bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of bacterial aerosol, particulate matter, and microclimatic parameters on animal welfare in Chorzów (Poland) zoological garden
Authors: Grzyb Jacek , Pawlak Krzysztof
Published: September 2020

Zoos are very popular facilities visited by entire families with children, who come there to watch live animals. Zoos also provide workplaces for a large number of people directly looking after the animals. For places designed to house animals, regardless of whether they are farm animals, pets, or zoo animals, a higher concentration of both dust and potentially harmful bioaerosols can be expected. Unfortunately, there are almost no studies concerning the concentration of bacterial bioaerosols and particulate matter in animal shelters that would answer the question whether the level of these pollutants is constant or variable and dependent on a particular zoo, group of animals, their number in enclosures, or season. This study aimed to assess the levels of bacterial aerosol in rooms intended for animals (giraffes, camels, elephants, kangaroos, and colobinae) in the Silesian Zoological Garden in Chorzów (Poland). The bioaerosol samples were collected using a six-stage Andersen cascade impactor to assess the concentrations and size distribution of airborne bacteria. Particulate matter (PM10) was assessed using an electronic dust meter. Measurements of microclimate parameters were carried out using the Airflow™ Instruments Velocity Meter TA440, while gas concentrations were determined applying GFG Microtector II G450. The results showed that the concentration of airborne bacteria varied significantly between facilities for the analyzed animal groups. The lowest concentration of the total bacterial aerosol was observed in enclosures for colobinae (approx. 850 CFU/m3), while the highest—in rooms for elephants (approx. 105,600 CFU/m3). The average share of respirable fraction of bacteria was quite high, with values ranging from 62.9 (colobinae) to 86.9% (elephants), indicating potential harmfulness to the health of exposed people. PM10 concentrations were relatively low (10–86 μg/m3) and did not exceed the limit values for occupational exposure. Moreover, the levels of bacterial bioaerosol in almost all cases did not exceed the limit values. As the animals constitute a significant source of bioaerosol, attention should be paid to thorough cleaning of animals and their shelters, as well as maintaining appropriate levels of microclimate parameters in the facilities.
The Importance of PbtO2 Probe Location for Data Interpretation in Patients with Intracerebral Hemorrhage
Authors: Lindner Anna , Rass Verena , Ianosi Bogdan-Andrei , Schiefecker Alois J. , Kofler Mario , Rhomberg Paul , Pfausler Bettina , Beer Ronny , Schmutzhard Erich , Thomé Claudius , Helbok Raimund
Published: September 2020

Background/objective

Monitoring of brain tissue oxygen tension (PbtO2) provides insight into brain pathophysiology after intracerebral hemorrhage (ICH). Integration of probe location is recommended to optimize data interpretation. So far, little is known about the importance of PbtO2 catheter location in ICH patients.

Methods

We prospectively included 40 ICH patients after hematoma evacuation (HE) who required PbtO2-monitoring. PbtO2-probe location was evaluated in all head computed tomography (CT) scans within the first 6 days after HE and defined as location in the healthy brain tissue or perilesional when the catheter tip was located within 1 cm of a focal lesion (hypodense or hyperdense). Generalized estimating equations were used to investigate levels of PbtO2 in relation to different probe locations.

Results

Patients were 60 [51–66] years old and had a median ICH-volume of 47 [29–60] mL. Neuromonitoring probes remained for a median of 6 [2–11] days. PbtO2-probes were located in healthy brain tissue in 18/40 (45%) patients and in perilesional brain tissue in 22/40 (55%) patients. In the acute phase after HE (0–72 h), PbtO2 levels were significantly lower (21 ± 12 mmHg vs. 29 ± 10 mmHg, p = 0.010) and brain tissue hypoxia (BTH) was more common in the perilesional area as compared to healthy brain tissue (46% vs. 19%, adjOR 4.0, 95% CI 1.54–10.58, p = 0.005). Episodes of BTH significantly decreased over time in patients with probes in perilesional location (p = 0.001) but remained stable in normal appearing area (p = 0.485). A significant association between BTH and poor functional outcome was only found when probes were located in the perilesional brain tissue (adjOR 6.6, 95% CI 1.3–33.8, p = 0.023).

Conclusions

In the acute phase, BTH was more common in the perilesional area compared to healthy brain tissue. The improvement of BTH in the perilesional area over time may be the result of targeted treatment interventions and tissue regeneration. Due to the localized measurement of invasive neuromonitoring devices, integration of probe location in the clinical management of ICH patients and in research protocols seems mandatory.
Lack of Coordination between Health Care and Social Care in Multi-Professional Teamwork - the Obstacle for Coherent Care of Older People Suffering from Multi-Morbidity
Authors: Melin Emilsson Ulla , Strid Anna-Lena , Söderberg Maria
Published: September 2020

The lack of a cohesive health and social care is a well-known problem of significance for ageing people in general and frail older people in particular. Responsibility for organising and conducting social care and healthcare for the elderly rests on different principals in different countries but difficulties with organisational coordination and collaboration between professions and authorities in social care and healthcare is an extensive concern worldwide. Regardless of the distribution of responsibilities, collaboration and coordination structures are complex and often lead to problems. However, the gap in the coordination between different organisations and the collaboration between professions, implying that frail older people with major care needs still living in their own homes are pinched, has received hardly any recognition. By closely following an implementation project focused on teamwork in order to improve collaboration and coordination between social care and healthcare, the purpose of this article is to fill this gap with the help of an example from Sweden. Data consisted of event diaries, observations, focus groups, structured questionnaires and interviews. Findings showed that multi-professional teams certainly were established, but did not work or last. Among the obstacles found the most prominent features were the various professions’ own organisations, territorial thinking and rivalries. The whole idea of the initiative to achieve a cohesive healthcare and social care for ageing frail older people fell through. By letting this happen, not only did the project hinder the development of better practice in serving older adults, but also cemented the problematic structures it was intended to dissolve.
Validation of Puck’s failure criterion for CFRP composites in the cryogenic regime
Authors: Hohe Jörg , Schober Michael , Weiss Klaus-Peter , Appel Simon
Published: September 2020

For future launch vehicles, lightweight cryogenic pressure vessels are required for storage of the liquid hydrogen fuel. For their structural assessment, reliable and validated failure criteria are required. The present contribution provides an overview over the results of an ongoing research activity concerned with the validation of Puck’s composite failure criterion in the cryogenic regime. In a first step, an experimental investigation on unidirectionally fiber reinforced materials on coupon level has been performed. This test campaign has been complemented by tests on small breadboard-type specimens with an angle-ply stacking sequence. The specimens were featuring holes and tapered sections to provide stress gradients and concentrations. Test were performed at ambient temperature and in a liquid Helium environment. Puck’s failure criterion has been applied and found to provide a good prediction of first ply failure in both environments.
Movement pattern of an ellipsoidal nanoparticle confined between solid surfaces: Theoretical model and molecular dynamics simulation
Authors: Shi Junqin , Zhu Xiangzheng , Sun Kun , Fang Liang
Published: September 2020

The movement pattern of ellipsoidal nanoparticles confined between copper surfaces was examined using a theoretical model and molecular dynamics simulation. Initially, we developed a theoretical model of movement patterns for hard ellipsoidal nanoparticles. Subsequently, the simulation indicated that there are critical values for increasing the axial ratio, driving velocity of the contact surface, and lowering normal loads (i.e., 0.83, 15 m/s, and 100 nN under the respective conditions), which in turn change the movement pattern of nanoparticles from sliding to rolling. Based on the comparison between the ratio of arm of force (e/h) and coefficient of friction (μ) the theoretical model was in good agreement with the simulations and accurately predicted the movement pattern of ellipsoidal nanoparticles. The sliding of the ellipsoidal nanoparticles led to severe surface damage. However, rolling separated the contact surfaces and thereby reduced friction and wear.
Die Artenkenntnis von Berliner Schüler_innen am Beispiel einheimischer Vögel
Authors: Sturm Ulrike , Voigt-Heucke Silke , Mortega Kim G. , Moormann Alexandra
Published: September 2020

Der dramatische Rückgang der Biodiversität gehört derzeit zu den größten Problemen weltweit. Das Verständnis, der Erhalt und die Förderung von Biodiversität sind eng verbunden mit Artenkenntnis. Einige Studien zeigten bereits, dass in der Gesellschaft – insbesondere auch bei jungen Menschen – die Kenntnis heimischer Arten gering ist und stetig abnimmt. Es liegen bislang noch keine Daten für Berlin vor. Wir haben daher in einer Querschnittsstudie 186 Schüler_innen der siebten Jahrgangsstufe an drei Schulen in Berlin hinsichtlich ihrer persönlichen Einschätzung der Kenntnis von acht in Berlin häufig vorkommender Vogelarten befragt und anschließend die tatsächlich vorhandene Artenkenntnis geprüft. Die Berliner Schüler_innen erkannten visuell im Mittel zwei Vogelarten und akustisch keine der getesteten Arten. Damit kann die Annahme einer geringen Artenkenntnis in Bezug auf heimische Vogelarten auch für Schüler_innen in Berlin bestätigt werden. Diese Ergebnisse zeigen, dass ein erhöhter Bedarf an der Vermittlung von Artenkenntnis besteht. Dem Erkennen und Beobachten von Tieren und Pflanzen – und damit die Wertschätzung der Vielfalt der Natur – muss mehr Bedeutung zugesprochen werden und geeignete Lernangebote weiterentwickelt und gefördert werden.
The right digital strategy for your business: an empirical analysis of the design and implementation of digital strategies in SMEs and LSEs
Authors: Becker Wolfgang , Schmid Oliver
Published: September 2020

The importance of digitalization continues to grow, with companies from all sectors and of various sizes subject to this influence. To remain competitive in the future, companies must recognize and overcome the opportunities and challenges of digitalization in the long term. To do this, companies can develop an entire digitization strategy that affects all areas of the business, enabling them to achieve a holistic digital transformation and ensure their survival in the digital age. Based on a qualitative–empirical research design, this study examines whether small and medium-sized enterprises (SMEs) and large enterprises (LSEs) have such a strategy, and how it is structured. In particular, it addresses the use of new technology, changes in value added, structural changes and the financing of digitalization. At the same time, there is an examination of any similarities and differences among the different company sizes.
Alternative Mitigation to Counter Resource Losses from the Lake Cumberland Drawdown, Kentucky
Authors: McCormack Valerie J. , Stackelbeck Kary
Published: September 2020

This article presents a case study of the process of developing and implementing mitigation as the result of adverse effects to cultural resources from the drawdown of Lake Cumberland, Kentucky. Signs of a dam failure in early 2007 triggered the U.S. Army Corps of Engineers (Corps) to implement the emergency drawdown. While the drawdown prevented a life safety catastrophe, it created a new erosion zone and exposed archaeological sites to looters. When it became clear that conventional Section 106 procedures to identify and evaluate these endangered archaeological resources were not an option, alternative and creative mitigation became a necessary approach for the Corps to meet its obligations under the National Historic Preservation Act. This article discusses the creative brainstorming among the Corps, Kentucky state historic preservation officer, and tribes that led to three alternative mitigation measures aimed at educational outreach, raising public awareness, and staff training. Furthermore, the article identifies challenges encountered during the implementation of the mitigation measures. Through the presentation of our mitigation journey, we share some of our lessons learned to improve awareness of the challenges and successes one may encounter during the execution of such alternative measures.
Creative Mitigation: Alternative Strategies for Resources, Stakeholders, and the Public
Authors: Douglass John G. , Manney Shelby A.
Published: September 2020

Standard mitigation treatment for adverse effects to significant cultural resources has historically been a combination of data recovery excavation along with artifact analysis, reporting, and curation, whose purpose is to move the undertaking forward. Over the past several decades, there has been increased interest and understanding of alternative, or creative, mitigation options in these situations, which may, in the end, be the best option for the resource and more meaningful to both project stakeholders and the public. This article, the first in this special issue on creative mitigation, introduces the regulatory and conceptual framework for creative mitigation and weaves themes introduced in subsequent articles in this issue.
Aligning community-engaged research competencies with online training resources across the Clinical and Translational Science Award Consortium
Authors: Piasecki Rebecca J. , Quarles Elisa D. , Bahouth Mona N. , Nandi Anwesha , Bilheimer Alicia , Carter-Edwards Lori , Dennison-Himmelfarb Cheryl R.
Published: September 2020

Introduction:

The extent to which Clinical and Translational Science Award (CTSA) programs offer publicly accessible online resources for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged publicly accessible online CEnR resources from CTSAs and mapped resources to CEnR core competency domains.

Methods:

Following a search and review of the current literature regarding CEnR competencies, CEnR core competency domains were identified and defined. A systematic review of publicly accessible online CEnR resources from all 64 current CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for the inclusion of each CEnR core competency domain. Domain scores across all resources were assessed using descriptive statistics.

Results:

Eight CEnR core competency domains were identified. Overall, 214 CEnR resources publicly accessible online from 35 CTSAs were eligible for review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%) and “Knowledge and relationships with communities” (40.2%) were the most frequently addressed domains, while “CEnR program evaluation” (12.1%) and “Dissemination and advocacy” (11.2%) were the least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized.

Conclusions:

Our findings guide CEnR stakeholders to identify publicly accessible online resources and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competency is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability.
Creating a centralized social media recruitment service for research teams at the University of Michigan
Authors: Doshi Aalap , Connally Lisa , Johnson Anita , Skrzypek Abbey
Published: September 2020

Successful social media recruitment requires specific expertise and constant upkeep, placing an inordinate burden on study teams. Over half of the study teams at the University of Michigan (U-M) surveyed about recruitment assistance needs indicated that they wanted to use social media as a recruitment strategy, but lacked the expertise to do so. We thus built a service to centralize social media recruitment across the university. This involved assembling the right expertise, creating a centralized social media profile, creating linkages to other digital recruitment platforms, building the financial structure, and operationalizing the service. So far, we have helped 94 study teams launch social media campaigns on Facebook and Instagram. These campaigns resulted in 1,653,675 users being reached, of which 20,546 users actively showed interest in participating in the corresponding studies. We followed 18 studies further, who reported a total of 345 social media participants as being enrolled, resulting in an average cost-per-contact (CPC) of $8.72 and an average cost-per-enrollee (CPE) of $55.21. The combination of communication expertise, streamlined administrative processes, and linkages to a centralized research participation registry has allowed us to help a large number of study teams seamlessly engage broad and diverse populations.
Lockdown logistics in consultation–liaison psychiatry
Authors: Barry H. , Doherty A. M. , Clancy M. , Moore S. , MacHale S.
Published: September 2020

We describe the adaptation of services to allow flexible and practical responses to the coronavirus-19 (COVID-19) public health crisis by four Consultation–Liaison Psychiatry (CLP) services; Galway University Hospital (GUH), Beaumont Hospital, University Hospital Waterford and St Vincent’s University Hospital (SVUH) CLP services. This article also illustrates close collaboration with community adult mental health services and Emergency Department (ED) colleagues to implement effective community diversion pathways and develop safe, effective patient assessment pathways within the EDs. It highlights the high levels of activity within each of the CLP services, while also signposting that many of the rapidly implemented changes to our practice may herald improvements to mental health patient care delivery in the post-COVID-19 world, if our psychiatry services receive appropriate resources.
Murchison Widefield Array detection of steep-spectrum, diffuse, non-thermal radio emission within Abell 1127
Authors: Duchesne S. W. , Johnston-Hollitt M. , Zhu Z. , Wayth R. B. , Line J. L. B.
Published: September 2020

Diffuse, non-thermal emission in galaxy clusters is increasingly being detected in low-frequency radio surveys and images. We present a new diffuse, steep-spectrum, non-thermal radio source within the cluster Abell 1127 found in survey data from the Murchison Widefield Array (MWA). We perform follow-up observations with the ‘extended’ configuration MWA Phase II with improved resolution to better resolve the source and measure its low-frequency spectral properties. We use archival Very Large Array S-band data to remove the discrete source contribution from the MWA data, and from a power law model fit we find a spectral index of –1.83±0.29 broadly consistent with relic-type sources. The source is revealed by the Giant Metrewave Radio Telescope at 150 MHz to have an elongated morphology, with a projected linear size of 850 kpc as measured in the MWA data. UsingChandraobservations, we derive morphological estimators and confirm quantitatively that the cluster is in a disturbed dynamical state, consistent with the majority of phoenices and relics being hosted by merging clusters. We discuss the implications of relying on morphology and low-resolution imaging alone for the classification of such sources and highlight the usefulness of the MHz to GHz radio spectrum in classifying these types of emission. Finally, we discuss the benefits and limitations of using the MWA Phase II in conjunction with other instruments for detailed studies of diffuse, steep-spectrum, non-thermal radio emission within galaxy clusters.
Fake It ‘Til You Make It: A Natural Experiment to Identify European Politicians’ Benefit from Twitter Bots
Authors: SILVA BRUNO CASTANHO , PROKSCH SVEN-OLIVER
Published: September 2020

Social media giants stand accused of facilitating illegitimate interference with democratic political processes around the world. Part of this problem are malicious bots: automated fake accounts passing as humans. However, we lack a systematic understanding of which politicians benefit most from them. We tackle this question by leveraging a Twitter purge of malicious bots in July 2018 and a new dataset on Twitter activity by all members of national parliaments (MPs) in the EU in 2018. Since users had no influence on how and when Twitter purged millions of bots, it serves as an exogenous intervention to investigate whether some parties or politicians lost more followers. We find drops in follower counts concentrated among radical right politicians, in particular those with strong anti-EU discourse. This is the first set of empirical, causally identified evidence supporting the idea that the radical right benefits more from malicious bots than other party families.
Age at menarche in Nigerian demographic surveys
Authors: Garenne Michel
Published: September 2020

Age at menarche was investigated using data collected from demographic surveys (WFS, DHS) conducted in Nigeria between 1982 and 2018, all of which were based on large representative samples of the female population. Linear-logistic regressions were used to estimate mean age at menarche, its trends and its risk factors. Mean age at menarche had underwent a marked secular decline from 15.02 years for girls born in 1933 to 13.78 years for girls born in 2003. In multivariate analysis, height (stature), body mass index (BMI), level of education and household wealth had independent effects on age at menarche, whereas urban residence had no effect. Socioeconomic gradients were large: +9 years of schooling was associated with a –0.52 year decrease in age at menarche, and +2 standard deviations in household wealth with a –0.33 year decrease. The impact of anthropometry was even greater: +2 standard deviations in height was associated with a –0.99 year decrease in age at menarche, and +2 standard deviations in BMI with a –1.42 year decrease. Northern provinces had a higher mean age at menarche than southern provinces. Compared with independent sources, long-term trends in age at menarche, as well as their fluctuations, appeared to be correlated with trends and fluctuations in income per capita and in under-five mortality, but not with divergent trends in adult height.
Motion Control and Trajectory Planning for Obstacle Avoidance of the Mobile Parallel Robot Driven by Three Tracked Vehicles
Authors: Shentu Shuzhan , Xie Fugui , Liu Xin-Jun , Gong Zhao
Published: September 2020

This paper proposes a mobile parallel robot (MPR) and focuses on obstacle avoidance. When analyzing the collision-free trajectories, the coupling constraints caused by the parallel mechanism and the obstacle should be emphatically solved. The solution is to divide the problem into two steps. First, the genetic algorithm is employed to search and optimize the feasible trajectories under the mechanism constraint of the MPR. Then the trajectory tracking controller is designed to make the tracked vehicles move cooperatively and track a trajectory asymptotically. Finally, simulations and experiments are carried out to verify the effectiveness of the solution.
The Stellar-INS Navigation Performance Influence Mechanism of Star Vector Orientation in the Field of View
Authors: Zhang Chunxi , Yang Yanqiang , Zhang Hao , Cai Xiaowen
Published: September 2020

The star sensor field of view varies from several arc-minutes to 20 degrees, which directly determines the star vector orientation in the field of view (FOV). Although the relationship between star vector orientation in the FOV and attitude accuracy has been revealed, the influence mechanism of star vector orientation on the integrated navigation performance of a stellar inertial navigation system has not been analysed. In order to improve the integrated accuracy, the main errors such as star sensor installation error, gyro error and initial platform angle error should be estimated online. It is significant to study the influence mechanism of star vector orientation on estimation of the above errors. In this paper, the star sensor sensitivity and the geometry factor are defined to feature the difference between the optical axis direction and the non-optical axis direction. The formulised mechanism and quantification results between star vector orientation and integration attitude and error estimation accuracy are clearly given. Simulation and ground testing were conducted and it was found that the larger the star vector orientation along the optical axis, the better the error estimation accuracy. In contrast, the attitude accuracy is weakly sensitive to the orientation of the star vector in conditions of appropriate posture adjustment and star observation scheme. This conclusion can offer universal guidance for the design and evaluation of stellar inertial navigation systems with narrow field of view or large field of view star sensors.
Descriptive epidemiology of coronavirus disease 2019 in Nigeria, 27 February–6 June 2020
Authors: Elimian K. O. , Ochu C. L. , Ilori E. , Oladejo J. , Igumbor E. , Steinhardt L. , Wagai J. , Arinze C. , Ukponu W. , Obiekea C. , Aderinola O. , Crawford E. , Olayinka A. , Dan-Nwafor C. , Okwor T. , Disu Y. , Yinka-Ogunleye A. , Kanu N. E. , Olawepo O. A. , Aruna O. , Michael C. A. , Dunkwu L. , Ipadeola O. , Naidoo D. , Umeokonkwo C. D. , Matthias A. , Okunromade O. , Badaru S. , Jinadu A. , Ogunbode O. , Egwuenu A. , Jafiya A. , Dalhat M. , Saleh F. , Ebhodaghe G. B. , Ahumibe A. , Yashe R. U. , Atteh R. , Nwachukwu W. E. , Ezeokafor C. , Olaleye D. , Habib Z. , Abdus-Salam I. , Pembi E. , John D. , Okhuarobo U. J. , Assad H. , Gandi Y. , Muhammad B. , Nwagwogu C. , Nwadiuto I. , Sulaiman K. , Iwuji I. , Okeji A. , Thliza S. , Fagbemi S. , Usman R. , Mohammed A. A. , Adeola-Musa O. , Ishaka M. , Aketemo U. , Kamaldeen K. , Obagha C. E. , Akinyode A. O. , Nguku P. , Mba N. , Ihekweazu C.
Published: September 2020

The objective of this study was to describe the epidemiology of COVID-19 in Nigeria with a view of generating evidence to enhance planning and response strategies. A national surveillance dataset between 27 February and 6 June 2020 was retrospectively analysed, with confirmatory testing for COVID-19 done by real-time polymerase chain reaction (RT-PCR). The primary outcomes were cumulative incidence (CI) and case fatality (CF). A total of 40 926 persons (67% of total 60 839) had complete records of RT-PCR test across 35 states and the Federal Capital Territory, 12 289 (30.0%) of whom were confirmed COVID-19 cases. Of those confirmed cases, 3467 (28.2%) had complete records of clinical outcome (alive or dead), 342 (9.9%) of which died. The overall CI and CF were 5.6 per 100 000 population and 2.8%, respectively. The highest proportion of COVID-19 cases and deaths were recorded in persons aged 31–40 years (25.5%) and 61–70 years (26.6%), respectively; and males accounted for a higher proportion of confirmed cases (65.8%) and deaths (79.0%). Sixty-six per cent of confirmed COVID-19 cases were asymptomatic at diagnosis. In conclusion, this paper has provided an insight into the early epidemiology of COVID-19 in Nigeria, which could be useful for contextualising public health planning.
Exploring by Boring: Geothermal Wells as Research Tools
Authors: Jordan Teresa , Fulton Patrick , Tester Jefferson , Asanuma Hiroshi , Bruhn David
Published: September 2020

As part of an effort to develop a geothermal energy source beneath its campus, Cornell University is planning to probe the “boring” old continental crust upon which many people live.
High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma
Authors: Yang Beng , Feng Xiaode , Liu Hua , Tong Rongliang , Wu Jingbang , Li Changbiao , Yu Hanxi , Chen Yunhao , Cheng Qiyang , Chen Junru , Cai Xianlei , Wu Wenxuan , Lu Yuejie , Hu Jiating , Liang Kejiong , Lv Zhen , Wu Jian , Zheng Shusen
Published: September 2020

Exosomes play an important role in intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). However, cellular communication between heterogeneous HCC cells with different metastatic potentials and the resultant cancer progression are not fully understood in HCC. Here, HCC cells with high-metastatic capacity (97hm and Huhm) were constructed by continually exerting selective pressure on primary HCC cells (MHCC-97H and Huh7). Through performing exosomal miRNA sequencing in HCC cells with different metastatic potentials (MHCC-97H and 97hm), many significantly different miRNA candidates were found. Among these miRNAs, miR-92a-3p was the most abundant miRNA in the exosomes of highly metastatic HCC cells. Exosomal miR92a-3p was also found enriched in the plasma of HCC patient-derived xenograft mice (PDX) model with high-metastatic potential. Exosomal miR-92a-3p promotes epithelial-mesenchymal transition (EMT) in recipient cancer cells via targeting PTEN and regulating its downstream Akt/Snail signaling. Furthermore, through mRNA sequencing in HCC cells with different metastatic potentials and predicting potential transcription factors of miR92a-3p, upregulated transcript factors E2F1 and c-Myc were found in high-metastatic HCC cells promote the expression of cellular and exosomal miR-92a-3p in HCC by directly binding the promoter of its host gene, miR17HG. Clinical data showed that a high plasma exosomal miR92a-3p level was correlated with shortened overall survival and disease-free survival, indicating poor prognosis in HCC patients. In conclusion, hepatoma-derived exosomal miR92a-3p plays a critical role in the EMT progression and promoting metastasis by inhibiting PTEN and activating Akt/Snail signaling. Exosomal miR92a-3p is a potential predictive biomarker for HCC metastasis, and this may provoke the development of novel therapeutic and preventing strategies against metastasis of HCC.
EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization
Authors: Zhang Bo , Miao Tianyu , Shen Xin , Bao Lirong , Zhang Cheng , Yan Caixia , Wei Wei , Chen Jiao , Xiao Liying , Sun Chongkui , Du Jintao , Li Yan
Published: September 2020

Chronic inflammation induced by persistent viruses infection plays an essential role in tumor progression, which influenced on the interaction between the tumor cells and the tumor microenvironment. Our earlier study showed that ATR, a key kinase participant in single-stranded DNA damage response (DDR), was obviously activated by Epstein–Barr virus (EBV) in nasopharyngeal carcinoma (NPC). However, how EBV-induced ATR activation promotes NPC by influencing inflammatory microenvironment, such as tumor-associated macrophages (TAMs), remains elusive. In this study, we showed that EBV could promote the expression of p-ATR and M2-type TAMs transformation in clinical NPC specimens. The expression of p-ATR and M2-type TAMs were closely correlated each other and involved in TNM stage, lymph node metastasis and poor prognosis of the patients. In addition, the expression levels of CD68+CD206+, Arg1, VEGF, and CCL22 were increased in EB+ CNE1 cells, and decreased when ATR was inhibited. In the nude mice, EBV-induced ATR activation promoted subcutaneous transplanted tumor growth, higher expression of Ki67 and lung metastasis via M2-type TAMs recruitment. Experimental data also showed that the polarization of M2, the declined tumor necrosis factor-α (TNF-α) and increased transforming growth factor-β (TGF-β) were associated with ATR. Meanwhile, ATR activation could promote PPAR-δ and inhibited c-Jun and p-JNK expression, then downregulate JNK pathway. Collectively, our current study demonstrated the EBV infection could activate the ATR pathway to accelerate the transition of TAMs to M2, suggesting ATR knockdown could be a potential effective treatment strategy for EBV-positive NPC.
Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis
Authors: Zhou Feiye , Liu Qianqian , Zhang Linlin , Zhu Qin , Wang Shushu , Zhu Kecheng , Deng Ruyuan , Liu Yun , Yuan Guoyue , Wang Xiao , Zhou Libin
Published: September 2020

The histone acetyltransferases CREB-binding protein (CBP) and its paralogue p300 are transcriptional coactivators which are essential for a multitude of signaling pathways and energy homeostasis. However, the role of CBP/p300 HAT domain in regulating energy balance is still unclear. Here, C57BL/6 mice fed with either normal chow diet (NCD) or high-fat diet (HFD) were administrated with A-485, a recently reported selective inhibitor of CBP/p300 HAT activity for 1 week and the metabolic change was analyzed. The white adipose tissue (WAT) weight and adipocyte size were reduced in A-485-administrated mice, with decreased expressions of lipogenic genes and transcriptional factors. In the liver of A-485-treated mice, the lipid content and lipogenic gene expressions were lowered while the binding of forkhead box O1 (FOXO1) to glucose-6-phosphatase (G6Pc) promoter was reduced, leading to decreased expression of G6Pc. In primary mouse hepatocytes, A-485 abolished cAMP-elicited mRNA expressions of key gluconeogenic enzymes and promoted FOXO1 protein degradation via increasing its ubiquitination. Thus, A-485 inhibits lipogenesis in WAT and liver as well as decreases hepatic glucose production via preventing FOXO1 acetylation, leading to its protein degradation through a proteasome-dependent pathway. The specific inhibition of CBP/p300 HAT will provide a novel therapeutic approach for metabolic diseases.
Using insurance data to quantify the multidimensional impacts of warming temperatures on yield risk
Authors: Perry Edward D. , Yu Jisang , Tack Jesse
Published: September 2020

Previous research predicts significant negative yield impacts from warming temperatures, but estimating the effects on yield risk and disentangling the relative causes of these losses remains challenging. Here we present new evidence on these issues by leveraging a unique publicly available dataset consisting of roughly 30,000 county-by-year observations on insurance-based measures of yield risk from 1989–2014 for U.S. corn and soybeans. Our results suggest that yield risk will increase in response to warmer temperatures, with a 1 °C increase associated with yield risk increases of approximately 32% and 11% for corn and soybeans, respectively. Using cause of loss information, we also find that additional losses under warming temperatures primarily result from additional reported occurrences of drought, with reported losses due to heat stress playing a smaller role. An implication of our findings is that the cost of purchasing crop insurance will increase for producers as a result of warming temperatures.
Ontogeny of arterial macrophages defines their functions in homeostasis and inflammation
Authors: Weinberger Tobias , Esfandyari Dena , Messerer Denise , Percin Gulce , Schleifer Christian , Thaler Raffael , Liu Lulu , Stremmel Christopher , Schneider Vanessa , Vagnozzi Ronald J. , Schwanenkamp Jennifer , Fischer Maximilian , Busch Katrin , Klapproth Kay , Ishikawa-Ankerhold Hellen , Klösges Lukas , Titova Anna , Molkentin Jeffery D. , Kobayashi Yasuhiro , Engelhardt Stefan , Massberg Steffen , Waskow Claudia , Perdiguero Elisa Gomez , Schulz Christian
Published: September 2020

Arterial macrophages have different developmental origins, but the association of macrophage ontogeny with their phenotypes and functions in adulthood is still unclear. Here, we combine macrophage fate-mapping analysis with single-cell RNA sequencing to establish their cellular identity during homeostasis, and in response to angiotensin-II (AngII)-induced arterial inflammation. Yolk sac erythro-myeloid progenitors (EMP) contribute substantially to adventitial macrophages and give rise to a defined cluster of resident immune cells with homeostatic functions that is stable in adult mice, but declines in numbers during ageing and is not replenished by bone marrow (BM)-derived macrophages. In response to AngII inflammation, increase in adventitial macrophages is driven by recruitment of BM monocytes, while EMP-derived macrophages proliferate locally and provide a distinct transcriptional response that is linked to tissue regeneration. Our findings thus contribute to the understanding of macrophage heterogeneity, and associate macrophage ontogeny with distinct functions in health and disease.
Predicting the frequencies of drug side effects
Authors: Galeano Diego , Li Shantao , Gerstein Mark , Paccanaro Alberto
Published: September 2020

A central issue in drug risk-benefit assessment is identifying frequencies of side effects in humans. Currently, frequencies are experimentally determined in randomised controlled clinical trials. We present a machine learning framework for computationally predicting frequencies of drug side effects. Our matrix decomposition algorithm learns latent signatures of drugs and side effects that are both reproducible and biologically interpretable. We show the usefulness of our approach on 759 structurally and therapeutically diverse drugs and 994 side effects from all human physiological systems. Our approach can be applied to any drug for which a small number of side effect frequencies have been identified, in order to predict the frequencies of further, yet unidentified, side effects. We show that our model is informative of the biology underlying drug activity: individual components of the drug signatures are related to the distinct anatomical categories of the drugs and to the specific drug routes of administration.
Imaging how thermal capillary waves and anisotropic interfacial stiffness shape nanoparticle supracrystals
Authors: Ou Zihao , Yao Lehan , An Hyosung , Shen Bonan , Chen Qian
Published: September 2020

Development of the surface morphology and shape of crystalline nanostructures governs the functionality of various materials, ranging from phonon transport to biocompatibility. However, the kinetic pathways, following which such development occurs, have been largely unexplored due to the lack of real-space imaging at single particle resolution. Here, we use colloidal nanoparticles assembling into supracrystals as a model system, and pinpoint the key role of surface fluctuation in shaping supracrystals. Utilizing liquid-phase transmission electron microscopy, we map the spatiotemporal surface profiles of supracrystals, which follow a capillary wave theory. Based on this theory, we measure otherwise elusive interfacial properties such as interfacial stiffness and mobility, the former of which demonstrates a remarkable dependence on the exposed facet of the supracrystal. The facet of lower surface energy is favored, consistent with the Wulff construction rule. Our imaging–analysis framework can be applicable to other phenomena, such as electrodeposition, nucleation, and membrane deformation.
Probing the heterogeneous structure of eumelanin using ultrafast vibrational fingerprinting
Authors: Grieco Christopher , Kohl Forrest R. , Hanes Alex T. , Kohler Bern
Published: September 2020

Eumelanin is a brown-black biological pigment with sunscreen and radical scavenging functions important to numerous organisms. Eumelanin is also a promising redox-active material for energy conversion and storage, but the chemical structures present in this heterogeneous pigment remain unknown, limiting understanding of the properties of its light-responsive subunits. Here, we introduce an ultrafast vibrational fingerprinting approach for probing the structure and interactions of chromophores in heterogeneous materials like eumelanin. Specifically, transient vibrational spectra in the double-bond stretching region are recorded for subsets of electronic chromophores photoselected by an ultrafast excitation pulse tuned through the UV-visible spectrum. All subsets show a common vibrational fingerprint, indicating that the diverse electronic absorbers in eumelanin, regardless of transition energy, contain the same distribution of IR-active functional groups. Aggregation of chromophores diverse in oxidation state is the key structural property underlying the universal, ultrafast deactivation behavior of eumelanin in response to photoexcitation with any wavelength.
Visualization of ferroaxial domains in an order-disorder type ferroaxial crystal
Authors: Hayashida T. , Uemura Y. , Kimura K. , Matsuoka S. , Morikawa D. , Hirose S. , Tsuda K. , Hasegawa T. , Kimura T.
Published: September 2020

Ferroaxial materials that exhibit spontaneous ordering of a rotational structural distortion with an axial vector symmetry have gained growing interest, motivated by recent extensive studies on ferroic materials. As in conventional ferroics (e.g., ferroelectrics and ferromagnetics), domain states will be present in the ferroaxial materials. However, the observation of ferroaxial domains is non-trivial due to the nature of the order parameter, which is invariant under both time-reversal and space-inversion operations. Here we propose that NiTiO3 is an order-disorder type ferroaxial material, and spatially resolve its ferroaxial domains by using linear electrogyration effect: optical rotation in proportion to an applied electric field. To detect small signals of electrogyration (order of 10−5 deg V−1), we adopt a recently developed difference image-sensing technique. Furthermore, the ferroaxial domains are confirmed on nano-scale spatial resolution with a combined use of scanning transmission electron microscopy and convergent-beam electron diffraction. Our success of the domain visualization will promote the study of ferroaxial materials as a new ferroic state of matter.
Dutch population structure across space, time and GWAS design
Authors: Byrne Ross P. , van Rheenen Wouter ,   Project MinE ALS GWAS Consortium, van den Berg Leonard H. , Veldink Jan H. , McLaughlin Russell L.
Published: September 2020

Previous genetic studies have identified local population structure within the Netherlands; however their resolution is limited by use of unlinked markers and absence of external reference data. Here we apply advanced haplotype sharing methods (ChromoPainter/fineSTRUCTURE) to study fine-grained population genetic structure and demographic change across the Netherlands using genome-wide single nucleotide polymorphism data (1,626 individuals) with associated geography (1,422 individuals). We identify 40 haplotypic clusters exhibiting strong north/south variation and fine-scale differentiation within provinces. Clustering is tied to country-wide ancestry gradients from neighbouring lands and to locally restricted gene flow across major Dutch rivers. North-south structure is temporally stable, with west-east differentiation more transient, potentially influenced by migrations during the middle ages. Despite superexponential population growth, regional demographic estimates reveal population crashes contemporaneous with the Black Death. Within Dutch and international data, GWAS incorporating fine-grained haplotypic covariates are less confounded than standard methods.
Elucidating the role of metal ions in carbonic anhydrase catalysis
Authors: Kim Jin Kyun , Lee Cheol , Lim Seon Woo , Adhikari Aniruddha , Andring Jacob T. , McKenna Robert , Ghim Cheol-Min , Kim Chae Un
Published: September 2020

Why metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 Å) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties.
Author Correction: Integrated nano-optomechanical displacement sensor with ultrawide optical bandwidth
Authors: Liu Tianran , Pagliano Francesco , van Veldhoven René , Pogoretskiy Vadim , Jiao Yuqing , Fiore Andrea
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PPDIST, global 0.1° daily and 3-hourly precipitation probability distribution climatologies for 1979–2018
Authors: Beck Hylke E. , Westra Seth , Tan Jackson , Pappenberger Florian , Huffman George J. , McVicar Tim R. , Gründemann Gaby J. , Vergopolan Noemi , Fowler Hayley J. , Lewis Elizabeth , Verbist Koen , Wood Eric F.
Published: September 2020

We introduce the Precipitation Probability DISTribution (PPDIST) dataset, a collection of global high-resolution (0.1°) observation-based climatologies (1979–2018) of the occurrence and peak intensity of precipitation (P) at daily and 3-hourly time-scales. The climatologies were produced using neural networks trained with dailyPobservations from 93,138 gauges and hourlyPobservations (resampled to 3-hourly) from 11,881 gauges worldwide. Mean validation coefficient of determination (R2) values ranged from 0.76 to 0.80 for the dailyPoccurrence indices, and from 0.44 to 0.84 for the daily peakPintensity indices. The neural networks performed significantly better than current state-of-the-art reanalysis (ERA5) and satellite (IMERG) products for allPindices. Using a 0.1 mm 3 h−1threshold,Pwas estimated to occur 12.2%, 7.4%, and 14.3% of the time, on average, over the global, land, and ocean domains, respectively. The highestPintensities were found over parts of Central America, India, and Southeast Asia, along the western equatorial coast of Africa, and in the intertropical convergence zone. The PPDIST dataset is available viawww.gloh2o.org/ppdist.