bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of rock bridges by infrared thermal imaging and modeling
Authors: Guerin Antoine , Jaboyedoff Michel , Collins Brian D. , Derron Marc-Henri , Stock Greg M. , Matasci Battista , Boesiger Martin , Lefeuvre Caroline , Podladchikov Yury Y.
Published: September 2019

Characterization of rock discontinuities and rock bridges is required to define stability conditions of fractured rock masses in both natural and engineered environments. Although remote sensing methods for mapping discontinuities have improved in recent years, remote detection of intact rock bridges on cliff faces remains challenging, with their existence typically confirmed only after failure. In steep exfoliating cliffs, such as El Capitan in Yosemite Valley (California, USA), rockfalls mainly occur along cliff-parallel exfoliation joints, with rock bridges playing a key role in the stability of partially detached exfoliation sheets. We employed infrared thermal imaging (i.e., thermography) as a new means of detecting intact rock bridges prior to failure. An infrared thermal panorama of El Capitan revealed cold thermal signatures for the surfaces of two granitic exfoliation sheets, consistent with the expectation that air circulation cools the back of the partially detached sheets. However, we also noted small areas of warm thermal anomalies on these same sheets, even during periods of nocturnal rock cooling. Rock attachment via rock bridges is the likely cause for the warm anomalies in the thermal data. 2-D model simulations of the thermal behavior of one of  the monitored sheets reproduce the observed anomalies and explain the temperature differences detected in the rock bridge area. Based on combined thermal and ground-based lidar imaging, and using geometric and rock fracture mechanics analysis, we are able to quantify the stability of both sheets. Our analysis demonstrates that thermography can remotely detect intact rock bridges and thereby greatly improve rockfall hazard assessment.
Generation of Transmission-Competent Human Malaria Parasites with Chromosomally-Integrated Fluorescent Reporters
Authors: McLean Kyle Jarrod , Straimer Judith , Hopp Christine S. , Vega-Rodriguez Joel , Small-Saunders Jennifer L. , Kanatani Sachie , Tripathi Abhai , Mlambo Godfree , Dumoulin Peter C. , Harris Chantal T. , Tong Xinran , Shears Melanie J. , Ankarklev Johan , Kafsack Björn F. C. , Fidock David A. , Sinnis Photini
Published: September 2019

Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer an integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and inhibitory antibodies.
Optimization of the energy for Breast monochromatic absorption X-ray Computed Tomography
Authors: Delogu Pasquale , Di Trapani Vittorio , Brombal Luca , Mettivier Giovanni , Taibi Angelo , Oliva Piernicola
Published: September 2019

The limits of mammography have led to an increasing interest on possible alternatives such as the breast Computed Tomography (bCT). The common goal of all X-ray imaging techniques is to achieve the optimal contrast resolution, measured through the Contrast to Noise Ratio (CNR), while minimizing the radiological risks, quantified by the dose. Both dose and CNR depend on the energy and the intensity of the X-rays employed for the specific imaging technique. Some attempts to determine an optimal energy for bCT have suggested the range 22 keV–34 keV, some others instead suggested the range 50 keV–60 keV depending on the parameters considered in the study. Recent experimental works, based on the use of monochromatic radiation and breast specimens, show that energies around 32 keV give better image quality respect to setups based on higher energies. In this paper we report a systematic study aiming at defining the range of energies that maximizes the CNR at fixed dose in bCT. The study evaluates several compositions and diameters of the breast and includes various reconstruction algorithms as well as different dose levels. The results show that a good compromise between CNR and dose is obtained using energies around 28 keV.
Assessment of the VDW interaction converting DMAPS from the thermal-motion form to the hydrogen-bonded form
Authors: Takahashi Masae , Matsui Hiroshi , Ikemoto Yuka , Suzuki Makoto , Morimoto Nobuyuki
Published: September 2019

Assessment of van der Waals (VDW) interactions is fundamental to all of the central quest of structure that regulates the biological function. VDW interactions contributing to intramolecular weak hydrogen bonding are regarded as an important force to regulate the thermal stimuli-sensitive function of sulfobetaine methacrylate, DMAPS. We present here the conversion from the thermal-motion form at room temperature to the weak-hydrogen-bonded form against thermal motion as a terahertz spectral change with a definite isosbestic point from an absorption peak of one form to the other. Vibrational absorptions are used as a probe for assessing VDW interactions in conjunction with highly reliable and well-established density functional theory (DFT) calculations for analysis. Complicated spectral features and uncertain conformations of DMAPS in the amorphous state are clearly resolved under the polarizable continuum model and the dispersion correction for the pure DFT calculations.
A multiplex qPCR approach for detection of pfhrp2 and pfhrp3 gene deletions in multiple strain infections of Plasmodium falciparum
Authors: Schindler Tobias , Deal Anna C. , Fink Martina , Guirou Etienne , Moser Kara A. , Mwakasungula Solomon M. , Mihayo Michael G. , Jongo Said A. , Chaki Prosper P. , Abdulla Salim , Valverde Paulo C. Manrique , Torres Katherine , Bijeri Jose R. , Silva Joana C. , Hoffman Stephen L. , Gamboa Dionicia , Tanner Marcel , Daubenberger Claudia
Published: September 2019

The rapid and accurate diagnosis of Plasmodium falciparum malaria infection is an essential factor in malaria control. Currently, malaria diagnosis in the field depends heavily on using rapid diagnostic tests (RDTs) many of which detect circulating parasite-derived histidine-rich protein 2 antigen (PfHRP2) in capillary blood. P. falciparum strains lacking PfHRP2, due to pfhrp2 gene deletions, are an emerging threat to malaria control programs. The novel assay described here, named qHRP2/3-del, is well suited for high-throughput screening of P. falciparum isolates to identify these gene deletions. The qHRP2/3-del assay identified pfhrp2 and pfhrp3 deletion status correctly in 93.4% of samples with parasitemia levels higher than 5 parasites/µL when compared to nested PCR. The qHRP2/3-del assay can correctly identify pfhrp2 and pfhrp3 gene deletions in multiple strain co-infections, particularly prevalent in Sub-Saharan countries. Deployment of this qHRP2/3-del assay will provide rapid insight into the prevalence and potential spread of P. falciparum isolates that escape surveillance by RDTs.
The earliest evidence of Acheulian occupation in Northwest Europe and the rediscovery of the Moulin Quignon site, Somme valley, France
Authors: Antoine Pierre , Moncel Marie-Hélène , Voinchet Pierre , Locht Jean-Luc , Amselem Daniel , Hérisson David , Hurel Arnaud , Bahain Jean-Jacques
Published: September 2019

The dispersal of hominin groups with an Acheulian technology and associated bifacial tools into northern latitudes is central to the debate over the timing of the oldest human occupation of Europe. New evidence resulting from the rediscovery and the dating of the historic site of Moulin Quignon demonstrates that the first Acheulian occupation north of 50°N occurred around 670–650 ka ago. The new archaeological assemblage was discovered in a sequence of fluvial sands and gravels overlying the chalk bedrock at a relative height of 40 m above the present-day maximal incision of the Somme River and dated by ESR on quartz to early MIS 16. More than 260 flint artefacts were recovered, including large flakes, cores and five bifaces. This discovery pushes back the age of the oldest Acheulian occupation of north-western Europe by more than 100 ka and bridges the gap between the archaeological records of northern France and England. It also challenges hominin dispersal models in Europe showing that hominins using bifacial technology, such as Homo heidelbergensis, were probably able to overcome cold climate conditions as early as 670–650 ka ago and reasserts the importance of the Somme valley, where Prehistory was born at the end of the 19th century.
Exome Sequencing Reveals Immune Genes as Susceptibility Modifiers in Individuals with α1-Antitrypsin Deficiency
Authors: Rigobello Chiara , Baraldo Simonetta , Tinè Mariaenrica , Ferrarotti Ilaria , Corsico Angelo Guido , Bazzan Erica , Turato Graziella , Balestro Elisabetta , Biondini Davide , Valle Giorgio , Saetta Marina , Cosio Manuel G.
Published: September 2019

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated to early onset emphysema, mainly imputable to Pi*ZZ genotype. In spite of the serious potential effects, many AATD individuals do not develop emphysema. To identify genes/variants potentially involved in emphysema development we studied 4 AATD families. Each family had at least one affected sibling with emphysema and one non-affected. Whole Exome Sequencing (WES) was performed on genomic DNA isolated from 9 individuals with AATD (4 affected/5 non-affected). Genetic variants confirmed at least in three families were prioritized using QueryOR and network analysis was used to verify enriched pathways. In affected subjects: 14 genes (57% immune-related) segregated in a recessive model and 21 (29% immune-related) in a dominant model. In non-affected subjects: 21 genes (43% immune-related) segregated in a recessive model and 50 (24% immune-related) in a dominant model. In affected siblings immune genes had an activating function, while where immune-suppressing in non-affected siblings involving antigen processing, MHC-I presentation, TCR and PD-1 signalling. This study describes possible genetic susceptibility factors for emphysema development in AATD, and suggests that gene variants involved in regulation of immune homeostasis and maintenance of self-tolerance contribute to the development or suppression of the disease.
Human decision-making biases in the moral dilemmas of autonomous vehicles
Authors: Frank Darius-Aurel , Chrysochou Polymeros , Mitkidis Panagiotis , Ariely Dan
Published: September 2019

The development of artificial intelligence has led researchers to study the ethical principles that should guide machine behavior. The challenge in building machine morality based on people’s moral decisions, however, is accounting for the biases in human moral decision-making. In seven studies, this paper investigates how people’s personal perspectives and decision-making modes affect their decisions in the moral dilemmas faced by autonomous vehicles. Moreover, it determines the variations in people’s moral decisions that can be attributed to the situational factors of the dilemmas. The reported studies demonstrate that people’s moral decisions, regardless of the presented dilemma, are biased by their decision-making mode and personal perspective. Under intuitive moral decisions, participants shift more towards a deontological doctrine by sacrificing the passenger instead of the pedestrian. In addition, once the personal perspective is made salient participants preserve the lives of that perspective, i.e. the passenger shifts towards sacrificing the pedestrian, and vice versa. These biases in people’s moral decisions underline the social challenge in the design of a universal moral code for autonomous vehicles. We discuss the implications of our findings and provide directions for future research.
A unique camouflaged mimarachnid planthopper from mid-Cretaceous Burmese amber
Authors: Jiang Tian , Szwedo Jacek , Wang Bo
Published: September 2019

Predation is a major driving force for the evolution of functional forms. Avoidance of visual predators has resulted in different kinds of anti-predator defences, such as: camouflage, crypsis, disruptive coloration, and masquerade or mimesis. Camouflage is one of the forms involving shape, colouration, structure and behaviour when the visual pattern and orientation of an animal can determine whether it lives or dies. Inferring the behaviour and function of an ancient organism from its fossilised remains is a difficult task, but in many cases it closely resembles that of its descendants on uniformitarian grounds. Here we report and discuss examples of morphological and behavioural traits involving camouflage named recently as a flatoidinisation syndrome, shown by the inclusion of a planthopper in mid-Cretaceous Burmese amber. We found a new genus and species of an extinct Cretaceous planthopper family Mimarachnidae showing peculiar complex morphological adaptations to camouflage it on tree bark. Due to convergence, it resembles an unrelated tropiduchid planthopper from Eocene Baltic amber and also a modern representatives of the planthopper family Flatidae. Flattening of the body, the horizontal position of the tegmina at repose, tegmina with an undulating margin and elevated, wavy longitudinal veins, together with colouration and more sedentary behavioral traits enable these different insects to avoid predators. Our discovery reveals flatoidinisation syndrome in mid-Cretaceous Burmese amber which may provide insights into the processes of natural selection and evolution in this ancient forest.
Staphylococcal enterotoxins modulate the effector CD4+ T cell response by reshaping the gene expression profile in adults with atopic dermatitis
Authors: Orfali Raquel Leao , Yoshikawa Fabio Seiti Yamada , Oliveira Luanda Mara da Silva , Pereira Natalli Zanete , de Lima Josenilson Feitosa , Ramos Yasmim Álefe Leuzzi , Duarte Alberto José da Silva , Sato Maria Notomi , Aoki Valeria
Published: September 2019

Staphylococcus aureuscolonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4+T cells demands further analysis. We aimed to analyze the CD4+T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4+T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4+T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-γ, and MIP-1β) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2andIL13)promoted by SEA in AD patients, associated to a compromised polyfunctional response particularly in CD4+CD38+T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such asEGR2induction, and may contribute to negative regulation of polyfunctional CD4+T cells in these patients.
De novo transcriptome provides insights into the growth behaviour and resveratrol and trans-stilbenes biosynthesis in Dactylorhiza hatagirea - An endangered alpine terrestrial orchid of western Himalaya
Authors: Dhiman Nisha , Sharma Nitesh Kumar , Thapa Pooja , Sharma Isha , Kumar Swarnkar Mohit , Chawla Amit , Shankar Ravi , Bhattacharya Amita
Published: September 2019

This is the first report on de novo transcriptome of Dactylorhiza hatagirea, a critically-endangered, terrestrial orchid of alpine Himalayas. The plant is acclaimed for medicinal properties but little is known about its secondary-metabolites profile or cues regulating their biosynthesis. De novo transcriptome analysis was therefore, undertaken to gain basic understanding on these aspects, while circumventing the acute limitation of plant material availability. 65,384 transcripts and finally, 37,371 unigenes were assembled de novo from a total of 236 million reads obtained from shoot, tuber and leaves of the plant. Dominance of differentially-expressing-genes (DEGs) related to cold-stress-response and plant-hormone-signal-transduction; and those involved in photosynthesis, sugar-metabolism and secondary-metabolite-synthesis provided insights into carbohydrate-partitioning in the plant during its preparation for freezing winter at natural habitat. DEGs of glucomannan, ascorbic acid, carotenoids, phylloquinone/naphthoquinones, indole alkaloids, resveratrol and stilbene biosynthesis revealed the secondary-metabolite profile of D. hatagirea. UHPLC results confirmed appreciable amounts of resveratrol and trans-stilbene in D. hatagirea tubers, for the first time. Expression analysis of 15 selected genes including those of phenylpropanoid pathway confirmed the validity of RNA-seq data. Opportunistic growth, temperature- and tissue-specific-differential-expression of secondary metabolite biosynthesis and stress tolerant genes were confirmed using clonal plants growing at 8, 15 and 25 °C.
Paramagnetic gold in a highly disordered Au-Ni-O alloy
Authors: Stamatelatos A. , Poulopoulos P. , Goschew A. , Fumagalli P. , Sarigiannidou E. , Rapenne L. , Opagiste C. , Grammatikopoulos S. , Wilhelm F. , Rogalev A.
Published: September 2019

Magnetic materials are usually classified into a distinct category such as diamagnets, paramagnets or ferromagnets. The enormous progress in materials science allows one nowadays, however, to change the magnetic nature of an element in a material. Gold, in bulk form, is traditionally a diamagnet. But in a ferromagnetic environment, it can adopt an induced ferromagnetic moment. Moreover, the growth of gold under certain conditions may lead to a spontaneous ferromagnetic or paramagnetic response. Here, we report on paramagnetic gold in a highly disordered Au–Ni–O alloy and focus on the unusual magnetic response. Such materials are mainly considered for plasmonic applications. Thin films containing Au, Ni and NiO are fabricated by co-deposition of Ni and Au in a medium vacuum of 2 × 10−2 mbar. As a result, Au is in a fully disordered state forming in some cases isolated nanocrystallites of up to 4 nm in diameter as revealed by high resolution transmission electron microscopy. The disorder and the environment, which is rich in oxygen, lead to remarkable magnetic properties of Au: an induced ferromagnetic and a paramagnetic state. This can be proven by measuring the x-ray magnetic circular dichroism. Our experiments show a way to establish and monitor Au paramagnetism in alloys.
An Experimental Approach to Rigorously Assess Paneth Cell α-Defensin (Defa) mRNA Expression in C57BL/6 Mice
Authors: Castillo Patricia A. , Nonnecke Eric B. , Ossorio Daniel T. , Tran Michelle T. N. , Goley Stephanie M. , Lönnerdal Bo , Underwood Mark A. , Bevins Charles L.
Published: September 2019

Abundant evidence from many laboratories supports the premise that α-defensin peptides secreted from Paneth cells are key mediators of host-microbe interactions in the small intestine that contribute to host defense and homeostasis. α-defensins are among the most highly expressed antimicrobial peptides at this mucosal surface in many mammals, including humans and mice; however, there is striking variation among species in the number and primary structure of α-defensin paralogs. Studies of these biomolecules in vivo are further complicated by striking variations between laboratory mouse strains. Herein, we report an experimental approach to determine with precision and specificity expression levels of α-defensin (Defa) mRNA in the small intestine of C57BL/6 mice through an optimized set of oligonucleotide primers for qRT-PCR assays and cloned cDNA plasmids corresponding to the Defa paralogs. This approach demonstrated marked differences in α-defensin expression in C57BL/6 mice with respect to proximal/distal anatomical location and developmental stage, which have not been described previously. These data underscore the importance of careful attention to method (primer choice, proximal vs. distal location, and developmental stage) in analysis of antimicrobial peptide expression and their impact.
Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses
Authors: Benedicto Aitor , Herrero Alba , Romayor Irene , Marquez Joana , Smedsrød Bård , Olaso Elvira , Arteta Beatriz
Published: September 2019

The prometastatic stroma generated through tumor cells/host cells interaction is critical for metastatic growth. To elucidate the role of ICAM-1 on the crosstalk between tumor and primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), implicated in tumor adhesion and angiogenesis, we performed in vitro cocultures and an in vivo model of liver metastasis of colorectal cancer (CRC). ICAM-1 blockade in the LSECs decreased the adhesion and transmigration of tumor cells through an LSEC in vitro and vivo. Cocultures of C26 cells and LSECs contained higher amounts of IL-1β, IL-6, PGE-2, TNF-α and ICAM-1 than monocultures. C26 cells incubated with sICAM-1 secreted higher amounts of PGE-2, IL-6, VEGF, and MMPs, while enhanced the migration of LSECs and HSCs. HSCs cultures activated by media from C26 cells pretreated with sICAM-1 contained the largest amounts of VEGF and MMPs. C26 cell activation with sICAM-1 enhanced their metastasizing potential in vivo, while tumor LFA-1 blockade reduced tumor burden and LSECs and HSC-derived myofibroblasts recruitment. In vivo ICAM-1 silencing produced similar results. These findings uncover LSEC ICAM-1 as a mediator of the CRC metastatic cascade in the liver and identifies it as target for the inhibition of liver colonization and metastatic progression.
Selection of reference genes for measuring the expression of aiiO in Ochrobactrum quorumnocens A44 using RT-qPCR
Authors: Krzyżanowska Dorota M. , Supernat Anna , Maciąg Tomasz , Matuszewska Marta , Jafra Sylwia
Published: September 2019

Reverse transcription quantitative PCR (RT-qPCR), a method of choice for quantification of gene expression changes, requires stably expressed reference genes for normalization of data. So far, no reference genes were established for the Alphaproteobacteria of the genus Ochrobactrum. Here, we determined reference genes for gene expression studies in O. quorumnocens A44. Strain A44 was cultured under 10 different conditions and the stability of expression of 11 candidate genes was evaluated using geNorm, NormFinder and BestKeeper. Most stably expressed genes were found to be rho, gyrB and rpoD. Our results can facilitate the choice of reference genes in the related Ochrobactrum strains. O. quorumnocens A44 is able to inactivate a broad spectrum of N-acyl homoserine lactones (AHLs) – the quorum sensing molecules of many Gram-negative bacteria. This activity is attributed to AiiO hydrolase, yet it remains unclear whether AHLs are the primary substrate of this enzyme. Using the established RT-qPCR setup, we found that the expression of the aiiO gene upon exposure to two AHLs, C6-HLS and 3OC12-HSL, does not change above the 1-fold significance threshold. The implications of this finding are discussed in the light of the role of quorum sensing-interfering enzymes in the host strains.
Percolation Phase Transition from Ionic Liquids to Ionic Liquid Crystals
Authors: Li Shen , Wang Yanting
Published: September 2019

Due to their complex molecular structures and interactions, phase behaviors of complex fluids are quite often difficult to be identified by common phase transition analysis methods. Percolation phase transition, on the other hand, only monitors the degree of connection among particles without strict geometric requirements such as translational or orientational order, and thus suitable for pinpointing phase transitions of complex fluids. As typical complex fluids, ionic liquids (ILs) exhibit phases beyond the description of simple liquid theories. In particular, with an intermediate cationic side-chain length, ILs can form the nanoscale segregated liquid (NSL) state, which will eventually transform into the ionic liquid crystal (ILC) structure when the side chains are adequately long. However, the microscopic mechanism of this transformation is still unclear. In this work, by means of coarse-grained molecular dynamics simulation, we show that, with increasing cationic side-chain length, some local pieces of non-polar domains are gradually formed by side chains aligned in parallel inside the NSL phase, before an abrupt percolation phase transition happens when the system transforms into the ILC phase. This work not only identifies that the NSL to ILC phase transition is a critical phenomenon, but also demonstrates the importance of percolation theory to complex fluids.
Recording mobile EEG in an outdoor environment reveals cognitive-motor interference dependent on movement complexity
Authors: Reiser Julian Elias , Wascher Edmund , Arnau Stefan
Published: September 2019

Oftentimes we find ourselves in situations in which we need to perform concurrent motor and cognitive tasks like simple locomotion while being cognitively involved. In the present study, we investigated in how far cognitive and motor functioning interfere in an outdoor environment. Our participants performed an auditory oddball task while concurrently completing various motor tasks on the outside premises of our institute. Beside behavioural responses and subjective workload ratings, we also analysed electrophysiological data recorded with a 30-channel mobile EEG montage. We observed an increase of subjective workload and decrease of performance with increasing movement complexity. Accordingly, we also found a decrease in the parietal P3 amplitude as well as in frontal midline Theta power with higher motor load. These results indicate that an increased movement complexity imposes a higher workload to the cognitive system, which, in turn, effectively reduces the availability of cognitive resources for the cognitive task. Overall this experiment demonstrates the feasibility of transferring classical paradigms of cognitive research to real-world settings. The findings support the notion of shared resources for motor and cognitive functions by demonstrating distinct modulations of correlates of cognitive processes across different motor tasks.
Modeling of partial dome collapse of La Soufrière of Guadeloupe volcano: implications for hazard assessment and monitoring
Authors: Peruzzetto Marc , Komorowski Jean-Christophe , Le Friant Anne , Rosas-Carbajal Marina , Mangeney Anne , Legendre Yoann
Published: September 2019

Over the past 9,150 years, at least 9 flank collapses have been identified in the history of La Soufrière of Guadeloupe volcano. On account of the volcano’s current unrest, the possibility of such a flank collapse should not be dismissed in assessing hazards for future eruptive magmatic as well as non-magmatic scenarios. We combine morphological and geophysical data to identify seven unstable structures (volumes ranging from 1 × 106 m3 to 100 × 106 m3), including one that has a volume compatible with the last recorded flank collapse in 1530 CE. We model their dynamics and emplacement with the SHALTOP numerical model and a simple Coulomb friction law. The best-fit friction coefficient to reproduce the 1530 CE event is tan(7°) = 0.13, suggesting the transformation of the debris avalanche into a debris flow, which is confirmed by the texture of mapped deposits. Various friction angles are tested to investigate less water-rich and less mobile avalanches. The most densely populated areas of Saint-Claude and Basse-Terre, and an area of Gourbeyre south of the Palmiste ridge, are primarily exposed in the case of the more voluminous and mobile flank collapse scenarios considered. However, topography has a prominent role in controlling flow dynamics, with barrier effects and multiple channels. Classical mobility indicators, such as the Heim’s ratio, are thus not adequate for a comprehensive hazard analysis.
Maternal anxiety, depression and asthma and adverse pregnancy outcomes – a population based study
Authors: Rejnö Gustaf , Lundholm Cecilia , Öberg Sara , Lichtenstein Paul , Larsson Henrik , D’Onofrio Brian , Larsson Kjell , Saltvedt Sissel , Brew Bronwyn K. , Almqvist Catarina
Published: September 2019

To evaluate associations between maternal anxiety or depression and adverse pregnancy outcomes, taking possible familial confounding and interaction with asthma into account, we conducted a cohort study of all singleton births in Sweden 2001–2013. We retrieved information about pregnancy, diagnoses of anxiety/depression, asthma, and prescribed medication from the Swedish Medical Birth, National Patient, and Prescribed Drug Registers. We estimated associations with regression models, performed cousin and sibling comparisons, and calculated interactions. In 950 301 identified pregnancies; 5.9% had anxiety/depression and 4.0% had asthma. Anxiety/depression was associated with adverse pregnancy outcomes (e.g. preeclampsia, adjusted Odds Ratio 1.17 (95% Confidence Interval 1.12, 1.22), instrumental delivery (1.14 (1.10, 1.18)), elective (1.62 (1.57, 1.68)) and emergency (1.32 (1.28, 1.35)) caesarean section (CS)). Their children had lower birth weight (−54 g (−59, −49)) and shorter gestational age (−0.29 weeks (−0.31, −0.28)). Associations were not confounded by familial factors and asthma did not modify the effect of anxiety/depression for outcomes other than elective CS, p < 0.001. In women with anxiety/depression diagnosis, untreated women had higher odds of elective CS compared to women on medication (1.30 (1.17, 1.43)). In conclusion, anxiety/depression should be considered when evaluating pregnant women’s risk of complications such as preeclampsia and non-vaginal deliveries.
The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immune- or DNA repair-related genes in cervical cancer patients
Authors: Joo Jungnam , Omae Yosuke , Hitomi Yuki , Park Boram , Shin Hye-Jin , Yoon Kyong-Ah , Sawai Hiromi , Tsuiji Makoto , Hayashi Tomonori , Kong Sun-Young , Tokunaga Katsushi , Kim Joo-Young
Published: September 2019

The present study investigated the association between single nucleotide polymorphisms (SNPs) in immune- or DNA repair-related genes and the integration pattern of human papillomavirus (HPV), a promising prognostic marker in cervical cancer. The HPV integration patterns of cervical cancer patients were determined by polymerase chain reaction and in situ hybridization, and categorized as episomal (group A), single-copy or multi-copy tandem repetition integrated (group B), and undetectable HPV types (group C). After sample and SNP quality control, 166,505 SNPs in 161 samples (38, 111, and 12 patients in groups A, B, and C, respectively) were examined. None of the SNPs reached genome-wide significance, and several candidate SNPs for future study were selected, including rs10999435 on chromosome 10q22, rs1322054 on chromosome 9q32-33, and rs10902171 on chromosome 11p15. Luciferase assay identified rs1322054 as the primary functional variant to regulate gene expression in immune cell. Further studies are needed to determine the genetic background of different integration patterns of HPV in cervical cancer patients.
One-year clinical evaluation of rotationally asymmetric multifocal intraocular lens with +1.5 diopters near addition
Authors: Oshika Tetsuro , Arai Hiroyuki , Fujita Yoshifumi , Inamura Mikio , Inoue Yasushi , Noda Toru , Miyata Kazunori
Published: September 2019

We conducted a one-year prospective, multicenter study to assess clinical outcomes after implantation of segmented, rotationally asymmetric multifocal intraocular lenses (IOLs) with +1.5 diopters (D) near addition. In this phase III clinical trial, 120 eyes of 65 patients undergoing phacoemulsification and implantation of Lentis Comfort LS-313 MF15 (Oculentis GmbH) were included. The ophthalmological examinations were performed before and 1 day, 1 week, 1, 3, 6, 9, and 12 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were measured. A defocus curve was obtained and patients were asked about the severity of photic phenomena. Postoperative distance and intermediate visual acuity was excellent, with UDVA, CDVA, UIVA, and DCIVA of approximately 20/20, 20/16, 20/25, 20/25 were attained, respectively. The level of near visual acuity was lower; UNVA and DCNVA remained at around 20/60 and 20/70, respectively. The defocus curve indicated that postoperative uncorrected visual acuity of 20/25 and 20/40 was obtained at as close as 67 cm and 50 cm, respectively. Contrast sensitivity was within the normal range, with a minimal level of subjective symptoms and high patient satisfaction. The rotationally asymmetric multifocal IOLs with +1.5 D near addition provided excellent distance and intermediate vision, but near vision was not enough for reading small prints. Contrast sensitivity was high, with very low incidences of photic phenomena and a high level of patient satisfaction.
A strategy of designing high-entropy alloys with high-temperature shape memory effect
Authors: Lee Je In , Tsuchiya Koichi , Tasaki Wataru , Oh Hyun Seok , Sawaguchi Takahiro , Murakami Hideyuki , Hiroto Takanobu , Matsushita Yoshitaka , Park Eun Soo
Published: September 2019

Shape memory effect, the ability to recover a pre-deformed shape on heating, results from a reversible martensitic transformation between austenite and martensite phases. Here, we demonstrate a strategy of designing high-entropy alloys (HEAs) with high-temperature shape memory effect in the CrMnFeCoNi alloy system. First, we calculate the difference in Gibbs free energy between face-centered-cubic (FCC) and hexagonal-close-packed (HCP) phases, and find a substantial increase in thermodynamic equilibrium temperature between the FCC and HCP phases through composition tuning, leading to thermally- and stress-induced martensitic transformations. As a consequence, the shape recovery temperature in non-equiatomic CrMnFeCoNi alloys can be increased to 698 K, which is much higher than that of conventional shape memory alloys (SMAs) and comparable to that of B2-based multi-component SMAs containing noble metals (Pd, Pt,etc.) or refractory metals (Zr, Hf,etc.). This result opens a vast field of applications of HEAs as a novel class of cost-effective high-temperature SMAs.
Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption
Authors: Avril Marion , Benjamin Max , Dols Mary-Margaret , Smith Joseph D.
Published: September 2019

Recent concepts suggest that bothPlasmodium falciparumfactors and coagulation contribute to endothelial activation and dysfunction in pediatric cerebral malaria (CM) pathology. However, there is still limited understanding of how these complex inflammatory stimuli are integrated by brain endothelial cells. In this study, we examined how mature-stageP.falciparuminfected erythrocytes (IE) interact with tumor necrosis factor α (TNFα) and thrombin in the activation and permeability of primary human brain microvascular endothelial cell (HBMEC) monolayers. Whereas trophozoite-stageP.falciparum-IE have limited effect on the viability of HBMEC or the secretion of pro-inflammatory cytokines or chemokines, except at super physiological parasite-host cell ratios, schizont-stageP.falciparum-IE induced low levels of cell death. Additionally, schizont-stage parasites were more barrier disruptive than trophozoite-stageP.falciparum-IE and prolonged thrombin-induced barrier disruption in both resting and TNFα-activated HBMEC monolayers. These results provide evidence that parasite products and thrombin may interact to increase brain endothelial permeability.
Characterization of the self-assembly of New Jersey polyomavirus VP1 into virus-like particles and the virus seroprevalence in Japan
Authors: Zhou Xianfeng , Bai Huimin , Kataoka Michiyo , Ito Masahiko , Muramatsu Masamichi , Suzuki Tetsuro , Li Tian-Cheng
Published: September 2019

New Jersey polyomavirus (NJPyV) was discovered in 2014 in a pancreatic transplant recipient’s vascular endothelial cells. Here, in the recombinant baculovirus system, VP1 protein of NJPyV expressed in insect cells was processed. The protein self-assembled into virus-like particles (NJPyV-LPs) in a cell-type-dependent manner, and the particles were then released into the culture media. Spherical ~50-nm-dia. NJPyV-LPs of uniform size with morphology resembling that of the native particles of polyomaviruses were purified from the fraction at 1.33 g/cm3 in supernatants of VP1-expressing Sf9 cells. We investigated the antigenic properties of purified NJPyV-LPs and performed a VLP-based enzyme immunoassay to determine the age-specific prevalence of NJPyV infection in a general Japanese population aged 1–70 years. The overall seropositivity rate of anti-NJPyV antibodies was only 1.8%. This might be explained by the low circulation of NJPyV in Japan. This is the first report of a large-scale serological survey of NJPyV in Asia (n = 1,050).
CAND1 regulates lunapark for the proper tubular network of the endoplasmic reticulum
Authors: Kajiho Hiroaki , Yamamoto Yasunori , Sakisaka Toshiaki
Published: September 2019

Endoplasmic reticulum (ER) tubules connect each other by three-way junctions, resulting in a tubular ER network. Oligomerization of three-way junction protein lunapark (Lnp) is important for its localization and the three-way junction stability. On the other hand, Lnp has an N-terminal ubiquitin ligase activity domain, which is also important for the three-way junction localization. To understand the mode of action of Lnp, we isolated Cullin-associated and neddylation-dissociated 1 (CAND1), a regulator of Skp1-Cul1-F-box (SCF) ubiquitin ligase, as a Lnp-binding protein by affinity chromatography. CAND1 and Lnp form a higher-molecular-weight complex in vitro, while they do not co-localize at the three-way junctions. CAND1 reduces the auto-ubiquitination activity of Lnp. CAND1 knockdown enhances proteasomal degradation of Lnp and reduces the tubular ER network in mammalian cells. These results suggest that CAND1 has the potency to promote the formation of the higher-molecular-weight complex with Lnp and reduce the auto-ubiquitination activity of Lnp, thereby regulating the three-way junction stability of the tubular ER network.
Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)
Authors: Yaku Keisuke , Okabe Keisuke , Gulshan Maryam , Takatsu Kiyoshi , Okamoto Hiroshi , Nakagawa Takashi
Published: September 2019

Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.
The potential of corn-soybean intercropping to improve the soil health status and biomass production in cool climate boreal ecosystems
Authors: Zaeem Muhammad , Nadeem Muhammad , Pham Thu Huong , Ashiq Waqar , Ali Waqas , Gilani Syed Shah Mohioudin , Elavarthi Sathya , Kavanagh Vanessa , Cheema Mumtaz , Galagedara Lakshman , Thomas Raymond
Published: September 2019

Intercropping (IC) is a promising approach used to improve soil health and sustainable crop production. However, it is unknown whether IC improve the soil health status and biomass productivity of crops cultivated in podzols under cool climate in boreal ecosystems. Two silage corn and three forage soybean genotypes were cultivated either as inter or monocrop (MC) treatments in a randomized complete block design. IC resulted in 28% increase in total forage production (FP). A reduction in rhizosphere soil pH (RS-pH) was observed in the IC treatments. Conversely, the rhizosphere soil acid phosphatase (RS-APase) activity was significantly higher (26–46%) in the IC treatments and occurred concomitant with a significant increase in available phosphorus (RS-Pavailable) (26–74%) in the rhizosphere. Furthermore, IC enhanced the active microbial composition and strong positive correlations were observed between RS-Pavailable, RS-APase, microbial biomass and FP; while RS-pH was negatively correlated with FP, RS-APase and RS-Pavailable. These findings suggested silage corn intercropped with forage soybean could be a viable approach to enhance FP through improved active microbial community structure, RS-APase activity and RS-Pavailable when cultivated on podzols in cool climate boreal ecosystem.
Breastfeeding and maternal cardiovascular risk factors: 1982 Pelotas Birth Cohort
Authors: Lima Natália P. , Bassani Diego G. , Magalhães Elma Izze S. , Barros Fernando C. , Horta Bernardo L.
Published: September 2019

This study evaluated the association of breastfeeding duration with maternal metabolic cardiovascular risk factors among women who have been prospectively followed since birth in a southern Brazilian city. In the unadjusted analysis, total cholesterol was higher among women who never breastfed in relation to those who breastfed ≥12 months. Among women with one livebirth, a shorter duration of breastfeeding was associated with lower HDL, while those with two or more livebirths and that breastfed for shorter time presented lower pulse wave velocity, glycaemia and non-HDL measures. After controlling for confounding variables, the magnitude of these associations decreased, and the confidence intervals included the reference. Concerning the duration of breastfeeding of the last child, the analysis was stratified by time since last birth. After controlling for confounders, systolic blood pressure was lower among women who breastfed 3 to <6 months and had a child within the last five years in relation to those who breastfed ≥6, but no clear trend was observed (p = 0.17). In conclusion, our findings suggest that there is no association between lactation and maternal cardiometabolic risk factors.
Increased regulatory B cells are involved in immune evasion in patients with gastric cancer
Authors: Murakami Yuki , Saito Hiroaki , Shimizu Shota , Kono Yusuke , Shishido Yuji , Miyatani Kozo , Matsunaga Tomoyuki , Fukumoto Yoji , Ashida Keigo , Sakabe Tomohiko , Nakayama Yuji , Fujiwara Yoshiyuki
Published: September 2019

Accumulating evidence has indicated that immune regulatory cells are involved in the establishment of tumoral immune evasion. However, the role of regulatory B cells (Bregs) in this remains unclear. Here, we identified a role for Bregs in immune evasion in gastric cancer (GC) patients. The frequency of peripheral Bregs was significantly higher in GC patients than in healthy controls (P = 0.0023). Moreover, the frequency of CD19+CD24hiCD27+ B cells in GC tissue was significantly higher than in peripheral blood and healthy gastric tissue. Carboxyfluorescein succinimidyl ester labeling revealed that CD19+CD24hiCD27+ B cells could suppress the proliferation of autologous CD4+ T cells. Moreover, CD19+CD24hiCD27+ B cells inhibited the production of interferon-gamma by CD4+ T cells. Double staining immunohistochemistry of interleukin-10 and CD19 revealed 5-year overall survival rates of 65.4% and 13.3% in BregLow and BregHigh groups, respectively (P < 0.0001). Multivariate analysis indicated that the frequency of Bregs was an independent prognostic indicator in GC patients. Taken together, our results show the existence of Bregs in GC tissue, and indicate that they are significantly correlated with the prognosis of GC patients.
A Plasmonic Approach to Study Protein Interaction Kinetics through the Dimerization of Functionalized Ag Nanoparticles
Authors: Mercadal Pablo A. , Motrich Ruben D. , Coronado Eduardo A.
Published: September 2019

Understanding the kinetics of protein interactions plays a key role in biology with significant implications for the design of analytical methods for disease monitoring and diagnosis in medical care, research and industrial applications. Herein, we introduce a novel plasmonic approach to study the binding kinetics of protein-ligand interactions following the formation of silver nanoparticles (Ag NPs) dimers by UV-Vis spectroscopy that can be used as probes for antigen detection and quantification. To illustrate and test the method, the kinetics of the prototype biotin-streptavidin (Biot-STV) pair interaction was studied. Controlled aggregates (dimers) of STV functionalized Ag NPs were produced by adding stoichiometric quantities of gliadin-specific biotinylated antibodies (IgG-Biot). The dimerization kinetics was studied in a systematic way as a function of Ag NPs size and at different concentrations of IgG-Biot. The kinetics data have shown to be consistent with a complex reaction mechanism in which only the Ag NPs attached to the IgG-Biot located in a specific STV site are able to form dimers. These results help in elucidating a complex reaction mechanism involved in the dimerization kinetics of functionalized Ag NPs, which can serve as probes in surface plasmon resonance-based bioassays for the detection and quantification of different biomarkers or analytes of interest.