bluuebunny/crossref_metadata_2025 huggingface dataset:
Spreading dynamics of superposed liquid drops on a spinning disk
Authors: Sahoo Subhadarshinee , Orpe Ashish V. , Doshi Pankaj
Published: January 2018

We have experimentally studied simultaneous spreading of superposed drops of two Newtonian liquids on top of a horizontal spinning disk using the flow visualization technique. An inner drop of high surface tension liquid is placed centrally on the disk followed by a drop of outer liquid (lower surface tension) placed exactly above that. The disk is then rotated at a desired speed for a range of volume ratios of two liquids. Such an arrangement of two superposed liquid drops does not affect the spreading behavior of the outer liquid but influences that of the inner liquid significantly. The drop spreads to a larger extent and breaks into more fingers (Nf) as compared to the case where the same liquid is spreading in the absence of outer liquid. The experimentally observed number of fingers is compared with the prediction using available theory for single liquid. It is found that the theory over-predicts the value of Nf for the inner liquid while it is covered by an outer liquid. We provide a theoretical justification for this observation using linear stability analysis. Our analysis demonstrates that for small but finite surface tension ratio of the two liquids, the presence of the outer interface reduces the value of the most unstable wave number which is equivalent to the decrease in the number of fingers observed experimentally. Finally, sustained rotation of the disk leads to the formation of droplets at the tip of the fingers traveling outwards.
Nonlinear resonances in the ABC-flow
Authors: Didov A. A. , Uleysky M. Yu.
Published: January 2018

In this paper, we study resonances of the ABC-flow in the near integrable case (C≪1). This is an interesting example of a Hamiltonian system with 3/2 degrees of freedom in which simultaneous existence of two resonances of the same order is possible. Analytical conditions of the resonance existence are received. It is shown numerically that the largest n:1 (n = 1, 2, 3) resonances exist, and their energies are equal to theoretical energies in the near integrable case. We provide analytical and numerical evidences for existence of two branches of the two largest n:1 (n = 1, 2) resonances in the region of finite motion.
The multi-state energy landscape of the SAM-I riboswitch: A single-molecule Förster resonance energy transfer spectroscopy study
Authors: Manz Christoph , Kobitski Andrei Yu. , Samanta Ayan , Jäschke Andres , Nienhaus G. Ulrich
Published: January 2018

RNA (ribonucleic acid) molecules are highly flexible biopolymers fluctuating at physiological temperatures among many different conformations that are represented by minima in a hierarchical conformational free energy landscape. Here we have employed single-molecule FRET (smFRET) to explore the energy landscape of the B. subtilis yitJ SAM-I riboswitch (RS). In this small RNA molecule, specific binding of an S-adenosyl-L-methionine (SAM) ligand in the aptamer domain regulates gene expression by inducing structural changes in another domain, the expression platform, causing transcription termination by the RNA polymerase. We have measured smFRET histograms over wide ranges of Mg2+ concentration for three RS variants that were specifically labeled with fluorescent dyes on different sites. In the analysis, different conformations are associated with discrete Gaussian model distributions, which are typically fairly broad on the FRET efficiency scale and thus can be extremely challenging to unravel due to their mutual overlap. Our earlier work on two SAM-I RS variants revealed four major conformations. By introducing a global fitting procedure which models both the Mg2+ concentration dependencies of the fractional populations and the average FRET efficiencies of the individual FRET distributions according to Mg2+ binding isotherms, we were able to consistently describe the histogram data of both variants at all studied Mg2+ concentrations. With the third FRET-labeled variant, however, we found significant deviations when applying the four-state model to the data. This can arise because the different FRET labeling of the new variant allows two states to be distinguished that were previously not separable due to overlap. Indeed, the resulting five-state model presented here consistently describes the smFRET histograms of all three variants as well as their variations with Mg2+ concentration. We also performed a triangulation of the donor position for two of the constructs to explore how the expression platform is oriented with respect to the aptamer.
Acoustic metamaterial panel for both fluid passage and broadband soundproofing in the audible frequency range
Authors: Jung Jae Woong , Kim Jae Eun , Lee Jin Woo
Published: January 2018

We present the design, including an experimental demonstration, of an acoustic metamaterial panel aimed at reducing incoming broadband noise in the audible frequency range while allowing an incoming fluid to pass through the holes formed in the panel. The noise reduction performance of the proposed acoustic metamaterial panel is attributed to an array of annular cavities enclosing the fluid passage holes. The acoustic behavior of the acoustic metamaterial panel is theoretically analyzed by the transfer matrix method, and an equivalent acoustic impedance of each annular cavity is included with its effective length in the derived transfer matrix. The effective bulk modulus for the acoustic metamaterial panel is then extracted from the transmission and reflection coefficients by using the retrieval method. It is shown that the frequency range of the negative effective bulk modulus coincides with the stop band of the acoustic metamaterial panel. The underlying physical mechanism for the negative effective bulk modulus is attributed to the out-of-phase motion of vibrating particles in adjacent annular cavities. A calculated transmission coefficient curve of the acoustic metamaterial panel is shown to be in good agreement with the measured one. The findings presented in this work should be useful in the design of a holey soundproof panel.
Fluorescence quenching and the “ring-mode” to “red-mode” transition in alkali inductively coupled plasmas
Authors: Huang M. , Bazurto R. , Camparo J.
Published: January 2018

The ring-mode to red-mode transition in alkali metal inductively coupled plasmas (ICPs) (i.e., rf-discharge lamps) is perhaps the most important physical phenomenon affecting these devices as optical pumping light sources for atomic clocks and magnetometers. It sets the limit on useful ICP operating temperature, thereby setting a limit on ICP light output for atomic-clock/magnetometer signal generation, and it is a temperature region of ICP operation associated with discharge instability. Previous work has suggested that the mechanism driving the ring-mode to red-mode transition is associated with radiation trapping, but definitive experimental evidence validating that hypothesis has been lacking. Based on that hypothesis, one would predict that the introduction of an alkali-fluorescence quenching gas (i.e., N2) into the ICP would increase the ring-mode to red-mode transition temperature. Here, we test that prediction, finding direct evidence supporting the radiation-trapping hypothesis.
Turbulence simulation taking account of inhomogeneity of neutral density in linear devices
Authors: Kasuya N. , Abe S. , Sasaki M. , Inagaki S. , Kobayashi T. , Yagi M.
Published: January 2018

It is important to consider a combination of inhomogeneities, which drive and/or damp instabilities in magnetized plasmas. The inhomogeneity of neutral particle density is taken into account for analyzing turbulent states in linear devices by combining two kinds of simulations in this research. One is a simulation for 2D profiles of neutral particles and the other is that for resistive drift wave turbulence. Radial and axial profiles of neutral particles are calculated by the Monte Carlo method with a configuration of linear device PANTA. The ratio for ionization of neutral particles depends on the electron temperature, and the higher temperature in the operation range makes the neutral density smaller near the center of the plasma. Then, the radial profile of the ion-neutral collision frequency is set by introducing these neutral density profiles into resistive drift wave turbulence simulations. Smaller ion-neutral collision frequency makes the instabilities more unstable, and its inhomogeneity enhances mean electrostatic potential formation. The eigenmode structure is changed with the inhomogeneous ion-neutral collision frequency, and convective derivative nonlinearity generates the azimuthal flow near the center of the plasma. Two roles of the neutral particles on the turbulence, the direct change in linear instabilities and formation of background flows, become clear.
Polydisperse particle-driven gravity currents in non-rectangular cross section channels
Authors: Zemach T.
Published: January 2018

We consider a high-Reynolds-number gravity current generated by polydisperse suspension of n types of particles distributed in a fluid of density ρi. Each class of particles in suspension has a different settling velocity. The current propagates along a channel of non-rectangular cross section into an ambient fluid of constant density ρa. The bottom and top of the channel are at z = 0, H, and the cross section is given by the quite general form −f1(z) ≤ y ≤ f2(z) for 0 ≤ z ≤ H. The flow is modeled by the one-layer shallow-water equations obtained for the time-dependent motion. We solve the problem by a finite-difference numerical code to present typical height h, velocity u, and mass fractions of particle (concentrations) (ϕ( j), j = 1, …, n) profiles. The runout length of suspensions in channels of power-law cross sections is analytically predicted using a simplified depth-averaged “box” model. We demonstrate that any degree of polydispersivity adds to the runout length of the currents, relative to that of equivalent monodisperse currents with an average settling velocity. The theoretical predictions are supported by the available experimental data. The present approach is a significant generalization of the particle-driven gravity current problem: on the one hand, now the monodisperse current in non-rectangular channels is a particular case of n = 1. On the other hand, the classical formulation of polydisperse currents for a rectangular channel is now just a particular case, f(z) = const., in the wide domain of cross sections covered by this new model.
Hexagonal boron nitride neutron detectors with high detection efficiencies
Authors: Maity A. , Grenadier S. J. , Li J. , Lin J. Y. , Jiang H. X.
Published: January 2018

Neutron detectors fabricated from 10B enriched hexagonal boron nitride (h-10BN or h-BN) epilayers have demonstrated the highest thermal neutron detection efficiency among solid-state neutron detectors to date at about 53%. In this work, photoconductive-like vertical detectors with a detection area of 1 × 1 mm2 were fabricated from 50 μm thick free-standing h-BN epilayers using Ni/Au and Ti/Al bilayers as ohmic contacts. Leakage currents, mobility-lifetime (μτ) products under UV photoexcitation, and neutron detection efficiencies have been measured for a total of 16 different device configurations. The results have unambiguously identified that detectors incorporating the Ni/Au bilayer on both surfaces as ohmic contacts and using the negatively biased top surface for neutron irradiation are the most desired device configurations. It was noted that high growth temperatures of h-10BN epilayers on sapphire substrates tend to yield a higher concentration of oxygen impurities near the bottom surface, leading to a better device performance by the chosen top surface for irradiation than by the bottom. Preferential scattering of oxygen donors tends to reduce the mobility of holes more than that of electrons, making the biasing scheme with the ability of rapidly extracting holes at the irradiated surface while leaving the electrons to travel a large average distance inside the detector at a preferred choice. When measured against a calibrated 6LiF filled micro-structured semiconductor neutron detector, it was shown that the optimized configuration has pushed the detection efficiency of h-BN neutron detectors to 58%. These detailed studies also provided a better understanding of growth-mediated impurities in h-BN epilayers and their effects on the charge collection and neutron detection efficiencies.
Orthogonal polynomials from Hermitian matrices. II
Authors: Odake Satoru , Sasaki Ryu
Published: January 2018

This is the second part of the project “unified theory of classical orthogonal polynomials of a discrete variable derived from the eigenvalue problems of Hermitian matrices.” In a previous paper, orthogonal polynomials having Jackson integral measures were not included, since such measures cannot be obtained from single infinite dimensional Hermitian matrices. Here we show that Jackson integral measures for the polynomials of the big q-Jacobi family are the consequence of the recovery of self-adjointness of the unbounded Jacobi matrices governing the difference equations of these polynomials. The recovery of self-adjointness is achieved in an extended ℓ2 Hilbert space on which a direct sum of two unbounded Jacobi matrices acts as a Hamiltonian or a difference Schrödinger operator for an infinite dimensional eigenvalue problem. The polynomial appearing in the upper/lower end of the Jackson integral constitutes the eigenvector of each of the two-unbounded Jacobi matrix of the direct sum. We also point out that the orthogonal vectors involving the q-Meixner (q-Charlier) polynomials do not form a complete basis of the ℓ2 Hilbert space, based on the fact that the dual q-Meixner polynomials introduced in a previous paper fail to satisfy the orthogonality relation. The complete set of eigenvectors involving the q-Meixner polynomials is obtained by constructing the duals of the dual q-Meixner polynomials which require the two-component Hamiltonian formulation. An alternative solution method based on the closure relation, the Heisenberg operator solution, is applied to the polynomials of the big q-Jacobi family and their duals and q-Meixner (q-Charlier) polynomials.
The development of an online risk calculator for the prediction of future syphilis among a high-risk cohort of men who have sex with men and transgender women in Lima, Peru
Authors: Allan-Blitz Lao-Tzu , Konda Kelika A. , Vargas Silver K. , Wang Xiaoyan , Segura Eddy R. , Fazio Boris M. , Calvo Gino M. , Caceres Carlos F. , Klausner Jeffrey D.
Published: January 2018

Background Syphilis incidence worldwide has rebounded since 2000, particularly among men who have sex with men (MSM). A predictive model for syphilis infection may inform prevention counselling and use of chemoprophylaxis. Methods: Data from a longitudinal cohort study of MSM and transgender women meeting high-risk criteria for syphilis who were followed quarterly for 2 years were analysed. Incidence was defined as a four-fold increase in rapid plasma reagin (RPR) titres or new RPR reactivity if two prior titres were non-reactive. Generalised estimating equations were used to calculate rate ratios (RR) and develop a predictive model for 70% of the dataset, which was then validated in the remaining 30%. An online risk calculator for the prediction of future syphilis was also developed. Results: Among 361 participants, 22.0% were transgender women and 34.6% were HIV-infected at baseline. Syphilis incidence was 19.9 cases per 100-person years (95% confidence interval (CI) 16.3–24.3). HIV infection (RR 2.22; 95% CI 1.54–3.21) and history of syphilis infection (RR 2.23; 95% 1.62–3.64) were significantly associated with incident infection. The final predictive model for syphilis incidence in the next 3 months included HIV infection, history of syphilis, number of male sex partners and sex role for anal sex in the past 3 months, and had an area under the curve of 69%. The online syphilis risk calculator based on those results is available at: www.syphrisk.net. Conclusions: Using data from a longitudinal cohort study among a population at high risk for syphilis infection in Peru, we developed a predictive model and online risk calculator for future syphilis infection. The predictive model for future syphilis developed in this study has a moderate predictive accuracy and may serve as the foundation for future studies.
Human bone perivascular niche-on-a-chip for studying metastatic colonization
Authors: Marturano-Kruik Alessandro , Nava Michele Maria , Yeager Keith , Chramiec Alan , Hao Luke , Robinson Samuel , Guo Edward , Raimondi Manuela Teresa , Vunjak-Novakovic Gordana
Published: January 2018

Significance

Improved human preclinical models are needed to better predict patients’ responses to anticancer drugs. Increasing the complexity of models may be a successful strategy only if crucial components of a tumor are identified, replicated, and controlled in vitro. We developed a perivascular niche to study metastatic colonization of the bone. Using a microfluidic chip, we exposed the niche to interstitial flow, oxygen gradients, and external forces, and established a dense vascular network. Cancer cells colonizing the bone resisted targeted therapy by entering a slow proliferative state. We expect that microfluidic niche-on-chip models will facilitate the development of drugs targeting persistent tumor cells into the bone and help manage the risk of metastatic relapse.
STAC proteins associate to the IQ domain of Ca
V
1.2 and inhibit calcium-dependent inactivation
Authors: Campiglio Marta , Costé de Bagneaux Pierre , Ortner Nadine J. , Tuluc Petronel , Van Petegem Filip , Flucher Bernhard E.
Published: January 2018

Significance

Association of the adaptor protein STAC3 to the calcium channel was recently identified as essential for skeletal muscle contraction. While STAC3 is expressed exclusively in skeletal muscle, the other two isoforms, STAC1 and STAC2, are found in the brain, but their function has not yet been investigated. Recently we identified the C1 domain of STAC as crucial for its association with calcium channels. However, the corresponding binding domain remained unknown. Here, we demonstrate that STAC proteins associate with the C terminus of Ca
V
1.2 at the IQ domain, and that this interaction results in the inhibition of calcium-dependent inactivation. Taken together, our data identify a functionally important STAC interaction domain and suggest that STAC proteins modulate calcium entry through Ca
V
1 channels.
Abrupt change of the superconducting gap structure at the nematic critical point in FeSe
1−x
S
x
Authors: Sato Yuki , Kasahara Shigeru , Taniguchi Tomoya , Xing Xiangzhuo , Kasahara Yuichi , Tokiwa Yoshifumi , Yamakawa Youichi , Kontani Hiroshi , Shibauchi Takasada , Matsuda Yuji
Published: January 2018

Significance

Electronic nematicity that spontaneously breaks the rotational symmetry of the underlying crystal lattice has been a growing issue in high-temperature superconductivity of iron pnictides/chalcogenides and cuprates. FeSe

1 −
x

S

x

, in which the nematicity can be tuned by isoelectronic sulfur substitution, offers a fascinating opportunity to clarify the direct relationship between the nematicity and superconductivity. Here, we discover a dramatic change in the superconducting gap structure at the critical concentration of sulfur where the nematicity disappears, i.e., nematic critical point. Our observation provides direct evidence that the orbital-dependent nature of the critical nematic fluctuations has a strong impact on the superconducting pairing interaction.
Seasonal variation in leaf age structure of the Eelgrass Zostera marina on the eastern coast of the Shandong Peninsula, China
Authors: Fang Chao , Zhang Peidong , Wang Xitao , Zhao Jiansheng , Li Wentao
Published: January 2018

Many important processes for Seagrass ecology depend on leaf age. Through biweekly census, from April to November 2015, seasonal variation in leaf age structure of the Eelgrass Zostera marina L. was studied in Swan Lake of Shandong Peninsula, China by examining density, dimensions and biomass of shoots relative to leaf ages. In addition, we examined if variability in leaf age structure was related to water temperature and/or underwater irradiance. The leaf density, number of leaves per shoot, leaf area index, total leaf area per shoot and leaf biomass of young and old Z. marina leaves were far less than those of the mature leaves with percentages of >50% in all leaf ages. The leaf age structure of mature Z. marina leaves exhibited a clear seasonal variation with significant peaks in early July, which corresponded with the seasonal changes in shoot density and biomass of Z. marina. The results demonstrated that mature leaves would be a leading component in leaf age structure of Z. marina. Curve Estimation revealed that the seasonal variation in leaf age structure of Eelgrass was closely positively related to water temperature. The results provided data that could prove helpful in quantitative studies of leaf-age dependent aspects of Seagrass ecology.
The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling
Authors: Petsalaki Eleni , Dandoulaki Maria , Zachos George
Published: January 2018

The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod–ZW10–Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore–microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2 checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10 through a small C-terminal region, and constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle functions do not require endosomal sorting complex required for transport–dependent membrane remodeling. These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores.
Deep Learning–Based Noise Reduction Approach to Improve Speech Intelligibility for Cochlear Implant Recipients
Authors: Lai Ying-Hui , Tsao Yu , Lu Xugang , Chen Fei , Su Yu-Ting , Chen Kuang-Chao , Chen Yu-Hsuan , Chen Li-Ching , Po-Hung Li Lieber , Lee Chin-Hui
Published: January 2018

Objective:

We investigate the clinical effectiveness of a novel deep learning–based noise reduction (NR) approach under noisy conditions with challenging noise types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear implant (CI) recipients.

Design:

The deep learning–based NR approach used in this study consists of two modules: noise classifier (NC) and deep denoising autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive experiments, we conduct qualitative and quantitative analyses on the NC module and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition performance of the NC + DDAE NR and classical single-microphone NR approaches for Mandarin-speaking CI recipients under different noisy conditions. The testing set contains Mandarin sentences corrupted by two types of maskers, two-talker babble noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two conventional NR techniques and the proposed deep learning–based approach are used to process the noisy utterances. We qualitatively compare the NR approaches by the amplitude envelope and spectrogram plots of the processed utterances. Quantitative objective measures include (1) normalized covariance measure to test the intelligibility of the utterances processed by each of the NR approaches; and (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients. These nine CI recipients use their own clinical speech processors during testing.

Results:

The experimental results of objective evaluation and listening test indicate that under challenging listening conditions, the proposed NC + DDAE NR approach yields higher intelligibility scores than the two compared classical NR techniques, under both matched and mismatched training-testing conditions.

Conclusions:

When compared to the two well-known conventional NR techniques under challenging listening condition, the proposed NC + DDAE NR approach has superior noise suppression capabilities and gives less distortion for the key speech envelope information, thus, improving speech recognition more effectively for Mandarin CI recipients. The results suggest that the proposed deep learning–based NR approach can potentially be integrated into existing CI signal processors to overcome the degradation of speech perception caused by noise.
Determination of Examination-Specific Diagnostic Reference Level in Computed Tomography by A New Quality Control-Based Dose Survey Method
Authors: Parsi Masoumeh , Sohrabi Mehdi , Mianji Fereidoun , Paydar Reza
Published: January 2018

A new “quality-control-based (QC-based) dose survey method” has been developed for determination of diagnostic reference levels (DRL) in Computed Tomography (CT) examinations. The “QC-based dose survey method” is based on the use of retrospective data in the QC documents and reports, which are typically available from the National Regulatory Authority database. The method was applied to 70 CT scanners in Tehran, Iran, by using the available QC reports from the database. The commonly used “data collection method” was also applied by filling each questionnaire on-site to validate the new method. Using the new QC-based and data collection methods, the DRLs of four common CT examinations: head, sinus, chest, and abdomen/pelvis were determined and compared. The DRLs determined by the “QC-based method” for head, sinus, chest, and abdomen/pelvis are 59, 29, 10, and 13 mGy, respectively, for the volume computed tomography dose index (CTDIVol) and 834, 235, 233, and 522 mGy-cm for the dose length product (DLP), respectively. The difference between the DRLs obtained by the two methods is on the average 6.7 ± 5.7%, which is within the acceptance tolerance level of the IAEA for QC dosimetry tests. The “QC-based dose survey method” is believed to be an effective alternative method to the other commonly used “data collection” and “direct dose measurement method” for determination of CT examination DRLs. This new method has unique characteristics such as simplicity, time and cost effectiveness, highly reduced clinical interruptions and collaborations, and potential for large-scale surveys with capability for more frequent review of national DRL values.
Initial Experience of Single-port Laparoscopic Multivisceral Resection for Locally Advanced Colon Cancer
Authors: Tei Mitsuyoshi , Otsuka Masahisa , Suzuki Yozo , Akamatsu Hiroki
Published: January 2018

Aim:

The aim of this study was to evaluate the safety and feasibility of single-port laparoscopic multivisceral resection (SLMVR) for locally advanced colon cancer invading or adhering to neighboring organs.

Method:

A prospectively collected database was collated of all patients undergoing SLMVR from January 2011 to December 2014. Short-term and long-term oncologic outcomes were evaluated.

Results:

Thirty consecutive patients who underwent SLMVR were identified and the completion rate was 90%. The R0 resection rate of the primary tumor was 100%. The postoperative complication rate was 23.3%. The 3-year relapse-free survival rates of patients with stage II (n=11) and stage III (n=12) disease were 80.8% and 54.6%, respectively. The 5-year overall survival rates of patients with stage II and stage III disease were 75.8% and 75.0% over a median follow-up of 42 months, respectively.

Conclusions:

SLMVR for locally advanced colon cancer is safe and feasible in selected patients.
Linear-Nonlinear-Time-Warp-Poisson models of neural activity
Authors: Lawlor Patrick N. , Perich Matthew G. , Miller Lee E. , Kording Konrad P.
Published: January 2018

Prominent models of spike trains assume only one source of variability – stochastic (Poisson) spiking – when stimuli and behavior are fixed. However, spike trains may also reflect variability due to internal processes such as planning. For example, we can plan a movement at one point in time and execute it at some arbitrary later time. Neurons involved in planning may thus share an underlying time-course that is not precisely locked to the actual movement. Here we combine the standard Linear-Nonlinear-Poisson (LNP) model with Dynamic Time Warping (DTW) to account for shared temporal variability. When applied to recordings from macaque premotor cortex, we find that time warping considerably improves predictions of neural activity. We suggest that such temporal variability is a widespread phenomenon in the brain which should be modeled.
A hypermorphic Nfkbid allele represents an Idd7 locus gene contributing to impaired thymic deletion of autoreactive diabetogenic CD8+ T-cells in NOD mice
Authors: Presa Maximiliano , Racine Jeremy J. , Dwyer Jennifer R. , Lamont Deanna J. , Ratiu Jeremy J. , Sarsani Vishal Kumar , Chen Yi-Guang , Geurts Aron , Schmitz Ingo , Stearns Timothy , Allocco Jennifer , Chapman Harold D. , Serreze David V.
Published: January 2018

In both NOD mice and humans, the development of type 1 diabetes (T1D) is dependent in part on autoreactive CD8+ T-cells recognizing pancreatic ß-cell peptides presented by often quite common MHC class I variants. Studies in NOD mice previously revealed the common H2-Kd and/or H2-Db class I molecules expressed by this strain acquire an aberrant ability to mediate pathogenic CD8+ T-cell responses through interactions with T1D susceptibility (Idd) genes outside the MHC. A gene(s) mapping to the Idd7 locus on proximal Chromosome 7 was previously shown to be an important contributor to the failure of the common class I molecules expressed by NOD mice to mediate the normal thymic negative selection of diabetogenic CD8+ T-cells. Using an inducible model of thymic negative selection and mRNA transcript analyses we initially identified an elevated Nfkbid expression variant is likely an NOD Idd7 region gene contributing to impaired thymic deletion of diabetogenic CD8+ T-cells. CRISPR/Cas9-mediated genetic attenuation of Nfkbid expression in NOD mice resulted in improved negative selection of autoreactive diabetogenic AI4 and NY8.3 CD8+ T-cells. These results indicated allelic variants of Nfkbid represent an Idd7 gene contributing to the efficiency of intrathymic deletion of diabetogenic CD8+ T-cells. However, while enhancing thymic deletion of pathogenic CD8+ T-cells, ablation of Nfkbid expression surprisingly accelerated T1D onset in NOD mice likely at least in part by numerically decreasing regulatory T- and B-lymphocytes (Tregs/Bregs), thereby reducing their peripheral immunosuppressive effects.
Imaging neural activity in the ventral nerve cord of behaving adultDrosophila
Authors: Chen Chin-Lin , Hermans Laura , Viswanathan Meera C. , Fortun Denis , Unser Michael , Cammarato Anthony , Dickinson Michael H. , Ramdya Pavan
Published: January 2018

To understand neural circuits that control limbs, one must measure their activity during behavior. Until now this goal has been challenging, because the portion of the nervous system that contains limb premotor and motor circuits is largely inaccessible to large-scale recording techniques in intact, moving animals – a constraint that is true for both vertebrate and invertebrate models. Here, we introduce a method for 2-photon functional imaging from the ventral nerve cord of behaving adultDrosophila melanogaster. We use this method to reveal patterns of activity across nerve cord populations during grooming and walking and to uncover the functional encoding of moonwalker ascending neurons (MANs), moonwalker descending neurons (MDNs), and a novel class of locomotion-associated descending neurons. This new approach enables the direct investigation of circuits associated with complex limb movements.
A population-based atlas of the human pyramidal tract in 410 healthy participants
Authors: Chenot Quentin , Tzourio-mazoyer Nathalie , Rheault François , Descoteaux Maxime , Crivello Fabrice , Zago Laure , Mellet Emmanuel , Jobard Gaël , Joliot Marc , Mazoyer Bernard , Petit Laurent
Published: January 2018

With the advances in diffusion MRI and tractography, numerous atlases of the human pyramidal tract (PyT) have been proposed but the inherent limitation of tractography to resolve crossing bundles within the centrum semiovale have so far prevented the complete description of the most lateral PyT projections. Here, we combined a precise manual positioning of individual subcortical regions of interest along the descending pathway of the PyT with a new bundle-specific tractography algorithm. This later is based on anatomical priors to improve streamlines tracking in crossing areas. We then extracted both left and right PyT in a large cohort of 410 healthy participants and built a population-based atlas of the whole-fanning PyT with a complete description of its most cortico-lateral projections. Clinical applications are envisaged, the whole-fanning PyT atlas being likely a better marker of corticospinal integrity metrics than those currently used within the frame of prediction of post-stroke motor recovery. The present population-based PyT, freely available, provides an interesting tool for clinical applications in order to locate specific PyT damage and its impact to the short and long-term motor recovery after stroke.
NormExpression: an R package to normalize gene expression data using evaluated methods
Authors: Wu Zhenfeng , Liu Weixiang , Jin Xiufeng , Yu Deshui , Wang Hua , Glusman Gustavo , Robinson Max , Liu Lin , Ruan Jishou , Shan Gao
Published: January 2018

Data normalization is a crucial step in the gene expression analysis as it ensures the validity of its downstream analyses. Although many metrics have been designed to evaluate the current normalization methods, the different metrics yield inconsistent results. In this study, we designed a new metric named Area Under normalized CV threshold Curve (AUCVC) and applied it with another metric mSCC to evaluate 14 commonly used normalization methods, achieving consistency in our evaluation results using both bulk RNA-seq and scRNA-seq data from the same library construction protocol. This consistency has validated the underlying theory that a sucessiful normalization method simultaneously maximizes the number of uniform genes and minimizes the correlation between the expression profiles of gene pairs. This consistency can also be used to analyze the quality of gene expression data. The gene expression data, normalization methods and evaluation metrics used in this study have been included in an R package named NormExpression. NormExpression provides a framework and a fast and simple way for researchers to evaluate methods (particularly some data-driven methods or their own methods) and then select a best one for data normalization in the gene expression analysis.
Effect of head volume conduction on directed connectivity estimated between reconstructed EEG sources
Authors: Anzolin Alessandra , Presti Paolo , Van de Steen Frederik , Astolfi Laura , Haufe Stefan , Marinazzo Daniele
Published: January 2018

Electrical activity recorded on the scalp using electroencephalography (EEG) results from the mixing of signals originating from different regions of the brain as well as from artefactual sources. In order to investigate the role of distinct brain areas in a given experiment, the signal recorded on the sensors is typically projected back into the brain (source reconstruction) using algorithms that address the so-called EEG “inverse problem”. Once that the activity of sources located inside of the brain has been reconstructed, it is often desirable to study the statistical dependencies among them, in particular to quantify directional dynamical interactions between brain areas. Unfortunately, even when performing source reconstruction, the superposition of signals that is due to the propagation of activity from sources to sensors cannot be completely undone, resulting in potentially biased estimates of directional functional connectivity. Here we perform a set of simulations involving interacting sources, and quantify source connectivity estimation performance as a function of the location of the sources, their distance to each other, the noise level, the source reconstruction algorithm, and the connectivity estimator. The generated source activity was projected onto the scalp and projected back to the cortical level using two source reconstruction algorithms, Linearly Constrained Minimum Variance (LCMV) beamforming and ‘Exact’ Low-resolution Tomography (eLORETA). In source space, directed connectivity was estimated using Multi-Variate Granger Causality (MVGC), Time-Reversed Granger Causality (TRGC) and Partial Directed Coherence (PDC), and the estimated connectivity was compared with the imposed ground truth. Our results demonstrate that all considered factors significantly affect the connectivity estimation performance.
Key components of the delirium syndrome and mortality: greater impact of acute change and disorganised thinking in a prospective cohort study
Authors: Diwell RA , Davis D , Vickerstaff V , Sampson EL
Published: January 2018

Background

Delirium increases the risk of mortality during an acute hospital admission. Full syndromal delirium (FSD) is associated with greatest risk and subsyndromal delirium (SSD) is associated with intermediate risk, compared to patients with no delirium - suggesting a dose-response relationship. It is not clear how individual diagnostic symptoms of delirium influence the association with mortality. Our objectives were to measure the prevalence of FSD and SSD, and assess the effect that FSD, SSD and individual symptoms of delirium (from the Confusion Assessment Method-short version (s-CAM)) have on mortality rates.

Methods

Exploratory analysis of a prospective cohort (aged ≥ 70 years) with acute (unplanned) medical admission (4/6/2007-4/11/2007). The outcome was mortality (data censored 6/10/2011). The principal exposures were FSD and SSD compared to no delirium (as measured by the CAM), along with individual delirium symptoms on the CAM. Cox regression was used to estimate the impact FSD and SSD and individual CAM items had on mortality.

Results

The cohort (n=610) mean age was 83 (SD 7); 59% were female. On admission, 11% had FSD and 33% had SSD. Of the key diagnostic symptoms for delirium, 17% acute onset, 19% inattention, 17% disorganised thinking and 17% altered level of consciousness. Unadjusted analysis found FSD had an increased hazard ratio (HR) of 2.31 (95%CI 1.71, 3.12), for SSD the HR was 1.26 (1.00, 1.59). Adjusted analysis remained significant for FSD (1.55 95%CI 1.10, 2.18) but nonsignificant for SSD (HR=0.92 95% CI 0.70, 1.19). Two CAM items were significantly associated with mortality following adjustment: acute onset and disorganised thinking.

Conclusion

We observed a dose-response relationship between mortality and delirium, FSD had the greatest risk and SSD having intermediate risk. The CAM items “acute onset” and “disorganised thinking” drove the associations observed. Clinically, this highlights the necessity of identifying individual symptoms of delirium.
The universal mechanism of intermediate filament transport
Authors: Robert Amélie , Tian Peirun , Adam Stephen A. , Goldman Robert D. , Gelfand Vladimir I.
Published: January 2018

Intermediate filaments (IFs) are a major component of the cytoskeleton that regulates a wide range of physiological properties in eukaryotic cells. In motile cells, the IF network has to adapt to constant changes of cell shape and tension. In this study, we used two cell lines that express vimentin and keratins 8/18 to study the dynamic behavior of these IFs. We demonstrated that both IF types undergo extensive transport along microtubules. This was an unexpected result as keratin filament remodeling has been described to depend on actin dynamics. We established the role of kinesin-1 in vimentin and keratin IF transport by knocking out KIF5B, the ubiquitous isoform of kinesin-1. Futhermore, we demonstrated that unlike typical membrane cargoes, transport of both types of IFs does not involve kinesin light chains, but requires the presence of the same region of the kinesin-1 tail, suggesting a unified mechanism of IF transport.
Unbiased construction of a temporally consistent morphological atlas of neonatal brain development
Authors: Schuh Andreas , Makropoulos Antonios , Robinson Emma C. , Cordero-Grande Lucilio , Hughes Emer , Hutter Jana , Price Anthony N. , Murgasova Maria , Teixeira Rui Pedro A. G. , Tusor Nora , Steinweg Johannes K. , Victor Suresh , Rutherford Mary A. , Hajnal Joseph V. , Edwards A. David , Rueckert Daniel
Published: January 2018

Premature birth increases the risk of developing neurocognitive and neurobe-havioural disorders. The mechanisms of altered brain development causing these disorders are yet unknown. Studying the morphology and function of the brain during maturation provides us not only with a better understanding of normal development, but may help us to identify causes of abnormal development and their consequences. A particular difficulty is to distinguish abnormal patterns of neurodevelopment from normal variation. The Developing Human Connectome Project (dHCP) seeks to create a detailed four-dimensional (4D) connectome of early life. This connectome may provide insights into normal as well as abnormal patterns of brain development. As part of this project, more than a thousand healthy fetal and neonatal brains will be scanned in vivo. This requires computational methods which scale well to larger data sets. We propose a novel groupwise method for the construction of a spatio-temporal model of mean morphology from cross-sectional brain scans at different gestational ages. This model scales linearly with the number of images and thus improves upon methods used to build existing public neonatal atlases, which derive correspondence between all pairs of images. By jointly estimating mean shape and longitudinal change, the atlas created with our method overcomes temporal inconsistencies, which are encountered when mean shape and intensity images are constructed separately for each time point. Using this approach, we have constructed a spatio-temporal atlas from 275 healthy neonates between 35 and 44 weeks post-menstrual age (PMA). The resulting atlas qualitatively preserves cortical details significantly better than publicly available atlases. This is moreover confirmed by a number of quantitative measures of the quality of the spatial normalisation and sharpness of the resulting template brain images.
Cyclic dominance emerges from the evolution of two inter-linked cooperative behaviours in the social amoeba
Authors: Shibasaki Shota , Shimada Masakazu
Published: January 2018

Evolution of cooperation has been one of the most important problems in sociobiology, and many researchers have revealed mechanisms that can facilitate the evolution of cooperation. However, most studies deal only with one cooperative behaviour, even though some organisms perform two or more cooperative behaviours. The social amoebaDictyostelium discoideumperforms two cooperative behaviours in starvation: fruiting body formation and macrocyst formation. Here, we constructed a model that couples these two behaviours, and we found that the two behaviours are maintained due to the emergence of cyclic dominance, although cooperation cannot evolve if only either of the two behaviours is performed. The common chemoattractant cyclic AMP is used in both fruiting body formation and macrocyst formation, providing a biological context for this coupling. Cyclic dominance emerges regardless of the existence of mating types or spatial structure in the model. In addition, cooperation can re-emerge in the population even after it goes extinct. These results indicate that the two cooperative behaviours of the social amoeba are maintained due to the common chemical signal that underlies both fruiting body formation and macrocyst formation. We demonstrate the importance of coupling multiple games when the underlying behaviours are associated with one another.
Local Delivery of Stromal Cell-Derived Factor-1α Improves the Pregnancy Rate of Injured Uterus through the Promotion of Endometrial and Vascular Regeneration
Authors: Cai Hongxai , Wu Bingbing , Liu Yixiao , Li Yu , Shi Libing , Gong Lin , Xia Yaxian , Heng BoonChin , Wu Huiling , Ouyang Hongwei , Zhu Zhenghua , Zou Xiaohui
Published: January 2018

Severe infection and mechanical injury of the uterus may lead to infertility and miscarriage. Currently, there is a lack of effective treatment modality for functional repair of uterine injury. To address this clinical challenge, this study aimed to develop a chemotactic composite scaffold by incorporating recombinant human stromal cell-derived factor-1α (rhSDF-1α) into a silk fibroin-bacterial cellulose (SF-BC) membrane carrier. A rat model of uterine injury was utilized for this study, which was composed of three groups: blank control, implantation with SF-BC only or SF-BC loaded with rhSDF-1α. The tissue regeneration efficacy of the three groups were analyzed and compared. The results showed that SF-BC loaded with rhSDF-1α significantly enhanced endometrial regeneration and arteriogenesis of the injured rat uterus, which led to improved pregnancy outcomes, thus indicating much promise for functional uterine repair and regeneration.
Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function
Authors: Vuolo Laura , Stevenson Nicola L. , Heesom Kate J. , Stephens David J.
Published: January 2018

The dynein-2 microtubule motor is the retrograde motor for intraflagellar transport. Mutations in dynein-2 components cause skeletal ciliopathies, notably Jeune syndrome. Dynein-2 comprises a heterodimer of two non-identical intermediate chains, WDR34 and WDR60. Here, we use knockout cell lines to demonstrate that each intermediate chain has a distinct role in cilia function. Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport, only WDR34 is essential for axoneme extension. In contrast, only WDR60 is essential for co-assembly of the other subunits. Furthermore, WDR60 cannot compensate for loss of WDR34 or vice versa. This work defines a functional asymmetry to match the subunit asymmetry within the dynein-2 motor. Analysis of causative point mutations in WDR34 and WDR60 can partially restore function to knockout cells. Our data show that Jeune syndrome is caused by defects in transition zone architecture as well as intraflagellar transport.

Here, Vuolo and colleagues use engineered knockout human cell lines to define roles for dynein-2 intermediate chains. WDR34 is required for axoneme extension, while WDR60 is not. Both subunits are required for cilia transition zone organization and bidirectional intraflagellar transport.