bluuebunny/crossref_metadata_2025 huggingface dataset:
Herbivory modulates soil CO2 fluxes after windthrow: a case study in temperate mountain forests
Authors: Mayer Mathias , Keßler David , Katzensteiner Klaus
Published: December 2019

Ungulate herbivory can alter functional plant communities of early-successional forest ecosystems. The consequences of such vegetation changes on soil carbon cycling are still not fully understood. Here, we used an ungulate exclusion experiment to investigate how different levels of herbivory and associated changes in vegetation succession modulate soil CO2 efflux and its heterotrophic and autotrophic sources following windthrow in temperate mountain forests. Our results indicate that only high levels of ungulate herbivory and associated vegetation shifts from tree to rather grass dominated plant communities affect soil CO2 fluxes. We did not find evidence that a moderate herbivory level and accompanied smaller shifts in the functional plant community affect soil CO2 fluxes. A greater soil CO2 efflux under the influence of high herbivory pressure was primarily attributed to accelerated heterotrophic respiration, likely due to warmer soil conditions. Moreover, autotrophic respiration from grass roots and associated microbial communities is suggested to contribute to higher soil CO2 fluxes. We conclude that intense herbivory and accompanied successional changes in the functional plant community enhance soil carbon losses following forest windthrow. This might have negative consequences for the soil carbon stocks and for the climate system.
Assessing Changes in Airflow and Energy Loss in a Progressive Tracheal Compression Before and After Surgical Correction
Authors: Xiao Qiwei , Cetto Raul , Doorly Denis J. , Bates Alister J. , Rose Jan N. , McIntyre Charlotte , Comerford Andrew , Madani Gitta , Tolley Neil S. , Schroter Robert
Published: December 2019

The energy needed to drive airflow through the trachea normally constitutes a minor component of the work of breathing. However, with progressive tracheal compression, patient subjective symptoms can include severe breathing difficulties. Many patients suffer multiple respiratory co-morbidities and so it is important to assess compression effects when evaluating the need for surgery. This work describes the use of computational prediction to determine airflow resistance in compressed tracheal geometries reconstructed from a series of CT scans. Using energy flux analysis, the regions that contribute the most to airway resistance during inhalation are identified. The principal such region is where flow emerging from the zone of maximum constriction undergoes breakup and turbulent mixing. Secondary regions are also found below the tongue base and around the glottis, with overall airway resistance scaling nearly quadratically with flow rate. Since the anatomical extent of the imaged airway varied between scans—as commonly occurs with clinical data and when assessing reported differences between research studies—the effect of sub-glottic inflow truncation is considered. Analysis shows truncation alters the location of jet breakup and weakly influences the pattern of pressure recovery. Tests also show that placing a simple artificial glottis in the inflow to a truncated model can replicate patterns of energy loss in more extensive models, suggesting a means to assess sensitivity to domain truncation in tracheal airflow simulations.
On the modelling and performance measurement of service networks with heterogeneous customers
Authors: Palmer Ryan , Utley Martin
Published: December 2019

Service networks are common throughout the modern world, yet understanding how their individual services effect each other and contribute to overall system performance can be difficult. An important metric in these systems is the quality of service. This is an often overlooked measure when modelling and relates to how customers are affected by a service. Presented is a novel perspective for evaluating the performance of multi-class queueing networks through a combination of operational performance and service quality—denoted the “flow of outcomes”. Here, quality is quantified by customers moving between or remaining in classes as a result of receiving service or lacking service. Importantly, each class may have different flow parameters, hence the positive/negative impact of service quality on the system’s operational performance is captured. A fluid–diffusion approximation for networks of stochastic queues is used since it allows for several complex flow dynamics: the sequential use of multiple services; abandonment and possible rejoin; reuse of the same service; multiple customers classes; and, class and time dependent parameters. The scalability of the approach is a significant benefit since, the modelled systems may be relatively large, and the included flow dynamics may render the system analytically intractable or computationally burdensome. Under the right conditions, this method provides a framework for quickly modelling large time-dependent systems. This combination of computational speed and the “flow of outcomes” provides new avenues for the analysis of multi-class service networks where both service quality and operational efficiency interact.
Bacillus atrophaeus HAB-5 secretion metabolites preventing occurrence of systemic diseases in tobacco plant
Authors: Rajaofera Mamy Jayne Nelly , Wang Yi , Jatoi Zaheer Amed , Jin Pengfei , Cui Hongguang , Lin Chunhua , Miao Weiguo
Published: December 2019

Finding synthetic pesticide alternatives for health and a healthy environment has become a crucial issue for scientific research. A number of studies have reported efficacy of Bacillus species on promoting plant development, as well as protecting plants against pathogen invasion, especially pathogenic fungi and bacteria. However, little was known about Bacillus species in controlling viral diseases. In this study, Bacillus atrophaeus strain HAB-5, isolated from cotton field, Xinjiang, China efficiently promoted the growth of tobacco plants. According to the results, the treatment with the strain HAB-5 increased the expression of NtEXP1 and NtEXP2. Then the Tobacco mosaic virus (TMV)/ Nicotiana tobacco system was employed to evaluate virus resistance induced by strain HAB-5. Tobacco leaves were treated with antimicrobial metabolites of strain HAB-5 (1 mg/mL), and 12 h later the treated leaves were challenged with TMV via rub-inoculation. The results showed that disease symptoms were obviously compromised by tobacco leaves treated with strain HAB-5, and the viral accumulation level was reduced extensively. Moreover, it was found that the signaling regulatory gene (NPR1), defense genes (PR-1a, PR-1b, Chia5), and hypertensive response related genes (Hsr203J, Hin1) were up-regulated in plants treated with the metabolites. Altogether, these accumulated results strongly support strain HAB-5 to be a biological controlling agent against TMV.
Correction to: Uncertainty and Resolution Analysis of 2D and 3D Inversion Models Computed from Geophysical Electromagnetic Data
Authors: Ren Zhengyong , Kalscheuer Thomas
Published: December 2019

An error has been found and should be corrected.
Development and Validation of the Guilt and Shame Questionnaire for Adolescents of Parents with a Mental Illness (GSQ-APMI)
Authors: Bosch Annick , van de Ven Monique , van Doesum Karin
Published: December 2019

Objectives

Children of parents with a mental illness (COPMI) often experience negative feelings, such as guilt and shame. These feelings may put them at risk of developing internalizing or externalizing problems. In the Netherlands, preventive peer support groups exist which aim at preventing experiencing negative feelings such as guilt and shame. However, current questionnaires which assess feelings of guilt and shame have limitations and therefore cannot be used to measure these feelings in adolescent COPMI. Moreover, it cannot be measured if these peer support groups succeed in preventing experiencing negative feelings, such as guilt and shame. The aim of this study was to develop and validate the ‘Guilt and Shame Questionnaire—for Adolescents of Parents with a Mental Illness (GSQ-APMI)’, which is specifically designed for adolescent COPMI aged 12–21 years.

Methods

The study consisted of three phases: phase 1, ‘Operationalization and Item Development’; phase 2, ‘Pilot Testing’; and phase 3, ‘Psychometric Properties’. Phase 2 included 79 adolescent COPMI; phase 3 included 47 adolescent COPMI.

Results

Results revealed that the GSQ-APMI is a reliable and valid questionnaire to measure feelings of guilt and shame in adolescent COPMI.

Conclusions

The GSQ-APMI is a short (10 items) and feasible instrument, ready to use in both research and clinical practice to establish feelings of guilt and shame in adolescent COPMI. The questionnaire results in two scale scores: one scale score reflecting feelings of guilt and one scale score reflecting feelings of shame.
Improved Source/Absorber Preparation for Radionuclide Spectrometry Based on Low-Temperature Calorimetric Detectors
Authors: Bockhorn L. , Paulsen M. , Beyer J. , Kossert K. , Loidl M. , Nähle O. J. , Ranitzsch P. C.-O. , Rodrigues M.
Published: December 2019

High-resolution beta spectrometry based on low-temperature calorimetric detectors requires high-quality source/absorber combinations in order to avoid spectrum artifacts and to achieve optimal detection efficiency. In this work, preparation techniques and quality control methods to fabricate reliable source/absorber assemblies with the radionuclide under investigation embedded into them are discussed.
Affectivity and the distinction between minimal and narrative self
Authors: Bortolan Anna
Published: December 2019

In the contemporary phenomenological literature it has been argued that it is possible to distinguish between two forms of selfhood: the “minimal” and “narrative” self. This paper discusses a claim which is central to this account, namely that the minimal and narrative self complement each other but are fundamentally distinct dimensions. In particular, I challenge the idea that while the presence of a minimal self is a condition of possibility for the emergence of a narrative self, the dynamics which characterise narrative selfhood do not have a structuring effect on minimal self-experience. I do so by drawing on both classical and contemporary phenomenological literature to show that at least certain forms of affective experience are complex phenomena in which minimal and narrative forms of selfhood are deeply entwined. More specifically, I claim that, due to their evaluative character, intentional and non-intentional affective states convey a pre-reflective experience of constitutive aspects of the narrative self. This enables me to argue that minimal and narrative selfhood are phenomenologically inextricable.
Toward the synthesis of thiadiazole-based therapeutic agents: synthesis, spectroscopic study, X-ray analysis, and cross-coupling reactions of the key intermediate 3,5-diiodo-1,2,4-thiadiazole
Authors: Boulhaoua Mohammed , Torvisco Ana , Pasinszki Tibor
Published: December 2019

The 1,2,4-thiadiazole moiety is an important component of several biologically active compounds, and varying substituents on this aromatic ring is one of the possible methods to develop novel thiadiazole-based drugs for medicine. A key building block to this end, namely 3,5-diiodo-1,2,4-thiadiazole (1), has been synthesized and characterized in this work for the first time. 1 has exhibited high selectivity for the replacement of iodine atom at position C5 (carbon next to sulfur) in Sonogashira-type cross-coupling reactions with phenylacetylene. Therefore, 3-iodo-5-(phenylethynyl)-1,2,4-thiadiazole (4) or 3,5-bis(phenylethynyl)-1,2,4-thiadiazole (5) could be synthesized selectively depending on reaction conditions. All three novel molecules have been characterized by NMR, IR, Raman, mass, and UV spectroscopies, and their solid phase structures have been determined by single-crystal X-ray diffraction. 1 is expected to be a key starting material for producing thiadiazole-based therapeutic agents using cross-coupling reactions.
On the Origin of Frictional Energy Dissipation
Authors: Hu Renfeng , Krylov Sergey Yu. , Frenken Joost W. M.
Published: December 2019

The origin of the friction between sliding bodies establishes an outstanding scientific problem. In this article, we demonstrate that the energy loss in each microscopic slip event between the bodies readily follows from the dephasing of phonons that are generated in the slip process. The dephasing mechanism directly links the typical timescales of the lattice vibrations with those of the experienced energy ‘dissipation’ and manifests itself as if the slip-induced motion were close to critically damped.

Graphical abstract
Comparison of Environmental Impacts of Deep-sea Tailings Placement Versus On-land Disposal
Authors: Kwong Y. T. John , Apte Simon C. , Asmund Gert , Haywood Michael D. E. , Morello Elisabetta B.
Published: December 2019

With increasing metal prices and declining ore grades, new mines are getting larger and mine waste disposal and management have become more difficult, particularly from an environmental perspective. While technologies keep on improving, the available space for terrestrial mine waste disposal is limited. Thus, several coastal countries still consider deep-sea tailings placement (DSTP) as a viable option. This brief review compares the environmental impacts of DSTP versus on-land disposal and suggests several factors to consider in selecting the most suitable options for mine waste disposal.
Support for the Death Penalty in Taiwan?: a Study of Value Conflict and Ambivalence
Authors: Jou Susyan , Hebenton Bill
Published: December 2019

While a substantial number of studies have examined public opinion on the death penalty in the USA, and more recently parts of Asia, including China, very few empirical studies have considered support for the death penalty in Taiwan. This paper examines public attitudes in Taiwan and the role of ‘value conflict’ in attitudes to both death penalty abolition and in the context of alternatives. Using the results of 1016 respondents drawn from a national face-to-face sample (n= 2039) survey conducted by the Taiwan Alliance to End the Death Penalty (TAEDP) in 2014, we demonstrate that public attitudes in Taiwan are simultaneously committed to many underlying values in conflict. The results also indicate that value conflict exists among the majority of the sample (more than 60 per cent) who are prepared to accept alternatives to abolition, and whom we can describe as ambivalent. Recognition of value conflict, ambivalence and the moral psychology underpinning public attitudes to the death penalty is essential, not only conceptually but to allow for a more appropriate and nuanced understanding of the abolitionist/retentionist debate.
Identification of new NBOH drugs in seized blotter papers: 25B-NBOH, 25C-NBOH, and 25E-NBOH
Authors: Machado Yuri , Coelho Neto José , Lordeiro Rogério Araújo , Alves Rosemeire Brondi , Piccin Evandro
Published: December 2019

Purpose

The recreational drug market remains dynamic. After the introduction of 25I-NBOH, an N-benzylphenethylamine and new psychoactive substance, as option for LSD and NBOMe drugs, new NBOH substances have been identified in recent years. Herein, we report our efforts for the identification and structural elucidation of three new NBOHs detected in seized blotter papers: 25B-NBOH, 25C-NBOH, and 25E-NBOH.

Methods

Blotter papers seized between 2017 and 2018 by local police force in Brazil were submitted to extraction, purification, identification and characterization using attenuated total reflectance-Fourier transform infrared spectroscopy, gas chromatography—mass spectrometry, liquid chromatography—tandem mass spectrometry, and one- and two-dimensional nuclear magnetic resonance spectroscopy.

Results

Three new NBOHs were characterized: 2-(((4-ethyl-2,5-dimethoxyphenethyl)amino)methyl)phenol (25E-NBOH, 2C-E-NBOH), 2-(((4-chloro-2,5-dimethoxyphenethyl)amino)methyl)phenol (25C-NBOH, 2C-C-NBOH), and 2-(((4-bromo-2,5-dimethoxyphenethyl)amino)methyl)phenol (25B-NBOH, 2C-B-NBOH).

Conclusions

To our knowledge, this is the first report for identification and detailed characterization of 25B-NBOH, 25C-NBOH, and 25E-NBOH in seized samples. NBOH substances are not under United Nations Conventions control. The identification of seized blotter papers between 2014 and beginning of 2019 showed that NBOH substances have become the main hallucinogenic drug in the region. These group are thermolabile under gas chromatographic conditions, demanding other analytical approaches of analysis to avoid misidentifications. Unfortunately, the knowledge about toxicology of NBOHs are limited.
Kommentare und Erwiderung zu: Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021
Authors: Bleninger Sara , Fürnrohr Michael , Kiesl Hans , Krämer Walter , Küchenhoff Helmut , Burgard Jan Pablo , Münnich Ralf , Rupp Martin
Published: December 2019

Burgard et al. (2020) stellen in ihrem Artikel zu Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021 Erweiterungen der Stichproben- und Schätzmethoden des Zensus 2011 vor, die kleine Gemeinden unter 10.000 Einwohnern in den Entscheidungsprozess integrieren. Die Dringlichkeit zur Lösung dieses Problems wurde ebenso im Urteil des Bundesverfassungsgerichts zur Volkszählung 2011 festgestellt. Ziel dieser Erwiderung ist eine eingehende Diskussion der Ergebnisse des vorangegangenen Beitrags mit namhaften Experten auf diesem Gebiet. Insbesondere geht es um eine Einordnung des Artikels in den Wissenschaftskontext (Krämer), die Bedeutung von Nichtstichprobenfehlern für den Zensus (Küchenhoff), den Zensus aus Sicht der Amtsstatistik (Bleninger und Fürnrohr) sowie aus statistisch-methodischer Sicht (Kiesl). Darüber hinaus werden aktuelle Entwicklungen vorgestellt.
Unravelling the variability and causes of smallholder maize yield gaps in Ethiopia
Authors: Assefa Banchayehu Tessema , Chamberlin Jordan , Reidsma Pytrik , Silva João Vasco , van Ittersum Martin K.
Published: December 2019

Ethiopia has achieved the second highest maize yield in sub-Saharan Africa. Yet, farmers’ maize yields are still much lower than on-farm and on-station trial yields, and only ca. 20% of the estimated water-limited potential yield. This article provides a comprehensive national level analysis of the drivers of maize yields in Ethiopia, by decomposing yield gaps into efficiency, resource and technology components, and accounting for a broad set of detailed input and crop management choices. Stochastic frontier analysis was combined with concepts of production ecology to estimate and explain technically efficient yields, the efficiency yield gap and the resource yield gap. The technology yield gap was estimated based on water-limited potential yields from the Global Yield Gap Atlas. The relative magnitudes of the efficiency, resource and technology yield gaps differed across farming systems; they ranged from 15% (1.6 t/ha) to 21% (1.9 t/ha), 12% (1.3 t/ha) to 25% (2.3 t/ha) and 54% (4.8 t/ha) to 73% (7.8 t/ha), respectively. Factors that reduce the efficiency yield gap include: income from non-farm sources, value of productive assets, education and plot distance from home. The resource yield gap can be explained by sub-optimal input use, from a yield perspective. The technology yield gap comprised the largest share of the total yield gap, partly due to limited use of fertilizer and improved seeds. We conclude that targeted but integrated policy design and implementation is required to narrow the overall maize yield gap and improve food security.
The Value of BECCS in IAMs: a Review
Authors: Köberle Alexandre C.
Published: December 2019

Purpose of Review

Integrated assessment model (IAM) scenarios consistent with Paris Agreement targets involve large negative emission technologies (NETs), mostly bioenergy with carbon capture and storage (BECCS). Such reliance on BECCS implies IAMs assign it a high value. Past analyses on the value of BECCS in IAMs have not explicitly addressed the role of model structure and assumptions as value drivers. This paper examines the extent to which the value of BECCS in IAMs is enhanced by model structure constraints and assumptions.

Recent Findings

Predominant use of high discount rates (3.5–5%) means models opt for delayed-action strategies for emissions mitigation that lead to high levels of cumulative net-negative emissions, while lower discount rates lead to reduce reliance on NETs. Until recently in the literature, most models limited NET options to only BECCS and afforestation, but introduction of other CDR options can reduce BECCS deployment. Constraints on grid penetration of variable renewable energy (VRE) is a determining factor on the level of BECCS deployment across models, and more constrained grid penetration of VREs leads to more BECCS in electricity generation.

This paper concludes BECCS derives significant value not only from the existing structure of IAMs but also from what isnotrepresented in models and by predominant use of high discount rates. Omissions include NETs other than BECCS and deforestation, low-carbon innovation in end-use technologies, grid resilience to intermittent sources, and energy use in agriculture production. As IAMs increasingly endogenize such constraints, the value of BECCS in resulting scenarios is likely to be dampened.
Penalized inference of the hematopoietic cell differentiation network via high-dimensional clonal tracking
Authors: Pellin Danilo , Biasco Luca , Aiuti Alessandro , Di Serio Maria Clelia , Wit Ernst C.
Published: December 2019

Background

During their lifespan, stem- or progenitor cells have the ability to differentiate into more committed cell lineages. Understanding this process can be key in treating certain diseases. However, up until now only limited information about the cell differentiation process is known.

Aim

The goal of this paper is to present a statistical framework able to describe the cell differentiation process at the single clone level and to provide a corresponding inferential procedure for parameters estimation and structure reconstruction of the differentiation network.

Approach

We propose a multidimensional, continuous-time Markov model with density-dependent transition probabilities linear in sub-population sizes and rates. The inferential procedure is based on an iterative calculation of approximated solutions for two systems of ordinary differential equations, describing process moments evolution over time, that are analytically derived from the process’ master equation. Network sparsity is induced by adding a SCAD-based penalization term in the generalized least squares objective function.

Results

The methods proposed here have been tested by means of a simulation study and then applied to a data set derived from a gene therapy clinical trial, in order to investigate hematopoiesis in humans,in-vivo. The hematopoietic structure estimated contradicts the classical dichotomy theory of cell differentiation and supports a novel myeloid-based model recently proposed in the literature.
A new method to simulate restricted variants of polarizationless P systems with active membranes
Authors: Gazdag Zsolt , Kolonits Gábor
Published: December 2019

According to the P conjecture by Gh. Păun, polarizationless P systems with active membranes cannot solve $${\mathbf {NP}}$$NP-complete problems in polynomial time. The conjecture is proved only in special cases yet. In this paper we consider the case where only elementary membrane division and dissolution rules are used and the initial membrane structure consists of one elementary membrane besides the skin membrane. We give a new approach based on the concept of object division polynomials introduced in this paper to simulate certain computations of these P systems. Moreover, we show how to compute efficiently the result of these computations using these polynomials.
Change management and adoption of health information technology (HIT)/eHealth in public hospitals in Ghana: A qualitative study
Authors: Yusif Salifu , Hafeez-Baig Abdul , Soar Jeffrey
Published: December 2019

In Ghana, as with other developing countries, there are several health information technology (HIT) initiatives as interventions to improve healthcare delivery. HIT implementation undoubtedly results in change. However, most studies relating to HIT implementation readiness have constantly neglected the role of change in successfully implementing HIT. This study intends to identify factors affecting successful change management as part of preparation towards successfully implementing HIT in public hospital in Ghana. To carry out this study, we conducted in-depth interviews with a matrix of HIT senior managers and thematically analyzed the data. The data was transcribed and uploaded into a Nvivo 11 software for analysis using thematic analysis techniques. Five (5) themes were discovered. They are: 1) Stakeholder participation; 2) Proof of experience in similar project; 3) Availability of committed change agents/all-levels-change representatives; 4) Clearly articulated change implementation strategy; and 5) Training and improvement mechanism (post-implementation). A fresh call is made for more attention to be paid to change as part of preparatory measures towards the adoption of HIT in Ghana using the five cardinal approaches identified as a guide.
Aware of the Future?
Authors: Lalot Fanny , Ahvenharju Sanna , Minkkinen Matti , Wensing Enrico
Published: December 2019

Abstract. Futures Consciousness refers to the capacity that a person has for understanding, anticipating, and preparing for the future. Although the concept is widely used in the field of futures research, no quantitative tool exists yet that assesses it. Drawing from a recent five-dimensional model that considers Time perspective, Agency beliefs, Openness to alternatives, Systems perception, and Concern for others as interrelated sub-dimensions of a general construct of Futures Consciousness, we developed a composite 20-item scale that measures Futures Consciousness as an interindividual difference. The psychometric properties of this new scale were examined through a dual approach of exploratory and confirmatory factorial analyses with a total of 1,301 participants in three languages (English, French, and Finnish). The scale’s structure proved satisfactory and fitted the hypothesized five-dimensional model in all three languages. Measures of internal and external validity (convergent and concurrent) also indicated good psychometric properties. Notably, individuals’ scores were positively related to the adoption of several social future-oriented behaviors such as pro-environmental and civic behavior. As such, the developed scale proves a reliable tool that could be of use for scholars and practitioners in futures studies as well as psychology.
Building a European exposure science strategy
Authors: Fantke Peter , von Goetz Natalie , Schlüter Urs , Bessems Jos , Connolly Alison , Dudzina Tatsiana , Ahrens Andreas , Bridges Jim , Coggins Marie A. , Conrad André , Hänninen Otto , Heinemeyer Gerhard , Kephalopoulos Stylianos , McLachlan Michael , Meijster Tim , Poulsen Veronique , Rother Dag , Vermeire Theo , Viegas Susana , Vlaanderen Jelle , Jeddi Maryam Zare , Bruinen de Bruin Yuri
Published: December 2019

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a ‘European Exposure Science Strategy’ 2020–2030, which is aligned with advances in science and technology.
Kirigami-inspired multiscale patterning of metallic structures via predefined nanotrench templates
Authors: Zheng Mengjie , Chen Yiqin , Liu Zhi , Liu Yuan , Wang Yasi , Liu Peng , Liu Qing , Bi Kaixi , Shu Zhiwen , Zhang Yihui , Duan Huigao
Published: December 2019

Reliable fabrication of multiscale metallic patterns with precise geometry and size at both the nanoscale and macroscale is of importance for various applications in electronic and optical devices. The existing fabrication processes, which usually involve film deposition in combination with electron-beam patterning, are either time-consuming or offer limited precision. Inspired by the kirigami, an ancient handicraft art of paper cutting, this work demonstrates an electron-beam patterning process for multiscale metallic structures with significantly enhanced efficiency and precision. Similar to the kirigami, in which the final pattern is defined by cutting its contour in a paper and then removing the unwanted parts, we define the target multiscale structures by first creating nanotrench contours in a metallic film via an electron-beam-based process and then selectively peeling the separated film outside the contours. Compared with the conventional approach, which requires the exposure of the whole pattern, much less exposure area is needed for nanotrench contours, thus enabling reduced exposure time and enhanced geometric precision due to the mitigated proximity effect. A theoretical model based on interface mechanics allows a clear understanding of the nanotrench-assisted selective debonding behaviour in the peeling process. By using this fabrication process, multiscale metallic structures with sub-10-nm up to submillimetre features can be reliably achieved, having potential applications for anti-counterfeiting and gap-plasmon-enhanced spectroscopy.
Quantitative phase imaging of erythrocytes under microfluidic constriction in a high refractive index medium reveals water content changes
Authors: Park Han Sang , Eldridge Will J. , Yang Wen-Hsuan , Crose Michael , Ceballos Silvia , Roback John D. , Chi Jen-Tsan Ashley , Wax Adam
Published: December 2019

Changes in the deformability of red blood cells can reveal a range of pathologies. For example, cells which have been stored for transfusion are known to exhibit progressively impaired deformability. Thus, this aspect of red blood cells has been characterized previously using a range of techniques. In this paper, we show a novel approach for examining the biophysical response of the cells with quantitative phase imaging. Specifically, optical volume changes are observed as the cells transit restrictive channels of a microfluidic chip in a high refractive index medium. The optical volume changes indicate an increase of cell’s internal density, ostensibly due to water displacement. Here, we characterize these changes over time for red blood cells from two subjects. By storage day 29, a significant decrease in the magnitude of optical volume change in response to mechanical stress was witnessed. The exchange of water with the environment due to mechanical stress is seen to modulate with storage time, suggesting a potential means for studying cell storage.
Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs
Authors: Niculescu A. B. , Le-Niculescu H. , Roseberry K. , Wang S. , Hart J. , Kaur A. , Robertson H. , Jones T. , Strasburger A. , Williams A. , Kurian S. M. , Lamb B. , Shekhar A. , Lahiri D. K. , Saykin A. J.
Published: December 2019

Short-term memory dysfunction is a key early feature of Alzheimer’s disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine- diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).
Coordinated transformation of the gut microbiome and lipidome of bowhead whales provides novel insights into digestion
Authors: Miller Carolyn A , Holm Henry C , Horstmann Lara , George John C , Fredricks Helen F , Van Mooy Benjamin A S , Apprill Amy
Published: December 2019

Whale digestion plays an integral role in many ocean ecosystems. By digesting enormous quantities of lipid-rich prey, whales support their energy intensive lifestyle, but also excrete nutrients important to ocean biogeochemical cycles. Nevertheless, whale digestion is poorly understood. Gastrointestinal microorganisms play a significant role in vertebrate digestion, but few studies have examined them in whales. To investigate digestion of lipids, and the potential contribution of microbes to lipid digestion in whales, we characterized lipid composition (lipidomes) and bacterial communities (microbiotas) in 126 digesta samples collected throughout the gastrointestinal tracts of 38 bowhead whales (Balaena mysticetus) harvested by Alaskan Eskimos. Lipidomes and microbiotas were strongly correlated throughout the gastrointestinal tract. Lipidomes and microbiotas were most variable in the small intestine and most similar in the large intestine, where microbiota richness was greatest. Our results suggest digestion of wax esters, the primary lipids in B. mysticetus prey representing more than 80% of total dietary lipids, occurred in the mid- to distal small intestine and was correlated with specific microorganisms. Because wax esters are difficult to digest by other marine vertebrates and constitute a large reservoir of carbon in the ocean, our results further elucidate the essential roles that whales and their gastrointestinal microbiotas play in the biogeochemical cycling of carbon and nutrients in high-latitude seas.
Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation
Authors: Wattenberg Max M. , Asch Daniella , Yu Shun , O’Dwyer Peter J. , Domchek Susan M. , Nathanson Katherine L. , Rosen Mark A. , Beatty Gregory L. , Siegelman Evan S. , Reiss Kim A.
Published: December 2019

Background

Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined.

Methods

Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS.

Results

The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25–0.74; 0.0068).

Conclusion

Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.
The involvement of PybZIPa in light-induced anthocyanin accumulation via the activation of PyUFGT through binding to tandem G-boxes in its promoter
Authors: Liu Hainan , Su Jun , Zhu Yangfan , Yao Gaifang , Allan Andrew C. , Ampomah-Dwamena Charles , Shu Qun , Lin-Wang Kui , Zhang Shaoling , Wu Jun
Published: December 2019

To gain insight into how anthocyanin biosynthesis is controlled by light in fruit, transcriptome and metabolome analyses were performed in the Chinese sand pear cultivar “Mantianhong” (Pyrus pyrifolia) after bagging and bag removal. We investigated transcriptional and metabolic changes and gene-metabolite correlation networks. Correlation tests of anthocyanin content and transcriptional changes revealed that 1,530 transcripts were strongly correlated with 15 anthocyanin derivatives (R2 > 0.9, P-value < 0.05), with the top 130 transcripts categorized as being associated with flavonoid metabolism, transcriptional regulation, and light signaling. The connection network revealed a new photosensitive transcription factor, PybZIPa, that might play an important role during light-induced anthocyanin accumulation. The overexpression of PybZIPa promoted anthocyanin accumulation in pear and strawberry fruit as well as tobacco leaves. Dual luciferase and Y1H assays further verified that PybZIPa directly activated the expression of PyUFGT by binding to tandem G-box motifs in the promoter, which was key to differential anthocyanin accumulation in debagged pear skin, and the number of G-box motifs affected the transcriptional activation of PyUFGT by PybZIPa. The results indicate that the light-induced anthocyanin biosynthesis regulatory mechanism in pear differs from that described in previous reports suggesting that a bZIP family member co-regulates anthocyanin biosynthesis with other transcription factors in apple and Arabidopsis. It was found that, in response to light, PybZIPa promoted anthocyanin biosynthesis by regulating important transcription factors (PyMYB114, PyMYB10, and PyBBX22) as well as structural genes (PyUFGT) via binding to G-boxes within promoters. This activation was amplified by the self-binding of PybZIPa to activate its own promoter. Overall, we demonstrate the utility of a multiomics integrative approach for discovering new functional genes and pathways underlying light-induced anthocyanin biosynthesis.
Global redox proteome and phosphoproteome analysis reveals redox switch in Akt
Authors: Su Zhiduan , Burchfield James G. , Yang Pengyi , Humphrey Sean J. , Yang Guang , Francis Deanne , Yasmin Sabina , Shin Sung-Young , Norris Dougall M. , Kearney Alison L. , Astore Miro A. , Scavuzzo Jonathan , Fisher-Wellman Kelsey H. , Wang Qiao-Ping , Parker Benjamin L. , Neely G. Gregory , Vafaee Fatemeh , Chiu Joyce , Yeo Reichelle , Hogg Philip J. , Fazakerley Daniel J. , Nguyen Lan K. , Kuyucak Serdar , James David E.
Published: December 2019

Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.
Hierarchical motor control in mammals and machines
Authors: Merel Josh , Botvinick Matthew , Wayne Greg
Published: December 2019

Advances in artificial intelligence are stimulating interest in neuroscience. However, most attention is given to discrete tasks with simple action spaces, such as board games and classic video games. Less discussed in neuroscience are parallel advances in “synthetic motor control”. While motor neuroscience has recently focused on optimization of single, simple movements, AI has progressed to the generation of rich, diverse motor behaviors across multiple tasks, at humanoid scale. It is becoming clear that specific, well-motivated hierarchical design elements repeatedly arise when engineering these flexible control systems. We review these core principles of hierarchical control, relate them to hierarchy in the nervous system, and highlight research themes that we anticipate will be critical in solving challenges at this disciplinary intersection.
General structural features that regulate integrin affinity revealed by atypical αVβ8
Authors: Wang Jianchuan , Su Yang , Iacob Roxana E. , Engen John R. , Springer Timothy A.
Published: December 2019

Integrin αVβ8, which like αVβ6 functions to activate TGF-βs, is atypical. Its β8 subunit binds to a distinctive cytoskeleton adaptor and does not exhibit large changes in conformation upon binding to ligand. Here, crystal structures, hydrogen-deuterium exchange dynamics, and affinity measurements on mutants are used to compare αVβ8 and αVβ6. Lack of a binding site for one of three βI domain divalent cations and a unique β6-α7 loop conformation in β8 facilitate movements of the α1 and α1’ helices at the ligand binding pocket toward the high affinity state, without coupling to β6-α7 loop reshaping and α7-helix pistoning that drive large changes in βI domain-hybrid domain orientation seen in other integrins. Reciprocal swaps between β6 and β8 βI domains increase affinity of αVβ6 and decrease affinity of αVβ8 and define features that regulate affinity of the βI domain and its coupling to the hybrid domain.
Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles
Authors: Xie Xiaodong , Nie Huifang , Zhou Yu , Lian Shu , Mei Hao , Lu Yusheng , Dong Haiyan , Li Fengqiao , Li Tao , Li Bifei , Wang Jie , Lin Min , Wang Chaihung , Shao Jingwei , Gao Yu , Chen Jianming , Xie Fangwei , Jia Lee
Published: December 2019

There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi’s sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine.
Contribution of oxic methane production to surface methane emission in lakes and its global importance
Authors: Günthel Marco , Donis Daphne , Kirillin Georgiy , Ionescu Danny , Bizic Mina , McGinnis Daniel F. , Grossart Hans-Peter , Tang Kam W.
Published: December 2019

Recent discovery of oxic methane production in sea and lake waters, as well as wetlands, demands re-thinking of the global methane cycle and re-assessment of the contribution of oxic waters to atmospheric methane emission. Here we analysed system-wide sources and sinks of surface-water methane in a temperate lake. Using a mass balance analysis, we show that internal methane production in well-oxygenated surface water is an important source for surface-water methane during the stratified period. Combining our results and literature reports, oxic methane contribution to emission follows a predictive function of littoral sediment area and surface mixed layer volume. The contribution of oxic methane source(s) is predicted to increase with lake size, accounting for the majority (>50%) of surface methane emission for lakes with surface areas >1 km2.
A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion
Authors: Boone Peter G. , Rochelle Lauren K. , Ginzel Joshua D. , Lubkov Veronica , Roberts Wendy L. , Nicholls P. J. , Bock Cheryl , Flowers Mei Lang , von Furstenberg Richard J. , Stripp Barry R. , Agarwal Pankaj , Borowsky Alexander D. , Cardiff Robert D. , Barak Larry S. , Caron Marc G. , Lyerly H. Kim , Snyder Joshua C.
Published: December 2019

Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes. Crainbow shows that mutations of ß-catenin (Ctnnb1) within the intestinal stem cell results in widespread expansion of oncogenes during perinatal development but not in adults. In contrast, mutations that extrinsically disrupt the stem cell microenvironment can spread in adult intestine without delay. We observe the rapid spread of premalignant clones in Crainbow mice expressing oncogenic Rspondin-3 (RSPO3), which occurs by increasing crypt fission and inhibiting crypt fixation. Crainbow modelling provides insight into how somatic mutations rapidly spread and a plausible mechanism for predetermining the intratumor heterogeneity found in colon cancers.