrum disorder (ASD) are important tools for clinicians and researchers. However, where a measure developed and validated for one population is used with another, its performance in this new context must be carefully examined. The RAADS-14, a brief ASD screen developed in Sweden, was evaluated with a sample of New Zealand adults ( N = 387), 41 of whom self-reported a prior diagnosis of ASD. The convergent validity of the RAADS-14 (Hypothesis 2) was supported by a strong positive correlation with the AQ-10 (short version of the Autism Spectrum Quotient), r = .81. Discriminant validity (Hypothesis 3) was also supported by a strong negative correlation with the EQ-Short (short version of the Empathy Quotient), r = −.75. However, the measure did not meet inferential criteria for internal consistency (Hypothesis 1), and confirmatory factor analysis (CFA) found a poor fit of the proposed three-factor model (Hypothesis 4) to the data. A cut-off score of 14/42 provided adequate sensitivity (95%) to detect participants with self-reported ASD diagnoses, but not adequate specificity (70%), suggesting a very high rate of false positives should be expected if relying on RAADS-14 scores alone to interpret presence of ASD. In sum, our results do not provide sufficient evidence of reliability and validity to support the use of the RAADS-14 with the New Zealand population. We provide suggestions for refinement of the RAADS-14 that may lead to increased reliability and validity.
Importance of Boundary Processes for Heat Uptake in the Subpolar North Atlantic
Authors: Desbruyères D. G. , Sinha B. , McDonagh E. L. , Josey S. A. , Holliday N. P. , Smeed D. A. , New A. L. , Megann A. , Moat B. I.
Published: July 2020

The decadal to multidecadal temperature variability of the intermediate (700–2,000 m) North Atlantic Subpolar Gyre (SPG) significantly imprints the global pattern of ocean heat uptake. Here, the origins and dominant pathways of this variability are investigated with an ocean analysis product (EN4), an ocean state estimate (ECCOv4), and idealized modeling approaches. Sustained increases and decreases of intermediate temperature in the SPG correlate with long‐lasting warm and cold states of the upper ocean with the largest anomalous vertical heat exchanges confined to the vicinity of continental boundaries and strong ocean currents. In particular, vertical diffusive processes along the boundaries of the Labrador, Irminger, and Newfoundland basins are important drivers of the recent intermediate depth warming trend observed during 1996–2014. The overall effect of those processes is captured by a one‐dimensional diffusive model with appropriate boundary‐like parametrization and demonstrated through the boundary‐focused downward propagation of a passive tracer in a 3‐D numerical simulation. Our results imply that the slow and quasi‐periodic ventilation of intermediate thermohaline properties and associated heat uptake in the SPG are not strictly driven by convection‐restratification events in the open seas but also receives a key contribution from boundary sinking and mixing. Increased skill for modeling and predicting intermediate‐depth ocean properties in the North Atlantic will hence require the appropriate representation of surface‐deep dynamical connections within the boundary currents encircling Greenland and Newfoundland.
Impact of Convectively Detrained Ice Crystals on the Humidity of the Tropical Tropopause Layer in Boreal Winter
Authors: Ueyama R. , Jensen E. J. , Pfister L. , Krämer M. , Afchine A. , Schoeberl M.
Published: July 2020

Deep convection detraining in the uppermost tropical troposphere is capable of transporting water vapor and ice into the tropical tropopause layer (TTL), but the impact of deep convection on the global and regional TTL water vapor budget remains uncertain. In particular, the role of convectively detrained ice crystals that remain suspended after active convection has subsided is not well understood. These ice crystals represent aging cirrus anvils detached from the convective core. We use a cloud microphysical model that tracks individual ice crystals throughout their lifetimes to quantify the impact of detrained ice on the humidity of the TTL during boreal winter. Convective influence of air parcels near the wintertime cold point tropical tropopause is determined by tracing thousands of backward trajectories through satellite‐derived, global, 3‐hourly convective cloud‐top altitude fields. Detrained ice, most of which is found over the tropical western Pacific, experiences cooling on the order of 1 K day−1 downstream of convection. Downstream cooling increases relative humidity and explains the observed supersaturated TTL over this region. Vapor in excess of saturation condenses onto the detrained ice, which ultimately brings the relative humidity down to saturation. Thus, convectively detrained ice crystals in aging anvils predominantly dehydrate the TTL, but the effect is small (0.01 ppmv). Moistening by active convection (0.30 ppmv), including the rapid sublimation of convectively lofted ice crystals near the tops of core anvils, overwhelms the dehydration by aging anvil ice crystals detrained from the core. The net effect is moistening by convective core anvils during boreal winter.
Structural heterogeneity of the mammalian polycomb repressor complex in immune regulation
Authors: Kang Seok-Jin , Chun Taehoon
Published: July 2020

Epigenetic regulation is mainly mediated by enzymes that can modify the structure of chromatin by altering the structure of DNA or histones. Proteins involved in epigenetic processes have been identified to study the detailed molecular mechanisms involved in the regulation of specific mRNA expression. Evolutionarily well-conserved polycomb group (PcG) proteins can function as transcriptional repressors by the trimethylation of histone H3 at the lysine 27 residue (H3K27me3) and the monoubiquitination of histone H2A at the lysine 119 residue (H2AK119ub). PcG proteins form two functionally distinct protein complexes: polycomb repressor complex 1 (PRC1) and PRC2. In mammals, the structural heterogeneity of each PRC complex is dramatically increased by several paralogs of its subunit proteins. Genetic studies with transgenic mice along with RNA-seq and chromatin immunoprecipitation (ChIP)-seq analyses might be helpful for defining the cell-specific functions of paralogs of PcG proteins. Here, we summarize current knowledge about the immune regulatory role of PcG proteins related to the compositional diversity of each PRC complex and introduce therapeutic drugs that target PcG proteins in hematopoietic malignancy.
A user guide for the online exploration and visualization of PCAWG data
Authors: Goldman Mary J. , Zhang Junjun , Fonseca Nuno A. , Cortés-Ciriano Isidro , Xiang Qian , Craft Brian , Piñeiro-Yáñez Elena , O’Connor Brian D. , Bazant Wojciech , Barrera Elisabet , Muñoz-Pomer Alfonso , Petryszak Robert , Füllgrabe Anja , Al-Shahrour Fatima , Keays Maria , Haussler David , Weinstein John N. , Huber Wolfgang , Valencia Alfonso , Park Peter J. , Papatheodorou Irene , Zhu Jingchun , Ferretti Vincent , Vazquez Miguel
Published: July 2020

The Pan-Cancer Analysis of Whole Genomes (PCAWG) project generated a vast amount of whole-genome cancer sequencing resource data. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we provide a user’s guide to the five publicly available online data exploration and visualization tools introduced in the PCAWG marker paper. These tools are ICGC Data Portal, UCSC Xena, Chromothripsis Explorer, Expression Atlas, and PCAWG-Scout. We detail use cases and analyses for each tool, show how they incorporate outside resources from the larger genomics ecosystem, and demonstrate how the tools can be used together to understand the biology of cancers more deeply. Together, the tools enable researchers to query the complex genomic PCAWG data dynamically and integrate external information, enabling and enhancing interpretation.
Author Correction: Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance
Authors: Oe Yuki , Wang Xiaowen , Patriarchi Tommaso , Konno Ayumu , Ozawa Katsuya , Yahagi Kazuko , Hirai Hirokazu , Tsuboi Takashi , Kitaguchi Tetsuya , Tian Lin , McHugh Thomas J. , Hirase Hajime
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Response outcomes gate the impact of expectations on perceptual decisions
Authors: Hermoso-Mendizabal Ainhoa , Hyafil Alexandre , Rueda-Orozco Pavel E. , Jaramillo Santiago , Robbe David , de la Rocha Jaime
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Molecular resolution imaging by post-labeling expansion single-molecule localization microscopy (Ex-SMLM)
Authors: Zwettler Fabian U. , Reinhard Sebastian , Gambarotto Davide , Bell Toby D. M. , Hamel Virginie , Guichard Paul , Sauer Markus
Published: July 2020

Expansion microscopy (ExM) enables super-resolution fluorescence imaging of physically expanded biological samples with conventional microscopes. By combining ExM with single-molecule localization microscopy (SMLM) it is potentially possible to approach the resolution of electron microscopy. However, current attempts to combine both methods remained challenging because of protein and fluorophore loss during digestion or denaturation, gelation, and the incompatibility of expanded polyelectrolyte hydrogels with photoswitching buffers. Here we show that re-embedding of expanded hydrogels enables dSTORM imaging of expanded samples and demonstrate that post-labeling ExM resolves the current limitations of super-resolution microscopy. Using microtubules as a reference structure and centrioles, we demonstrate that post-labeling Ex-SMLM preserves ultrastructural details, improves the labeling efficiency and reduces the positional error arising from linking fluorophores into the gel thus paving the way for super-resolution imaging of immunolabeled endogenous proteins with true molecular resolution.
Publisher Correction: MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia
Authors: Itskovich Svetlana S. , Gurunathan Arun , Clark Jason , Burwinkel Matthew , Wunderlich Mark , Berger Mikaela R. , Kulkarni Aishwarya , Chetal Kashish , Venkatasubramanian Meenakshi , Salomonis Nathan , Kumar Ashish R. , Lee Lynn H.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spiking neurons with spatiotemporal dynamics and gain modulation for monolithically integrated memristive neural networks
Authors: Duan Qingxi , Jing Zhaokun , Zou Xiaolong , Wang Yanghao , Yang Ke , Zhang Teng , Wu Si , Huang Ru , Yang Yuchao
Published: July 2020

As a key building block of biological cortex, neurons are powerful information processing units and can achieve highly complex nonlinear computations even in individual cells. Hardware implementation of artificial neurons with similar capability is of great significance for the construction of intelligent, neuromorphic systems. Here, we demonstrate an artificial neuron based on NbOx volatile memristor that not only realizes traditional all-or-nothing, threshold-driven spiking and spatiotemporal integration, but also enables dynamic logic including XOR function that is not linearly separable and multiplicative gain modulation among different dendritic inputs, therefore surpassing neuronal functions described by a simple point neuron model. A monolithically integrated 4 × 4 fully memristive neural network consisting of volatile NbOx memristor based neurons and nonvolatile TaOx memristor based synapses in a single crossbar array is experimentally demonstrated, showing capability in pattern recognition through online learning using a simplified δ-rule and coincidence detection, which paves the way for bio-inspired intelligent systems.
Structure of the yeast Swi/Snf complex in a nucleosome free state
Authors: Wang Chengcheng , Guo Zhouyan , Zhan Xiechao , Yang Fenghua , Wu Mingxuan , Zhang Xiaofeng
Published: July 2020

SWI/SNF remodelers play a key role in regulating chromatin architecture and gene expression. Here, we report the cryo-EM structure of the Saccharomyces cerevisiae Swi/Snf complex in a nucleosome-free state. The structure consists of a stable triangular base module and a flexible Arp module. The conserved subunits Swi1 and Swi3 form the backbone of the complex and closely interact with other components. Snf6, which is specific for yeast Swi/Snf complex, stabilizes the binding of the ATPase-containing subunit Snf2 to the base module. Comparison of the yeast Swi/Snf and RSC complexes reveals conserved structural features that govern the assembly and function of these two subfamilies of chromatin remodelers. Our findings complement those from recent structures of the yeast and human chromatin remodelers and provide further insights into the assembly and function of the SWI/SNF remodelers.
Publisher Correction: Materializing rival ground states in the barlowite family of kagome magnets: quantum spin liquid, spin ordered, and valence bond crystal states
Authors: Smaha Rebecca W. , He Wei , Jiang Jack Mingde , Wen Jiajia , Jiang Yi-Fan , Sheckelton John P. , Titus Charles J. , Wang Suyin Grass , Chen Yu-Sheng , Teat Simon J. , Aczel Adam A. , Zhao Yang , Xu Guangyong , Lynn Jeffrey W. , Jiang Hong-Chen , Lee Young S.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A self-organizing, living library of time-series data
Authors: Fulcher Ben D. , Lubba Carl H. , Sethi Sarab S. , Jones Nick S.
Published: July 2020

Time-series data are measured across the sciences, from astronomy to biomedicine, but meaningful cross-disciplinary interactions are limited by the challenge of identifying fruitful connections. Here we introduce the web platform,CompEngine, a self-organizing, living library of time-series data, that lowers the barrier to forming meaningful interdisciplinary connections between time series. Using a canonical feature-based representation,CompEngineplaces all time series in a common feature space, regardless of their origin, allowing users to upload their data and immediately explore diverse data with similar properties, and be alerted when similar data is uploaded in future. In contrast to conventional databases which are organized by assigned metadata,CompEngineincentivizes data sharing by automatically connecting experimental and theoretical scientists across disciplines based on the empirical structure of the data they measure.CompEngine’s growing library of interdisciplinary time-series data also enables the comprehensive characterization of time-series analysis algorithms across diverse types of empirical data.
Phenotypic plasticity in diaspore production of a amphi-basicarpic cold desert annual that produces polymorphic diaspores
Authors: Gan Lu , Lu Juanjuan , Baskin Jerry M. , Baskin Carol C. , Tan Dunyan
Published: July 2020

Phenotypic plasticity has been studied in diaspore-dimorphic species, but no such study has been done on a diaspore-polymorphic species. Our aim was to determine the effects of abiotic and biotic factors on phenotypic plasticity of the diaspore-polymorphic cold desert annual Ceratocarpus arenarius. Plants produced from dispersal units near the soil surface (a, basicarps) and at the middle (c) and upper (f) parts of the plant canopy were subjected to different levels of soil moisture, nutrient supply and intramorph and intermorph densities. Different levels of these biotic and abiotic factors resulted in significant variation in total plant mass, diaspore mass, mass allocation to stem and reproductive organs and total number and proportion of morphs a, c and f on an individual. The effect of stress on number and mass of a dispersal unit morph varied by treatment, with dispersal unit f having the highest CV and dispersal unit a the lowest. The success of this diaspore polymorphic species in its rainfall-unpredictable environment likely is enhanced by plasticity in production of the different types of diaspores.
A method to analyze the sensitivity ranking of various abiotic factors to acoustic densities of fishery resources in the surface mixed layer and bottom cold water layer of the coastal area of low latitude: a case study in the northern South China Sea
Authors: Sun Mingshuai , Cai Yancong , Zhang Kui , Zhao Xianyong , Chen Zuozhi
Published: July 2020

This is an exploratory analysis combining artificial intelligence algorithms, fishery acoustics technology, and a variety of abiotic factors in low-latitude coastal waters. This approach can be used to analyze the sensitivity level between the acoustic density of fishery resources and various abiotic factors in the surface mixed layer (the water layer above the constant thermocline) and the bottom cold water layer (the water layer below the constant thermocline). The fishery acoustic technology is used to obtain the acoustic density of fishery resources in each water layer, which is characterized by Nautical Area Scattering Coefficient values (NASC), and the artificial intelligence algorithm is used to rank the sensitivity of various abiotic factors and NASC values of two water layers, and the grades are classified according to the cumulative contribution percentage. We found that stratified or multidimensional analysis of the sensitivity of abiotic factors is necessary. One factor could have different levels of sensitivity in different water layers, such as temperature, nitrite, water depth, and salinity. Besides, eXtreme Gradient Boosting and random forests models performed better than the linear regression model, with 0.2 to 0.4 greater R2 value. The performance of the models had smaller fluctuations with a larger sample size.
Depression, neuroticism and 2D:4D ratio: evidence from a large, representative sample
Authors: Lautenbacher Leopold Maria , Neyse Levent
Published: July 2020

A body of literature reports higher rates of depression and neuroticism in female samples compared to male samples. Numerous studies have investigated the role of prenatal sex hormone exposure in this sex difference, using the ratio between the second and fourth digit of the hand (“2D:4D”) as a putative marker. However, the sample sizes of those studies were mostly small and results remained inconclusive. The aim of the present study is to test the suggested associations between depression, neuroticism and the 2D:4D ratio in a large, representative sample of over 3,000 German individuals. It was hypothesized that a higher 2D:4D (supposedly representing a more “feminine” prenatal hormone exposure) would positively predict (1) one’s history of depression as well as (2) neuroticism rates and (3) acute depressive symptom scores. Controlling for biological sex, we only found suggestive evidence for linear associations with neuroticism in the case of left hand 2D:4D ratios and the mean 2D:4D of both hands. However, additional analyses indicated that these results may have been spurious due to confounding. Our findings suggest that the 2D:4D ratio is not a relevant predictor of depression, while there was mixed evidence in the case of neuroticism.
Inverse optimal control with time-varying objectives: application to human jumping movement analysis
Authors: Westermann Kevin , Lin Jonathan Feng-Shun , Kulić Dana
Published: July 2020

Analysis of complex human movements can provide valuable insights for movement rehabilitation, sports training, humanoid robot design and control, and human–robot interaction. To accomplish complex movement, the central nervous system must coordinate the musculo-skeletal system to achieve task and internal (e.g., effort minimisation) objectives. This paper proposes an inverse optimal control approach for analysing complex human movement that does not assume that the control objective(s) remains constant throughout the movement. The movement trajectory is assumed to be optimal with respect to a cost function composed of the sum of weighted basis cost functions, which may be time varying. The weights of the cost function are recovered using a sliding window. To illustrate the proposed approach, a dataset consisting of standing broad jump to targets at three different distances is collected. The method can be used to extract control objectives that influence task success, identify different motion strategies/styles, as well as to observe how control strategy changes during the motor learning process. Kinematic analysis confirms that the identified control objectives, including centre-of-mass takeoff vector and foot placement upon landing are important to ensure that a given participant lands on the target. The dataset, including nearly 800 jump trajectories from 22 participants is also provided.
Behavioural responses of white sharks to specific baits during cage diving ecotourism
Authors: Becerril-García Edgar E. , Hoyos-Padilla Edgar M. , Micarelli Primo , Galván-Magaña Felipe , Sperone Emilio
Published: July 2020

This study describes the effect of different baits on the attraction, surface behaviour and conditioning of white sharks Carcharodon carcharias during local ecotourism activities. The sightings, behaviours, and pictures used for photographic identification were obtained during August to November 2012–2014 onboard tourist boats in Guadalupe Island, Mexico. Four types of baits were used: (1) frozen bait; (2) frozen bait and natural chum; (3) fresh fish bait; and (4) mackerel bags. Data were analysed according to sex, maturity and the total of sharks using 6,145 sightings of 121 white sharks. The type of bait showed no significant difference on the effectiveness to attracting sharks. Ethological analysis showed that the type of bait had a significant effect on the shark’s surface behaviour during its interactions with boats. Natural chum and fresh baits showed short term behavioural patterns constituted by increased number of violent interactions with the bait, while the frozen bait did not generate a defined behavioural pattern. Conditioning of white sharks was determined by the number of interactions and the consumption frequency of the bait. Fifty nine percent of sharks (n = 41) showed no conditioning, 36% (n = 25) showed a low risk and only 5% (n = 3) were found to have a high risk of conditioning. The results suggest that current ecotourism has no effect on the conditioning of the white sharks, and that all baits have a similar effectiveness for attracting the sharks. However, a different behavioural pattern was observed when fresh bait and chum were used, which could increase the potential of accidents during ecotourism.
The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone
Authors: Ilas Dragos C. , Baboolal Thomas G. , Churchman Sarah M. , Jones William G. , Giannoudis Peter V. , Bühring Hans-Jörg , McGonagle Dennis , Jones Elena
Published: July 2020

Osteoarthritis (OA), the most common joint disorder, is characterised by progressive structural changes in both the cartilage and the underlying subchondral bone. In late disease stages, subchondral bone sclerosis has been linked to heightened osteogenic commitment of bone marrow stromal cells (BMSCs). This study utilised cell sorting and immunohistochemistry to identify a phenotypically-distinct, osteogenically-committed BMSC subset in human OA trabecular bone. Femoral head trabecular bone tissue digests were sorted into CD45-CD271+CD56+CD146-, CD45-CD271+CD56-CD146+ and CD45-CD271+CD56-CD146-(termed double-negative, DN) subsets, and CD45+CD271-hematopoietic-lineage cells served as control. Compared to the CD146+ subset, the CD56+ subset possessed a lower-level expression of adipocyte-associated genes and significantly over 100-fold higher-level expression of many osteoblast-related genes including osteopontin and osteocalcin, whilst the DN subset presented a transcriptionally ‘intermediate’ BMSC population. All subsets were tri-potential following culture-expansion and were present in control non-OA trabecular bone. However, while in non-OA bone CD56+ cells only localised on the bone surface, in OA bone they were additionally present in the areas of new bone formation rich in osteoblasts and newly-embedded osteocytes. In summary, this study reveals a distinct osteogenically-committed CD271+CD56+ BMSC subset and implicates it in subchondral bone sclerosis in hip OA. CD271+CD56+ subset may represent a future therapeutic target for OA and other bone-associated pathologies.
Digital and analogue modulation and demodulation scheme using vortex-based spin torque nano-oscillators
Authors: Jenkins Alex S. , Alvarez Lara San Emeterio , Freitas Paulo P. , Ferreira Ricardo
Published: July 2020

In conventional communications systems, information is transmitted by modulating the frequency, amplitude or phase of the carrier signal, which often occurs in a binary fashion over a very narrow bandwidth. Recently, ultra-wideband signal transmission has gained interest for local communications in technologies such as autonomous local sensor networks and on-chip communications, which presents a challenge for conventional electronics. Spin-torque nano-oscillators (STNOs) have been studied as a potentially low power highly tunable frequency source, and in this report we expand on this to show how a specific dynamic phase present in vortex-based STNOs makes them also well suited as Wideband Analogue Dynamic Sensors (WADS). This multi-functionality of the STNOs is the basis of a new modulation and demodulation scheme, where nominally identical devices can be used to transmit information in both a digital or analogue manner, with the potential to allow the highly efficient transmittance of data.