bluuebunny/crossref_metadata_2025 huggingface dataset:
Abiotic and biotic stresses induce a core transcriptome response in rice
Authors: Cohen Stephen P. , Leach Jan E.
Published: April 2019

Environmental stresses greatly limit crop yield. With the increase in extreme weather events due to climate change and the constant pressure of diseases and pests, there is an urgent need to develop crop varieties that can tolerate multiple stresses. However, our knowledge of how plants broadly respond to stress is limited. Here, we explore the rice core stress response via meta-analysis of publicly available rice transcriptome data. Our results confirm that rice universally down-regulates photosynthesis in response to both abiotic and biotic stress. Rice also generally up-regulates hormone-responsive genes during stress response, most notably genes in the abscisic acid, jasmonic acid and salicylic acid pathways. We identified several promoter motifs that are likely involved in stress-responsive regulatory mechanisms in rice. With this work, we provide a list of candidate genes to study for improving rice stress tolerance in light of environmental stresses. This work also serves as a proof of concept to show that meta-analysis of diverse transcriptome data is a valid approach to develop robust hypotheses for how plants respond to stress.
Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication
Authors: da Silva Novaes Antônio , Borges Fernanda Teixeira , Maquigussa Edgar , Varela Vanessa Araújo , Dias Marcos Vinicios Salles , Boim Mirian Aparecida
Published: April 2019

Mesangial cells stimulated with high glucose (HG) exhibit increased intracellular angiotensin II (AngII) synthesis that is correlated with the upregulation of AngII target genes, such as profibrotic cytokines. The intracrine effects of AngII can be mediated by several molecules transferred to other cells via exosomes (Exos), which play a key role in cellular communication under many physiological and pathological conditions. The aim of this study was to investigate the effects of exosomes derived from HG-stimulated human mesangial cells (HG-HMCs) on normal unstimulated HMCs. Exosomes from HMCs (C-Exos) and HG-HMCs (HG-Exos) were obtained from cell culture supernatants. HMCs were incubated with C-Exos or HG-Exos. HG stimulus induced a change in the amount but not the size of Exos. Both C-Exos and HG-Exos contained angiotensinogen and renin, but no angiotensin converting enzyme was detected. Compared with HMCs treated with C-Exos, HMCs treated with HG-Exos presented higher levels of fibronectin, angiotensinogen, renin, AT1and AT2receptors, indicating that HG-Exos modified the function of normal HMCs. These results suggest that the intercellular communication through Exos may have pathophysiological implications in the diabetic kidney.
Drug prioritization using the semantic properties of a knowledge graph
Authors: Malas Tareq B. , Vlietstra Wytze J. , Kudrin Roman , Starikov Sergey , Charrout Mohammed , Roos Marco , Peters Dorien J. M. , Kors Jan A. , Vos Rein , ‘t Hoen Peter A. C. , van Mulligen Erik M. , Hettne Kristina M.
Published: April 2019

Compounds that are candidates for drug repurposing can be ranked by leveraging knowledge available in the biomedical literature and databases. This knowledge, spread across a variety of sources, can be integrated within a knowledge graph, which thereby comprehensively describes known relationships between biomedical concepts, such as drugs, diseases, genes, etc. Our work uses the semantic information between drug and disease concepts as features, which are extracted from an existing knowledge graph that integrates 200 different biological knowledge sources. RepoDB, a standard drug repurposing database which describes drug-disease combinations that were approved or that failed in clinical trials, is used to train a random forest classifier. The 10-times repeated 10-fold cross-validation performance of the classifier achieves a mean area under the receiver operating characteristic curve (AUC) of 92.2%. We apply the classifier to prioritize 21 preclinical drug repurposing candidates that have been suggested for Autosomal Dominant Polycystic Kidney Disease (ADPKD). Mozavaptan, a vasopressin V2 receptor antagonist is predicted to be the drug most likely to be approved after a clinical trial, and belongs to the same drug class as tolvaptan, the only treatment for ADPKD that is currently approved. We conclude that semantic properties of concepts in a knowledge graph can be exploited to prioritize drug repurposing candidates for testing in clinical trials.
Improving the accuracy of Cu(ii)–nitroxide RIDME in the presence of orientation correlation in water-soluble Cu(ii)–nitroxide rulers
Authors: Ritsch Irina , Hintz Henrik , Jeschke Gunnar , Godt Adelheid , Yulikov Maxim
Published: April 2019

Detailed analysis of artefacts in the Cu(ii)–nitroxide RIDME experiments, related to orientation averaging, echo-crossing, ESEEM and background-correction is presented.
Using van der Waals heterostructures based on two-dimensional blue phosphorus and XC (X = Ge, Si) for water-splitting photocatalysis: a first-principles study
Authors: Ren Kai , Ren Chongdan , Luo Yi , Xu Yujing , Yu Jin , Tang Wencheng , Sun Minglei
Published: April 2019

BlueP/SiC and BlueP/GeC vdW heterostructures are high-efficiency photocatalysts for water-splitting at pH 0 and 7, respectively.
1H-Detected quadrupolar spin–lattice relaxation measurements under magic-angle spinning solid-state NMR
Authors: Makrinich Maria , Goldbourt Amir
Published: April 2019

Proton detection and phase-modulated pulse saturation enable the measurement of spin–lattice relaxation times of “invisible” quadrupolar nuclei with extensively large quadrupolar couplings.
Single-crystal-to-single-crystal guest exchange in columnar assembled brominated triphenylamine bis-urea macrocycles
Authors: Sindt Ammon J. , Smith Mark D. , Berens Samuel , Vasenkov Sergey , Bowers Clifford R. , Shimizu Linda S.
Published: April 2019

Crystals of brominated triphenylamine bis-urea macrocycles are robust materials which can undergo single-crystal-to-single-crystal guest exchange inside 1-dimensional columns.
A three-component supramolecular nanocomposite as a heavy-atom-free photosensitizer
Authors: Kumar P. P. Praveen , Yadav Pranjali , Shanavas Asifkhan , Thurakkal Shameel , Joseph Joshy , Neelakandan Prakash P.
Published: April 2019

The preparation of a supramolecular nanocomposite containing BODIPY, tryptophan and gold nanoparticles capable of photosensitized generation of singlet oxygen is reported.
Exclusion principle repulsion effects on the covalent bond beyond the Born–Oppenheimer approximation
Authors: Sarsa A. , Alcaraz-Pelegrina J. M. , Le Sech C.
Published: April 2019

Electronic depletion of the covalent bond by the Pauli exclusion principle repulsion. Energies and quantum forces are calculated.
Exciton dissociation in an NIR-active triohybrid nanocrystal leading to efficient generation of reactive oxygen species
Authors: Patwari Jayita , Joshi Harmit , Mandal Harahari , Roy Lopamudra , Bhattacharya Chinmoy , Lemmens Peter , Pal Samir Kumar
Published: April 2019

Exciton dissociation: the key factor in generating ROS under IR light irradiation.
Metal-free and benign approach for the synthesis of dihydro-5′H-spiro[benzo[c]chromene-8,4′-oxazole]-5′,6(7H)-dione scaffolds as masked amino acids
Authors: Shafiee Behnaz , Duffield Joseph , Timm Rudy , Liyanage Rohana , Lay Jackson O. , Khosropour Ahmad R. , Amiri Rudbari Hadi , Beyzavi M. Hassan
Published: April 2019

Eco-friendly one-pot synthesis of new masked amino acids is described.
Cell factory engineering for improved production of natural products
Authors: Nielsen Jens
Published: April 2019

Natural product biosynthesis is inherently linked with the primary metabolism in terms of providing precursors and co-factors.
Microfluidics tubing as a synthesizer for ordered microgel networks
Authors: Ma Shaohua
Published: April 2019

A microfluidics synthesizer for ordered networks of a range of microgels, including GelMa, Matrigel and droplet-like microgels.
Self-templating growth of Sb2Se3@C microtube: a convention-alloying-type anode material for enhanced K-ion batteries
Authors: Yi Zheng , Qian Yong , Tian Jie , Shen Kangze , Lin Ning , Qian Yitai
Published: April 2019

A convention-alloying-type hollow Sb2Se3@C microtube was prepared for K-ion battery anode via a self-templated route.
A selenium-containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy
Authors: Tang Chu , Du Yang , Liang Qian , Cheng Zhen , Tian Jie
Published: April 2019

We have developed a HDAC6-selective inhibitor, SelSA, which can be utilized as a target for the detection and treatment of ERα(+) breast cancer and TNBC. The biodistribution study showed that SelSA can specifically target the breast tumor and display potent antitumor effects in vivo. This result will help to better improve the treatment efficacy against breast cancer.
Investigating long‐term vehicle speed prediction based on BP‐LSTM algorithms
Authors: Yufang Li , Mingnuo Chen , Wanzhong Zhao
Published: April 2019

Vehicle speed prediction is quite essential for many intelligent vehicular and transportation applications. Accurate on‐road vehicle speed prediction is challenging because individual vehicle speed is affected by many factors related to driver–vehicle–road–traffic system, e.g. the traffic conditions, vehicle type, and driver's behavior, in either a deterministic or stochastic way. Also machine learning makes vehicle speed predictions more accessible by exploring the potential relationship between the vehicle speed and its main factors based on the historical driving data in the context of vehicular networks. This study proposes a novel data‐driven vehicle speed prediction method based on back propagation‐long short‐term memory (BP‐LSTM) algorithms for long‐term individual vehicle speed prediction along the planned route. Also Pearson correlation coefficient is adopted to analyse the correlation of driver–vehicle–road–traffic historical characteristic parameters for the enhancement of the model's computing efficiency. Finally, a real natural driving data in Nanjing is used to evaluate the prediction performance with a result that the proposed vehicle speed prediction method outperforms other ones in terms of prediction accuracy. Moreover, based on the predicted vehicle speed, this work studies and analyses its effectiveness in two scenarios of energy consumption prediction and travel time prediction.
Modeling the dynamics of hepatitis E via the Caputo–Fabrizio derivative
Authors: Khan Muhammad Altaf , Hammouch Zakia , Baleanu Dumitru
Published: April 2019

A virus that causes hepatitis E is known as (HEV) and regarded on of the reason for lever inflammation. In mathematical aspects a very low attention has been paid to HEV dynamics. Therefore, the present work explores the HEV dynamics in fractional derivative. The Caputo–Fabriizo derivative is used to study the dynamics of HEV. First, the essential properties of the model will be presented and then describe the HEV model with CF derivative. Application of fixed point theory is used to obtain the existence and uniqueness results associated to the model. By using Adams–Bashfirth numerical scheme the solution is obtained. Some numerical results and tables for arbitrary order derivative are presented.
Corneal Endothelial Decompensation after Ocular Chemical Burn: Description of a New Finding
Authors: Steinemann Alexandra , Blaser Frank , Livny Eitan , Baenninger Philipp , Marti Marvin , Gerber-Hollbach Nadine , Eggenschwiler Laura , Gatzioufas Zisis , Goldblum David
Published: April 2019

Background Ocular chemical burn is an ophthalmological emergency. Therefore, chemical injuries should be promptly addressed in order to initiate the appropriate treatment as soon as possible and optimize the visual prognosis. We present a retrospective study of ten cases with ocular chemical burn including one with superglue and one with a liquid plaster material injury and describe their clinical course.

History and Signs Ten adult patients (34 – 92 years, 8 males) presented with moderate to severe alkali or neutral chemical burns in our emergency clinics. They exhibited a variable degree of conjunctival injection, limbal ischemia, corneal erosion, and Descemetʼs folds.

Therapy and Outcome Patients were treated and complete corneal epithelial closure was achieved in all cases without significant signs of limbal stem cell insufficiency. Corneal endothelial insufficiency was observed in all cases. Nine patients had to be listed for corneal endothelial keratoplasty and one was treated with Descemetʼs stripping endothelial automated keratoplasty.

Conclusions Isolated corneal endothelial decompensation after chemical burns has not yet been described. The pathophysiological explanation of this observation remains, however, unknown. In view of this rare complication, it is important to follow patients after chemical ocular burn for possible development of endothelial decompensation.
Bestimmung der Immunglobulin-G-Versorgung beim neugeborenen
Kalb
Authors: Hampe Marian , Wehrend Axel
Published: April 2019

Eine ausreichende Versorgung mit kolostralen Antikörpern innerhalb der ersten
Lebensstunden ist für die Entwicklung und den Gesundheitsstatus junger Kälber
entscheidend. Es ist sinnvoll, im Rahmen der Bestandskontrolle und -beratung die
Immunglobulinaufnahme beim Einzeltier, insbesondere aber auf Herdenebene zu
überprüfen, um eine tierschutzgerechte und wirtschaftliche Kälberaufzucht zu
ermöglichen. Aufgrund der aufwendigen laborgebundenen und zum Teil
zeitintensiven direkten Messung der aufgenommenen Immunglobuline mittels
radialer Immundiffusion (RID) oder ELISA wurde in zahlreichen Studien versucht,
indirekte Methoden zu entwickeln, die vor allem kostengünstig und vor Ort
verfügbar sein sollen. Diese versuchen, durch korrelierte Messgrößen einen
Rückschluss auf die aufgenommene Menge kolostraler Antikörper zu ermöglichen. In
zahlreichen Überprüfungen zeigten sich bei den einzelnen Methoden allerdings zum
Teil erhebliche Differenzen hinsichtlich Spezifität und Sensitivität im
Vergleich mit den direkten Nachweisverfahren. In diesem Artikel werden neben RID
und ELISA die Aktivitätsmessung der γ-Glutamyltransferase (GGT), die Bestimmung
der Gesamtproteinkonzentration im Serum mittels Refraktometrie sowie des
Zinksulfattrübungstests vorgestellt und ihre Vor- und Nachteile in der Anwendung
dargelegt. Insbesondere die Refraktometrie und eingeschränkt die Messung der
GGT-Aktivität stellen für den Praktiker eine Alternative zur laborgebundenen
IgG-Messung dar. Trotz alledem existiert keine ideale Schnellmessmethode, sodass
bei den jeweiligen Verfahren Störfaktoren beachtet werden müssen.
Benigne Neoplasien der Orbita
Authors: von Sonnleithner Christoph , Zorn Malte , Bertelmann Eckart
Published: April 2019

Die Vielfalt orbitaler Raumforderungen ist außerordentlich groß. Manche Entitäten sind sehr selten. Das häufigste Symptom ist der Exophthalmus, daneben können Bulbusdislokation, Strabismus, Schmerzen, Sehverschlechterung und Gesichtsfeldausfälle auftreten. Die Therapie der Wahl bei den meisten symptomatischen benignen Neoplasien der Orbita ist die chirurgische Resektion.
Readability of Patient Education Texts Presented on the Internet Related to Vaccines
Authors: Bağcı Zafer , Kozanhan Betul , Tutar Mahmut Sami
Published: April 2019

Objective This study aimed to compare the readability and the contents of the patient information texts regarding vaccination on Turkish Internet sites.

Material and Methods Websites were searched in the Google search engine using the keywords “what is vaccination?” “benefits of vaccination,” “harms of vaccination,” and “side effects of vaccination” in May 2018. Readability was determined using Ateşman and Bezirci–Yilmaz formulas. According to Ateşman readability formula, the higher the readability of a text, the easier it can be read. Readability of “health-care professional” websites was compared with that of “non–health-care professional” websites. The content of the websites was analyzed by two pediatricians.

Results After the exclusion of the website not fulfilling the criteria, 44 websites, of which 20 were created by health-care professionals and 24 by non–health-care professionals, were evaluated. Ateşman readability scores were 53.62 ± 14.27 and 54.30 ± 8.60 for websites created by health-care professionals and non–health-care professionals, respectively. Mean readability level was “moderately difficult” for both groups according to Ateşman formula, and there was no significant difference between the two groups (p = 0.83). Mean readability level was categorized as at “secondary-high school” with Bezirci–Yilmaz readability formula, and there was no significant difference between the two groups (p = 0.68). The percentage of the contents of websites prepared by health-care professionals was found to be significantly higher when compared with non–health-care professionals (p = 0.04).

Conclusion It was found that the readability of the patient information texts in the web pages related to vaccination was moderately difficult and that the text content was insufficient. To improve the readability, short sentences should be prepared by health-care professionals with few words and syllables. Existing texts should be revised in the light of current information.
Resonant cavity enhanced photodiodes on GaSb for the mid-wave infrared
Authors: Craig A. P. , Al-Saymari F. , Jain M. , Bainbridge A. , Savich G. R. , Golding T. , Krier A. , Wicks G. W. , Marshall A. R.
Published: April 2019

We report the design, growth, processing, and characterization of resonant cavity enhanced photodiodes for the midwave infrared at ∼3.72 μm on GaSb. Using AlAsSb/GaSb mirrors, AlAsSb barrier and spacer layers and a thin 96 nm InAsSb absorber, we observed dark current and detectivity behavior superior to common InAsSb nBn detectors in the literature, with peak specific detectivity values of 8×1010 and 1×1010 cm Hz1/2 W−1 measured at 250 K and 300 K, respectively. In the same temperature range, the linewidth of the detector response was <44 nm and the quality factor ∼80. The peak quantum efficiency was >60% where the enhancement due to the resonant cavity was ∼20x. We estimate that the devices can operate close to, or slightly above, the background-limited infrared performance limit imposed on broadband detectors for a 300 K scene.
Full stress tensor measurement using fluorescence spectroscopy
Authors: Grutzik S. J. , Teague M. C.
Published: April 2019

Photoluminescent spectral peak positions are known to shift as a function of mechanical stress state. This has been demonstrated at macroscales to determine mean stress and mesoscales to determine mean stress and a quantity related to shear stress. Here, we propose a method to utilize traction-free surface conditions and knowledge of material orientation to solve for two in-plane displacement fields given two measured spectral peak positions measured at a grid of points. It is then possible to calculate the full stress tensor at each measurement point. This is a significant advancement over the previous ability to measure one or two stress quantities. We validate the proposed method using a simple, two-grain geometry and show that it produces the same mean stress and shear stress measure as the existing direct method. We also demonstrate determination of the full stress field in a polycrystalline alumina specimen.
Analytical energy gradients for ionized states using equation-of-motion coupled-cluster theory with spin-orbit coupling
Authors: Zhou Xiaojun , Cao Zhanli , Wang Fan
Published: April 2019

Spin-orbit coupling (SOC) may have a significant effect on the structure and harmonic frequencies of particularly heavy p-block element compounds. However, reports on analytical energy gradients with SOC are scarce, especially for excited states. In this work, we implemented analytical energy gradients for ionized states using the equation-of-motion coupled-cluster (CC) theory at the CC singles and doubles level (EOM-IP-CCSD) with SOC. Effects of SOC on structure and harmonic frequencies as well as properties for both the ground and some excited states of open-shell compounds with one unpaired electron can be investigated efficiently with the present implementation. A closed-shell reference is required in the calculations, and SOC is included in post-Hartree-Fock treatment. Relativistic effective core potentials are employed in dealing with both scalar relativistic effects and SOC, and we treat perturbations that are even under time reversal in this work. Both time-reversal symmetry and double point group symmetry for D2h* and its subgroups are exploited in the implementation. The method is applicable to states which can be reached by removing one electron from a closed-shell reference state. The results of some open-shell cations indicate the importance of SOC on structures and harmonic frequencies of heavy element compounds.
The contributions of junctions and nanowires/nanotubes in conductive networks
Authors: Ponzoni Andrea
Published: April 2019

Electrical transport in networked materials occurs through percolative clusters composed of a random distribution of two kinds of interconnected elements: elementary nanostructures and nanostructure-nanostructure junctions. Rationalizing the contribution of these microscopic elements to the macroscopic resistance of the system is a fundamental issue to develop this class of materials and related devices. Focusing on networks composed of high-aspect-ratio nanostructures, such as nanowires (NWs) or nanotubes (NTs), these concepts are still raising controversy in modeling and interpretation of experimental data. Despite these incongruences and the large variations induced by disorder in the electrical properties of such networked systems, this work shows that the ratio between the junction and the nanostructure resistance is nearly the same at the microscopic and macroscopic levels, regardless of the network features. In other words, this means that we may assess the relative contribution of nanostructures and junctions to the macroscopic network resistance directly from the knowledge of its microscopic building blocks. Based on experimental data available in the literature, this result is proven to hold for different materials and network densities, ranging from inorganic NWs to organic carbon NTs and from the percolation critical density nc up to, at least, five times nc, respectively.
Recent developments in the diagnosis of drug-resistant tuberculosis
Authors: Nicol Mark P , Cox Helen
Published: April 2019

Urgent steps are required to control the drug-resistant tuberculosis (TB) epidemic worldwide. Individualised treatment, using detailed drug-susceptibility test results to guide choice of antibiotics, improves patient outcomes and minimises adverse effects. Recent years have seen substantial advances in our ability to provide rapid, detailed drug-resistance profiles using genotypic methods for detection of mutations conferring drug-resistance. Rapid testing using real-time PCR to target the most important drug-resistance mutations allows the diagnosis of drug resistance to be made with the first diagnostic test, even in low resource settings. The use of whole genome sequencing to infer resistance to a range of different drugs facilitates earlier tailoring of therapy and detection of resistant subpopulations in mixed infections. Low burden countries, such as Australia are well positioned to lead the development and refinement of these new methods, to accelerate the incorporation of these new tools into TB control programs in high burden countries.
Systematic assessment of the sex ratio at birth for all countries and estimation of national imbalances and regional reference levels
Authors: Chao Fengqing , Gerland Patrick , Cook Alex R. , Alkema Leontine
Published: April 2019

Significance

This study provides information on sex ratio at birth (SRB) reference levels and SRB imbalance. Using a comprehensive database and a Bayesian estimation model, we estimate that SRB reference levels are significantly different from the commonly assumed historical norm of 1.05 for most regions. We identify 12 countries with strong statistical evidence of SRB imbalance: Albania, Armenia, Azerbaijan, China, Georgia, Hong Kong (SAR of China), India, Republic of Korea, Montenegro, Taiwan (Province of China), Tunisia, and Vietnam.
Climate change and educational attainment in the global tropics
Authors: Randell Heather , Gray Clark
Published: April 2019

Climate change may negatively impact education among children via exposure to extreme temperature and precipitation conditions. We link census data from 29 countries across the global tropics to high-resolution gridded climate data to understand how climatic conditions experienced in utero and during early childhood affect educational attainment at ages 12 to 16. We show that exposure to higher-than-average temperatures during the prenatal and early-life period is associated with fewer years of schooling in Southeast Asia. In this region, a child who experiences temperatures 2 SDs above average is predicted to attain 1.5 fewer years of schooling than one who experiences average temperatures. In addition, early-life rainfall is positively correlated with attainment in West and Central Africa as well as Southeast Asia, and negatively correlated with attainment in Central America and the Caribbean. While we expected that children from the most educated households would be buffered from these effects, we discover that they tend to experience the greatest educational penalties when exposed to hotter early-life conditions and, in some regions, to drier conditions. For example, among the most educated households in West and Central Africa, predicted schooling is 1.8 years lower for children who experience early-life rainfall 2 SDs below average versus 2 SDs above average, while the difference is just 0.8 years for children from the least educated households. These results suggest that development and educational gains in the tropics could be undermined by climate change, even for better-off households.
Megalithic tombs in western and northern Neolithic Europe were linked to a kindred society
Authors: Sánchez-Quinto Federico , Malmström Helena , Fraser Magdalena , Girdland-Flink Linus , Svensson Emma M. , Simões Luciana G. , George Robert , Hollfelder Nina , Burenhult Göran , Noble Gordon , Britton Kate , Talamo Sahra , Curtis Neil , Brzobohata Hana , Sumberova Radka , Götherström Anders , Storå Jan , Jakobsson Mattias
Published: April 2019

Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics.
Cancer stemness, intratumoral heterogeneity, and immune response across cancers
Authors: Miranda Alex , Hamilton Phineas T. , Zhang Allen W. , Pattnaik Swetansu , Becht Etienne , Mezheyeuski Artur , Bruun Jarle , Micke Patrick , de Reynies Aurélien , Nelson Brad H.
Published: April 2019

Significance

The exclusion of immune cells from the tumor microenvironment has been associated with poor prognosis in the majority of cancers. We report that when considering 21 solid cancer types, immune cell exclusion is widely associated with the presence of a stem cell-like phenotype in tumors (“stemness”). Stemness positively correlates with higher intratumoral heterogeneity, possibly by protecting antigenic clones from elimination by the immune system. The activation of a stemness program appears to limit antitumor immune responses via tumor cell-intrinsic silencing of endogenous retrovirus expression, repression of type I interferon signaling, and up-regulation of immunosuppressive checkpoints. Our work suggests that targeting the stemness phenotype in cancer will promote T cell infiltration and render tumors more responsive to immune control.
Rapid screening of engineered microbial therapies in a 3D multicellular model
Authors: Harimoto Tetsuhiro , Singer Zakary S. , Velazquez Oscar S. , Zhang Joanna , Castro Samuel , Hinchliffe Taylor E. , Mather William , Danino Tal
Published: April 2019

Significance

An emerging area of synthetic biology is the engineering of bacteria to diagnose and treat various diseases in the body. However, the lack of physiologically relevant in vitro testing environments to rapidly screen bacterial therapies limits their development for clinical use. Here, we develop a platform that enables parallel and long-term monitoring of engineered bacteria in multicellular spheroids. Using this system, we rapidly screened tumor-targeting bacteria engineered to deliver a library of anticancer molecules via synthetic gene circuits. We demonstrate high similarity between in vitro and in vivo results and show broad applicability of the system with various bacterial species and cell types. This technology may serve to accelerate future clinical applications for synthetic biology.
DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm
Authors: Kim M. Yvonne , Ono Akemi , Scholten Stefan , Kinoshita Tetsu , Zilberman Daniel , Okamoto Takashi , Fischer Robert L.
Published: April 2019

Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In
Arabidopsis
, active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown. One candidate is the rice
REPRESSOR OF SILENCING
1a (ROS1a)
gene, which is related to
DME
and is essential for rice seed viability and pollen function. Here, we report genome-wide analyses of DNA methylation in wild-type and
ros1a
mutant sperm and vegetative cells. We find that the rice vegetative cell genome is locally hypomethylated compared with sperm by a process that requires ROS1a activity. We show that many ROS1a target sequences in the vegetative cell are hypomethylated in the rice central cell, suggesting that ROS1a also demethylates the central cell genome. Similar to
Arabidopsis
, we show that sperm non-CG methylation is indirectly promoted by DNA demethylation in the vegetative cell. These results reveal that DNA glycosylase-mediated DNA demethylation processes are conserved in
Arabidopsis
and rice, plant species that diverged 150 million years ago. Finally, although global non-CG methylation levels of sperm and egg differ, the maternal and paternal embryo genomes show similar non-CG methylation levels, suggesting that rice gamete genomes undergo dynamic DNA methylation reprogramming after cell fusion.
Protease-independent action of tissue plasminogen activator in brain plasticity and neurological recovery after ischemic stroke
Authors: Pu Hongjian , Shi Yejie , Zhang Lili , Lu Zhengyu , Ye Qing , Leak Rehana K. , Xu Fei , Ma Shubei , Mu Hongfeng , Wei Zhishuo , Xu Na , Xia Yuguo , Hu Xiaoming , Hitchens T. Kevin , Bennett Michael V. L. , Chen Jun
Published: April 2019

Significance

Therapies that boost brain plasticity and repair processes without deleterious side effects have the potential to transform the clinical management of stroke. Here we report that tissue plasminogen activator (tPA), known as a clot buster for clinical treatment of ischemic stroke, exerts additional neurorestorative effects in a murine model of stroke by stimulating axonal regeneration and facilitating functional recovery. Importantly, functional restoration was independent of tPA’s proteolytic activity—a mutant, protease-inactive form of tPA, tPA-S478A, was as effective as regular tPA. Results of our preclinical studies support the view that tPA-S478A has the therapeutic potential to enhance brain regeneration and functional restoration in stroke victims. Unlike regular tPA, tPA-S478A does not bear the risk of inducing intracerebral hemorrhage.
Indian annual ambient air quality standard is achievable by completely mitigating emissions from household sources
Authors: Chowdhury Sourangsu , Dey Sagnik , Guttikunda Sarath , Pillarisetti Ajay , Smith Kirk R. , Di Girolamo Larry
Published: April 2019

Significance

The Indian government has initiated programs to reduce household use of biomass cookfuels, but their motivation does not include ambient pollution reductions. We estimate ambient exposure reductions that result and subsequent health benefits of seven different scenarios that mirror plausible mitigation policies to address household energy needs currently met by biomass combustion for cooking and water- and space heating, and by kerosene for lighting. If all households transitioned to clean fuels, ∼13% of premature mortality in India could be averted from the reduction in ambient pollution, and the average ambient PM
2.5
concentration in the country would meet national PM
2.5
standards. These results will assist in assessing current policies and making decisions on future mitigation policies to tackle air pollution.
Influence of shoe drop on running kinematics and kinetics in female runners
Authors: Besson Thibault , Morio Cédric , Millet Guillaume Y. , Rossi Jérémy
Published: April 2019

This study investigated the effects of shoe drop on lower limb kinematics and kinetics in female runners.

Fifteen healthy female runners ran on a 15‐m runway at their preferred speed with three different shoe‐drop conditions: 0 (D0), 6 (D6) and 10 (D10) mm. Three‐dimensional marker positions and ground reaction forces were recorded to analyse kinetic and kinematic parameters using zero‐ (0D) and one‐dimensional (1D) metrics (statistical parametric mapping, SPM). Regarding 0D parameters, significantly higher loading rates and transient peaks were found in D0 compared to D6 and D10 conditions (both p < .01). For 1D analysis, significantly higher ankle dorsiflexion moments were found in D0 compared to D6 and D10 during the braking phase (p < .01). Lower knee extension moments between 52% and 55% and 61% and 65% of contact time (p < .05) were also found. No difference was found between D6 and D10 conditions (p > .05). As previously shown in men, this study demonstrates that shoe drop influences running kinematic and kinetic patterns. Using SPM analysis in conjunction with classical analysis, the study adds new understanding on the influence of shoes on joint moment during contact time.
A delayed gating approach for interference-free ratio-based phosphor thermometry
Authors: Mendieta Aldo , Fond Benoît , Dragomirov Plamen , Beyrau Frank
Published: April 2019

Accurate surface temperature measurements present vast difficulties in numerous technical applications, especially when imaging fast temperature changes. One example is spray-induced surface cooling, where temperature variations occur on the sub-millisecond timescale. Phosphor thermometry relies on changes in the photoluminescence properties (typically the lifetime or the emission spectrum) of phosphor materials for temperature determination. For temperature imaging in situations where short measurement durations are critical such as on fast moving objects or short and intense heat transfer events, the spectral method is preferred. However, in many situations, fluorescence signals over a broad spectral range originate from fuel, flame radicals, optical windows or even the chemical binder used to coat the phosphor material and may interfere with the measurements.

In this work, we investigate a delay strategy for the spectral method that prevents interference from fluorescence sources by using a phosphor with a microsecond-range-lifetime. By applying a short delay (<1 µs), between excitation and detection, short-lived interfering fluorescence signals can be efficiently avoided. The temporal and spectral content of the fluorescence from the substrate, binder and fuel are investigated with a photomultiplier tube and a spectrometer respectively. The delayed gating strategy is then implemented for temperature imaging of the wetted side of a spray impinged surface with a tin-doped phosphor, (Sr,Mg)3(PO4)2:Sn2+; selected for its suitable lifetime (26 µs @ 300 K) and high temperature sensitivity. Calibration measurements for coated surfaces show that by avoiding fluorescence from the binder, the temperature sensitivity is improved from 0.3% K−1 to 0.8% K−1 at 293 K. Furthermore the calibration curve repeatability between two similar coatings is enhanced. Finally, temperature measurements of the cooling induced by a fluorescing impinging gasoline spray was successfully performed with this strategy owing the same level of measurement precision (0.5 K) as with a non-fluorescing fuel (n-hexane UV grade).
A combinatorial 𝔰𝔩₂-action and the Sperner property for the weak order
Authors: Gaetz Christian , Gao Yibo
Published: April 2019

We construct a simple combinatorially-defined representation of

s
l

2

\mathfrak {sl}_2

which respects the order structure of the weak order on the symmetric group. This is used to prove that the weak order has the strong Sperner property, and is therefore a Peck poset, solving a problem raised by Björner [Orderings of Coxeter groups, Amer. Math. Soc., Providence, RI, 1984, pp. 175–195]; a positive answer to this question had been conjectured by Stanley [Some Schubert shenanigans, preprint, 2017].
Probing the unidentified Fermi blazar-like population using optical polarization and machine learning
Authors: Liodakis I , Blinov D
Published: April 2019

The Fermi γ-ray space telescope has revolutionized our view of the γ-ray sky and the high-energy processes in the Universe. While the number of known γ-ray emitters has increased by orders of magnitude since the launch of Fermi, there is an ever increasing number of, now more than a thousand, detected point sources whose low-energy counterpart is to this day unknown. To address this problem, we combined optical polarization measurements from the RoboPol survey as well as other discriminants of blazars from publicly available all-sky surveys in machine learning (ML, random forest and logistic regression) frameworks that could be used to identify blazars in the Fermi unidentified fields with an accuracy of >95 per cent. Out of the potential observational biases considered, blazar variability seems to have the most significant effect reducing the predictive power of the frameworks to ${\sim }80\hbox{-}85{{\ \rm per\ cent}}$. We apply our ML framework to six unidentified Fermi fields observed using the RoboPol polarimeter. We identified the same candidate source proposed by Mandarakas et al. for 3FGL J0221.2 + 2518.
HERBS I: Metallicity and alpha enhancement along the Galactic bulge minor axis
Authors: Duong L , Asplund M , Nataf D M , Freeman K C , Ness M , Howes L M
Published: April 2019

To better understand the origin and evolution of the Milky Way bulge, we have conducted a survey of bulge red giant branch and clump stars using the High Efficiency and Resolution Multi-Element Spectrograph on the Anglo–Australian Telescope. We targeted ARGOS survey stars with predetermined bulge memberships, covering the full metallicity distribution function. The spectra have signal-to-noise ratios comparable to, and were analysed using the same methods as the GALAH survey. In this work, we present the survey design, stellar parameters, distribution of metallicity, and alpha-element abundances along the minor bulge axis at latitudes b = −10°, − 7.5°, and −5°. Our analysis of ARGOS stars indicates that the centroids of ARGOS metallicity components should be located ≈0.09 dex closer together. The vertical distribution of α-element abundances is consistent with the varying contributions of the different metallicity components. Closer to the plane, alpha abundance ratios are lower as the metal-rich population dominates. At higher latitudes, the alpha abundance ratios increase as the number of metal-poor stars increases. However, we find that the trend of alpha-enrichment with respect to metallicity is independent of latitude. Comparison of our results with those of GALAH DR2 revealed that for [Fe/H] ≈ −0.8, the bulge shares the same abundance trend as the high-α disc population. However, the metal-poor bulge population ([Fe/H] ≲ −0.8) show enhanced alpha abundance ratios compared to the disc/halo. These observations point to fairly rapid chemical evolution in the bulge, and that the metal-poor bulge population does not share the same similarity with the disc as the more metal-rich populations.
Baryons in the Cosmic Web of IllustrisTNG – I: gas in knots, filaments, sheets, and voids
Authors: Martizzi Davide , Vogelsberger Mark , Artale Maria Celeste , Haider Markus , Torrey Paul , Marinacci Federico , Nelson Dylan , Pillepich Annalisa , Weinberger Rainer , Hernquist Lars , Naiman Jill , Springel Volker
Published: April 2019

We analyse the IllustrisTNG simulations to study the mass, volume fraction, and phase distribution of gaseous baryons embedded in the knots, filaments, sheets, and voids of the Cosmic Web from redshift z = 8 to redshift z = 0. We find that filaments host more star-forming gas than knots, and that filaments also have a higher relative mass fraction of gas in this phase than knots. We also show that the cool, diffuse intergalactic medium [IGM; $T\lt 10^5 \, {\rm K}$, $n_{\rm H}\lt 10^{-4}(1+z) \, {\rm cm^{-3}}$] and the warm-hot intergalactic medium [WHIM; $10^5 \lt T\lt 10^7 \, {\rm K}$, $n_{\rm H} \lt 10^{-4}(1+z)\, {\rm cm^{-3}}$] constitute ${\sim } 39$ and ${\sim } 46{{\ \rm per\ cent}}$ of the baryons at redshift z = 0, respectively. Our results indicate that the WHIM may constitute the largest reservoir of missing baryons at redshift z = 0. Using our Cosmic Web classification, we predict the WHIM to be the dominant baryon mass contribution in filaments and knots at redshift z = 0, but not in sheets and voids where the cool, diffuse IGM dominates. We also characterize the evolution of WHIM and IGM from redshift z = 4 to redshift z = 0, and find that the mass fraction of WHIM in filaments and knots evolves only by a factor of ∼2 from redshift z = 0 to 1, but declines faster at higher redshift. The WHIM only occupies $4\!-\!11{{\ \rm per\ cent}}$ of the volume at redshift 0 ≤ z ≤ 1. We predict the existence of a significant number of currently undetected O vii and Ne ix absorption systems in cosmic filaments, which could be detected by future X-ray telescopes like Athena.
Predicting Outcomes After Surgical Decompression for Mild Degenerative Cervical Myelopathy: Moving Beyond the mJOA to Identify Surgical Candidates
Authors: Badhiwala Jetan H , Hachem Laureen D , Merali Zamir , Witiw Christopher D , Nassiri Farshad , Akbar Muhammad A , Almenawer Saleh A , Schomacher Markus , Wilson Jefferson R , Fehlings Michael G
Published: April 2019

BACKGROUND

Patients with mild degenerative cervical myelopathy (DCM) represent a heterogeneous population, and indications for surgical decompression remain controversial.

OBJECTIVE

To dissociate patient phenotypes within the broader population of mild DCM associated with degree of impairment in baseline quality of life (QOL) and surgical outcomes.

METHODS

This was a post hoc analysis of patients with mild DCM (modified Japanese Orthopedic Association [mJOA] 15-17) enrolled in the AOSpine CSM-NA/CSM-I studies. A k-means clustering algorithm was applied to baseline QOL (Short Form-36 [SF-36]) scores to separate patients into 2 clusters. Baseline variables and surgical outcomes (change in SF-36 scores at 1 yr) were compared between clusters. A k-nearest neighbors (kNN) algorithm was used to evaluate the ability to classify patients into the 2 clusters by significant baseline clinical variables.

RESULTS

One hundred eighty-five patients were eligible. Two groups were generated by k-means clustering. Cluster 1 had a greater proportion of females (44% vs 28%, P = .029) and symptoms of neck pain (32% vs 11%, P = .001), gait difficulty (57% vs 40%, P = .025), or weakness (75% vs 59%, P = .041). Although baseline mJOA correlated with neither baseline QOL nor outcomes, cluster 1 was associated with significantly greater improvement in disability (P = .003) and QOL (P < .001) scores following surgery. A kNN algorithm could predict cluster classification with 71% accuracy by neck pain, motor symptoms, and gender alone.

CONCLUSION

We have dissociated a distinct patient phenotype of mild DCM, characterized by neck pain, motor symptoms, and female gender associated with greater impairment in QOL and greater response to surgery.