bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of FAMIL2 in Simulating the Climatology and Seasonal‐to‐Interannual Variability of Tropical Cyclone Characteristics
Authors: Li Jinxiao , Bao Qing , Liu Yimin , Wu Guoxiong , Wang Lei , He Bian , Wang Xiaocong , Li Jiandong
Published: March 2019

We evaluate the ability of the latest generation atmospheric general circulation model from State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, Institute of Atmospheric Physics, Chinese Academy of Sciences (namely, FAMIL2) in simulating some key characteristics (genesis location, track, number, and intensity) of tropical cyclones (TCs) in terms of their climatology and seasonal to interannual variability. A standard 1° × 1° atmospheric model intercomparison project experiment is carried out for the period 1979–2002, and the last 20 years of outputs are used for analysis. The same period from International Best Track Archive for Climate Stewardship (IBTrACS) is used as the observation for comparison purposes. The evaluations focus on TC activity at the global scale as well as in the three key regions of the northern Indian Ocean (NIO), western Pacific (WP) and northern Atlantic (NA). With respect to the simulated TC climatology, FAMIL2 shows notable ability in correctly reproducing the main characteristics of the genesis locations, tracks, and numbers of TC, particularly over the key regions of TC activity in the Northern Hemisphere; whereas, it underestimates the intensities of TC, as is the case with many state‐of‐the‐art climate models operating at a medium resolution. On seasonal‐to‐interannual time scales, meanwhile, FAMIL2 successfully reproduces the seasonal cycles of TC numbers over the NIO and WP regions, the former being characterized by double TC peaks (in May and October) and the latter by a maximum peak season in August. However, the model only captures these features approximately. For the simulated interannual variability of TC activity, the correlation coefficients of 20‐year TC numbers between FAMIL2 and IBTrACS are 0.22, 0.51 (95% confidence interval), and 0.49 (95% confidence interval) for the NIO, WP, and NA, respectively. We also examine the possible reasons behind the performance of FAMIL2 by investigating its subseasonal signs related to the Madden‐Julian Oscillation (MJO) and convectively coupled equatorial waves. The TC genesis potential index is employed to investigate the possible impacts of the large‐scale dynamic fields on the simulation of TC activity. Finally, the biases of simulated TC activity, as well as possible solutions for these biases, are discussed with respect to the horizontal resolution of the model. A TC forecasting case study is introduced as a first step in applying FAMIL2 to a TC forecasting system.
Aerosol Mixing State: Measurements, Modeling, and Impacts
Authors: Riemer N. , Ault A. P. , West M. , Craig R. L. , Curtis J. H.
Published: March 2019

Atmospheric aerosols are complex mixtures of different chemical species, and individual particles exist in many different shapes and morphologies. Together, these characteristics contribute to the aerosol mixing state. This review provides an overview of measurement techniques to probe aerosol mixing state, discusses how aerosol mixing state is represented in atmospheric models at different scales, and synthesizes our knowledge of aerosol mixing state's impact on climate‐relevant properties, such as cloud condensation and ice nucleating particle concentrations, and aerosol optical properties. We present these findings within a framework that defines aerosol mixing state along with appropriate mixing state metrics to quantify it. Future research directions are identified, with a focus on the need for integrating mixing state measurements and modeling.
Shift Happens! Adjusting Stage‐Discharge Rating Curves to Morphological Changes at Known Times
Authors: Mansanarez V. , Renard B. , Coz J. Le , Lang M. , Darienzo M.
Published: March 2019

Establishing streamflow time series in unstable rivers is challenged by changes in the stage‐discharge relation after floods. Then, the field hydrologist must develop a new stage‐discharge rating curve using new calibration data but also using some information from previous calibration data and previous rating curves. The process includes a large amount of informal expert knowledge and hydraulic assumptions seldom made explicit. This paper develops a stage‐period‐discharge (SPD) model based on the physical interpretation of changes in the stage‐discharge relation across a series of stability periods defined by known dates and times. Using simple hydraulic equations, the user provides prior knowledge on the controls, their static and varying parameters, and their possible changes. As a single model is used for all the periods, the estimation of all rating curves can be performed in one go: All gaugings hence provide information to estimate the static parameters and the varying parameters for the relevant periods. Bayesian inference is used, providing a natural way to include prior knowledge and to quantify uncertainty. The generality and some key properties of the method are demonstrated through application to two hydrometric stations, differing in hydraulic configuration and in number and type of changes. Specific experiments demonstrate the ability of the SPD model to transfer information across periods. Consequently, rating curves are more precisely estimated than by separately estimating them for each period. The SPD model provides a hydraulically based, transparent, and user‐friendly approach to replace manual shift corrections traditionally applied in operational practice, with a quantification of uncertainties.
Quantification and Prediction of Nighttime Evapotranspiration for Two Distinct Grassland Ecosystems
Authors: Groh J. , Pütz T. , Gerke H. H. , Vanderborght J. , Vereecken H.
Published: March 2019

Evapotranspiration (ET) is, after precipitation, the second largest flux at the land surface in the water cycle and occurs mainly during daytime. Less attention has been given to water fluxes from the land surface into the atmosphere during nighttime (i.e., between sunset and sunrise). The nighttime ET (ETN) may be estimated based on models that use meteorological data; however, due to missing experimental long‐term data, the verification of ETN estimates is limited. In this paper, the amount of ETN for two grassland ecosystems was determined from highly temporally resolved and precise weighing lysimeter data. We found that annual ETN ranged between 3.5% and 9.5% of daytime annual ET (ETD) and occurred mainly during wet soil and canopy surface conditions, which suggests that ETN is largely related to evaporation. ETN was positively correlated with wind speed. Dew formation, ranging from 4.8% to 6.4% of annual precipitation, was in absolute terms larger than ETN. The prediction of ETN with the Penman‐Monteith model improved if the aerodynamic and surface resistance parameters were based on vegetation height observations and the nighttime stomatal resistance parameter was assumed to be zero. The occurrence of hot days during the observation period showed to increase average ETN rates. Our results suggest that ETN can be observed with precision weighing lysimeters, was a not negligible component in the water balance of the grassland ecosystems, and thus needs more attention when simulating land surface hydrological processes.
Luna B. Leopold: Geoscience Pioneer
Authors: Prestegaard Karen
Published: March 2019

He conducted river morphology research based on systematic and reproducible measurements, pushing fluvial hydrology to become a more quantitative science.
Circularly and elliptically polarized light under water and the Umov effect
Authors: Ding Yitian , Pau Stanley
Published: March 2019

Total internal reflection occurs when light is incident on the interface of high- and low-refractive-index materials at an angle greater than the critical angle. Sunlight with high degree of linear polarization, such as atmospheric scattered skylight, can be converted with a high efficiency up to 53% to circular and elliptical polarizations by total internal reflection under water in the region outside Snell’s window. The degree of circular polarization is observed to be inversely dependent on the albedo of underwater objects and is shown to be a direct consequence of the Umov effect. Our results are important for underwater polarimetry, surveillance applications and studies of marine animals’ polarized vision near the water-air interface.
Comparison of human isogeneic Wharton’s jelly MSCs and iPSC-derived MSCs reveals differentiation-dependent metabolic responses to IFNG stimulation
Authors: Devito Liani , Klontzas Michail E. , Cvoro Aleksandra , Galleu Antonio , Simon Marisa , Hobbs Carl , Dazzi Francesco , Mantalaris Athanasios , Khalaf Yacoub , Ilic Dusko
Published: March 2019

Variability among donors, non-standardized methods for isolation, and characterization contribute to mesenchymal stem/stromal cell (MSC) heterogeneity. Induced pluripotent stem cell (iPSCs)-derived MSCs would circumvent many of current issues and enable large-scale production of standardized cellular therapy. To explore differences between native MSCs (nMSCs) and iPSC-derived MSCs (iMSCs), we developed isogeneic lines from Wharton’s jelly (WJ) from the umbilical cords of two donors (#12 and #13) under xeno-free conditions. Next, we reprogrammed them into iPSCs (iPSC12 and iPSC13) and subsequently differentiated them back into iMSCs (iMSC12 and iMSC13) using two different protocols, which we named ARG and TEX. We assessed their differentiation capability, transcriptome, immunomodulatory potential, and interferon-γ (IFNG)-induced changes in metabolome. Our data demonstrated that although both differentiation protocols yield iMSCs similar to their parental nMSCs, there are substantial differences. The ARG protocol resulted in iMSCs with a strong immunomodulatory potential and lower plasticity and proliferation rate, whereas the TEX protocol raised iMSCs with a higher proliferation rate, better differentiation potential, though weak immunomodulatory response. Our data suggest that, following a careful selection and screening of donors, nMSCs from umbilical’s cord WJ can be easily reprogrammed into iPSCs, providing an unlimited source of material for differentiation into iMSCs. However, the differentiation protocol should be chosen depending on their clinical use.
DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental atrial fibrillation
Authors: Zhang Deli , Hu Xu , Li Jin , Liu Jia , Baks-te Bulte Luciënne , Wiersma Marit , Malik Noor-ul-Ann , van Marion Denise M. S. , Tolouee Marziyeh , Hoogstra-Berends Femke , Lanters Eva A. H. , van Roon Arie M. , de Vries Antoine A. F. , Pijnappels Daniël A. , de Groot Natasja M. S. , Henning Robert H. , Brundel Bianca J. J. M.
Published: March 2019

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD+), induces further DNA damage and contractile dysfunction. Accordingly, NAD+ replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD+ depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF.
A highly selective and recyclable NO-responsive nanochannel based on a spiroring opening−closing reaction strategy
Authors: Sun Yao , Chen Sen , Chen Xiaoya , Xu Yuling , Zhang Siyun , Ouyang Qingying , Yang Guangfu , Li Haibing
Published: March 2019

Endogenous nitric oxide (NO) is an important messenger molecule, which can directly activate K+ transmission and cause relaxation of vascular smooth muscle. Here, inspired by the K+ channel of smooth muscle cells, we report, a novel NO-regulated artificial nanochannel based on a spiro ring opening−closing reaction strategy. This nanofluidic diode system shows an outstanding NO selective response owing to the specific reaction between o-phenylenediamine (OPD) and NO on the channel surface with high ion rectification ratio (~6.7) and ion gating ratio (~4). Moreover, this NO gating system exhibits excellent reversibility and stability as well as high selectivity response. This system not only helps us understand the process of NO directly regulating biological ion channels, but also has potential application value in the field of biosensors.
A post-translational modification of human Norovirus capsid protein attenuates glycan binding
Authors: Mallagaray Alvaro , Creutznacher Robert , Dülfer Jasmin , Mayer Philipp H. O. , Grimm Lena Lisbeth , Orduña Jose Maria , Trabjerg Esben , Stehle Thilo , Rand Kasper D. , Blaum Bärbel S. , Uetrecht Charlotte , Peters Thomas
Published: March 2019

Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.
Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes
Authors: Wang Wei , Lin Liyuan , Du Yahui , Song Yanling , Peng Xiaoman , Chen Xing , Yang Chaoyong James
Published: March 2019

Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.
Mitochondrial origins of fractional control in regulated cell death
Authors: Santos Luís C. , Vogel Robert , Chipuk Jerry E. , Birtwistle Marc R. , Stolovitzky Gustavo , Meyer Pablo
Published: March 2019

Individual cells in clonal populations often respond differently to environmental changes; for binary phenotypes, such as cell death, this can be measured as a fractional response. These types of responses have been attributed to cell-intrinsic stochastic processes and variable abundances of biochemical constituents, such as proteins, but the influence of organelles is still under investigation. We use the response to TNF-related apoptosis inducing ligand (TRAIL) and a new statistical framework for determining parameter influence on cell-to-cell variability through the inference of variance explained, DEPICTIVE, to demonstrate that variable mitochondria abundance correlates with cell survival and determines the fractional cell death response. By quantitative data analysis and modeling we attribute this effect to variable effective concentrations at the mitochondria surface of the pro-apoptotic proteins Bax/Bak. Further, our study suggests that inhibitors of anti-apoptotic Bcl-2 family proteins, used in cancer treatment, may increase the diversity of cellular responses, enhancing resistance to treatment.
Large-scale network analysis reveals the sequence space architecture of antibody repertoires
Authors: Miho Enkelejda , Roškar Rok , Greiff Victor , Reddy Sai T.
Published: March 2019

The architecture of mouse and human antibody repertoires is defined by the sequence similarity networks of the clones that compose them. The major principles that define the architecture of antibody repertoires have remained largely unknown. Here, we establish a high-performance computing platform to construct large-scale networks from comprehensive human and murine antibody repertoire sequencing datasets (>100,000 unique sequences). Leveraging a network-based statistical framework, we identify three fundamental principles of antibody repertoire architecture: reproducibility, robustness and redundancy. Antibody repertoire networks are highly reproducible across individuals despite high antibody sequence dissimilarity. The architecture of antibody repertoires is robust to the removal of up to 50–90% of randomly selected clones, but fragile to the removal of public clones shared among individuals. Finally, repertoire architecture is intrinsically redundant. Our analysis provides guidelines for the large-scale network analysis of immune repertoires and may be used in the future to define disease-associated and synthetic repertoires.
The hammam effect or how a warm ocean enhances large scale atmospheric predictability
Authors: Faranda Davide , Alvarez-Castro M. Carmen , Messori Gabriele , Rodrigues David , Yiou Pascal
Published: March 2019

The atmosphere’s chaotic nature limits its short-term predictability. Furthermore, there is little knowledge on how the difficulty of forecasting weather may be affected by anthropogenic climate change. Here, we address this question by employing metrics issued from dynamical systems theory to describe the atmospheric circulation and infer the dynamical properties of the climate system. Specifically, we evaluate the changes in the sub-seasonal predictability of the large-scale atmospheric circulation over the North Atlantic for the historical period and under anthropogenic forcing, using centennial reanalyses and CMIP5 simulations. For the future period, most datasets point to an increase in the atmosphere’s predictability. AMIP simulations with 4K warmer oceans and 4 × atmospheric CO2 concentrations highlight the prominent role of a warmer ocean in driving this increase. We term this the hammam effect. Such effect is linked to enhanced zonal atmospheric patterns, which are more predictable than meridional configurations.
Dispersal homogenizes communities via immigration even at low rates in a simplified synthetic bacterial metacommunity
Authors: Fodelianakis Stilianos , Lorz Alexander , Valenzuela-Cuevas Adriana , Barozzi Alan , Booth Jenny Marie , Daffonchio Daniele
Published: March 2019

Selection and dispersal are ecological processes that have contrasting roles in the assembly of communities. Variable selection diversifies and strong dispersal homogenizes them. However, we do not know whether dispersal homogenizes communities directly via immigration or indirectly via weakening selection across habitats due to physical transfer of material, e.g., water mixing in aquatic ecosystems. Here we examine how dispersal homogenizes a simplified synthetic bacterial metacommunity, using a sequencing-independent approach based on flow cytometry and mathematical modeling. We show that dispersal homogenizes the metacommunity via immigration, not via weakening selection, and even when immigration is four times slower than growth. This finding challenges the current view that dispersal homogenizes communities only at high rates and explains why communities are homogeneous at small spatial scales. It also offers a benchmark for sequence-based studies in natural microbial communities where immigration rates can be inferred solely by using neutral models.
On the nature of “skeletal” biofilm patterns, “hidden” heterogeneity and the role of bubbles to reveal them
Authors: Greener Jesse
Published: March 2019

A short communication on the recent paper by Jang et al. discusses the role of “mushroom” structures and effects of nearly static bubbles on nascent biofilms.
Different adsorption-degradation behavior of methylene blue and Congo red in nanoceria/H2O2 system under alkaline conditions
Authors: Wei Xiaoshu , Wang Yi , Feng Yuqian , Xie Xiaomin , Li Xiaofeng , Yang Sen
Published: March 2019

The Fenton-like activity of nanoceria has attracted intensive attention for wastewater treatment in recent years. During the Fenton-like reaction, the adsorption of organic pollutants on catalyst surface plays a key role in their degradation. In this work, the adsorption-degradation of methylene blue (MB) and Congo red (CR) in nanoceria/H2O2 system was investigated under alkaline conditions. The MB exhibited weak adsorption on nanoceria surface via electrostatic attraction, while strong Lewis acid–base interactions between CR and cerium ions was observed. Moreover, the adsorption of MB was enhanced in the presence of H2O2 by the formation of surface peroxide species, but an adsorption competition existed between H2O2 and CR. With more Ce3+, CeO2 nanorods could degrade CR efficiently as Fenton-like catalyst. But the degradation of MB catalyzed by ceria was much lower than that of CR in the presence of H2O2.
Machine learning-powered antibiotics phenotypic drug discovery
Authors: Zoffmann Sannah , Vercruysse Maarten , Benmansour Fethallah , Maunz Andreas , Wolf Luise , Blum Marti Rita , Heckel Tobias , Ding Haiyuan , Truong Hoa Hue , Prummer Michael , Schmucki Roland , Mason Clive S. , Bradley Kenneth , Jacob Asha Ivy , Lerner Christian , Araujo del Rosario Andrea , Burcin Mark , Amrein Kurt E. , Prunotto Marco
Published: March 2019

Identification of novel antibiotics remains a major challenge for drug discovery. The present study explores use of phenotypic readouts beyond classical antibacterial growth inhibition adopting a combined multiparametric high content screening and genomic approach. Deployment of the semi-automated bacterial phenotypic fingerprint (BPF) profiling platform in conjunction with a machine learning-powered dataset analysis, effectively allowed us to narrow down, compare and predict compound mode of action (MoA). The method identifies weak antibacterial hits allowing full exploitation of low potency hits frequently discovered by routine antibacterial screening. We demonstrate that BPF classification tool can be successfully used to guide chemical structure activity relationship optimization, enabling antibiotic development and that this approach can be fruitfully applied across species. The BPF classification tool could be potentially applied in primary screening, effectively enabling identification of novel antibacterial compound hits and differentiating their MoA, hence widening the known antibacterial chemical space of existing pharmaceutical compound libraries. More generally, beyond the specific objective of the present work, the proposed approach could be profitably applied to a broader range of diseases amenable to phenotypic drug discovery.
Multi-Modal Haptic Feedback for Grip Force Reduction in Robotic Surgery
Authors: Abiri Ahmad , Pensa Jake , Tao Anna , Ma Ji , Juo Yen-Yi , Askari Syed J. , Bisley James , Rosen Jacob , Dutson Erik P. , Grundfest Warren S.
Published: March 2019

Minimally invasive robotic surgery allows for many advantages over traditional surgical procedures, but the loss of force feedback combined with a potential for strong grasping forces can result in excessive tissue damage. Single modality haptic feedback systems have been designed and tested in an attempt to diminish grasping forces, but the results still fall short of natural performance. A multi-modal pneumatic feedback system was designed to allow for tactile, kinesthetic, and vibrotactile feedback, with the aims of more closely imitating natural touch and further improving the effectiveness of HFS in robotic surgical applications and tasks such as tissue grasping and manipulation. Testing of the multi-modal system yielded very promising results with an average force reduction of nearly 50% between the no feedback and hybrid (tactile and kinesthetic) trials (p < 1.0E-16). The multi-modal system demonstrated an increased reduction over single modality feedback solutions and indicated that the system can help users achieve average grip forces closer to those normally possible with the human hand.
Interactions of newly synthesized platinum nanoparticles with ICR-191 and their potential application
Authors: Borowik Agnieszka , Banasiuk Rafal , Derewonko Natalia , Rychlowski Michal , Krychowiak-Masnicka Marta , Wyrzykowski Dariusz , Ziabka Magdalena , Woziwodzka Anna , Krolicka Aleksandra , Piosik Jacek
Published: March 2019

One of the greatest challenges of modern medicine is to find cheaper and easier ways to produce transporters for biologically active substances, which will provide selective and efficient drug delivery to the target cells, while causing low toxicity towards healthy cells. Currently, metal-based nanoparticles are considered a successful and viable solution to this problem. In this work, we propose the use of novel synthesis method of platinum nanoparticles (PtNPs) connected with their precise biophysical characterization and assessment of their potential toxicity. To work as an efficient nanodelivery platform, nanoparticles should interact with the desired active compounds spontaneously and non-covalently. We investigated possible direct interactions of PtNPs with ICR-191, a model acridine mutagen with well-established biophysical properties and mutagenic activity, by Dynamic Light Scattering, fluorescence spectroscopy, and Isothermal Titration Calorimetry. Moreover, to determine the biological activity of ICR-191-PtNPs aggregates, we employed Ames mutagenicity test, eukaryotic cell line analysis and toxicity test against the model organism Caenorhabditis elegans. PtNPs’ interesting physicochemical properties associated to the lack of toxicity in a tested range of concentrations, as well as their ability to modulate ICR-191 biological activity, suggest that these particles successfully work as potential delivery platforms for different biologically active substances.
Strain Engineering of Germanium Nanobeams by Electrostatic Actuation
Authors: Ayan Arman , Turkay Deniz , Unlu Buse , Naghinazhadahmadi Parisa , Oliaei Samad Nadimi Bavil , Boztug Cicek , Yerci Selcuk
Published: March 2019

Germanium (Ge) is a promising material for the development of a light source compatible with the silicon microfabrication technology, even though it is an indirect-bandgap material in its bulk form. Among various techniques suggested to boost the light emission efficiency of Ge, the strain induction is capable of providing the wavelength tunability if the strain is applied via an external force. Here, we introduce a method to control the amount of the axial strain, and therefore the emission wavelength, on a suspended Ge nanobeam by an applied voltage. We demonstrate, based on mechanical and electrical simulations, that axial strains over 4% can be achieved without experiencing any mechanical and/or electrical failure. We also show that the non-uniform strain distribution on the Ge nanobeam as a result of the applied voltage enhances light emission over 6 folds as compared to a Ge nanobeam with a uniform strain distribution. We anticipate that electrostatic actuation of Ge nanobeams provides a suitable platform for the realization of the on-chip tunable-wavelength infrared light sources that can be monolithically integrated on Si chips.
Demonstration of End-to-End Automation of DNA Data Storage
Authors: Takahashi Christopher N. , Nguyen Bichlien H. , Strauss Karin , Ceze Luis
Published: March 2019

Synthetic DNA has emerged as a novel substrate to encode computer data with the potential to be orders of magnitude denser than contemporary cutting edge techniques. However, even with the help of automated synthesis and sequencing devices, many intermediate steps still require expert laboratory technicians to execute. We have developed an automated end-to-end DNA data storage device to explore the challenges of automation within the constraints of this unique application. Our device encodes data into a DNA sequence, which is then written to a DNA oligonucleotide using a custom DNA synthesizer, pooled for liquid storage, and read using a nanopore sequencer and a novel, minimal preparation protocol. We demonstrate an automated 5-byte write, store, and read cycle with a modular design enabling expansion as new technology becomes available.
Unveiling the influence of device stiffness in single macromolecule unfolding
Authors: Florio G. , Puglisi G.
Published: March 2019

Single-molecule stretching experiments on DNA, RNA, and other biological macromolecules opened up the possibility of an impressive progress in many fields of life and medical sciences. The reliability of such experiments may be crucially limited by the possibility of determining the influence of the apparatus on the experimental outputs. Here we deduce a model that let us analytically evaluate such influence, fundamental for the interpretation of Single Molecule Force Spectroscopy experiments and intermolecular interactions phenomena. As we show, our model is coherent with previous numerical results and quantitively reproduce AFM experimental tests on titin macromolecules and P-selectin with variable probe stiffnesses.
In vitro micro-physiological model of the inflamed human adipose tissue for immune-metabolic analysis in type II diabetes
Authors: Kongsuphol Patthara , Gupta Shilpi , Liu Yunxiao , Bhuvanendran Nair Gourikutty Sajay , Biswas Subhra K. , Ramadan Qasem
Published: March 2019

Chronic inflammation mediated by the interaction of immune cells and adipocytes is a key underlying factor in obesity-associated type 2 diabetes mellitus (T2DM). Therefore, methods to investigate adipocyte-immune cells interaction and their immuno-metabolic status in obese/T2DM subjects not only serve as an early indicator of disease development but also provide an insight into disease mechanism. A microfluidic-basedin vitromodel of the human adipose that is interfaced with a co-culture of immune cell has been developed forin vitroimmune-metabolic analysis. This miniaturized system integrates a biologically activein vitrocellular system within a perfusion-based microfluidic device for mimicking the major processes that characterize the interaction of adipose tissue with immune cells. A viable immune competent model of the adipocytes/PBMCs co-culture has been demonstrated and characterized. Our testing results showed that the inflammatory cytokine profile obtained from the on-chip culture agrees with those from static transwell based co-culture with more intense responses observed in the chip-based system. The microfluidic chip also allows time-resolved measurement of cytokines that provide reliable data and detailed mechanisms of inflammation. In addition, glucose uptake by the adipocytes from the chip-based cultures showed correlated insulin responsivity/resistivity to the expression of the cytokine profile in different dynamic culture conditions. Testing of the known diabetic drug, metformin, and neutraceutical compound, omega-3, on-chip show agreeable results as compared to the previously reported data. This organotypic culture system offers a physiologically relevant model that exhibits a key characteristic of type 2 diabetic adipose tissues and can be used to study the T2DM mechanisms and diabetic drug screening.
Effect of planting patterns on yield, nutrient accumulation and distribution in maize and soybean under relay intercropping systems
Authors: Raza Muhammad Ali , Bin Khalid Muhammad Hayder , Zhang Xia , Feng Ling Yang , Khan Imran , Hassan Muhammad Jawad , Ahmed Mukhtar , Ansar Muhammad , Chen Yuan Kai , Fan Yuan Fang , Yang Feng , Yang Wenyu
Published: March 2019

Planting patterns affect nitrogen (N), phosphorus (P), and potassium (K) acquisition and distribution in maize and soybean under intercropping conditions. Here we reveal that strip relay-intercropping increases the N, P, and K uptake and distribution across plant organs (root, straw, and seed) of maize and soybean, accelerates the dry-matter production of intercrop-species, and compensates the slight maize yield loss by considerably increasing the soybean yield. In a two-year experiment, soybean was planted with maize in different planting patterns (SI, 50:50 cm and SII, 40:160 cm) of relay-intercropping, both planting patterns were compared with sole cropping of maize (SM) and soybean (SS). As compared to SI, SII increased the N, P, and K accumulation in each organ of soybean by 20, 32, and 18 (root) %, 71, 61, and 76 (straw) %, and 68, 65, and 62 (seed) %, respectively, whereas decreased the N, P, and K accumulation in each organ of maize by 1, 4, and 8 (root) %, 1, 10, and 3 (straw) %, and 5, 10, and 8 (seed) %, respectively. Overall, in SII, relay-cropped soybean accumulated 91% of total nutrient uptake (TNU) of sole soybean plants, and relay-cropped maize accumulated 94% of TNU of sole maize plants.
Symptom dimensions in people affected by long-term neurological conditions: a factor analysis of a patient-centred palliative care outcome symptom scale
Authors: Wilson Rebecca , Hepgul Nilay , Saha Romi A. , Higginson Irene J. , Gao Wei
Published: March 2019

Long-term neurological conditions (LTNCs) often cause debilitating symptoms. Better understanding of symptom dimensions in LTNCs is needed to support health professionals and improve care. This can be achieved by exploring the factor structure of a standardised measure of symptoms in LTNC patients. The symptom subscale of the Integrated Palliative Outcome Scale for LTNCs (IPOS Neuro-S24) comprises 24 items measuring symptom severity. Descriptive statistics and psychometric properties of the scale were assessed, followed by differential item functioning (DIF), exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Data from N = 238 patients were analysed. The mean IPOS Neuro S-24 score was 27.0 (possible range 0–96) and floor effects were found for 21 items. The scale had good internal consistency (Cronbach’s alpha = 0.77). Weak evidence of DIF was found for nine items. All but one item (falls) loaded onto four factors with loadings > 0.3. The factors represented four clinically meaningful symptom dimensions: fatigue, motor symptoms, oral problems and non-motor symptoms. We identified a reliable four-factor structure of symptom experience in LTNC patients. The results suggest that symptom dimensions are common across LTNCs. The IPOS Neuro S-24 is an appropriate tool to measure symptoms in LTNC patients, which may improve care.
Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis
Authors: Pandey Vimal , Ranjan Nikhil , Narne Parimala , Babu Phanithi Prakash
Published: March 2019

Gliomas are incurable solid tumors with extremely high relapse rate and definite mortality. As gliomas readily acquire resistance to only approved drug, temozolomide (TMZ), there is increasing need to overcome drug resistance by novel therapeutics or by repurposing the existing therapy. In the current study, we investigated antitumor efficacy of roscovitine, a Cdk inhibitor, in combination with TMZ in vitro (U87, U373, LN 18 and C6 cell lines) and in vivo (orthotopic glioma model in Wistar rats) glioma models. We observed that TMZ treatment following a pre-treatment with RSV significantly enhanced chemo-sensitivity and suppressed the growth of glioma cells by reducing Cdk-5 activity and simultaneous induction of autophagy and Caspase-3 mediated apoptosis. Additionally, reduced expression of Ki67, GFAP and markers of angiogenesis (CD31, VEGF) was observed in case of TMZ + RSV treatments. Also, presence of reactive astrocytes in peri-tumoral areas and in areas around blood vessels was completely diminished in TMZ + RSV treated brain sections. Taken together, results in the current study provide evidence that RSV in conjunction with TMZ restricts glioma growth, reduces angiogenesis and also eliminates reactive astrocytes thereby preventing the spread of glioma to adjacent healthy brain tissues and thus might be more potent therapeutic option for glioma.
Transmission patterns of HIV-1 non-R5 strains in Poland
Authors: Smoleń-Dzirba Joanna , Rosińska Magdalena , Kruszyński Piotr , Janiec Janusz , Cycoń Mariusz , Bratosiewicz-Wąsik Jolanta , Beniowski Marek , Bociąga-Jasik Monika , Jabłonowska Elżbieta , Szetela Bartosz , Wąsik Tomasz J.
Published: March 2019

HIV-1 env sequencing enables predictions of viral coreceptor tropism and phylogenetic investigations of transmission events. The aim of the study was to estimate the contribution of non-R5 strains to the viral spread in Poland. Partial proviral env sequences were retrieved from baseline blood samples of patients with newly diagnosed HIV-1 infection between 2008–2014, including 46 patients with recent HIV-1 infection (RHI), and 246 individuals with long-term infection (LTHI). These sequences were subjected to the genotypic coreceptor tropism predictions and phylogenetic analyses to identify transmission clusters. Overall, 27 clusters with 57 sequences (19.5%) were detected, including 15 sequences (26.3%) from patients with RHI. The proportion of non-R5 strains among all study participants was 23.3% (68/292), and was comparable between patients with RHI and LTHI (11/46, 23.9% vs 57/246, 23.2%; p = 1.000). All 11 patients with non-R5 strains and RHI were men having sex with men (MSM). Among these patients, 4 had viral sequences grouped within phylogenetic cluster with another sequence of non-R5 strain obtained from patient with LTHI, indicating potential acquisition of non-R5 HIV-1 for at least 4/46 (8.7%) patients with RHI. We were unable to confirm the contribution of patients with RHI to the forward transmission of non-R5 strains, but a relatively high proportion of non-R5 strains among them deserves attention due to the limited susceptibility to CCR5 antagonists.
New insights into the origin and evolution of α-amylase genes in green plants
Authors: Ju Liangliang , Pan Zhifen , Zhang Haili , Li Qiao , Liang Junjun , Deng Guangbing , Yu Maoqun , Long Hai
Published: March 2019

Gene duplication is a source of genetic materials and evolutionary changes, and has been associated with gene family expansion. Functional divergence of duplicated genes is strongly directed by natural selections such as organism diversification and novel feature acquisition. We show that, plant α-amylase gene family (AMY) is comprised of six subfamilies (AMY1-AMY6) that fell into two ancient phylogenetic lineages (AMY3 and AMY4). Both AMY1 and AMY2 are grass-specific and share a single-copy ancestor, which is derived from grass AMY3 genes that have undergone massive tandem and whole-genome duplications during evolution. Ancestral features of AMY4 and AMY5/AMY6 genes have been retained among four green algal sequences (Chrein_08.g362450, Vocart_0021s0194, Dusali_0430s00012 and Monegl_16464), suggesting a gene duplication event following Chlorophyceae diversification. The observed horizontal gene transfers between plant and bacterial AMYs, and chromosomal locations of AMY3 and AMY4 genes in the most ancestral green body (C. reinhardtii), provide evidences for the monophyletic origin of plant AMYs. Despite subfamily-specific sequence divergence driven by natural selections, the active site and SBS1 are well-conserved across different AMY isoforms. The differentiated electrostatic potentials and hydrogen bands-forming residue polymorphisms, further imply variable digestive abilities for a broad substrates in particular tissues or subcellular localizations.
Predictive Value of [18F]FDG PET/CT for Lymph Node Metastasis in Rectal Cancer
Authors: Kim Sung Hoon , Song Bong-Il , Kim Beong Woo , Kim Hae Won , Won Kyoung Sook , Bae Sung Uk , Jeong Woon Kyung , Baek Seong Kyu
Published: March 2019

[18F]Fluorodeoxyglucose ([18F]FDG) Positron emission tomography/computed tomography (PET/CT) is commonly used for rectal cancer staging, but improved diagnostic methods for nodal metastases are needed. We aimed to evaluate whether the combination model of the metabolic tumor volume of primary tumor (T_MTV) and maximum standardized uptake value of lymph node (N_SUVmax) on pretreatment [18F]FDG PET/CT could improve nodal metastases prediction in rectal cancer. We enrolled a total of 166 rectal cancer patients who underwent pretreatment [18F]FDG PET/CT and surgical resection without neoadjuvant treatment between January 2009 and August 2016. Visual and semiquantitative PET/CT parameters were obtained. Associations between clinicopathological, PET/CT-derived variables and nodal metastases were evaluated by logistic regression analysis. Nodal metastases were confirmed histologically in 68 of the 166 patients (41%). Uni- and multivariate analyses demonstrated T_MTV and N_SUVmax were independent predictive factors for nodal metastases. The c-statistics of the combination model was 0.806 (Standard Error, 0.034; 95% Confidence Interval, 0.737–0.863), which showed significant improvement compared to T_MTV (0.698, P = 0.0002) or N_SUVmax (0.720, P = 0.0008) alone. T_MTV and N_SUVmax are independently correlated with nodal metastases. Furthermore, the combination model showed improved performance for risk prediction; thus, [18F]FDG PET/CT might have a role in rectal cancer staging and treatment planning.
Fully fledged enantiornithine hatchling revealed by Laser-Stimulated Fluorescence supports precocial nesting behavior
Authors: Kaye Thomas G. , Pittman Michael , Marugán-Lobón Jesús , Martín-Abad Hugo , Sanz José Luis , Buscalioni Angela D.
Published: March 2019

Laser-Stimulated Fluorescence (LSF) is used to identify fully fledged feathering in the hatchling enantiornithine bird specimen MPCM-LH-26189, supporting precocial nesting behavior in this extinct group. The LSF results include the detection of a long pennaceous wing feather as well as cover feathers around the body. The LSF technique showed improved detection limits over and above synchrotron and UV imaging which had both been performed on this specimen. The findings underscore the value of using a wide range of analytical techniques.
Caveolin 1 is Associated with Upregulated Claudin 2 in Necrotizing Enterocolitis
Authors: Ares Guillermo , Buonpane Christie , Sincavage John , Yuan Carrie , Wood Douglas R. , Hunter Catherine J.
Published: March 2019

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency of neonates. Epithelial tight junction (TJ) proteins, such as claudins, are essential for regulation and function of the intestinal barrier. Rho kinase (ROCK) affects cellular permeability and TJ regulation. We hypothesized that TJ protein changes would correlate with increased permeability in experimental NEC, and ROCK inhibitors would be protective against NEC by regulation of key claudin proteins. We tested this hypothesis using an in vivo rat pup model, an in vitro model of experimental NEC, and human intestinal samples from patients with and without NEC. Experimental NEC was induced in rats via hypoxia and bacteria-containing formula, and in Caco-2 cells by media inoculated with LPS. The expression of claudins was measured by gene and protein analysis. Experimental NEC in rat pups and Caco-2 cells had increased permeability compared to controls. Gene and protein expression of claudin 2 was increased in experimental NEC. Sub-cellular fractionation localized increased claudin 2 protein to the cytoskeleton. ROCK inhibition was associated with normalization of these alterations and decreased severity of experimental NEC. Co-immunoprecipitation of caveolin-1 with claudin 2 suggests that caveolin-1 may act as a shuttle for the internalization of claudin 2 seen in experimental NEC. In conclusion, NEC is associated with intestinal permeability and increased expression of claudin 2, increased binding of caveolin-1 and claudin 2, and increased trafficking of claudin 2 to the cytoskeleton.
Clock advance and magnitude limitation through fault interaction: the case of the 2016 central Italy earthquake sequence
Authors: Pino Nicola Alessandro , Convertito Vincenzo , Madariaga Raul
Published: March 2019

Faults communicate with each other. Strong earthquakes perturb stress over large volumes modifying the load on nearby faults and their resistance to slip. The causative fault induces permanent or transient perturbations that can change the time to the next seismic rupture with respect to that expected for a steadily accumulating stress. For a given fault, an increase of stress or a strength decrease would drive it closer to - or maybe even trigger - an earthquake. This is usually perceived as an undesired circumstance. However, with respect to the potential damage, a time advance might not necessarily be a bad thing. Here we show that the central Italy seismic sequence starting with the Amatrice earthquake on 24 August 2016 advanced the 30 October Norcia earthquake (MW = 6.5), but limited its magnitude by inhibiting the rupture on large portions of the fault plane. The preceding events hastened the mainshock and determined its features by shaping a patch of concentrated stress. During the Norcia earthquake, the coseismic slip remained substantially confined to this patch. Our results demonstrate that monitoring the seismicity with very dense networks and timely analyses can make it feasible to map rupture prone areas.
Automated identification of flagella from videomicroscopy via the medial axis transform
Authors: Walker Benjamin J. , Ishimoto Kenta , Wheeler Richard J.
Published: March 2019

Ubiquitous in eukaryotic organisms, the flagellum is a well-studied organelle that is well-known to be responsible for motility in a variety of organisms. Commonly necessitated in their study is the capability to image and subsequently track the movement of one or more flagella using videomicroscopy, requiring digital isolation and location of the flagellum within a sequence of frames. Such a process in general currently requires some researcher input, providing some manual estimate or reliance on an experiment-specific heuristic to correctly identify and track the motion of a flagellum. Here we present a fully-automated method of flagellum identification from videomicroscopy based on the fact that the flagella are of approximately constant width when viewed by microscopy. We demonstrate the effectiveness of the algorithm by application to captured videomicroscopy of Leishmania mexicana, a parasitic monoflagellate of the family Trypanosomatidae. ImageJ Macros for flagellar identification are provided, and high accuracy and remarkable throughput are achieved via this unsupervised method, obtaining results comparable in quality to previous studies of closely-related species but achieved without the need for precursory measurements or the development of a specialised heuristic, enabling in general the automated generation of digitised kinematic descriptions of flagellar beating from videomicroscopy.