bluuebunny/crossref_metadata_2025 huggingface dataset:
Label-free sorting of soft microparticles using a bioinspired synthetic cilia array
Authors: Sohrabi Salman , Tan Jifu , Yunus Doruk Erdem , He Ran , Liu Yaling
Published: May 2018

Isolating cells of interest from a heterogeneous population has been of critical importance in biological studies and clinical applications. In this study, a novel approach is proposed for utilizing an active ciliary system in microfluidic devices to separate particles based on their physical properties. In this approach, the bottom of the microchannel is covered with an equally spaced cilia array of various patterns which is actuated by an external stimuli. 3D simulations are carried out to study cilia-particle interaction and isolation dynamic in a microfluidic channel. It is observed that these elastic hair-like filaments can influence particle's trajectories differently depending on their biophysical properties. This modeling study utilizes immersed boundary method coupled with the lattice Boltzmann method. Soft particles and cilia are implemented through the spring connected network model and point-particle scheme, respectively. It is shown that cilia array with proper stimulation is able to continuously and non-destructively separate cells into subpopulations based on their size, shape, and stiffness. At the end, a design map for fabrication of a programmable microfluidic device capable of isolating various subpopulations of cells is developed. This biocompatible, label-free design can separate cells/soft microparticles with high throughput which can greatly complement existing separation technologies.
Optically controlled redshift switching effects in hybrid fishscale metamaterials
Authors: Wang Yu , Zhu Jinwei , Zhang Hao , Zhang Wenxing , Dong Guohua , Ye Peng , Lv Tingting , Zhu Zheng , Li Yuxiang , Guan Chunying , Shi Jinhui
Published: May 2018

We numerically demonstrate optically controlled THz response in a hybrid fishscale metamaterial with embedded photoconductive silicon at oblique incidence of TE wave. The oblique incidence allows excitation of Fano-type trapped mode resonance in a 2-fold rotational symmetric metamaterial. The hybrid fishscale metamaterial exhibits an optically controlled redshift switching effect in the THz range. The switching effect is dominated by the conductivity of the silicon instead of mechanically adjusting angles of incidence. The tuning frequency range is up to 0.3THz with a large modulation depth and high transmission in the “ON” state. The fishscale metamaterial-based switching has been experimentally verified by its microwave counterpart integrated by variable resistors. Our work provides an alternative route to realize tunable Fano-type response in metamaterials and is of importance to active manipulation, sensing and switching of THz waves in practical applications.
Incorporating mechanical strain in organs-on-a-chip: Lung and skin
Authors: Guenat Olivier T. , Berthiaume François
Published: May 2018

In the last decade, the advent of microfabrication and microfluidics and an increased interest in cellular mechanobiology have triggered the development of novel microfluidic-based platforms. They aim to incorporate the mechanical strain environment that acts upon tissues and in-vivo barriers of the human body. This article reviews those platforms, highlighting the different strains applied, and the actuation mechanisms and provides representative applications. A focus is placed on the skin and the lung barriers as examples, with a section that discusses the signaling pathways involved in the epithelium and the connective tissues.
Magnitude of parallel pseudo potential in a magnetosonic shock wave
Authors: Ohsawa Yukiharu
Published: May 2018

The parallel pseudo potential F, which is the integral of the parallel electric field along the magnetic field, in a large-amplitude magnetosonic pulse (shock wave) is theoretically studied. Particle simulations revealed in the late 1990's that the product of the elementary charge and F can be much larger than the electron temperature in shock waves, i.e., the parallel electric field can be quite strong. However, no theory was presented for this unexpected result. This paper first revisits the small-amplitude theory for F and then investigates the parallel pseudo potential F in large-amplitude pulses based on the two-fluid model with finite thermal pressures. It is found that the magnitude of F in a shock wave is determined by the wave amplitude, the electron temperature, and the kinetic energy of an ion moving with the Alfvén speed. This theoretically obtained expression for F is nearly identical to the empirical relation for F discovered in the previous simulation work.
Absorption and resonance Raman characteristics of β-carotene in water-ethanol mixtures, emulsion and hydrogel
Authors: Meinhardt-Wollweber Merve , Suhr Christian , Kniggendorf Ann-Kathrin , Roth Bernhard
Published: May 2018

Absorption or resonance Raman scattering are often used to identify and even quantify carotenoids in situ. We studied the absorption spectra, the Raman spectra and their resonance behavior of β-carotene in different molecular environments set up as mixtures from lipid (emulsion) and non-polar (ethanol) solvents and a polar component (water) with regard to their application as references for in situ measurement. We show how both absorption profiles and resonance spectra of β-carotene strongly depend on the molecular environment. Most notably, our data suggests that the characteristic bathochromic absorption peak of J-aggregates does not contribute to carotenoid resonance conditions, and show how the Raman shift of the C=C stretching mode is dependent on both, the molecular environment and the excitation wavelength. Overall, the spectroscopic data collected here is highly relevant for the interpretation of in situ spectroscopic data in terms of carotenoid identification and quantification by resonance Raman spectroscopy as well as the preparation of reference samples. In particular, our data promotes careful consideration of appropriate molecular environment for reference samples.
Incremental viscosity by non-equilibrium molecular dynamics and the Eyring model
Authors: Heyes D. M. , Dini D. , Smith E. R.
Published: May 2018

The viscoelastic behavior of sheared fluids is calculated by Non-Equilibrium Molecular Dynamics (NEMD) simulation, and complementary analytic solutions of a time-dependent extension of Eyring’s model (EM) for shear thinning are derived. It is argued that an “incremental viscosity,” ηi, or IV which is the derivative of the steady state stress with respect to the shear rate is a better measure of the physical state of the system than the conventional definition of the shear rate dependent viscosity (i.e., the shear stress divided by the strain rate). The stress relaxation function, Ci(t), associated with ηi is consistent with Boltzmann’s superposition principle and is computed by NEMD and the EM. The IV of the Eyring model is shown to be a special case of the Carreau formula for shear thinning. An analytic solution for the transient time correlation function for the EM is derived. An extension of the EM to allow for significant local shear stress fluctuations on a molecular level, represented by a gaussian distribution, is shown to have the same analytic form as the original EM but with the EM stress replaced by its time and spatial average. Even at high shear rates and on small scales, the probability distribution function is almost gaussian (apart from in the wings) with the peak shifted by the shear. The Eyring formula approximately satisfies the Fluctuation Theorem, which may in part explain its success in representing the shear thinning curves of a wide range of different types of chemical systems.
The dependence of Schottky junction (I–V) characteristics on the metal probe size in nano metal–semiconductor contacts
Authors: Rezeq Moh’d , Ali Ahmed , Patole Shashikant P. , Eledlebi Khouloud , Dey Ripon Kumar , Cui Bo
Published: May 2018

We have studied the dependence of Schottky junction (I–V) characteristics on the metal contact size in metal–semiconductor (M–S) junctions using different metal nanoprobe sizes. The results show strong dependence of (I–V) characteristics on the nanoprobe size when it is in contact with a semiconductor substrate. The results show the evolution from sub-10 nm reversed Schottky diode behavior to the normal diode behavior at 100 nm. These results also indicate the direct correlation between the electric field at the M–S interface and the Schottky rectification behavior. The effect of the metal contact size on nano-Schottky diode structure is clearly demonstrated, which would help in designing a new type of nano-devices at sub-10 nm scale.
Research on thermal conductivity of HGMs at vacuum in room temperature
Authors: Wang Ping , Liao Bin , An Zhenguo , Yan Kaiqi , Zhang Jingjie
Published: May 2018

Hollow glass microspheres (HGMs) can be used as thermal insulation materials owing to its hollow structure which brings excellent thermal insulation property and low density. At present, most researches on thermal conductivity of HGMs are focused on polymer matrix/HGMs composite materials. However, thermal conductivity of HGMs at vacuum in room temperature has rarely been investigated. In this work, thermal conductivity of six types of HGMs (T17 (0.17g/cm3), T20 (0.20g/cm3), T22 (0.22g/cm3), T25 (0.25g/cm3), T32 (0.32g/cm3) and T40 (0.40g/cm3)) at vacuum in room temperature were calculated by heat transfer of solid conduction and radiation. The calculation results showed that thermal conductivity of HGMs would be decreased by an order of magnitude compared with no vacuum. In order to verify the calculation and study vacuum thermal insulation properties of HGMs, thermal conductivity of above-mentioned HGMs at no vacuum and high vacuum in room temperature were measured by a self-made thermal conductivity measuring apparatus which was based on the transient plane source (TPS) method. The experimental results showed that thermal conductivity of HGMs were in the range of 4.2030E-02 to 6.3300E-02 W/m·K (at no vacuum) and 3.8160E-03 to 4.9660E-03 W/m·K (at high vacuum). The results indicated that experimental thermal conductivity was consistent with the calculation results and both of them were all decreased by 8-13 times at vacuum compared with no vacuum. In addition, the relationship with physical properties and thermal conductivity of HGMs has been discussed in detail. In conclusion, HGMs possess excellent thermal insulation performance at high vacuum in room temperature and have potential to further reduce thermal conductivity at the same conditions.
George William Kenneth 'Ken' Cavill 1922–2017
Authors: Clark Doreen V. , Genion Jennifer A.
Published: May 2018

Ken Cavill knew from his high school years that his career lay in science. Whilst completing his Bachelor of Science at the University of Sydney he chose to focus on organic chemistry and made his academic career in that field. Ken gained his PhD at Liverpool University in England in 1949 and was awarded a DSc from that university in 1957. He was employed during World War 2 at W. Hermon Slade & Co., and then as a lecturer in chemistry at Sydney Technical College, becoming a senior lecturer at the newly formed University of New South Wales (UNSW), where he had a distinguished career in research and teaching until his retirement in 1982. He received the first personal chair awarded by the university in 1964 and was made a Fellow of the Australian Academy of Science in 1969. He was made an emeritus professor by UNSW in 1983. He actively pursued collaboration between chemistry and biology, and pioneered studies in Australia on the chemistry of insect venoms, attractants and repellents, leaving a legacy of a well-respected body of work in this field. Ken was awarded a Centenary of Federation Medal in 2001 for his service to Australian society and science in the field of organic biological chemistry. Pursuing his love of Australiana, he devoted his retirement to researching and writing about Australian silverware and jewellery manufacturers of the nineteenth and early twentieth centuries.
An adaptive management case study for managing macropods on Maria Island National Park, Tasmania, Australia: adding devils to the detail
Authors: Ingram Janeane
Published: May 2018

Adaptive management is driven by structured decision making and evidence from monitoring in a ‘learning’ framework that guides management actions. In a conservation context, this iterative approach includes evaluation of the impacts on natural processes. On Maria Island National Park, Tasmania, Australia, introduced Forester kangaroo, Bennetts wallaby and Tasmanian pademelon have been intensively managed by an annual cull since 1994. Management actions were triggered by high parasite loads, intense grazing pressure and high juvenile mortality during drought periods. Criticism of the annual cull from animal welfare groups initiated the development of an adaptive management approach for decision making that replaces the historic ‘trial and error’ process. Following a comprehensive review of the existing macropod management program in 2011, an integrated monitoring strategy was established to provide evidence for informed decision making. Assessments of animal health and estimates of population trends are the key indicators for management actions to occur. Maintaining viable macropod populations and protecting natural values form the basis of management objectives. Management actions in each year, for each species, represent ‘treatments’ as spatial replication is not possible at such a small scale. An adaptive management approach for macropod management on Maria Island has resulted in only one species being culled in 2014 and 2015 for the first time in almost 20 years. However the recent introduction of a major predator, the Tasmanian devil, has increased uncertainty for long-term macropod management on Maria Island with no cull occurring in 2016 and 2017.
Review of emissions from smouldering peat fires and their contribution to regional haze episodes
Authors: Hu Yuqi , Fernandez-Anez Nieves , Smith Thomas E. L. , Rein Guillermo
Published: May 2018

Smouldering peat fires, the largest fires on Earth in terms of fuel consumption, are reported in six continents and are responsible for regional haze episodes. Haze is the large-scale accumulation of smoke at low altitudes in the atmosphere. It decreases air quality, disrupts transportation and causes health emergencies. Research on peat emissions and haze is modest at best and many key aspects remain poorly understood. Here, we compile an up-to-date inter-study of peat fire emission factors (EFs) found in the literature both from laboratory and from field studies. Tropical peat fires yield larger EFs for the prominent organic compounds than boreal and temperate peat fires, possibly due to the higher fuel carbon content (56.0 vs 44.2%). In contrast, tropical peat fires present slightly lower EFs for particulate matter with diameter ≤2.5 μm (PM2.5) for unknown reasons but are probably related to combustion dynamics. An analysis of the modified combustion efficiency, a parameter widely used for determining the combustion regime of wildfires, shows it is partially misunderstood and highly sensitive to unknown field variables. This is the first review of the literature on smouldering peat emissions. Our integration of the existing literature allows the identification of existing gaps in knowledge and is expected to accelerate progress towards mitigation strategies.
Strong and highly variable push of ocean waves on Southern Ocean sea ice
Authors: Stopa Justin E. , Sutherland Peter , Ardhuin Fabrice
Published: May 2018

Significance

Southern Ocean sea ice plays a key role in regulating the uptake of carbon and heat by the global ocean. In this context, ocean waves have a strong influence, including ice break-up and pancake formation. These processes explain large differences in sea-ice properties between Arctic and Antarctic. Waves also decay in the ice, exerting a force in their propagation direction that compacts the ice. Here, we provide an extensive dataset on wave heights and its decay in sea ice, using satellite imagery. Wave decay can be much faster than previously reported but is highly variable. The resulting wave force on the ice can have a profound impact on both ice extent and thickness.
Trace, Revelation, and Interpretant in Archaeological Research: The Graffiti of Huaca Colorada, Peru
Authors: Swenson Edward
Published: May 2018

Romantic notions that the advancement of archaeological knowledge depends on the thrill of unanticipated discoveries departs from the standard practice of interpreting data according to impartial research designs. However, the unexpected find commonly stymies the deductive testing of hypothesis, and the material traces (signs) upon which research relies often disrupt the course of archaeological investigations. The main objective of this article is to demonstrate that the distinct semiotic affordances of material remains can significantly affect archaeological interpretations. The undertheorized epistemological problems of revelation in archaeology are brought to bear through an examination of the spectral quality of graffiti etched onto the walls of the Moche ceremonial site of Huaca Colorada in northern Peru (CE 650–850). An interpretation of the graffiti in relationship to rituals of human sacrifice and architectural renovation demonstrates that the power of the monument was founded on its semiotic density; the complex layering of signs—that continually spawned new signs—created a place of limitless discovery and affect that profoundly shaped perceptions of the huaca for both Moche visitors and later archaeologists alike. Ultimately, the graffiti provide a rare data set that permits a consideration of the effects of signs as “intepretants” in the tradition of Peirce.
The Meaning Making of the Built Environment in the Fascist City: A Semiotic Approach
Authors: Nanni Antonio , Bellentani Federico
Published: May 2018

This article draws on interpretative semiotics to address how spatial designers endow the built environment with meaning. From a semiotic perspective, designing the built environment is an activity that extends beyond its physical reshaping. Designers use complex sociosemiotic strategies to funnel users’ interpretations, drawing upon their manifold resources. Analyzing these strategies is important to not naturalize the dominant meaning that is inscribed in the built environment. As a case study, we analyze spatial design in the city of Forlì, Italy, during the Fascist regime (1922–43). Through the case study, we delineate two complimentary design strategies: typification and environmental propaganda. Typification establishes and uses familiar types of buildings to channel individual interpretations; environmental propaganda spreads cultural artifacts and enacts political rituals about the built environment. Both of these strategies try to steer users’ interpretations of the built environment in everyday life. Finally, we provide a detailed analysis of a particular built form in Forlì—the headquarters of the Opera Nazionale Balilla—showing how these strategies were deployed for this particular building.
Rogue Pixels: Indexicality and Algorithmic Camouflage
Authors: Paulsen Kris
Published: May 2018

The resolution of publicly available satellite photography is limited to 50 cm a pixel. Every pixel in a satellite image is a single, solid color. The reasons for the resolution limit are tactical as well as protective: according to forensic architect Eyal Weizman, it maintains the privacy of individuals on the ground as well as makes the consequences of state violence harder to investigate. A uniformly colored pixel can be evidence of a drone attack or proof that it never happened. The indexical evidence ambivalently sustains both interpretations. If camouflage has been traditionally thought of as a blending into the contiguous environment, often geared toward a camera’s gaze, in this essay I look to the reorientation of camouflage away from the adjacent surroundings and toward the mediating structures of the interface and database. The objective of camouflage is now to merge into arrays of information and to slip below the threshold of detectability. This essay examines the work of artists and activists, such as Hito Steyerl, Zach Blas, and Adam Harvey, who strategize ways of becoming “rogue pixels” hiding in “the cracks of our standards of resolution,” resisting the means by which our bodies are indexed on virtual interfaces and algorithmically parsed as data.
Not Citizens of a Classical Mediterranean: Muslim Youth from Marseille Elude a Linguistic Gentrification by the French State
Authors: Evers Cécile
Published: May 2018

A moral panic is afoot in contemporary France surrounding what place French-Muslim youth hold within the national identity. The French state, in particular, is actively engaged in regimenting what it means to be a young Muslim person from France. This article examines how, during Marseille’s year (2013) as the European Capital of Culture, the municipal government and the local branch of the Ministère de l’Éducation Nationale spearheaded several initiatives, a number of which focused on Arabic-language education, with the aim of transforming French-Muslim youth from Marseille’s housing projects into secular, upwardly mobile individuals. Ethnographic inquiry with the youth targeted by such “linguistic gentrification” programs reveals that the state’s reimagining of them in these terms remained largely at odds with how they themselves understood their identities. This article, as such, illustrates the analytical importance of attending to people’s uptake when evaluating the eventual scope of top-down discourses and projects, while also offering an example of how the label “Mediterranean” functions as a spatiotemporal shifter, deployed by different groups to activate alternative accounts of history, the present, and the future.
Design of robotic cells based on relative handling modules with use of SolidWorks system
Authors: Gaponenko E V , Anciferov S I
Published: May 2018

The article presents a diagramed engineering solution for a robotic cell with six degrees of freedom for machining of complex details, consisting of the base with a tool installation module and a detail machining module made as parallel structure mechanisms. The output links of the detail machining module and the tool installation module can move along X-Y-Z coordinate axes each. A 3D-model of the complex is designed in the SolidWorks system. It will be used further for carrying out engineering calculations and mathematical analysis and obtaining all required documentation.
Affairs of Humanity: Arguments for Humanitarian Intervention in England and Europe, 1698–1715
Authors: Arnold Catherine S
Published: May 2018

Why and how did a new type of intervention, intended to prevent rulers from punishing individuals for their religious beliefs and justified using natural law, emerge in England during the first decade of the eighteenth century? This article traces its origins to the War of the Spanish Succession, when Huguenot publicists and diplomats petitioned English politicians to negotiate freedom for Huguenot prisoners in France. In campaigning for prisoners’ freedom rather than for the restoration of Huguenot corporate rights in France, Huguenot publicists and diplomats had to justify intervention in universalising, non-confessional terms. Because those prisoners were not protected by treaty law, the laws of war, or the laws of France, they cited Protestant and humanist traditions of natural law and theories of natural sociability to justify negotiating their release. In so doing, they invited European readers, politicians and monarchs to sympathise with distant strangers—and even to take political action on their behalf—not only because they shared a common faith, but also because they belonged to human society and shared a common humanity. These arguments circulated both in print and among European diplomats, altering the conduct of international affairs. In England, this article shows, Huguenot campaigns influenced debates about intervention and English foreign policy-making. Thus, this article suggests a new narrative for the diffusion of humanitarian argument in eighteenth-century western European political culture.
Robotic Assisted MRI-Guided Interventional Interstitial MR-Guided Focused Ultrasound Ablation in a Swine Model
Authors: MacDonell Jacquelyn , Patel Niravkumar , Fischer Gregory , Burdette E Clif , Qian Jiang , Chumbalkar Vaibhav , Ghoshal Goutam , Heffter Tamas , Williams Emery , Gounis Matthew , King Robert , Thibodeau Juliette , Bogdanov Gene , Brooks Olivia W , Langan Erin , Hwang Roy , Pilitsis Julie G
Published: May 2018

BACKGROUND

Ablative lesions are current treatments for epilepsy and brain tumors. Interstitial magnetic resonance (MR) guided focused ultrasound (iMRgFUS) may be an alternate ablation technique which limits thermal tissue charring as compared to laser therapy (LITT) and can produce larger ablation patterns nearer the surface than transcranial MR guided focused ultrasound (tcMRgFUS).

OBJECTIVE

To describe our experience with interstitial focused ultrasound (iFUS) ablations in swine, using MR-guided robotically assisted (MRgRA) delivery.

METHODS

In an initial 3 animals, we optimized the workflow of the robot in the MR suite and made modifications to the robotic arm to allow range of motion. Then, 6 farm pigs (4 acute, 2 survival) underwent 7 iMRgFUS ablations using MRgRA. We altered dosing to explore differences between thermal dosing in brain as compared to other tissues. Imaging was compared to gross examination.

RESULTS

Our work culminated in adjustments to the MRgRA, iMRgFUS probes, and dosing, culminating in 2 survival surgeries; swine had ablations with no neurological sequelae at 2 wk postprocedure. Immediately following iMRgFUS therapy, diffusion-weighted imaging, and T1 weighted MR were accurate reflections of the ablation volume. T2 and fluid-attenuated inversion-recovery (FLAIR) images were accurate reflections of ablation volume 1-wk postprocedure.

CONCLUSION

We successfully performed MRgRA iFUS ablation in swine and found intraoperative and postoperative imaging to correlate with histological examination. These data are useful to validate our system and to guide imaging follow-up for thermal ablation lesions in brain tissue from our therapy, tcMRgFUS, and LITT.
Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma
Authors: Pratt Drew , Dominah Gifty , Lobel Graham , Obungu Arnold , Lynes John , Sanchez Victoria , Adamstein Nicholas , Wang Xiang , Edwards Nancy A , Wu Tianxia , Maric Dragan , Giles Amber J , Gilbert Mark R , Quezado Martha , Nduom Edjah K
Published: May 2018

BACKGROUND

Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results.

OBJECTIVE

To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification.

METHODS

Using tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n = 56) and validated expression (n = 183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+ cell populations in post-treatment glioblastoma.

RESULTS

Using a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n = 125, log-rank P < .001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n = 60, log-rank P = .015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96, P = .021). Analysis of TCGA data confirmed decreased overall survival in recurrent non–glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n = 12, log-rank P = .023), but not in glioblastoma as a group (n = 444, log-rank P = .135). PD-L1 RISH showed a significant correlation with IHC (P < .0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma.

CONCLUSION

A 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1/PD-L1 blockade.
Preliminary exploration of a computerized cognitive battery and comparison with traditional testing in patients with high-grade glioma
Authors: Cerhan Jane H , Caine Chip , Anderson S Keith , Johnson Derek R , Lachance Daniel H , Yan Elizabeth , Brown Paul D
Published: May 2018

Background

Cognitive function is an important outcome measure in many brain tumor clinical trials, and investigators are interested in employing the most efficient methods of cognitive assessment for this purpose. Computerized testing can be appealing because of the perceived ease of use and electronic data generated. Traditional tests may have the advantage of accumulated validity evidence and comparability across historic trials.

Methods

We evaluated feasibility of a Cogstate battery in 39 patients with high-grade glioma, and compared it with a commonly used paper-and-pencil battery.

Results

Both batteries were well tolerated and rated equally likeable. Correlations between the batteries were low to low-moderate. More patients showed impairment at baseline and decline across trials on traditional tests.

Conclusions

Both batteries were well tolerated, but the most complicated tasks (from both batteries) could not be completed by all subjects. Preliminary validity evidence for the Cogstate tasks was mixed, but a larger sample is needed.
Generation of defined neural populations from pluripotent stem cells
Authors: McComish Sarah F. , Caldwell Maeve A.
Published: May 2018

Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS). The ability to produce patient- and disease-specific iPSC lines has created a new age of disease modelling. Human iPSC may be derived from adult somatic cells and subsequently patterned into numerous distinct cell types. The ability to derive defined and regionalized neural populations from iPSC provides a powerful
in vitro
model of CNS disorders.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
The gene regulatory network of mESC differentiation: a benchmark for reverse engineering methods
Authors: Meisig Johannes , Blüthgen Nils
Published: May 2018

A large body of data have accumulated that characterize the gene regulatory network of stem cells. Yet, a comprehensive and integrative understanding of this complex network is lacking. Network reverse engineering methods that use transcriptome data to derive these networks may help to uncover the topology in an unbiased way. Many methods exist that use co-expression to reconstruct networks. However, it remains unclear how these methods perform in the context of stem cell differentiation, as most systematic assessments have been made for regulatory networks of unicellular organisms. Here, we report a systematic benchmark of different reverse engineering methods against functional data. We show that network pruning is critical for reconstruction performance. We also find that performance is similar for algorithms that use different co-expression measures, i.e. mutual information or correlation. In addition, different methods yield very different network topologies, highlighting the challenge of interpreting these resulting networks as a whole.

This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Integrating Hi-C and FISH data for modeling 3D organizations of chromosomes
Authors: Abbas Ahmed , He Xuan , Zhou Bin , Zhu Guangxiang , Ma Zishan , Gao Jun-Tao , Zhang Michael Q , Zeng Jianyang
Published: May 2018

The new advances in various experimental techniques that provide complementary in-formation about the spatial conformations of chromosomes have inspired researchers to develop computational methods to fully exploit the merits of individual data sources and combine them to improve the modeling of chromosome structure. In this paper, we propose GEM-FISH, a first method for reconstructing the 3D models of chromosomes through systematically integrating both Hi-C and FISH data with the prior biophysical knowledge of a polymer model. Comprehensive tests on a set of chromosomes for which both Hi-C and FISH data were available have demonstrated that GEM-FISH can reconstruct the 3D models of chromosomes with more accurate spatial organizations of TADs and compartments than using only Hi-C data. In addition, GEM-FISH can accurately capture the spatial proximity of loop loci and the colocalization of loci from the same sub-compartments. Moreover, our reconstructed 3D models of chromosomes revealed novel patterns of spatial distributions of super-enhancers which can provide useful insights into understanding the functional roles of these super-enhancers in gene regulation. All these results demonstrated that, through integrating both Hi-C and FISH data into a unified framework, GEM-FISH can provide a better tool for modeling the 3D organizations of chromosomes than using the Hi-C data alone.
Bioinformatic characterisation of the effector repertoire of the strawberry pathogen Phytophthora cactorum
Authors: Armitage Andrew D. , Lysøe Eric , Nellist Charlotte F. , Lewis Laura A. , Cano Liliana M. , Harrison Richard J. , Brurberg May Bente
Published: May 2018

The oomycete pathogen Phytophthora cactorum causes crown rot, a major disease of cultivated strawberry. We report the draft genome of P. cactorum isolate 10300, cultured from symptomatic Fragaria x ananassa tissue. Our analysis revealed that there are a large number of genes encoding putative secreted effectors in the genome, including nearly 200 RxLR domain containing effectors, 77 Crinklers (CRN) grouped into 38 families and numerous apoplastic effectors, such as phytotoxins (PcF proteins) and necrosis inducing proteins. As in other Phytophthora species, the genomic environment of many RxLR and CRN genes differed from core eukaryotic genes, a hallmark of the two-speed genome. We found genes homologous to known Phytophthora infestans avirulence genes including Avr1, Avr3b, Avr4, Avrblb1 and AvrSmira2 indicating effector sequence conservation between Phytophthora species of Clade 1A and 1C. The reported P. cactorum genome sequence and associated annotations represent a comprehensive resource for avirulence gene discovery in other Phytophthora species from Clade 1 and will facilitate effector informed breeding strategies in other crops.
Supragingival plaque microbiome ecology and functional potential in the context of health and disease
Authors: Espinoza Josh L , Harkins Derek M. , Torralba Manolito , Gomez Andres , Highlander Sarah K. , Jones Marcus B. , Leong Pamela , Saffery Richard , Bockmann Michelle , Kuelbs Claire , Inman Jason M. , Hughes Toby , Craig Jeffrey M. , Nelson Karen E. , Dupont Chris L.
Published: May 2018

To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely-related previously-uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first completeGracilibacteriagenomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology and our results provide the information needed for next generation diagnostic tools and therapeutics for caries.
A comparison of auditory oddball responses in dorsolateral prefrontal cortex, basolateral amygdala and auditory cortex of macaque
Authors: Camalier Corrie R. , Scarim Kaylee C. , Mishkin Mortimer , Averbeck Bruno B.
Published: May 2018

The mismatch negativity (MMN) is an event-related potential component seen in response to unexpected “novel” stimuli, such as in an auditory oddball task. The MMN is of wide interest and application, but the neural responses that generate it are poorly understood. This is in part due to differences in design and focus between animal and human oddball paradigms. For example, one of the main explanatory models, the “predictive error hypothesis”, posits differences in timing and selectivity between signals carried in auditory and prefrontal cortex. However these predictions have not been fully tested because 1) noninvasive techniques used in humans lack the combined spatial and temporal precision necessary for these comparisons, and 2) single-neuron studies in animal models, which combine spatial and temporal precision, have not focused on higher order contributions to novelty signals. In addition, accounts of the MMN traditionally do not address contributions from subcortical areas known to be involved in novelty detection, such as the amygdala. To better constrain hypotheses and to address methodological gaps between human and animal studies, we recorded single neuron activity from the auditory cortex, dorsolateral prefrontal cortex, and basolateral amygdala of two macaque monkeys during an auditory oddball paradigm modeled after that used in humans. Consistent with predictions of the predictive error hypothesis, novelty signals in prefrontal cortex were generally later than in auditory cortex, and were abstracted from stimulus-specific effects seen in auditory cortex. However, we found signals in amygdala that were comparable in magnitude and timing to those in prefrontal cortex, and both prefrontal and amygdala signals were generally much weaker than those in auditory cortex. These observations place useful quantitative constraints on putative generators of the auditory oddball-based MMN, and additionally indicate that there are subcortical areas, such as the amygdala, that may be involved in novelty detection in an auditory oddball paradigm.
Long-read sequencing identified a causal structural variant in an exome-negative case and enabled preimplantation genetic diagnosis
Authors: Miao Hefan , Zhou Jiapeng , Yang Qi , Liang Fan , Wang Depeng , Ma Na , Gao Bodi , Du Juan , Lin Ge , Wang Kai , Zhang Qianjun
Published: May 2018

For a proportion of individuals judged clinically to have a recessive Mendelian disease, only one pathogenic variant can be found from clinical whole exome sequencing (WES), posing a challenge to genetic diagnosis and genetic counseling. Here we describe a case study, where WES identified only one pathogenic variant for an individual suspected to have glycogen storage disease type Ia (GSD-Ia), which is an autosomal recessive disease caused by bi-allelic mutations in the G6PC gene. Through Nanopore long-read whole-genome sequencing, we identified a 7kb deletion covering two exons on the other allele, suggesting that complex structural variants (SVs) may explain a fraction of cases when the second pathogenic allele is missing from WES on recessive diseases. Both breakpoints of the deletion are within Alu elements, and we designed Sanger sequencing and quantitative PCR assays based on the breakpoints for preimplantation genetic diagnosis (PGD) for the family planning on another child. Four embryos were obtained after in vitro fertilization (IVF), and an embryo without deletion in G6PC was transplanted after PGD and was confirmed by prenatal diagnosis, postnatal diagnosis, and subsequent lack of disease symptoms after birth. In summary, we present one of the first examples of using long-read sequencing to identify causal yet complex SVs in exome-negative patients, which subsequently enabled successful personalized PGD.
Profiles of cooperative brains: A discriminant analysis of cleaner and client fish monoaminergic responses to different social contexts
Authors: Maximino Caio , Gomes Ana Cristina R. , de Abreu Murilo S. , Cardoso Sónia C. , Lima-Maximino Monica , Winberg Svante , Soares Marta C.
Published: May 2018

Vertebrate cognitive function requires a dynamic coordination of multiple specialized areas of the brain. The challenge here is to understand how these brain areas respond in dependence to the neurophysiological mechanisms in place, as to enable the successful processing of information. For instance, social and cooperative behaviour has been linked to the activation of some specific brain areas, mostly associated with reward processing. Here we evaluated a classic model system of cooperation between species of fish and compared datasets of brain monoaminergic response. We analysed by using multivariate discriminant analysis the exposure of cleaners, Labroides dimidiatus, to several social-related conditions, as well as the response of one client species, Naso elegans, to similar contexts. We demonstrate that the variable appraisal of each social challenge contributes to brain dopaminergic and serotonergic changes, in cleaners and clients, with both showing the diencephalon and optic tectum as main areas of metabolite response. The role of the serotoninergic system activation was mostly demonstrated at the diencephalon and cerebellum of cleaners, a response that was driven by mutualistic interaction, contact with client. Our current evidence is the first to jointly demonstrate the level of selective similarity in brain monoaminergic mechanisms that underlie fish mutualistic and social engagement, for both sides of these partnerships.
NECorr, a Tool to Rank Gene Importance in Biological Processes using Molecular Networks and Transcriptome Data
Authors: Liseron-Monfils Christophe , Olson Andrew , Ware Doreen
Published: May 2018

The challenge of increasing crop yield while decreasing plants’ susceptibility to various stresses can be lessened by understanding plant regulatory processes in a tissue-specific manner. Molecular network analysis techniques were developed to aid in understanding gene inter-regulation. However, few tools for molecular network mining are designed to extract the most relevant genes to act upon. In order to find and to rank these putative regulator genes, we generated NECorr, a computational pipeline based on multiple-criteria decision-making algorithms. With the objective of ranking genes and their interactions in a selected condition or tissue, NECorr uses the molecular network topology as well as global gene expression analysis to find hub genes and their condition-specific regulators. NECorr was applied to Arabidopsis thaliana flower tissue and identifies known regulators in the developmental processes of this tissue as well as new putative regulators. NECorr will accelerate translational research by ranking candidate genes within a molecular network of interest.
Overlooked roles of DNA damage and maternal age in generating human germline mutations
Authors: Gao Ziyue , Moorjani Priya , Sasani Thomas , Pedersen Brent , Quinlan Aaron , Jorde Lynn , Amster Guy , Przeworski Molly
Published: May 2018

Although the textbook view is that most germline mutations arise from replication errors, when analyzing largede novomutation datasets in humans, we find multiple lines of evidence that call that understanding into question. Notably, despite the drastic increase in the ratio of male to female germ cell divisions after the onset of spermatogenesis, even young fathers contribute three times more mutations than young mothers, and this ratio barely increases with parental ages. This surprising finding points to a substantial contribution of damage-induced mutations. Indeed, C to G transversions and CpG transitions, which together constitute one third of all mutations, show genomic distributions and sex-specific age dependencies indicative of doublestrand break repair and methylation-associated damage, respectively. Moreover, the data indicate that maternal age at conception influences the mutation rate both because of the accumulation of damage in oocytes and potentially through an influence on the number of postzygotic mutations.
Pseudomonas aeruginosadisplays a dormancy phenotype during long-term survival in water
Authors: Lewenza Shawn , Abboud Jason , Poon Karen , Kobryn Madison , Humplik Istvan , Bell John Rainer , Mardan Laura , Reckseidler-Zenteno Shauna
Published: May 2018

Pseudomonas aeruginosais capable of long-term survival in water, which may serve as a reservoir for infection. Although viable cell counts of PAO1 incubated in water remain stable throughout 8 weeks, LIVE/DEAD® staining indicated a high proportion of cells stained with propidium iodide (PI). The proportion of PI-stained cells increased by 4 weeks, then decreased again by 8 weeks, suggesting an adaptive response. This was also evident in an observed shift in cell morphology from a rod to a coccoid shape after 8 weeks. Fluorescence-activated cell sorting (FACS) was used to recover PI-stained cells, which were plated and shown to be viable, indicating that PI-stained cells were membrane-compromised but still cultivable. PAO1 mid-log cells in water were labeled with the dsDNA-binding dye PicoGreen® to monitor viability as well as DNA integrity, which demonstrated that the population remains viable and transitions towards increased dsDNA staining. Metabolic activity was found to decrease significantly in water by 4 weeks. The PAO1 outer membrane became less permeable and more resistant to polymyxin B damage in water, and the profile of total membrane lipids changed over time. None of the individual mutants within a library of ~2500 mapped, mini-Tn5-luxtransposon mutants were found to have decreased survival in water. Among the ~1400 transcriptionalluxfusions, gene expression in water revealed that the majority of genes were repressed, but subsets of genes were induced at particular time points. In summary, these results indicate thatP. aeruginosais dormant in water and this adaptation involves a complex pattern of gene regulation and changes to the cell to promote long-term survival and antibiotic tolerance. The approach ofP. aeruginosaincubated in water may be useful to study antibiotic tolerance and the mechanisms of dormancy and survival in nutrient limiting conditions.