bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Disasters on Community Medical Screening Examination and Vaccination Rates: The Case of the Sewol Ferry Disaster in Ansan, Korea
Authors: Kang EunKyo
Published: April 2020

Objective:

In April 2014, the Sewol ferry sank off the coast of Korea, resulting in 304 deaths. Of these, 250 were local high school students from Ansan, and the disaster severely affected their community. This study investigated the association of this disaster with health examination, cancer screening rate, and vaccination rate.

Methods:

The study subjects were adults ages ≥19 years (11 026 Ansan residents and 1 361 624 non-residents of Ansan) who participated in the 2011–2016 Korea Community Health Survey. The national health screening program examination rate, cancer screening rate, and influenza vaccination rate in Ansan residents and non-residents were assessed and their responses compared using chi-square tests, multiple logistic regression analyses, and a stratification analysis according to depression.

Results:

After the disaster (2014–2016), non-residents received more health screening (adjusted odds ratio [aOR] = 1.13, P < 0.001), cancer screening (aOR = 1.41, P < 0.001), and vaccination (aOR = 1.10, P = 0.002) than Ansan residents. This difference was more evident in the group without a depressive mood.

Conclusion:

People living in disaster areas show lower rates of medical screening examination and receive fewer vaccinations after the disaster. To decrease health impacts by disaster, efforts to increase community health screenings and vaccinations may be needed.
Shining a Light on Glyphosate-Based Herbicide Hazard, Exposures and Risk: Role of Non-Hodgkin Lymphoma Litigation in the USA
Authors: BENBROOK Charles
Published: April 2020

Roundup, and other glyphosate-based herbicides, are the most heavily used pesticides in the history of the USA and globally. In March 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a “probable human carcinogen”. A portion of the 695,000 Americans then living in 2015 with non-Hodgkin lymphoma (NHL) became aware of IARC’s decision. Several thousand Roundup–NHL lawsuits had been filed by the end of 2017, rising to 18,400 by July 2019 and 42,000 by November 2019. Three cases have gone to trial, each won by the plaintiffs. The author has served as an expert witness for the plaintiffs in this litigation and has been compensated for his time spent. The impact of the litigation on the independent assessment of the science useful in determining whether glyphosate and glyphosate-based herbicide exposures are linked to NHL is reviewed, as is why the US Environmental Protection Agency (EPA) and IARC reached such different judgements regarding glyphosate human cancer hazard and risk. Two important “lessons learned” regarding the EPA versus IARC assessment of glyphosate cancer hazard and risk are highlighted. The first arises from differences in the magnitude of applicator risks from mostly dermal exposures to formulated glyphosate-based herbicides compared to just dietary exposures to technical glyphosate. The second relates to missed opportunities to markedly lower applicator exposures and risks with little or no impact on sales via reformulation, added warnings and worker safety provisions, company-driven stewardship programmes and greater determination by the EPA in the 1980s to compel Monsanto to add common-sense worker protection provisions onto Roundup labels (eg “wear gloves when applying this product”). Policy reforms designed to alleviate systemic problems with how pesticide hazards, exposures and risks are analysed, regulated and mitigated are described.
Egonets as systematically biased windows on society
Authors: Feld Scott L. , McGail Alec
Published: April 2020

A person’s egonet, the set of others with whom that person is connected, is a personal sample of society which especially influences that person’s experience and perceptions of society. We show that egonets systematically misrepresent the general population because each person is included in as many egonets as that person has “friends.” Previous research has recognized that this unequal weighting in egonets leads many people to find that their friends have more friends than they themselves have. This paper builds upon that research to show that people’s egonets provide them with systematically biased samples of the population more generally. We discuss how this ubiquitous egonet bias may have far reaching implications for people’s experiences and perceptions of frequencies of other people’s ties and traits in ways that may influence their own feelings and behaviors. In particular, these egonet biases may help explain people’s tendencies to disproportionately experience and overestimate the prevalence of certain types of deviance and other social behaviors and consequently be influenced toward them. We illustrate egonet bias with analyses of all friends among 63,731 Facebook users. We call for further empirical investigation of egonet biases and their consequences for individuals and society.
AN UPDATED HISTORY OF PRE-CONTACT NEW ENGLAND: NEW AMS DATES FOR THE HORNBLOWER II AND FRISBY-BUTLER ARCHAEOLOGICAL SITES
Authors: Watson Jessica E
Published: April 2020

Faunal assemblages from the pre-Contact period sites Frisby-Butler and Hornblower II on Marthaʼs Vineyard, Massachusetts, USA, remain unstudied since excavation during the 1980s. This project establishes radiocarbon (14C) dates from faunal remains and evaluates occupation and abandonment at each site. 14C measurements were collected from 17 specimens and 13 dates from previous analyses were re-examined. Dates were identified from the archaeological time periods Transitional Archaic (2700–3700 BP), Early Woodland (2000–2700 BP), and Late Woodland (450–1200 BP) at Frisby-Butler. Occupation likely represented seasonal visitations during autumn and winter to hunt based on white-tailed deer (Odocoileus virginianus) demographic profiles. A combined dataset of new and re-calibrated 14C measurements from Hornblower II date to the Late Archaic (3700–6000 BP), Early Woodland, Middle Woodland (1200–2000 BP), and Late Woodland periods. Settlement was focused on gathering warm-weather foods like demersal fish and lakebirds. Together, the sites demonstrate periodic seasonal use of the southwest coast of the island throughout the Late Holocene and fit within an established regional pattern in southern New England.
Translating the promise of 5HT4 receptor agonists for the treatment of depression
Authors: Murphy Susannah E , de Cates Angharad N , Gillespie Amy L , Godlewska Beata R , Scaife Jessica C , Wright Lucy C , Cowen Philip J , Harmer Catherine J
Published: April 2020

Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.
Ambiguity and Conflict in Policy Implementation: The Case of the New Care Models (Vanguard) Programme in England
Authors: COLEMAN ANNA , BILLINGS JENNY , ALLEN PAULINE , MIKELYTE RASA , CROKE SARAH , MACINNES JULIE , CHECKLAND KATH
Published: April 2020

Policy driven change is challenging, with a significant gap between theory and practice. A key tension in enacting such change is achieving a balance between bottom-up development of local, context-specific approaches, and top-down, centrally determined policy solutions and their mutual sequencing. Ideal type models of the policy-making process envisage a rational ordered approach, driven by evidence and accompanied by ongoing evaluation of outcomes (Parsons, 1995, p77); however, the reality is far more complex. We examine the implementation and early operation of the New Care Models (NCM) Vanguard programme in England, using Matland’s (1995) ambiguity-conflict model, to explore the aims and expectations of the programme. We consider the relationship between top-down and bottom-up approaches to policy development and draw attention to the pressures coming from what was initially perceived as a permissive policy approach of encouraging experimentation, whilst also requiring rapid learning, scale and spread. We suggest that future programmes for large-scale policy implementation initiatives could be crafted differently to take account of the environment of implementation and render ambitions more realistic. Rather than aiming to create a set of definite products and templates, it may be that a set of principles for design and implementation should be developed and spread.
Detection of Intermediate Spoofing Attack on Global Navigation Satellite System Receiver Through Slope Based Metrics
Authors: Khan Abdul Malik , Iqbal Naveed , Khan Adnan Ahmed , Khan Muhammad Faisal , Ahmad Attiq
Published: April 2020

A spoofing attack on a global navigation satellite system (GNSS) receiver is a threat to a significant community of GNSS users due to the high stakes involved. This paper investigates the use of slope based metrics for the detection of spoofing. The formulation of slope based metrics involves monitoring correlators along with tracking correlators in the receiver's channel, which are slaved to the prompt tracking correlator. In this study, using some candidate metrics, detectors have been formed through the analysis of simulated spoofing attacks. A theoretical variance of each metric has also been calculated as a reference for the threshold. A threshold is estimated using the measured variance from the clean signals, for specific false alarm rate. By using the measured threshold, detectors are formed based on slope metrics. These detectors have been tested using TEXBAT data. The results show that the differential slope metrics have good performance. The results have also been compared with some other techniques of spoofing detection.
The challenges and considerations of community-based preparedness at the onset of COVID-19 outbreak in Iran, 2020
Authors: Moradzadeh Rahmatollah
Published: April 2020

COVID-19 as an emerging disease has spread to 183 countries and territories worldwide as of 20 March 2020. The first COVID-19 case (i.e. the index case) in Iran was observed in the city of Qom on 19 February 2020. One of the cities of Markazi Province is Delijan, which shares a border with Qom. Consequently, COVID-19 has quickly spread in this city because a large population commutes daily between the two cities. This study aimed to report the challenges and considerations of community-based preparedness at the onset of COVID-19 outbreak in a city of Iran in 2020.
SMT-based verification of data-aware processes: a model-theoretic approach
Authors: Calvanese Diego , Ghilardi Silvio , Gianola Alessandro , Montali Marco , Rivkin Andrey
Published: April 2020

In recent times, satisfiability modulo theories (SMT) techniques gained increasing attention and obtained remarkable success in model-checking infinite-state systems. Still, we believe that whenever more expressivity is needed in order to specify the systems to be verified, more and more support is needed from mathematical logic and model theory. This is the case of the applications considered in this paper: we study verification over a general model of relational, data-aware processes, to assess (parameterized) safety properties irrespectively of the initial database (DB) instance. Toward this goal, we take inspiration from array-based systems and tackle safety algorithmically via backward reachability. To enable the adoption of this technique in our rich setting, we make use of the model-theoretic machinery of model completion, which surprisingly turns out to be an effective tool for verification of relational systems and represents the main original contribution of this paper. In this way, we pursue a twofold purpose. On the one hand, we isolate three notable classes for which backward reachability terminates, in turn witnessing decidability. Two of such classes relate our approach to conditions singled out in the literature, whereas the third one is genuinely novel. On the other hand, we are able to exploit SMT technology in implementations, building on the well-known MCMT (Model Checker Modulo Theories) model checker for array-based systems and extending it to make all our foundational results fully operational. All in all, the present contribution is deeply rooted in the long-standing tradition of the application of model theory in computer science. In particular, this paper applies these ideas in an original mathematical context and shows how these techniques can be used for the first time to empower algorithmic techniques for the verification of infinite-state systems based on arrays, so as to make such techniques applicable to the timely, challenging settings of data-aware processes.
Gewalt in der Pflege
Authors: Oelke Uta
Published: April 2020

Zusammenfassung. Gewalt ist leider keine Ausnahme im Pflegealltag. Dass der Bildungsarbeit diesbezüglich eine hohe präventive, reflexive und auf den Selbstschutz der Pflegenden abzielende Bedeutung zukommt, zeigen die 2019 erschienenen Rahmenpläne zur Gestaltung der generalistischen Pflegeausbildung. Eine Auseinandersetzung mit Gewaltphänomenen ist hier sowohl in den Bildungs- und Kompetenzzielen als auch für Lernsituationen und Lernaufgaben vorgesehen. Szenische Bildungsarbeit bietet hier ein hohes Potenzial.
Zum aktuellen Stand der Qualifikation von Lehrkräften im Hinblick auf das Pflegeberufereformgesetz (PflBRefG)
Authors: Frieß Christian , Wobst Silvia , Zacharias Peggy , Koch Sebastian
Published: April 2020

Zusammenfassung. Die Einführung der generalistischen Pflegeausbildung im Jahr 2020 wird das Berufsbild der Pflege tiefgreifend verändern und die Anforderungen an die Lehrkräfte erhöhen. Zum aktuellen Stand liegen im Hinblick auf das Pflegereformgesetz und die damit verbundenen Vorgaben an die Qualifikation von Lehrkräften kaum vergleichbare Daten vor.
Stem cell-derived polarized hepatocytes
Authors: Dao Thi Viet Loan , Wu Xianfang , Belote Rachel L. , Andreo Ursula , Takacs Constantin N. , Fernandez Joseph P. , Vale-Silva Luis Andre , Prallet Sarah , Decker Charlotte C. , Fu Rebecca M. , Qu Bingqian , Uryu Kunihiro , Molina Henrik , Saeed Mohsan , Steinmann Eike , Urban Stephan , Singaraja Roshni R. , Schneider William M. , Simon Sanford M. , Rice Charles M.
Published: April 2020

Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined basolateral and apical membranes separated by tight junctions. We show that polarized HLCs secrete cargo directionally: Albumin, urea, and lipoproteins are secreted basolaterally, whereas bile acids are secreted apically. Further, we show that enterically transmitted hepatitis E virus (HEV) progeny particles are secreted basolaterally as quasi-enveloped particles and apically as naked virions, recapitulating essential steps of the natural infectious cycle in vivo. We also provide proof-of-concept that polarized HLCs can be used for pharmacokinetic and drug-drug interaction studies. This novel system provides a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism in a more physiologically relevant setting.
Spatial contextual effects in primary visual cortex limit feature representation under crowding
Authors: Henry Christopher A. , Kohn Adam
Published: April 2020

Crowding is a profound loss of discriminability of visual features, when a target stimulus is surrounded by distractors. Numerous studies of human perception have characterized how crowding depends on the properties of a visual display. Yet, there is limited understanding of how and where stimulus information is lost in the visual system under crowding. Here, we show that macaque monkeys exhibit perceptual crowding for target orientation that is similar to humans. We then record from neuronal populations in monkey primary visual cortex (V1). These populations show an appreciable loss of information about target orientation in the presence of distractors, due both to divisive and additive modulation of responses to targets by distractors. Our results show that spatial contextual effects in V1 limit the discriminability of visual features and can contribute substantively to crowding.
The Litsea genome and the evolution of the laurel family
Authors: Chen Yi-Cun , Li Zhen , Zhao Yun-Xiao , Gao Ming , Wang Jie-Yu , Liu Ke-Wei , Wang Xue , Wu Li-Wen , Jiao Yu-Lian , Xu Zi-Long , He Wen-Guang , Zhang Qi-Yan , Liang Chieh-Kai , Hsiao Yu-Yun , Zhang Di-Yang , Lan Si-Ren , Huang Laiqiang , Xu Wei , Tsai Wen-Chieh , Liu Zhong-Jian , Van de Peer Yves , Wang Yang-Dong
Published: April 2020

The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of theLitsea cubebagenome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny ofFUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.
Accelerated dryland expansion regulates future variability in dryland gross primary production
Authors: Yao Jingyu , Liu Heping , Huang Jianping , Gao Zhongming , Wang Guoyin , Li Dan , Yu Haipeng , Chen Xingyuan
Published: April 2020

Drylands cover 41% of Earth’s surface and are the largest source of interannual variability in the global carbon sink. Drylands are projected to experience accelerated expansion over the next century, but the implications of this expansion on variability in gross primary production (GPP) remain elusive. Here we show that by 2100 total dryland GPP will increase by 12 ± 3% relative to the 2000–2014 baseline. Because drylands will largely expand into formerly productive ecosystems, this increase in dryland GPP may not increase global GPP. Further, GPP per unit dryland area will decrease as degradation of historical drylands outpaces the higher GPP of expanded drylands. Dryland expansion and climate-induced conversions among sub-humid, semi-arid, arid, and hyper-arid subtypes will lead to substantial changes in regional and subtype contributions to global dryland GPP variability. Our results highlight the vulnerability of dryland subtypes to more frequent and severe climate extremes and suggest that regional variations will require different mitigation strategies.
A primer on emerging field-deployable synthetic biology tools for global water quality monitoring
Authors: Thavarajah Walter , Verosloff Matthew S. , Jung Jaeyoung K. , Alam Khalid K. , Miller Joshua D. , Jewett Michael C. , Young Sera L. , Lucks Julius B.
Published: April 2020

Tracking progress towards Target 6.1 of the United Nations Sustainable Development Goals, “achieving universal and equitable access to safe and affordable drinking water for all”, necessitates the development of simple, inexpensive tools to monitor water quality. The rapidly growing field of synthetic biology has the potential to address this need by isolating DNA-encoded sensing elements from nature and reassembling them to create field-deployable “biosensors” that can detect pathogenic or chemical water contaminants. Here, we describe current water quality monitoring strategies enabled by synthetic biology and compare them to previous approaches used to detect three priority water contaminants (i.e., fecal pathogens, arsenic, and fluoride), as well as explain the potential for engineered biosensors to simplify and decentralize water quality monitoring. We conclude with an outlook on the future of biosensor development, in which we discuss their adaptability to emerging contaminants (e.g., metals, agricultural products, and pharmaceuticals), outline current limitations, and propose steps to overcome the field’s outstanding challenges to facilitate global water quality monitoring.
Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity
Authors: Nadar Robin A. , Farbod Kambiz , der Schilden Karlijn Codee-van , Schlatt Lukas , Crone Barbara , Asokan Nandini , Curci Alessandra , Brand Michael , Bornhaeuser Martin , Iafisco Michele , Margiotta Nicola , Karst Uwe , Heskamp Sandra , Boerman Otto C. , van den Beucken Jeroen J. J. P. , Leeuwenburgh Sander C. G.
Published: April 2020

Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes to confirm preferential accumulation of these Pt-based drugs in metabolically active bone. In vitro NMR studies revealed that release of Pt from Pt BP complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. These Pt-BP complexes formed less Pt-DNA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of Pt from Pt-BP complexes proceeded relatively slow. Subsequently, radioactive 195mPt-BP complexes were synthesized using 195mPt(NO3)2(en) as precursor and injected intravenously into mice. Specific accumulation of 195mPt-BP was observed at skeletal sites with high metabolic activity using micro-SPECT/CT imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195mPt BP co-localized with calcium in the trabeculae of mice tibia.
Milk lactoperoxidase decreases ID1 and ID3 expression in human oral squamous cell carcinoma cell lines
Authors: Panahipour Layla , Biasi Maria De , Bokor Theresa Sophia , Thajer Alexandra , Haiden Nadja , Gruber Reinhard
Published: April 2020

Milk consumption may modify the risk of squamous cell carcinoma. The role of milk to modulate the gene expression in oral squamous cell carcinoma cells has not been investigated so far. Here, HSC2 oral squamous carcinoma cells were exposed to an aqueous fraction of human milk and a whole-genome array was performed. Among the genes that were significantly reduced by human and cow milk were the DNA-binding protein inhibitor 1 (ID1), ID3 and Distal-Less Homeobox 2 (DLX2) in HSC2 cells. Also, in TR146 oral squamous carcinoma cells, there was a tendency towards a decreased gene expression. Upon size fractionation, lactoperoxidase but not lactoferrin and osteopontin was identified to reduce ID1 and ID3 in HSC2 cells. Dairy products and hypoallergenic infant formula failed to decrease the respective genes. These data suggest that milk can reduce the expression of transcription factors in oral squamous carcinoma cells.
Foot strike pattern during running alters muscle-tendon dynamics of the gastrocnemius and the soleus
Authors: Yong Jennifer R. , Dembia Christopher L. , Silder Amy , Jackson Rachel W. , Fredericson Michael , Delp Scott L.
Published: April 2020

Running is thought to be an efficient gait due, in part, to the behavior of the plantar flexor muscles and elastic energy storage in the Achilles tendon. Although plantar flexor muscle mechanics and Achilles tendon energy storage have been explored during rearfoot striking, they have not been fully characterized during forefoot striking. This study examined how plantar flexor muscle-tendon mechanics during running differs between rearfoot and forefoot striking. We used musculoskeletal simulations, driven by joint angles and electromyography recorded from runners using both rearfoot and forefoot striking running patterns, to characterize plantar flexor muscle-tendon mechanics. The simulations revealed that foot strike pattern affected the soleus and gastrocnemius differently. For the soleus, forefoot striking decreased tendon energy storage and fiber work done while the muscle fibers were shortening compared to rearfoot striking. For the gastrocnemius, forefoot striking increased muscle activation and fiber work done while the muscle fibers were lengthening compared to rearfoot striking. These changes in gastrocnemius mechanics suggest that runners planning to convert to forefoot striking might benefit from a progressive eccentric gastrocnemius strengthening program to avoid injury.
Observation of sub-wavelength phase structure of matter wave with two-dimensional optical lattice by Kapitza-Dirac diffraction
Authors: Wen Kai , Meng Zengming , Wang Pengjun , Wang Liangwei , Chen Liangchao , Huang Lianghui , Zhou Lihong , Cui Xiaoling , Zhang Jing
Published: April 2020

We report an experimental demonstration of generation and measurement of sub-wavelength phase structure of a Bose-Einstein condensate (BEC) with two-dimensional optical lattice. This is implemented by applying a short lattice pulse on BEC in the Kapitza-Dirac (or Raman-Nath) regime, which, in the classical picture, corresponds to phase modulation imprinted on matter wave. When the phase modulation is larger than 2π in a lattice cell, the periodicity of phase naturally forms the sub-wavelength phase structure. By converting the phase information into amplitude, we are able to measure the sub-wavelength structure through the momentum distribution of BEC via the time-of-flight absorption image. Beyond the classical treatment, we further demonstrate the importance of quantum fluctuations in the formation of sub-wavelength phase structure by considering different lattice configurations. Our scheme provides a powerful tool for exploring the fine structure of a lattice cell as well as topological defects in matter wave.
Intracellular nonequilibrium fluctuating stresses indicate how nonlinear cellular mechanical properties adapt to microenvironmental rigidity
Authors: Wei Ming-Tzo , Jedlicka Sabrina S. , Ou-Yang H. Daniel
Published: April 2020

Living cells are known to be in thermodynamically nonequilibrium, which is largely brought about by intracellular molecular motors. The motors consume chemical energies to generate stresses and reorganize the cytoskeleton for the cell to move and divide. However, since there has been a lack of direct measurements characterizing intracellular stresses, questions remained unanswered on the intricacies of how cells use such stresses to regulate their internal mechanical integrity in different microenvironments. This report describes a new experimental approach by which we reveal an environmental rigidity-dependent intracellular stiffness that increases with intracellular stress - a revelation obtained, surprisingly, from a correlation between the fluctuations in cellular stiffness and that of intracellular stresses. More surprisingly, by varying two distinct parameters, environmental rigidity and motor protein activities, we observe that the stiffness-stress relationship follows the same curve. This finding provides some insight into the intricacies by suggesting that cells can regulate their responses to their mechanical microenvironment by adjusting their intracellular stress.
3D Printing of Inertial Microfluidic Devices
Authors: Razavi Bazaz Sajad , Rouhi Omid , Raoufi Mohammad Amin , Ejeian Fatemeh , Asadnia Mohsen , Jin Dayong , Ebrahimi Warkiani Majid
Published: April 2020

Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.
Three novel variants identified within ECM-related genes in Chinese Han keratoconus patients
Authors: Xu Xiayan , Zhang Xin , Cui Yilei , Yang Hao , Ping Xiyuan , Wu Jing , Yu Xiaoning , Jin Xiuming , Huang Xiaodan , Shentu Xingchao
Published: April 2020

As the primary indication for corneal transplantation, the pathogenesis of keratoconus remains elusive. Aiming to identify whether any mutation from extracellular-matrix (ECM)-related genes contributes to the patients with sporadic cases of keratoconus (KC) from Chinese Han population, one hundred and fifty-three participants in total were enrolled in our study, including fifty-three KC patients and one hundred healthy controls. Mutational analysis of three ECM-related genes (LOX, COL5A1 and TIMP3) with next-generation sequencing and Sanger sequencing was performed. To further confirm the function of three ECM-related genes in the pathogenesis of keratoconus, we performed Real-time Quantitative PCR in vitro. Results showed that three new sequence variants (c.95 G > A in LOX, c.1372 C > T in COL5A1 and c.476 C > T in TIMP3) were identified in aforementioned ECM-related genes in KC patients without being detected among the healthy controls. According to the results of QPCR, we found that the expression levels of LOX and TIMP3 were decreased in the KC patients, while COL5A1 showed no significant difference of expression. This is the first time to screen so many ECM-related genes in Chinese keratoconus patients using next-generation sequencing. We find numerous underlying causal variants, enlarging lots of mutation spectrums and thus providing new sites for other investigators to replicate and for further research.
Platelets disrupt vasculogenic mimicry by cancer cells
Authors: Martini Carmela , Thompson Emma J. , Hyslop Stephanie R. , Cockshell Michaelia P. , Dale Brian J. , Ebert Lisa M. , Woods Anthony E. , Josefsson Emma C. , Bonder Claudine S.
Published: April 2020

Tumour vasculature supports the growth and progression of solid cancers with both angiogenesis (endothelial cell proliferation) and vasculogenic mimicry (VM, the formation of vascular structures by cancer cells themselves) predictors of poor patient outcomes. Increased circulating platelet counts also predict poor outcome for cancer patients but the influence of platelets on tumour vasculature is incompletely understood. Herein, we show with in vitro assays that platelets did not influence angiogenesis but did actively inhibit VM formation by cancer cell lines. Both platelet sized beads and the releasates from platelets were partially effective at inhibiting VM formation suggesting that direct contact maximises the effect. Platelets also promoted cancer cell invasion in vitro. B16F10 melanomas in Bcl-xPlt20/Plt20 thrombocytopenic mice showed a higher content of VM than their wildtype counterparts while angiogenesis did not differ. In a xenograft mouse model of breast cancer with low-dose aspirin to inactivate the platelets, the burden of MDA-MB-231-LM2 breast cancer cells was reduced and the gene expression profile of the cancer cells was altered; but no effect on tumour vasculature was observed. Taken together, this study provides new insights into the action of platelets on VM formation and their involvement in cancer progression.
Memristive GAN in Analog
Authors: Krestinskaya O. , Choubey B. , James A. P.
Published: April 2020

Generative Adversarial Network (GAN) requires extensive computing resources making its implementation in edge devices with conventional microprocessor hardware a slow and difficult, if not impossible task. In this paper, we propose to accelerate these intensive neural computations using memristive neural networks in analog domain. The implementation of Analog Memristive Deep Convolutional GAN (AM-DCGAN) using Generator as deconvolutional and Discriminator as convolutional memristive neural network is presented. The system is simulated at circuit level with 1.7 million memristor devices taking into account memristor non-idealities, device and circuit parameters. The design is modular with crossbar arrays having a minimum average power consumption per neural computation of 47nW. The design exclusively uses the principles of neural network dropouts resulting in regularization and lowering the power consumption. The SPICE level simulation of GAN is performed with 0.18 μm CMOS technology and WOx memristive devices with RON = 40 kΩ and ROFF = 250 kΩ, threshold voltage 0.8 V and write voltage at 1.0 V.
RETRACTED ARTICLE: In situ structural characterization of early amyloid aggregates in Alzheimer’s disease transgenic mice and Octodon degus
Authors: Benseny-Cases Núria , Álvarez-Marimon Elena , Aso Ester , Carmona Margarita , Klementieva Oxana , Appelhans Dietmar , Ferrer Isidre , Cladera Josep
Published: April 2020

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer’s disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.
Distinct inactivated bacterial-based immune modulators vary in their therapeutic efficacies for treating disease based on the organ site of pathology
Authors: Kalyan Shirin , Bazett Mark , Sham Ho Pan , Bosiljcic Momir , Luk Beryl , Dhanji Salim , Costa Amanda M. , Wong Stephanie W. Y. , Netea Mihai G. , Mullins David W. , Gunn Hal
Published: April 2020

Recent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: (1) only adaptive immunity confers immunological memory; and, (2) innate immunity lacks specificity. This work describes the observation that innate immune effector cells appear to be differentially recruited to specific pathological sites when mobilized by distinct inactivated bacterial-based stimuli administered subcutaneously. The studies presented suggest that the immune system, upon detecting the first signs of a potential infection by a specific pathogen, tends to direct its resources to the compartment from which that pathogen is most likely originating. The findings from this work puts forth the novel hypothesis that the immunotherapeutic efficacy of a microbial-based stimulus for innate immune mobilization depends on the correct selection of the microbial species used as the stimulant and its relationship to the organ in which the pathology is present.
Digital rock physics and laboratory considerations on a high-porosity volcanic rock
Authors: Schepp Laura L. , Ahrens Benedikt , Balcewicz Martin , Duda Mandy , Nehler Mathias , Osorno Maria , Uribe David , Steeb Holger , Nigon Benoit , Stöckhert Ferdinand , Swanson Donald A. , Siegert Mirko , Gurris Marcel , Saenger Erik H.
Published: April 2020

Digital rock physics combines microtomographic imaging with advanced numerical simulations of effective material properties. It is used to complement laboratory investigations with the aim to gain a deeper understanding of relevant physical processes related to transport and effective mechanical properties. We apply digital rock physics to reticulite, a natural mineral with a strong analogy to synthetic open-cell foams. We consider reticulite an end-member for high-porosity materials with a high stiffness and brittleness. For this specific material, hydro-mechanical experiments are very difficult to perform. Reticulite is a pyroclastic rock formed during intense Hawaiian fountaining events. The honeycombed network of bubbles is supported by glassy threads and forms a structure with a porosity of more than 80%. Comparing experimental with numerical results and theoretical estimates, we demonstrate the high potential of in situ characterization with respect to the investigation of effective material properties. We show that a digital rock physics workflow, so far applied to conventional rocks, yields reasonable results for high-porosity rocks and can be adopted for fabricated foam-like materials with similar properties. Numerically determined porosities, effective elastic properties, thermal conductivities and permeabilities of reticulite show a fair agreement to experimental results that required exeptionally high experimental efforts.
Peripheral proinflammatory Th1/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis
Authors: Jin Mengmeng , Günther Rene , Akgün Katja , Hermann Andreas , Ziemssen Tjalf
Published: April 2020

Neuroinflammation is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), but only limited data are available on systematic peripheral and central immune cell profiles in ALS. We studied detailed immune profiles of 73 ALS patients and 48 healthy controls (controls) in peripheral blood by fluorescence-activated cell sorting as well as cytokine expression profiles in serum. In a subgroup of 16 ALS patients and 10 controls we additionally studied cerebrospinal fluid (CSF) samples. In peripheral blood, T cell subtypes presented a shift towards pro-inflammatory Th 1 and Th 17 cells whereas anti-inflammatory Th2 and T regulatory cells were decreased. Important players in innate immunity including distinct monocyte (Mo) and natural killer (NK) cell subtypes were changed in ALS patients compared to controls. Pro-inflammatory serum cytokines such as interleukin (IL)-1 beta, IL-6 and interferon-gamma (IFN-gamma) were increased and the anti-inflammatory cytokine IL-10 was decreased. Correlation analysis revealed moderate negative correlations between Th1 and Th17 to the ALS functional rating scale revised (ALSFRS-R) and to forced vital capacity. In CSF samples, no relevant alteration of the immune profile was found. In conclusion, the immune profile in ALS was shifted towards a Th1/Th17 cell-mediated pro-inflammatory immune response and correlated to disease severity and progression. Large prospective studies are needed to confirm these findings.
Identification of microRNAs in bovine faeces and their potential as biomarkers of Johne’s Disease
Authors: Shaughnessy Ronan G. , Farrell Damien , Stojkovic Bojan , Browne John A. , Kenny Kevin , Gordon Stephen V.
Published: April 2020

Extracellular microRNAs (miRNAs) are detectable in the peripheral blood and have been touted as potential biomarkers for a range of maladies. The presence and biomarker potential of miRNAs in other biofluids has been less thoroughly explored, particularly in the veterinary realm. Faecal miRNAs are a case in point; while they have been identified largely in rodents and humans, they have not been reported in cattle but may have prognostic or diagnostic value for Johne’s Disease (JD) in cattle, a chronic granulomatous inflammation of the ileum caused by Mycobacterium avium subspecies paratuberculosis (MAP). The aim of this study was thus to characterise the bovine faecal miRNome and to determine the utility of these transcripts as biomarkers for JD. Real-time PCR arrays consisting of 752 miRNA targets, optimised for detection of human miRNA, were used to screen RNA purified from faecal samples obtained from confirmed JD clinical cases vs. healthy controls. Two hundred and fifty-eight miRNAs were detected in bovine faeces, three of which are potentially novel orthologs of known human miRNAs. Differential abundance of three miRNA was evident in animals with clinical JD as compared to healthy controls. Our study has therefore identified a variety of miRNAs in bovine faeces and has demonstrated their utility in differentiating healthy animals from those with late-stage JD, providing potential biomarkers for MAP infection and disease progression.
Micro-scale interactions between Arabidopsis root hairs and soil particles influence soil erosion
Authors: De Baets Sarah , Denbigh Thomas D. G. , Smyth Kevin M. , Eldridge Bethany M. , Weldon Laura , Higgins Benjamin , Matyjaszkiewicz Antoni , Meersmans Jeroen , Larson Emily R. , Chenchiah Isaac V. , Liverpool Tanniemola B. , Quine Timothy A. , Grierson Claire S.
Published: April 2020

Soil is essential for sustaining life on land. Plant roots play a crucial role in stabilising soil and minimising erosion, although these mechanisms are still not completely understood. Consequently, identifying and breeding for plant traits to enhance erosion resistance is challenging. Root hair mutants in Arabidopsis thaliana were studied using three different quantitative methods to isolate their effect on root-soil cohesion. We present compelling evidence that micro-scale interactions of root hairs with surrounding soil increase soil cohesion and reduce erosion. Arabidopsis seedlings with root hairs were more difficult to detach from soil, compost and sterile gel media than those with hairless roots, and it was 10-times harder to erode soil from roots with than without hairs. We also developed a model that can consistently predict the impact root hairs make to soil erosion resistance. Our study thus provides new insight into the mechanisms by which roots maintain soil stability.
The nature of ferromagnetism in the chiral helimagnet Cr1/3NbS2
Authors: Sirica N. , Vilmercati P. , Bondino F. , Pis I. , Nappini S. , Mo S. -K. , Fedorov A. V. , Das P. K. , Vobornik I. , Fujii J. , Li L. , Sapkota D. , Parker D. S. , Mandrus D. G. , Mannella N.
Published: April 2020

The chiral helimagnet Cr1/3NbS2 hosts exotic spin textures, whose influence on the magneto-transport properties make this material an ideal candidate for future spintronic applications. To date, the interplay between macroscopic magnetic and transport degrees of freedom is believed to result from a reduction in carrier scattering following spin order. Here, we present electronic structure measurements across the helimagnetic transition temperature TC that challenges this view. We show that the Fermi surface is comprised of strongly hybridized Nb- and Cr-derived electronic states, and that spectral weight close to the Fermi level increases anomalously as the temperature is lowered below TC. These findings are rationalized on the basis of first principle density functional theory calculations, which reveal a large nearest-neighbor exchange energy, suggesting the interaction between local spin moments and hybridized Nb- and Cr-derived itinerant states to go beyond the perturbative interaction of Ruderman-Kittel-Kasuya-Yosida, suggesting instead a mechanism rooted in a Hund’s exchange interaction.
A comparative study of semi-flexible linear and ring polymer conformational change in an anisotropic environment
Authors: Chen Anpu , Zhang Bingjie , Zhao Nanrong
Published: April 2020

We adopt a Langevin-dynamics based simulation to systematically study the conformational change of a semi-flexible probed polymer in a rod crowding environment.
Direct embedding and versatile placement of electrodes in 3D printed microfluidic-devices
Authors: Castiaux Andre D. , Currens Emily R. , Martin R. Scott
Published: April 2020

In this paper, we describe how PolyJet 3D printing technology can be used to fully integrate electrode materials into microfluidic devices during the print process.
Inhibition of 3D colon cancer stem cell spheroids by cytotoxic RuII-p-cymene complexes of mesalazine derivatives
Authors: Acharya Sourav , Ghosh Subhashis , Maji Moumita , Parambil Ajmal Roshan Unniram , Singh Sandeep , Mukherjee Arindam
Published: April 2020

RuII-p-cymene complexes of imidazole–mesalazine based ligands kill bulk and stem colon cancer cells with tight regulation over stemness markers.
Conformational impact of aliphatic side chains in local anaesthetics: benzocaine, butamben and isobutamben
Authors: Insausti A. , Calabrese C. , Parra M. , Usabiaga I. , Vallejo-López M. , Écija P. , Basterretxea F. J. , Grabow J.-U. , Caminati W. , Lesarri A. , Cocinero E. J.
Published: April 2020

A comprehensive conformational analysis and the impact of side chains on local anaesthetics in the case of benzocaine, butamben and isobutamben.
Catalytic asymmetric synthesis of diazabicyclo[3.1.0]hexanes by 1,3-dipolar cycloaddition of azomethine ylides with azirines
Authors: Molina Alba , Díaz-Tendero Sergio , Adrio Javier , Carretero Juan C.
Published: April 2020

A practical CuI/(R)-Fesulphos catalyzed 1,3-dipolar cycloaddition of azomethine ylides with azirines has been developed to produce highly valuable enantioenriched diazabicyclo[3.1.0]hexanes.