bluuebunny/crossref_metadata_2025 huggingface dataset:
Change in IQ in schizophrenia patients and their siblings: a controlled longitudinal study
Authors: Van Haren N. E. M. , Van Dam D. S. , Stellato R. K. ,   Genetic Risk and Outcome of Psychosis (GROUP) investigators
Published: January 2019

Background

Lower intelligence quotient (IQ) has frequently been reported in patients with schizophrenia. However, it is unclear whether IQ declines (further) after illness onset and what the familial contribution is to this change. Therefore, we investigate IQ changes during the course of illness in patients with non-affective psychosis, their siblings and controls.

Methods

Data are part of the longitudinal Genetic Risk and Outcome of Psychosis (GROUP) study in the Netherlands and Belgium. Participants underwent three measurements, each approximately 3 years apart. A total of 1022 patients with non-affective psychosis [illness duration: 4.34 (s.d.= 4.50) years], 977 of their siblings, and 565 controls had at least one measure of IQ (estimated from four subtests of the WAIS-III).

Results

At baseline, IQ was significantly lower in patients (IQ = 97.8) and siblings (IQ = 108.2;p< 0.0001) than in controls (IQ = 113.0;p< 0.0001), and in patients as compared with siblings (p< 0.0001). Over time, IQ increased in all groups. In siblings, improvement in IQ was significantly more pronounced (+0.7 points/year) than in patients (+0.5 points/year;p< 0.0001) and controls (+0.3 points/year;p< 0.0001). IQ increase was not significantly correlated with improvement in (sub)clinical outcome in any of the groups.

Conclusions

During the first 10 years of the illness, IQ increases to a similar (and subtle) extent in a relatively high-functioning group of schizophrenia patients and controls, despite the lower IQ in patients at baseline. In addition, the siblings’ IQ was intermediate at baseline, but over time the increase in IQ was more pronounced.
Modeling Population Dynamics of Kochia (Bassia scoparia) in Response to Diverse Weed Control Options
Authors: Osipitan O. Adewale , Dille J. Anita , Bagavathiannan Muthukumar V. , Knezevic Stevan Z.
Published: January 2019

Kochia [Bassia scoparia(L.) A. J. Scott] is a problematic weed species across the Great Plains, as it is spreading fast and has developed herbicide-resistant biotypes. It is imperative to understand key life-history stages that promote population expansion ofB. scopariaand control strategies that would provide effective control of these key stages, thereby reducing population growth. Diversifying weed control strategies has been widely recommended for the management of herbicide-resistant weeds. Therefore, the objectives of this study were to develop a simulation model to assess the population dynamics ofB. scopariaand to evaluate the effectiveness of diverse weed control strategies on long-term growth rates ofB. scopariapopulations. The model assumed the existence of a glyphosate-resistant (GR) biotype in theB. scopariapopulation, but at a very low proportion in a crop rotation that included glyphosate-tolerant corn (Zea maysL.) and soybean [Glycine max(L.) Merr.]. The parameter estimates used in the model were obtained from various ecological and management studies onB. scoparia. Model simulations indicated that seedling recruitment and survival to seed production were more important than seedbank persistence forB. scopariapopulation growth rate. Results showed that a diversified management program, including glyphosate, could provide excellent control ofB. scopariapopulations and potentially eliminate already evolved GRB. scopariabiotypes within a given location. The most successful scenario was a diverse control strategy that included one or two preplant tillage operations followed by preplant or PRE application of herbicides with residual activities and POST application of glyphosate; this strategy reduced seedling recruitment, survival, and seed production during the growing season, with tremendous negative impacts on long-term population growth and resistance risk inB. scoparia.
Naturwissenschaftliche Einstellungen angehender pädagogischer Fachkräfte
Authors: Drexl Doris , Born-Rauchenecker Eva , Kalicki Bernhard
Published: January 2019

Zusammenfassung. Im Projekt LuPE wurde ein Unterrichtskonzept für den Fachschulunterricht entwickelt, welches angehende pädagogische Fachkräfte zu einer alltagsintegrierten naturwissenschaftlichen Bildungsbegleitung im Kindergarten befähigen soll. Deren Einstellungen und motivationale Orientierungen zu Naturwissenschaften entscheiden häufig über die Qualität von Bildungsprozessen und müssen für die Unterrichtskonzeptentwicklung berücksichtigt werden. In vorliegender Arbeit werden die Ergebnisse der Einstellungsbefragung bei angehenden Fachkräften zu Naturwissenschaften referiert, die im Rahmen der formativen Evaluation durchgeführt wurde. Anhand einer Stichprobe von 198 Fachschülerinnen und Fachschülern (m = 43; w = 155) wurden das naturwissenschaftliche und didaktische Selbstkonzept sowie das Interesse an Naturwissenschaften im Zusammenhang mit Personenmerkmalen (Geschlecht, Alter, Schulabschluss) untersucht und mögliche Änderungen der Einstellungen im Verlauf eines Schuljahres mit LuPE-Unterricht geprüft (Erhebungszeitpunkte: T1 = 2015, T2 = 2016). Es zeigt sich ein eher geringes Interesse an Naturwissenschaften sowie ein eher geringes naturwissenschaftliches Selbstkonzept, wobei sich Fachschülerinnen noch schlechter einschätzen als Fachschüler. Das Selbstkonzept elementarspezifisches naturwissenschaftliches Wissen und das naturwissenschaftliche Selbstkonzept wird 2016 höher eingeschätzt als 2015.
Fully Developed Superrotation Driven by the Mean Meridional Circulation in a Venus GCM
Authors: Sugimoto Norihiko , Takagi Masahiro , Matsuda Yoshihisa
Published: January 2019

Fully developed superrotation is reproduced for the first time in very long term simulations with a dynamical Venus general circulation model (GCM) driven by a zonally averaged component of the realistic solar heating only. Starting from a motionless state with temperature distribution including a low static stability layer in the lower cloud layer, the fast superrotating zonal flow of ~100 m/s is established after 500 Earth years. In this experiment, the mean meridional circulation is responsible for generating the superrotation, because effects of thermal tides, topography, radiation process, and cloud physics are excluded in the present simulations. Sensitivity experiments indicate that the vertical eddy viscosity smaller than 0.02 m2/s is necessary for the fast superrotation to appear. The low static stability layer also strongly affects the superrotation with high‐latitude jets through angular momentum transport by baroclinic/barotropic instability in the cloud layer.
Evaluating Simulations of Interhemispheric Transport: Interhemispheric Exchange Time Versus SF6 Age
Authors: Yang Huang , Waugh Darryn W. , Orbe Clara , Patra Prabir K. , Jöckel Patrick , Lamarque Jean‐Francois , Tilmes Simone , Kinnison Douglas , Elkins James W. , Dlugokencky Edward J.
Published: January 2019

Two recent studies using sulfur hexafluoride (SF6) observations to evaluate interhemispheric transport in two different ensembles of atmospheric chemistry models reached different conclusions on model performance. We show here that the different conclusions are due to the use of different metrics and not differences in the performance of the models. For both model ensembles, the multimodel mean interhemispheric exchange time τex agrees well with observations, but in nearly all models the SF6 age in the southern hemisphere is older than observed. This occurs because transport from the northern extratropics into the tropics is too slow in most models, and the SF6 age is more sensitive to this bias than τex. Thus, simulating τex correctly does not necessarily mean that transport from northern midlatitudes into the southern hemisphere is correct. It also suggests that more attention needs to be paid to evaluating transport from northern midlatitudes into the tropics.
Dynamics of Surface‐Water Connectivity in a Low‐Gradient Meandering River Floodplain
Authors: Czuba Jonathan A. , David Scott R. , Edmonds Douglas A. , Ward Adam S.
Published: January 2019

High‐resolution topography reveals that floodplains along meandering rivers in Indiana commonly contain intermittently flowing channel networks. We investigated how the presence of floodplain channels affects lateral surface‐water connectivity between a river and floodplain (specifically exchange flux and timescales of transport) as a function of flow stage in a low‐gradient river‐floodplain system. We constructed a two‐dimensional, surface‐water hydrodynamic model using Hydrologic Engineering Center's River Analysis System (HEC‐RAS) 2D along 32 km of floodplain (56 km along the river) of the East Fork White River near Seymour, Indiana, USA, using lidar elevation data and surveyed river bathymetry. The model was calibrated using land‐cover specific roughness to elevation‐discharge data from a U.S. Geological Survey gage and validated against high‐water marks, an aerial photo showing the spatial extent of floodplain inundation, and measured flow velocities. Using the model results, we analyzed the flow in the river, spatial patterns of inundation, flow pathways, river‐floodplain exchange, and water residence time on the floodplain. Our results highlight that bankfull flow is an oversimplified concept for explaining river‐floodplain connectivity because some stream banks are overtopped and major low‐lying floodplain channels are inundated roughly 19 days per year. As flow increased, inundation of floodplain channels at higher elevations dissected the floodplain, until the floodplain channels became fully inundated. Additionally, we found that river‐floodplain exchange was driven by bank height or channel orientation depending on flow conditions. We propose a conceptual model of river‐floodplain connectivity dynamics and developed metrics to analyze quantitatively complex river‐floodplain systems.
Predicting Wave‐Induced Sediment Resuspension at the Perimeter of Lakes Using a Steady‐State Spectral Wave Model
Authors: Roberts D. C. , Moreno‐Casas P. , Bombardelli F. A. , Hook S. J. , Hargreaves B. R. , Schladow S. G.
Published: January 2019

A steady‐state spectral wave model, STWAVE, is evaluated as a tool for predicting wave‐induced sediment resuspension in lake littoral zones. Steady‐state wave height and bed‐shear stress estimates are tested against 2 years of high‐frequency wave height and turbidity data from six littoral measurement stations in Lake Tahoe. Average wave and sediment resuspension response to a broad range of wind conditions are well captured by the model. Despite steady‐state assumptions, the model reproduces patterns in wave height and sediment resuspension under time‐varying wind conditions at sites with different wave exposure. Model results are insensitive to the measurement location of wind data input among six offshore meteorological buoys. Uniform and variable wind field assumptions yield similar resuspension predictions. Results representing the steady‐state response to spatially uniform wind speed‐direction combinations enable output from a single set of model runs to serve as a reasonable static reference for hindcasting and predicting wave resuspension patterns. This obviates the need for repeated model runs, making STWAVE output an efficient tool for exploring long‐term spatio‐temporal patterns in nearshore wave forcing. Application of this tool is limited by wave height overprediction for short fetches and presumably by the validity of uniform wind field assumptions over very long fetches. Applied successfully at Lake Tahoe, we find that the north and east shores, exposed to the prevailing southwesterly winds, see resuspension conditions upward of 3,000 hr/year, while the south and west shores typically see less than 500. Location‐specific resuspension hours can vary by upward of ±200 hr/year due to shifting interannual wind patterns.
Estimation of Surface Soil Moisture With Downscaled Land Surface Temperatures Using a Data Fusion Approach for Heterogeneous Agricultural Land
Authors: Bai Liangliang , Long Di , Yan La
Published: January 2019

Field‐scale surface soil moisture (SSM, 0–10 cm), which is closely linked with land surface temperature (LST), is particularly important to agricultural water resource management. Active and passive microwave remote sensing‐based SSM retrievals on the order of kilometer squared resolutions are difficult to apply to heterogeneous agricultural land surfaces that may need SSM data at a resolution of 30 m. In this study, the High‐resolution Urban Thermal Sharpener and Enhanced Spatial and Temporal Adaptive Reflectance Fusion Model were applied to downscale optical and thermal remote sensing data simultaneously by blending Landsat and MODIS red‐near infrared‐LST data, with the ultimate goal to generate field‐scale SSM values from the trapezoidal approach. To evaluate the performance of the downscaled LSTE (based on the Enhanced Spatial and Temporal Adaptive Reflectance Fusion Model method) and SSM, an irrigation district (Area 1) in Inner Mongolia and an irrigation district in the North China Plain (Area 2) with varying spatial heterogeneity were selected as the testbeds. Results indicated that the downscaled LSTE was highly consistent with synchronous Landsat LSTH and in situ LST measurements in Area 1, with the root‐mean‐square error ranging from 0.73 to 2.75 K. Compared with the MODIS SSM, the average root‐mean‐square error of the downscaled SSM improved from 0.048 to 0.038 cm3/cm3 for both areas. The downscaled LSTE and SSM developed in this study enhance the spatiotemporal resolutions of the SSM estimates, maximizing the potential of remotely sensed information for agricultural water resource management.
The risks of HCV infection among Brazilian crack cocaine users: incorporating diagnostic test uncertainty
Authors: Coutinho Carolina , Bastos Leonardo S. , da Mota Jurema Corrêa , Toledo Lidiane , Costa Katia , Bertoni Neilane , Bastos Francisco I.
Published: January 2019

Despite the initiative by WHO and other international organizations to eliminate HCV in the medium term, hepatitis C infection is still a major public health problem. Even non-injecting drugs users who engage in harmful or addictive drug use are at greater risk of acquiring the infection, when compared to the general population. This study evaluate risk factors for HCV infection in users of crack/cocaine in Brazil, using multilevel models that incorporate variations in the sensitivity and specificity of the respective diagnostic tests. The sample included all the participants of a national survey on street crack cocaine users with serologically reactive result in the rapid test for the HCV as well as 4 non-reactive controls, matched by sex, age category, and major geographic region of residence. Multilevel logistic regression models were used, with and without incorporation of the diagnostic test’s sensitivity and specificity values. The odds of HCV infection were 85% higher among polydrug users, 7.81 times higher among injecting drug users, and 3.69 times higher in those reporting to have genital ulcers. Statistical modeling strategies that incorporate the sensitivity and specificity of diagnostic tests in challenging settings are useful for studying the association between risk factors and infection status.
Unique Spin Vortices and Topological Charges in Quantum Dots with Spin-orbit Couplings
Authors: Luo Wenchen , Naseri Amin , Sirker Jesko , Chakraborty Tapash
Published: January 2019

Spin textures of one or two electrons in a quantum dot with Rashba or Dresselhaus spin-orbit couplings reveal several intriguing properties. We show here that even at the single-electron level stable spin vortices with tunable topological charges exist. These topological textures appear in the ground state of the dots. The textures are stabilized by time-reversal symmetry breaking and are robust against the eccentricity of the dot. The topological charge is directly related to the sign of the z component of the spin in a large dot, allowing a direct probe of its topological properties. This would clearly pave the way to possible future topological spintronics. The phenomenon of spin vortices persists for the interacting two-electron dot in the presence of a magnetic field.
Intrinsic and extrinsic noise of gene expression in lineage trees
Authors: Thomas Philipp
Published: January 2019

Cell-to-cell heterogeneity is driven by stochasticity in intracellular reactions and the population dynamics. While these sources are usually studied separately, we develop an agent-based framework that accounts for both factors while tracking every single cell of a growing population. Apart from the common intrinsic variability, the framework also predicts extrinsic noise without the need to introduce fluctuating rate constants. Instead, extrinsic fluctuations are explained by cell cycle fluctuations and differences in cell age. We provide explicit formulas to quantify mean molecule numbers, intrinsic and extrinsic noise statistics in two-colour experiments. We find that these statistics differ significantly depending on the experimental setup used to observe the cells. We illustrate this fact using (i) averages over an isolated cell lineage tracked over many generations as observed in the mother machine, (ii) population snapshots with known cell ages as recorded in time-lapse microscopy, and (iii) snapshots with unknown cell ages as measured from static images or flow cytometry. Applying the method to models of stochastic gene expression and feedback regulation elucidates that isolated lineages, as compared to snapshot data, can significantly overestimate the mean number of molecules, overestimate extrinsic noise but underestimate intrinsic noise and have qualitatively different sensitivities to cell cycle fluctuations.
Phase controlled SERS enhancement
Authors: Zheng Yuanhui , Rosa Lorenzo , Thai Thibaut , Ng Soon Hock , Juodkazis Saulius , Bach Udo
Published: January 2019

Surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Several studies have shown that SERS intensities are significantly increased when an optical interference substrate composed of a dielectric spacer and a reflector is used as a supporting substrate. However, the origin of this additional enhancement has not been systematically studied. In this paper, high sensitivity SERS substrates composed of self-assembled core-satellite nanostructures and silica-coated silicon interference layers have been developed. Their SERS enhancement is shown to be a function of the thickness of silica spacer on a more reflective silicon substrate. Finite difference time domain modeling is presented to show that the SERS enhancement is due to a spacer contribution via a sign change of the reflection coefficients at the interfaces. The magnitude of the local-field enhancement is defined by the interference of light reflected from the silica-air and silica-silicon interfaces, which constructively added at the hot spots providing a possibility to maximize intensity in the nanogaps between the self-assembled nanoparticles by changing the thickness of silica layer. The core-satellite assemblies on a 135 nm silica-coated silicon substrate exhibit a SERS activity of approximately 13 times higher than the glass substrate.
Enhanced Bell state measurement for efficient measurement-device-independent quantum key distribution using 3-dimensional quantum states
Authors: Jo Yonggi , Bae Kwangil , Son Wonmin
Published: January 2019

We propose an enhanced discrimination measurement for tripartite 3-dimensional entangled states in order to improve the discernible number of orthogonal entangled states. The scheme suggests 3-dimensional Bell state measurement by exploiting composite two 3-dimensional state measurement setups. The setup relies on state-of-the-art techniques, a multi-port interferometer and nondestructive photon number measurements that are used for the post-selection of suitable ensembles. With this scheme, the sifted signal rate of measurement-device-independent quantum key distribution using 3-dimensional quantum states is improved by up to a factor of three compared with that of the best existing setup.
Terrestrial locomotion energy costs vary considerably between species: no evidence that this is explained by rate of leg force production or ecology
Authors: Halsey Lewis G. , White Craig R.
Published: January 2019

Inter-specifically, relative energy costs of terrestrial transport vary several-fold. Many pair-wise differences of locomotor costs between similarly-sized species are considerable, and are yet to be explained by morphology or gait kinematics. Foot contact time, a proxy for rate of force production, is a strong predictor of locomotor energy costs across species of different size and might predict variability between similarly sized species. We tested for a relationship between foot contact time and metabolic rate during locomotion from published data. We investigated the phylogenetic correlation between energy expenditure rate and foot contact time, conditioned on fixed effects of mass and speed. Foot contact time does not explain variance in rate of energy expenditure during locomotion, once speed and body size are accounted for. Thus, perhaps surprisingly, inter-specific differences in the mass-independent net cost of terrestrial transport (NCOT) are not explained by rates of force production. We also tested for relationships between locomotor energy costs and eco-physiological variables. NCOT did not relate to any of the tested eco-physiological variables; we thus conclude either that interspecific differences in transport cost have no influence on macroecological and macrophysiological patterns, or that NCOT is a poor indicator of animal energy expenditure beyond the treadmill.
Simulating the NaK Eutectic Alloy with Monte Carlo and Machine Learning
Authors: Reitz Douglas M. , Blaisten-Barojas Estela
Published: January 2019

Combining atomistic simulations and machine learning techniques can expedite significantly the materials discovery process. We present an application of such methodological combination for the prediction of the melting transition and amorphous-solid behavior of the NaK alloy at the eutectic concentration. We show that efficient prediction of these properties is possible via machine learning methods trained on the topological local structural properties. The configurations resulting from Monte Carlo annealing of the NaK eutectic alloy are analyzed with topological attributes based on the Voronoi tessellation and using expectation-maximization clustering and Random Forest classification. We show that the Voronoi topological fingerprints make an accurate and fast prediction of the alloy thermal behavior by cataloguing the atomic configurations into three distinct phases: liquid, amorphous solid, and crystalline solid. Melting is found at 230 K by the sharp split of configurations classified as crystalline solid and as liquid. With the proposed metrics, an arrest-motion temperature is identified at 130–140 K through a top down clustering of the atomic configurations catalogued as amorphous solid. This statistical learning paradigm is not restricted to eutectic alloys or thermodynamics, extends the utility of topological attributes in a significant way, and harnesses the discovery of new material properties.
Directional sub-femtosecond charge transfer dynamics and the dimensionality of 1T-TaS2
Authors: Kühn Danilo , Müller Moritz , Sorgenfrei Florian , Giangrisostomi Erika , Jay Raphael M. , Ovsyannikov Ruslan , Mårtensson Nils , Sánchez-Portal Daniel , Föhlisch Alexander
Published: January 2019

For the layered transition metal dichalcogenide 1T-TaS2, we establish through a unique experimental approach and density functional theory, how ultrafast charge transfer in 1T-TaS2 takes on isotropic three-dimensional character or anisotropic two-dimensional character, depending on the commensurability of the charge density wave phases of 1T-TaS2. The X-ray spectroscopic core-hole-clock method prepares selectively in- and out-of-plane polarized sulfur 3p orbital occupation with respect to the 1T-TaS2 planes and monitors sub-femtosecond wave packet delocalization. Despite being a prototypical two-dimensional material, isotropic three-dimensional charge transfer is found in the commensurate charge density wave phase (CCDW), indicating strong coupling between layers. In contrast, anisotropic two-dimensional charge transfer occurs for the nearly commensurate phase (NCDW). In direct comparison, theory shows that interlayer interaction in the CCDW phase – not layer stacking variations – causes isotropic three-dimensional charge transfer. This is presumably a general mechanism for phase transitions and tailored properties of dichalcogenides with charge density waves.
EnABLe: An agent-based model to understand Listeria dynamics in food processing facilities
Authors: Zoellner Claire , Jennings Rachel , Wiedmann Martin , Ivanek Renata
Published: January 2019

Detection of pathogens in food processing facilities by routine environmental monitoring (EM) is essential to reduce the risk of foodborne illness but is complicated by the complexity of equipment and environment surfaces. To optimize design of EM programs, we developed EnABLe (“Environmental monitoring with an Agent-Based Model of Listeria”), a detailed and customizable agent-based simulation of a built environment. EnABLe is presented here in a model system, tracing Listeria spp. (LS) (an indicator for conditions that allow the presence of the foodborne pathogen Listeria monocytogenes) on equipment and environment surfaces in a cold-smoked salmon facility. EnABLe was parameterized by existing literature and expert elicitation and validated with historical data. Simulations revealed different contamination dynamics and risks among equipment surfaces in terms of the presence, level and persistence of LS. Grouping of surfaces by their LS contamination dynamics identified connectivity and sanitary design as predictors of contamination, indicating that these features should be considered in the design of EM programs to detect LS. The EnABLe modeling approach is particularly timely for the frozen food industry, seeking science-based recommendations for EM, and may also be relevant to other complex environments where pathogen contamination presents risks for direct or indirect human exposure.
ENOblock inhibits the pathology of diet-induced obesity
Authors: Cho Haaglim , Lee Ji-Hyung , Um JungIn , Kim Sunwook , Kim Yukyung , Kim Woong-Hee , Kim Yong Sook , Pagire Haushabhau S. , Ahn Jin Hee , Ahn Youngkeun , Chang Young-Tae , Jung Da-Woon , Williams Darren R.
Published: January 2019

Obesity is a medical condition that impacts on all levels of society and causes numerous comorbidities, such as diabetes, cardiovascular disease, and cancer. We assessed the suitability of targeting enolase, a glycolysis pathway enzyme with multiple, secondary functions in cells, to treat obesity. Treating adipocytes with ENOblock, a novel modulator of these secondary ‘moonlighting’ functions of enolase, suppressed the adipogenic program and induced mitochondrial uncoupling. Obese animals treated with ENOblock showed a reduction in body weight and increased core body temperature. Metabolic and inflammatory parameters were improved in the liver, adipose tissue and hippocampus. The mechanism of ENOblock was identified as transcriptional repression of master regulators of lipid homeostasis (Srebp-1a and Srebp-1c), gluconeogenesis (Pck-1) and inflammation (Tnf-α and Il-6). ENOblock treatment also reduced body weight gain, lowered cumulative food intake and increased fecal lipid content in mice fed a high fat diet. Our results support the further drug development of ENOblock as a therapeutic for obesity and suggest enolase as a new target for this disorder.
A panel of eGFP reporters for single base editing by APOBEC-Cas9 editosome complexes
Authors: Martin A. St. , Salamango D. J. , Serebrenik A. A. , Shaban N. M. , Brown W. L. , Harris R. S.
Published: January 2019

The prospect of introducing a single C-to-T change at a specific genomic location has become feasible with APOBEC-Cas9 editing technologies. We present a panel of eGFP reporters for quantification and optimization of single base editing by APOBEC-Cas9 editosomes. Reporter utility is demonstrated by comparing activities of seven human APOBEC3 enzymes and rat APOBEC1 (BE3). APOBEC3A and RNA binding-defective variants of APOBEC3B and APOBEC3H display the highest single base editing efficiencies. APOBEC3B catalytic domain complexes also elicit the lowest frequencies of adjacent off-target events. However, unbiased deep-sequencing of edited reporters shows that all editosomes have some degree of local off-target editing. Thus, further optimization is required to generate true single base editors and the eGFP reporters described here have the potential to facilitate this process.
Multi-photon ionisation spectroscopy for rotational state preparation of $${{\bf{N}}}_{{\bf{2}}}^{{\boldsymbol{+}}}$$
Authors: Gardner Amy , Softley Timothy , Keller Matthias
Published: January 2019

In this paper we investigate the 2 + 1′ resonance enhanced multi-photon ionisation (REMPI) of molecular nitrogen via the a1Πg(v = 6) intermediate state and analyse its feasibility to generate molecular nitrogen ions in a well defined ro-vibrational state. This is an important tool for high precision experiments based on trapped molecular ions, and is crucial for studying the time variation of the fundamental constant mp/me using $${{\rm{N}}}_{2}^{+}$$

N

2

+

. The transition is not reported in the literature and detailed spectral analysis has been conducted to extract the molecular constants of the intermediate state. By carefully choosing the intermediate ro-vibrational state, the ionisation laser wavelength and controlling the excitation laser pulse energy, unwanted formation of rotationally excited molecular ions can be suppressed and ro-vibrational ground state ions can be generated with high purity.
Evolutionary structure and timing of major habitat shifts in Crocodylomorpha
Authors: Wilberg Eric W. , Turner Alan H. , Brochu Christopher A.
Published: January 2019

Extant crocodylomorphs are semiaquatic ambush predators largely restricted to freshwater or estuarine environments, but the group is ancestrally terrestrial and inhabited a variety of ecosystems in the past. Despite its rich ecological history, little effort has focused on elucidating the historical pattern of ecological transitions in the group. Traditional views suggested a single shift from terrestrial to aquatic in the Early Jurassic. However, new fossil discoveries and phylogenetic analyses tend to imply a multiple-shift model. Here we estimate ancestral habitats across a comprehensive phylogeny and show at least three independent shifts from terrestrial to aquatic and numerous other habitat transitions. Neosuchians first invade freshwater habitats in the Jurassic, with up to four subsequent shifts into the marine realm. Thalattosuchians first appear in marine habitats in the Early Jurassic. Freshwater semiaquatic mahajangasuchids are derived from otherwise terrestrial notosuchians. Within nearly all marine groups, some species return to freshwater environments. Only twice have crocodylomorphs reverted from aquatic to terrestrial habitats, both within the crown group. All living non-alligatorid crocodylians have a keratinised tongue with salt-excreting glands, but the lack of osteological correlates for these adaptations complicates pinpointing their evolutionary origin or loss. Based on the pattern of transitions to the marine realm, our analysis suggests at least four independent origins of saltwater tolerance in Crocodylomorpha.
Ag(I) and Au(III) Mercaptobenzothiazole complexes induced apoptotic cell death
Authors: Sherine Jositta , Upadhyay Arun , Mishra Amit , Kumar Deepak , Pal Samanwita , Harinipriya S.
Published: January 2019

2-Mercaptobenzothiazole (MBT) complexes of Ag(I) and Au(III) were synthesized by wet chemical method. The structural, optical, 1HNMR, ICP – MS and electrochemical studies of the complexes were carried out. The TUNEL assay studies of Ag(I)MBT and Au(III)MBT complexes on A549 cell line indicated induced apoptosis in the cells. TUNEL assay showed 60% cell viability for Ag(I)MBT whereas 80% for Au(III)MBT. Thus Ag(I)MBT can induce cell apoptosis in cells at a higher rate than Au(III)MBT. Therefore these complexes studied here can be a viable option as anti – proliferating agent.
Through synapses to spatial memory maps via a topological model
Authors: Dabaghian Yuri
Published: January 2019

Various neurophysiological and cognitive functions are based on transferring information between spiking neurons via a complex system of synaptic connections. In particular, the capacity of presynaptic inputs to influence the postsynaptic outputs–the efficacy of the synapses–plays a principal role in all aspects of hippocampal neurophysiology. However, a direct link between the information processed at the level of individual synapses and the animal’s ability to form memories at the organismal level has not yet been fully understood. Here, we investigate the effect of synaptic transmission probabilities on the ability of the hippocampal place cell ensembles to produce a cognitive map of the environment. Using methods from algebraic topology, we find that weakening synaptic connections increase spatial learning times, produce topological defects in the large-scale representation of the ambient space and restrict the range of parameters for which place cell ensembles are capable of producing a map with correct topological structure. On the other hand, the results indicate a possibility of compensatory phenomena, namely that spatial learning deficiencies may be mitigated through enhancement of neuronal activity.
Open-Source Multiparametric Optocardiography
Authors: Cathey Brianna , Obaid Sofian , Zolotarev Alexander M. , Pryamonosov Roman A. , Syunyaev Roman A. , George Sharon A. , Efimov Igor R.
Published: January 2019

Since the 1970s fluorescence imaging has become a leading tool in the discovery of mechanisms of cardiac function and arrhythmias. Gradual improvements in fluorescent probes and multi-camera technology have increased the power of optical mapping and made a major impact on the field of cardiac electrophysiology. Tandem-lens optical mapping systems facilitated simultaneous recording of multiple parameters characterizing cardiac function. However, high cost and technological complexity restricted its proliferation to the wider biological community. We present here, an open-source solution for multiple-camera tandem-lens optical systems for multiparametric mapping of transmembrane potential, intracellular calcium dynamics and other parameters in intact mouse hearts and in rat heart slices. This 3D-printable hardware and Matlab-based RHYTHM 1.2 analysis software are distributed under an MIT open-source license. Rapid prototyping permits the development of inexpensive, customized systems with broad functionality, allowing wider application of this technology outside biomedical engineering laboratories.
Serum levels of fibroblast growth factor-2 distinguish Takayasu arteritis from giant cell arteritis independent of age at diagnosis
Authors: Fukui Shoichi , Kuwahara-Takaki Ayako , Ono Nobuyuki , Sato Shuntaro , Koga Tomohiro , Kawashiri Shin-ya , Iwanaga Nozomi , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Migita Kiyoshi , Arinobu Yojiro , Niiro Hiroaki , Tada Yoshifumi , Akashi Koichi , Maeda Takahiro , Kawakami Atsushi
Published: January 2019

Takayasu arteritis (TAK) and giant cell arteritis (GCA) are two major variants of large vessel vasculitis, and age is a major factor in their differential diagnosis. We sought to determine whether the two diseases exist on the same spectrum. We compared the serum levels of multiple cytokines and chemokines in 25 patients with TAK, 20 patients with GCA, and sex- and age-matched healthy donors for either condition (HD-TAK and HD-GCA). To evaluate the effects of age on the levels of cytokines and chemokines, we performed multiple logistic regression analysis using the least absolute shrinkage and selection operator (LASSO) method. The levels of IL-1RA, IL-10, GM-CSF, G-CSF, FGF-2, eotaxin, and IP-10 were significantly different between TAK and GCA, but no differences were found in the levels of IL-6, IL-12(p40), IL-17, IFN-γ, and TNF-α. Significant differences in the levels of IL-1RA, IL-10, GM-CSF, eotaxin, and IP-10 were observed between the HD-TAK and HD-GCA groups. Multiple logistic regression analysis demonstrated that only FGF-2 and IP-10 could significantly distinguish the diseases when added to age. Multiple logistic analysis using factors selected by the LASSO method revealed that FGF-2 was the only significant factor to distinguish the diseases when added to age. Among numerous cytokines and chemokines analyzed, only FGF-2 could be used together with age at diagnosis to differentiate TAK and GCA. Our results suggested the importance of considering the effects of age on serum cytokines.
Polarization induced control of optical trap potentials in binary liquids
Authors: Mondal Dipankar , Dinda Sirshendu , Bandyopadhyay Soumendra Nath , Goswami Debabrata
Published: January 2019

We illustrate control of a polarized laser optical trapping potential landscape through the nonideal mixing of binary liquids. The inherent trapping potential asymmetry (ITPA) present in the trapping region results from the asymmetric intensity distribution in focal volume due to the high numerical aperture objective lens. Experimentally, we show that this ITPA effect can be modified and/or removed by the use of binary liquid mixtures. From our femtosecond optical tweezers experiments, we determine the topograph of the trapping potential base on the fluctuation-dissipation theorem. Additionally, the Brownian motion of the trapped bead is sensitive to the frictional force (FF) of the surroundings that is exerted by clusters of water and alcohol binary mixture through extended hydrogen bonding. Thus, using these two effects, ITPA and FF of the medium, we have shown that one can indeed modify the effective trapping potential landscape. Water-alcohol binary mixtures display a nonlinear dependence on the microrheological properties of the solvent composition as a result of rigid cluster formation. Volumetrically, at about 30% methanol in water binary mixture, the trapping asymmetry is minimal. In this particular binary mixture composition, the hydrophobic part of the methanol molecule is surrounded by ‘cages’ of water molecules. Enhanced H-bonding network of water molecules results in higher viscosity, which contributes to the higher frictional force. Increased viscosity decreases the degree of anisotropy due to hindered dipolar rotation. However, at higher methanol concentrations, the methanol molecules are no longer contained within the water cages and are free to move, which decrease their overall bulk viscosity. Thus, for pure solvents, experimentally measured anisotropy matches quite well with the theoretical prediction, but this fails in case of the binary mixtures due to the increased frictional force exerted by binary mixtures that result from the formation of cage-like structures.
Regulation of volatile and non-volatile pheromone attractants depends upon male social status
Authors: Thoß M. , Luzynski K. C. , Enk V. M. , Razzazi-Fazeli E. , Kwak J. , Ortner I. , Penn D. J.
Published: January 2019

We investigated the regulation of chemical signals of house mice living in seminatural social conditions. We found that male mice more than doubled the excretion of major urinary proteins (MUPs) after they acquired a territory and become socially dominant. MUPs bind and stabilize the release of volatile pheromone ligands, and some MUPs exhibit pheromonal properties themselves. We conducted olfactory assays and found that female mice were more attracted to the scent of dominant than subordinate males when they were in estrus. Yet, when male status was controlled, females were not attracted to urine with high MUP concentration, despite being comparable to levels of dominant males. To determine which compounds influence female attraction, we conducted additional analyses and found that dominant males differentially upregulated the excretion of particular MUPs, including the pheromone MUP20 (darcin), and a volatile pheromone that influences female reproductive physiology and behavior. Our findings show that once male house mice become territorial and socially dominant, they upregulate the amount and types of excreted MUPs, which increases the intensities of volatiles and the attractiveness of their urinary scent to sexually receptive females.
Two macrocycle-based sensors for anions sensing
Authors: Liu Yingjie , Zhao Zhixiang , Huo Ran , Liu Qingxiang
Published: January 2019

Two macrocyclic bis-benzimidazolium salts 2 and 4 (23-membered for 2 and 25-membered for 4) were prepared, and their structures were confirmed by X-ray crystallography, 1H NMR and 13C NMR spectroscopy. The research of anion recognitions using 2 or 4 as hosts were carried out with the methods of fluorescence and ultraviolet spectroscopy, 1H NMR titrations, MS and IR spectra. The experiment results show that 2 can detect acetate anion and 4 can detect nitrate anion with favorable selectivity and sensitivity.
Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function
Authors: Saxena Vijay , Fitch James , Ketz John , White Peter , Wetzel Amy , Chanley Melinda A. , Spencer John D. , Becknell Brian , Pierce Keith R. , Arregui Sam W. , Nelson Raoul D. , Schwartz George J. , Velazquez Victoria , Walker Logan A. , Chen Xi , Yan Pearlly , Hains David S. , Schwaderer Andrew L.
Published: January 2019

The renal collecting duct consists of intercalated cells (ICs) and principal cells (PCs). We have previously demonstrated that collecting ducts have a role in the innate immune defense of the kidney. Transcriptomics is an important tool used to enhance systems-level understanding of cell biology. However, transcriptomics performed on whole kidneys provides limited insight of collecting duct cell gene expression, because these cells comprise a small fraction of total kidney cells. Recently we generated reporter mouse models to enrich collecting duct specific PC and ICs and reported targeted gene expression of anti-microbial peptide genes. Here we report transcriptomics on enriched ICs and PCs and performed a pilot study sequencing four single ICs. We identified 3,645 genes with increased relative expression in ICs compared to non-ICs. In comparison to non-PCs, 2,088 genes had higher relative expression in PCs. IC associated genes included the innate interleukin 1 receptor, type 1 and the antimicrobial peptide (AMP) adrenomedullin. The top predicted canonical pathway for enriched ICs was lipopolysaccharide/Interleukin 1 mediated inhibition of Retinoid X Receptor alpha function and decreased Retinoid X Receptor expression was confirmed to occur 1-hour post experimental murine UTI in ICs but not in non-ICs.
Assessing robustness of radiomic features by image perturbation
Authors: Zwanenburg Alex , Leger Stefan , Agolli Linda , Pilz Karoline , Troost Esther G. C. , Richter Christian , Löck Steffen
Published: January 2019

Image features need to be robust against differences in positioning, acquisition and segmentation to ensure reproducibility. Radiomic models that only include robust features can be used to analyse new images, whereas models with non-robust features may fail to predict the outcome of interest accurately. Test-retest imaging is recommended to assess robustness, but may not be available for the phenotype of interest. We therefore investigated 18 combinations of image perturbations to determine feature robustness, based on noise addition (N), translation (T), rotation (R), volume growth/shrinkage (V) and supervoxel-based contour randomisation (C). Test-retest and perturbation robustness were compared for combined total of 4032 morphological, statistical and texture features that were computed from the gross tumour volume in two cohorts with computed tomography imaging: I) 31 non-small-cell lung cancer (NSCLC) patients; II): 19 head-and-neck squamous cell carcinoma (HNSCC) patients. Robustness was determined using the 95% confidence interval (CI) of the intraclass correlation coefficient (1, 1). Features with CI ≥ 0:90 were considered robust. The NTCV, TCV, RNCV and RCV perturbation chain produced similar results and identified the fewest false positive robust features (NSCLC: 0.2–0.9%; HNSCC: 1.7–1.9%). Thus, these perturbation chains may be used as an alternative to test-retest imaging to assess feature robustness.
Scanning the genomes of parents for imprinted loci acting in their un-genotyped progeny
Authors: Blunk Inga , Mayer Manfred , Hamann Henning , Reinsch Norbert
Published: January 2019

Depending on their parental origin, alleles at imprinted loci are fully or partially inactivated through epigenetic mechanisms. Their effects contribute to the broader class of parent-of-origin effects. Standard methodology for mapping imprinted quantitative trait loci in association studies requires phenotypes and parental origin of marker alleles (ordered genotypes) to be simultaneously known for each individual. As such, many phenotypes are known from un-genotyped offspring in ongoing breeding programmes (e.g. meat animals), while their parents have known genotypes but no phenotypes. By theoretical considerations and simulations, we showed that the limitations of standard methodology can be overcome in such situations. This is achieved by first estimating parent-of-origin effects, which then serve as dependent variables in association analyses, in which only imprinted loci give a signal. As a theoretical foundation, the regression of parent-of-origin effects on the number of B-alleles at a biallelic locus — representing the un-ordered genotype — equals the imprinting effect. The applicability to real data was demonstrated for about 1800 genotyped Brown Swiss bulls and their un-genotyped fattening progeny. Thus, this approach unlocks vast data resources in various species for imprinting analyses and offers valuable clues as to what extent imprinted loci contribute to genetic variability.
HPLC analysis of CSF hypocretin-1 in type 1 and 2 narcolepsy
Authors: Sakai Noriaki , Matsumura Mari , Lin Ling , Mignot Emmanuel , Nishino Seiji
Published: January 2019

Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level. We found that the majority of hcrt-1 immunoreactivity in extracted CSF was derived from unauthentic hcrt-1 peaks, which are predicted to be inactive metabolites, and the intact hcrt-1 peptide was less than 10% of the gross amount, suggesting that the regular RIA for CSF hcrt-1 measures largely reflect the unauthentic hcrt-1-related metabolites rather than the intact one. As expected, all hcrt-1-related peaks were abolished in type 1 with hcrt-1 deficiency. Importantly, we also found that the sum of the authentic hcrt-1 peptide (peaks 3 and 4) significantly decreased in non-deficient type 1 and tended to decrease in type 2 narcoleptic patients although the levels with the regular RIA in non-extracted CSF was equivalent to healthy controls. Immunoreactivity with unauthentic hcrt-1 metabolites may masks the possible decline in authentic hcrt-1 level caused by the partial loss of hcrt neurons. Our findings may provide new insights into the degradation of the hcrt-1 peptide and the pathophysiology of narcolepsy.