bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility evaluation of a neutron grating interferometer with an analyzer grating based on a structured scintillator
Authors: Kim Youngju , Kim Jongyul , Kim Daeseung , Hussey Daniel. S. , Lee Seung Wook
Published: March 2018

We introduce an analyzer grating based on a structured scintillator fabricated by a gadolinium oxysulfide powder filling method for a symmetric Talbot-Lau neutron grating interferometer. This is an alternative way to analyze the Talbot self-image of a grating interferometer without using an absorption grating to block neutrons. Since the structured scintillator analyzer grating itself generates the signal for neutron detection, we do not need an additional scintillator screen as an absorption analyzer grating. We have developed and tested an analyzer grating based on a structured scintillator in our symmetric Talbot-Lau neutron grating interferometer to produce high fidelity absorption, differential phase, and dark-field contrast images. The acquired images have been compared to results of a grating interferometer utilizing a typical absorption analyzer grating with two commercial scintillation screens. The analyzer grating based on the structured scintillator enhances interference fringe visibility and shows a great potential for economical fabrication, compact system design, and so on. We report the performance of the analyzer grating based on a structured scintillator and evaluate its feasibility for the neutron grating interferometer.
Experimental and numerical investigations of temporally and spatially periodic modulated wave trains
Authors: Houtani H. , Waseda T. , Tanizawa K.
Published: March 2018

A number of studies on steep nonlinear waves were conducted experimentally with the temporally periodic and spatially evolving (TPSE) wave trains and numerically with the spatially periodic and temporally evolving (SPTE) ones. The present study revealed that, in the vicinity of their maximum crest height, the wave profiles of TPSE and SPTE modulated wave trains resemble each other. From the investigation of the Akhmediev-breather solution of the nonlinear Schrödinger equation (NLSE), it is revealed that the dispersion relation deviated from the quadratic dependence of frequency on wavenumber and became linearly dependent instead. Accordingly, the wave profiles of TPSE and SPTE breathers agree. The range of this agreement is within the order of one wave group of the maximum crest height and persists during the long-term evolution. The findings extend well beyond the NLSE regime and can be applied to modulated wave trains that are highly nonlinear and broad-banded. This was demonstrated from the numerical wave tank simulations with a fully nonlinear potential flow solver based on the boundary element method, in combination with the nonlinear wave generation method based on the prior simulation with the higher-order spectral model. The numerical wave tank results were confirmed experimentally in a physical wave tank. The findings of this study unravel the fundamental nature of the nonlinear wave evolution. The deviation of the dispersion relation of the modulated wave trains occurs because of the nonlinear phase variation due to quasi-resonant interaction, and consequently, the wave geometry of temporally and spatially periodic modulated wave trains coincides.
An alternative way to increase the power gain of resonant rings
Authors: Zhuang Dehao , Liu Yunqi , Wang Fang , Lin Lin , Feng Liwen , Quan Shengwen , Liu Kexin
Published: March 2018

Resonant rings which can amplify RF power through the coupling of waves are used for high power breakdown tests, unidirectional filters, or pulse-shaping techniques. Usually, the RF output terminal of a resonant ring is connected to a matched load. For the resonant ring at Peking University, the matched load has been replaced by a waveguide shorting plate to obtain higher conditioning power for the 1.3 GHz capacitive type power couplers. The power gain is increased significantly with this short termination with the same input RF power. Working mechanism analysis, experiments, and results of this modified resonant ring will be presented.
Dielectric response and transport properties of alkylammonium formate ionic liquids
Authors: Nazet Andreas , Buchner Richard
Published: March 2018

Dielectric relaxation spectra of three members of the alkylammonium formate family of protic ionic liquids (PILs), namely, ethylammonium formate (EAF), n-butylammonium formate (BuAF), and n-pentylammonium formate (PeAF), as well as the pseudo-PIL triethylamine + formic acid (molar ratio 1:2; TEAF) have been studied over a wide frequency (50 MHz to 89 GHz) and temperature range (5–65 °C), complemented by measurements of their density, viscosity, and conductivity. It turned out that the dominating relaxation of EAF, BuAF, and PeAF arises from both cation and anion reorientations which are synchronized in their dynamics due to hydrogen bonding. Amplitudes and relaxation times of this mode reflect the—compared to nitrate—different nature of H bonding between the formate anion and ethylammonium cation, as well as increasing segregation of the PIL structure into polar and non-polar domains. The TEAF data suggest that its dominating relaxation is due to the rotation of the complex triethylamine⋅(formic acid)2 in which no significant proton transfer to an ion pair occurred. Weak dissociation of this complex into ions was postulated to account for the high conductivity of TEAF.
Thermal vibration of rectangular single-layered black phosphorus predicted by orthotropic plate model
Authors: Zhang Yiqing , Wang Lifeng , Jiang Jingnong
Published: March 2018

Vibrational behavior is very important for nanostructure-based resonators. In this work, an orthotropic plate model together with a molecular dynamics (MD) simulation is used to investigate the thermal vibration of rectangular single-layered black phosphorus (SLBP). Two bending stiffness, two Poisson's ratios, and one shear modulus of SLBP are calculated using the MD simulation. The natural frequency of the SLBP predicted by the orthotropic plate model agrees with the one obtained from the MD simulation very well. The root of mean squared (RMS) amplitude of the SLBP is obtained by MD simulation and the orthotropic plate model considering the law of energy equipartition. The RMS amplitude of the thermal vibration of the SLBP is predicted well by the orthotropic plate model compared to the MD results. Furthermore, the thermal vibration of the SLBP with an initial stress is also well-described by the orthotropic plate model.
Observations of a field-aligned ion/ion-beam instability in a magnetized laboratory plasma
Authors: Heuer P. V. , Weidl M. S. , Dorst R. S. , Schaeffer D. B. , Bondarenko A. S. , Tripathi S. K. P. , Van Compernolle B. , Vincena S. , Constantin C. G. , Niemann C. , Winske D.
Published: March 2018

Collisionless coupling between super Alfvénic ions and an ambient plasma parallel to a background magnetic field is mediated by a set of electromagnetic ion/ion-beam instabilities including the resonant right hand instability (RHI). To study this coupling and its role in parallel shock formation, a new experimental configuration at the University of California, Los Angeles utilizes high-energy and high-repetition-rate lasers to create a super-Alfvénic field-aligned debris plasma within an ambient plasma in the Large Plasma Device. We used a time-resolved fluorescence monochromator and an array of Langmuir probes to characterize the laser plasma velocity distribution and density. The debris ions were observed to be sufficiently super-Alfvénic and dense to excite the RHI. Measurements with magnetic flux probes exhibited a right-hand circularly polarized frequency chirp consistent with the excitation of the RHI near the laser target. We compared measurements to 2D hybrid simulations of the experiment.
Move a plateau, change a climate
Authors: Berkowitz Rachel
Published: March 2018

Climate models explore how changes in the Tibetan Plateau’s latitudinal position and elevation may have affected ancient Asia’s climate.
DOE grapples with its future uranium supply
Authors: Kramer David
Published: March 2018

Proliferation concerns factor into the decision on whether new domestic production capability is needed.
Plasma electrolytic oxidation coatings with fungicidal properties
Authors: Pezzato Luca , Cerchier Pietrogiovanni , Brunelli Katya , Bartolozzi Alessandra , Bertani Roberta , Dabalà Manuele
Published: March 2018

Plasma electrolytic oxidation (PEO) is a relatively new surface treatment that permits to increase the corrosion and wear resistance of metals. One of the peculiarities of the process is the possibility to incorporate into the produced coating the particles suspended in the electrolyte. In this work, micrometric silver particles were added in the PEO coating to innovatively give a fungicidal effect to the samples due to the presence of silver, whose fungicidal effect is well known. PEO coatings were produced on aluminium alloy 7075 using an electrolyte containing sodium silicate and silver particles. The thickness, morphology, composition and corrosion resistance of the obtained coatings were studied. The fungicidal properties were evaluated with contact tests of 2 and 4 h using Candida albicans ATCC 10231. Silver particles were homogeneously distributed in the coating and the silver-containing samples were characterised by improved corrosion resistance and high fungicidal activity.
Characterisation of electroplated Ni45Fe55 thin films on n-Si (111)
Authors: Chenna A. , Benbrahim N. , Hamadou L. , Boudinar S. , Kadri A. , Chainet E. , Dahmane Y.
Published: March 2018

Electrodeposition of NiFe films, on hydrogen-terminated n-Si (111)-H from acidic dilute sulphate solution, was studied by electrochemical measurements at room temperature in the presence and absence of saccharin. The electroplating process kinetics was investigated by voltammetric study and the effect of Fe2+ concentration on the deposit composition was studied as well with energy dispersive spectrometry analysis. The average composition of the Ni45Fe55 film was obtained for Fe2+ concentration in the range of [0.030–0.035] mol L−1 at a current density of −6 mA cm−2. Correlation between Fe2+ concentration in the NiFe deposit and electronic properties was examined by electrochemical impedance spectroscopy. Film roughness depends on Fe2+ concentration and a smoother deposit was obtained for the Ni45Fe55 film. Very low coercivity (less than 1.3 Oe) was measured in the Ni45Fe55 film with a nominal thickness of 640 nm. The very soft magnetic properties of the NiFe films provide information about the low level of inhomogeneities present in these films.
Down-regulation of senescence marker protein 30 by iron-specific chelator deferoxamine drives cell senescence
Authors: Inoue Hirofumi , Hanawa Nobuaki , Katsumata-Tsuboi Rie , Katsumata Shi-Ichi , Takahashi Nobuyuki , Uehara Mariko
Published: March 2018

To our knowledge, this is the first study to report down-regulation of senescence marker protein 30 (SMP30) by iron-specific chelator deferoxamine (DFO) on FAO cell senescence, using a DNA microarray. Furthermore, DFO treatment increased senescence marker β-galactosidase activity, whereas this activity was attenuated by overexpression of SMP30. Our data suggested that down-regulation of SMP30 drives cell senescence in iron-chelated condition.
Translation and language errors in the Indonesian–English translation
Authors: Dewi Haru Deliana
Published: March 2018

This paper is a small part of my dissertation which particularly describes translation and language errors based on trends in Translation Studies. Translation and language errors are important to assess the quality of a translation product. However, little or almost none of the literature has discussed the translation and language errors in the Indonesian–English language pair. This study aims to discover the types of translation and language errors mostly found in the Indonesian–English translation. The data were obtained by conducting several projects in the translation classes of LBI (Lembaga Bahasa International – International Language Institution) of the Faculty of Humanities (FIB) of Universitas Indonesia (UI) for 2 years from 2013 to 2015 by asking the students to do translation from an Indonesian text into English. The results show that the most frequent errors occurring are incorrect usage, grammatical errors, and omissions. This paper can be considered as preliminary research on translation and language errors in the Indonesian–English language pair which should be further investigated.
Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematodeCaenorhabditis elegans
Authors: Barnes Dawn E. , Watabe Eichi , Ono Kanako , Kwak Euiyoung , Kuroyanagi Hidehito , Ono Shoichiro
Published: March 2018

Tropomyosin, one of the major actin filament–binding proteins, regulates actin–myosin interaction and actin-filament stability. Multicellular organisms express a number of tropomyosin isoforms, but understanding of isoform-specific tropomyosin functions is incomplete. The nematode Caenorhabditis elegans has a single tropomyosin gene, lev-11, which has been reported to express four isoforms by using two separate promoters and alternative splicing. Here, we report a fifth tropomyosin isoform, LEV-11O, which is produced by alternative splicing that includes a newly identified seventh exon, exon 7a. By visualizing specific splicing events in vivo, we find that exon 7a is predominantly selected in a subset of the body wall muscles in the head, while exon 7b, which is the alternative to exon 7a, is utilized in the rest of the body. Point mutations in exon 7a and exon 7b cause resistance to levamisole-­induced muscle contraction specifically in the head and the main body, respectively. Overexpression of LEV-11O, but not LEV-11A, in the main body results in weak levamisole resistance. These results demonstrate that specific tropomyosin isoforms are expressed in the head and body regions of the muscles and contribute differentially to the regulation of muscle contractility.
Genetic Diversity of Cryptosporidium hominis in a Bangladeshi Community as Revealed by Whole-Genome Sequencing
Authors: Gilchrist Carol A , Cotton James A , Burkey Cecelia , Arju Tuhinur , Gilmartin Allissia , Lin Ye , Ahmed Emtiaz , Steiner Kevin , Alam Masud , Ahmed Shahnawaz , Robinson Guy , Zaman Sultan Uz , Kabir Mamun , Sanders Mandy , Chalmers Rachel M , Ahmed Tahmeed , Ma Jennie Z , Haque Rashidul , Faruque Abu S G , Berriman Matthew , Petri William A
Published: March 2018

In the developing world, Cryptosporidium is one of the top causes of infant diarrhea. In a Bangladesh community we have discovered that a substantial amount of genetic recombination and genetic polymorphism in surface proteins occurs in the Cryptosporidium hominis parasite.
Theoretical implications of the galactic radial acceleration relation of McGaugh, Lelli, and Schombert
Authors: Nesbet Robert K
Published: March 2018

Velocities in stable circular orbits about galaxies, a measure of centripetal gravitation, exceed the expected Kepler/Newton velocity as orbital radius increases. Standard Λ cold dark matter (ΛCDM) attributes this anomaly to galactic dark matter. McGaugh et al. have recently shown for 153 disc galaxies that observed radial acceleration is an apparently universal function of classical acceleration computed for observed galactic baryonic mass density. This is consistent with the empirical modified Newtonian dynamics (MOND) model, not requiring dark matter. It is shown here that suitably constrained ΛCDM and conformal gravity (CG) also produce such a universal correlation function. ΛCDM requires a very specific dark matter distribution, while the implied CG non-classical acceleration must be independent of galactic mass. All three constrained radial acceleration functions agree with the empirical baryonic v4 Tully–Fisher relation. Accurate rotation data in the nominally flat velocity range could distinguish between MOND, ΛCDM, and CG.
The Influence of Hearing Aid Gain on Gap-Detection Thresholds for Children and Adults With Hearing Loss
Authors: Brennan Marc A. , McCreery Ryan W. , Buss Emily , Jesteadt Walt
Published: March 2018

Objectives:

The objective of this experiment was to examine the contributions of audibility to the ability to perceive a gap in noise for children and adults. Sensorineural hearing loss (SNHL) in adulthood is associated with a deficit in gap detection. It is well known that reduced audibility in adult listeners with SNHL contributes to this deficit; however, it is unclear the extent to which hearing aid amplification can restore gap-detection thresholds, and the effect of childhood SNHL on gap-detection thresholds have not been described. For adults, it was hypothesized that restoring the dynamic range of hearing for listeners with SNHL would lead to approximately normal gap-detection thresholds. Children with normal hearing (NH) exhibit poorer gap-detection thresholds than adults. Because of their hearing loss, children with SNHL have less auditory experience than their peers with NH. Yet, it is unknown the extent to which auditory experience impacts their ability to perceive gaps in noise. Even with the provision of amplification, it was hypothesized that children with SNHL would show a deficit in gap detection, relative to their peers with normal hearing, because of reduced auditory experience.

Design:

The ability to detect a silent interval in noise was tested by adapting the stimulus level required for detection of gap durations between 3 and 20 ms for adults and children with and without SNHL. Stimulus-level thresholds were measured for participants with SNHL without amplification and with two prescriptive procedures—the adult and child versions of the desired sensation level i/o program—using a hearing aid simulator. The child version better restored the normal dynamic range than the adult version. Adults and children with NH were tested without amplification.

Results:

When fitted using the procedure that best restored the dynamic range, adults with SNHL had stimulus-level thresholds similar to those of adults with normal hearing. Compared to the children with NH, the children with SNHL required a higher stimulus level to detect a 5-ms gap, despite having used the procedure that better restored the normal dynamic range of hearing. Otherwise, the two groups of children had similar stimulus-level thresholds.

Conclusion:

These findings suggest that apparent deficits in temporal resolution, as measured using stimulus-level thresholds for the detection of gaps, are dependent on age and audibility. These novel results indicate that childhood SNHL may impair temporal resolution as measured by stimulus-level thresholds for the detection of a gap in noise. This work has implications for understanding the effects of amplification on the ability to perceive temporal cues in speech.
Leadership Advocacy
Authors: Porter-O'Grady Tim
Published: March 2018

Nurses have historically played a key role in advocacy and service for all members of the community, including those who are traditionally underserved by other providers or the health system. Nurses from a local Atlanta community health system, both clinical and administrative, have continued this tradition by developing an advocacy and service program for the downtown homeless of Atlanta. From its beginnings as a highly informal volunteer program to its current structure as a strongly integrated community health center for the underserved and homeless of Atlanta, local nurses have demonstrated their strong value of service advocacy. Their leadership, insight, discipline, and strategic development have facilitated the growth of a focused, viable health service network for marginalized people of the city of Atlanta.
Public Health Opportunities to Improve Late-Adolescent Immunization
Authors: Clark Sarah J. , Cowan Anne E. , Wells Katelyn B.
Published: March 2018

Seven state/local immunization program managers were convened to discuss how public health immunization programs could enhance their efforts to promote adolescent vaccination, with an emphasis on late adolescence (ages 16-18 years). The Centers for Disease Control and Prevention's revised childhood immunization schedule for 2017 and a recently proposed preventive care platform at 16 years of age provide a unique opportunity to focus on increasing adolescent immunization rates in this population. Public health officials discussed challenges to immunizing this population and suggested key strategies for supporting late-adolescent immunization, including partnerships between public health and immunization providers; nationally supported public information campaigns; and using immunization data specific to this population to track progress.
Effects of Clonidine on the Cardiovascular, Renal, and Inflammatory Responses to Experimental Bacteremia
Authors: Calzavacca Paolo , Booth Lindsea C. , Lankadeva Yugeesh R. , Bailey Simon R. , Burrell Louise M. , Bailey Michael , Bellomo Rinaldo , May Clive N.
Published: March 2018

Introduction:

Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses.

Methods:

In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 h, a high clinical dose of clonidine (HCDC) [1.0 μg/kg/h], a low clinical dose of clonidine (LCDC) [0.25 μg/kg/h] or vehicle, was infused for 8 h.

Results:

Animals developed hyperdynamic, hypotensive sepsis with acute kidney injury. The HCDC decreased heart rate (153 ± 6 to 119 ± 7 bpm) and cardiac output (5.6 ± 0.4 to 5.0 ± 0.4 L/min), with no reduction in mean arterial pressure (MAP). In contrast, LCDC increased cardiac output with peripheral vasodilatation. Both doses induced a large transient increase in urine output, an increase in plasma osmolality and, with the high dose, an increase in plasma arginine vasopressin. Sepsis increased plasma interleukin-6 (IL-6) and IL-10 and clonidine further increased IL-10 (1.6 ± 0.1 to 3.3 ± 0.7 ng/mL), but not IL-6. Clonidine reduced rectal temperature. During recovery from sepsis, MAP returned to baseline values more rapidly in the HCDC group (P < 0.001).

Conclusions:

In hyperdynamic, hypotensive sepsis, the effects of clonidine at clinically relevant doses are complex and dose dependent. HCDC attenuated sepsis-related increases in heart rate and cardiac output, with little effect on arterial pressure. It also induced a water diuresis, increased AVP, reduced body temperature, and had an anti-inflammatory action. Low-dose clonidine had similar but less pronounced effects, except that it induced moderate vasodilatation and increased cardiac output.
Sexual Satisfaction Changes Reported by Men After Their Partners' Robotic-Assisted Laparoscopic Sacrocolpopexies
Authors: Culligan Patrick J. , Haughey Sean , Lewis Christa , Priestley Jennifer , Salamon Charbel
Published: March 2018

Objectives

This study aimed to compare the preoperative and postoperative sexual satisfaction reported by male sexual partners of women undergoing surgical correction of pelvic organ prolapse.

Methods

This was a single-center prospective cohort study. Heterosexual, sexually active English-speaking couples in which the women were planning to undergo robotic-assisted laparoscopic sacrocolpopexy for correction of pelvic organ prolapse were eligible for enrollment in the study. Validated sexual function questionnaires—the Sexual Experience Questionnaire (SEX-Q; Mulhall et al. J Sex Med. 2008) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (Rogers, et al. Int Urogynecol J Pelvic Floor Dysfunct. 2003)—were used to evaluate preoperative and postoperative male and female sexual experience, respectively. These preoperative scores were compared using paired t tests. The Student t and the Mann-Whitney tests were used to compare study-eligible couples with noneligible couples and to compare study participants with nonparticipants.

Results

During the study enrollment period, 92 couples met the inclusion criteria and 45 of those were enrolled. Complete data sets of preoperative and postoperative questionnaires were obtained for 36 couples. After their partners' successful reconstructive surgery, male study subjects reported improved total SEX-Q scores (mean ± SD, 71 ± 16.7 vs 76.5 ± 17.8; P = 0.025). Within the subscales of the SEX-Q, there was significant improvement between preoperative and postoperative “individual satisfaction” scores (mean ± SD, 65.7 ± 16.8 vs 78.9 ± 17.5; P < 0.0001), but not within the “erectile dysfunction” or “couple satisfaction” subscales. Female partners reported improved Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 scores after surgery (mean ± SD, 36.6 ± 5.5 vs 40.0 ± 4.6; P = 0.003).

Conclusions

Sexually active heterosexual men and women reported improved sexual experience after successful prolapse repair.
Restoration of Kv7 channel mediated inhibition reduces cued-reinstatement of cocaine seeking
Authors: Parrilla-Carrero Jeffrey , Buchta William C. , Goswamee Priyodarshan , Culver Oliver , McKendrick Greer , Harlan Benjamin , Moutal Aubin , Penrod Rachel , Khanna Rajesh , Kalivas Peter , Riegel Arthur C.
Published: March 2018

Cocaine addicts display increased sensitivity to drug-associated cues, due in part to pathological changes in the prelimbic cortex (PL-PFC). The cellular mechanisms underlying cue-induced reinstatement of cocaine seeking remain unknown. Reinforcement learning for addictive drugs may produce persistent maladaptations in intrinsic excitability within sparse subsets of PFC pyramidal neurons. Using a male rat model of relapse to cocaine-seeking, we sampled over 600 neurons to examine spike frequency adaptation (SFA) and after-hyperpolarizations (AHPs), two systems that attenuate low frequency inputs to regulate neuronal synchronization. We observed that training to self-administer cocaine or nondrug (sucrose) reinforcers decreased SFA and AHPs in a sub-population of PL-PFC neurons, but only with cocaine did the resulting hyper-excitability persist through extinction training and increase during reinstatement. In neurons with intact SFA, dopamine enhanced excitability by inhibiting Kv7 potassium channels that mediate SFA. However, dopamine effects were occluded in neurons from cocaine-experienced rats, where SFA and AHPs were reduced. Pharmacological stabilization of Kv7 channels with retigabine restored SFA and Kv7 channel function in neuroadapted cells. When microinjected bilaterally into the PL-PFC 10 minutes prior to reinstatement testing, retigabine reduced cue-induced reinstatement of cocaine seeking. Lastly, using cFos-GFP transgenic rats, we found that the loss of SFA correlated with the expression of cFos-GFP following both extinction and re-exposure to drug-associated cues. Taken together, these data suggest that cocaine self-administration desensitizes inhibitory Kv7 channels in a subpopulation of PL-PFC neurons. This sub-population of neurons may represent a persistent neural ensemble responsible for driving drug seeking in response to cues.

Significance Statement

Long after the cessation of drug use, cues associated with cocaine still elicit drug-seeking behavior, in part by activation of the prelimbic cortex (PL-PFC). The underlying cellular mechanisms governing these activated neurons remain unclear. Using a rat model of relapse to cocaine seeking, we identified a population of PL-PFC neurons that become hyperexcitable following chronic cocaine self-administration. These neurons show persistent loss of spike frequency adaptation, reduced after-hyperpolarizations, decreased sensitivity to dopamine, and reduced Kv7 channel mediated inhibition. Stabilization of Kv7 channel function with retigabine normalized neuronal excitability, restored Kv7 channel currents, and reduced drug-seeking behavior when administered into the PL-PFC prior to reinstatement. These data highlight a persistent adaptation in a subset of PL-PFC neurons that may contribute to relapse vulnerability.
The CRF-R1 regulation of VTA-GABAergic plasticity is suppressed by CB1 receptor inhibition following chronic exposure to ethanol
Authors: Harlan Benjamin , Becker Howard , Woodward John , Riegel Arthur
Published: March 2018

Dopamine neurons in the ventral tegmental area (VTA) influence learned behaviors and neuropsychiatric diseases including addiction. The stress peptide corticotrophin-releasing factor (CRF) contributes to relapse to drug and alcohol seeking following withdrawal, although the cellular actions are poorly understood. In this study, we show that presynaptic CRF type 1 receptors (CRF-R1) potentiate GABA release onto mouse VTA dopamine neurons via a PKC-Ca2+signaling mechanism. In na1ve animals, activation of CRF-R1 by bath application of CRF or ethanol enhanced GABAAinhibitory postsynaptic currents (IPSCs). Following three days of withdrawal from four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure, spontaneous IPSC frequency was enhanced while CRF- and ethanol-potentiation of IPSCs was intact. However, withdrawal for 3 weeks or more was associated with reduced spontaneous IPSC frequency and diminished CRF and ethanol responses. Long-term withdrawal was also accompanied by decreased sensitivity to the CB1 receptor agonist WIN55212 as well as greatly enhanced sensitivity to the CB1 antagonist AM-251. Inclusion of BAPTA in the internal recording solution restored the responsiveness to CRF or ethanol and reduced the potentiating actions of AM251. Together, these data suggest that GABAAinhibition of VTA dopamine neurons is regulated by presynaptic actions of CRF and endocannabinoids and that long-term withdrawal from CIE treatment enhances endocannabinoid mediated inhibition, thereby suppressing CRF facilitation of GABA release. Such findings have implications for understanding the impact of chronic alcohol on stress-related, dopamine-mediated alcohol seeking behaviors.
Neuroticism Impairs the Use of Reward Values for Decision-Making inMajor Depression
Authors: Rupprechter Samuel , Stankevicius Aistis , Huys Quentin , Steele J. Douglas , Seriès Peggy
Published: March 2018

Depression is a debilitating condition with a high prevalence, but aetiology and pathophysiology are still unclear. Various reward-learning paradigms have been used to show impairments in depression. Both trait pessimism and neuroticism are associated with depression, but their link with the impairments in reward learning and decision-making have not been investigated. A Pavlovian conditioning task was performed by 32 subjects, 15 with depression. Participants had to estimate the probability of some fractal stimuli to be associated with a binary reward, based on a few observations. They then had to make a choice between one of the observed fractals and another target for which the reward probability was explicitly given. Computational modelling was used to succinctly describe participants’ behaviour. Patients performed worse than controls at the task. Computational modelling revealed that this was caused by behavioural impairments during both learning and decision phases. Neuroticism scores across participants were significantly correlated with participants’ inability to follow their internal value estimations. Our results demonstrate behavioural differences in probabilistic reward learning between depressed patients and healthy controls. Neuroticism was associated with the impaired ability to follow internal reward values and consequently with worse decision-making.
Performance of convolutional neural networks for identification of bacteria in 3D microscopy datasets
Authors: Hay Edouard A , Parthasarathy Raghuveer
Published: March 2018

Three-dimensional microscopy is increasingly prevalent in biology due to the development of techniques such as multiphoton, spinning disk confocal, and light sheet fluorescence microscopies. These methods enable unprecedented studies of life at the microscale, but bring with them larger and more complex datasets. New image processing techniques are therefore called for to analyze the resulting images in an accurate and efficient manner. Convolutional neural networks are becoming the standard for classification of objects within images due to their accuracy and generalizability compared to traditional techniques. Their application to data derived from 3D imaging, however, is relatively new and has mostly been in areas of magnetic resonance imaging and computer tomography. It remains unclear, for images of discrete cells in variable backgrounds as are commonly encountered in fluorescence microscopy, whether convolutional neural networks provide sufficient performance to warrant their adoption, especially given the challenges of human comprehension of their classification criteria and their requirements of large training datasets. We therefore applied a 3D convolutional neural network to distinguish bacteria and non-bacterial objects in 3D light sheet fluorescence microscopy images of larval zebrafish intestines. We find that the neural network is as accurate as human experts, outperforms random forest and support vector machine classifiers, and generalizes well to a different bacterial species through the use of transfer learning. We also discuss network design considerations, and describe the dependence of accuracy on dataset size and data augmentation. We provide source code, labeled data, and descriptions of our analysis pipeline to facilitate adoption of convolutional neural network analysis for three-dimensional microscopy data.

Author summary

The abundance of complex, three dimensional image datasets in biology calls for new image processing techniques that are both accurate and fast. Deep learning techniques, in particular convolutional neural networks, have achieved unprecedented accuracies and speeds across a large variety of image classification tasks. However, it is unclear whether or not their use is warranted in noisy, heterogeneous 3D microscopy datasets, especially considering their requirements of large, labeled datasets and their lack of comprehensible features. To asses this, we provide a case study, applying convolutional neural networks as well as feature-based methods to light sheet fluorescence microscopy datasets of bacteria in the intestines of larval zebrafish. We find that the neural network is as accurate as human experts, outperforms the feature-based methods, and generalizes well to a different bacterial species through the use of transfer learning.
New perspectives on multilocus ancestry informativeness
Authors: Tal Omri , Tran Tat Dat
Published: March 2018

We present an axiomatic approach formultilocus informativenessmeasures for determining the amount of information that a set of polymorphic genetic markers provides about individual ancestry. We then reveal several surprising properties of a decision-theoretic based measure that is consistent with the set of proposed criteria formultilocus informativeness. In particular, these properties highlight the interplay between information originating from population priors and the information extractable from the population genetic variants. This analysis then reveals a certain deficiency ofmutual informationbasedmultilocus informativenessmeasures when such population priors are incorporated. Finally, we analyse and quantify the inevitable inherent decrease ininformativenessdue to learning from finite population samples.
Phase-Amplitude Coupling of Neural Oscillations can be Effectively Probed with Concurrent TMS-EEG
Authors: Glim Sarah , Okazaki Yuka O. , Nakagawa Yumi , Mizuno Yuji , Hanakawa Takashi , Kitajo Keiichi
Published: March 2018

Despite the widespread use of transcranial magnetic stimulation (TMS), knowledge of its neurophysiological mode of action is still incomplete. Recently, TMS has been proposed to synchronise neural oscillators, and to thereby increase the detectability of corresponding oscillations at the population level. As oscillations in the human brain are known to interact within nested hierarchies via phase-amplitude coupling, TMS might also be able to increase the macroscopic detectability of such coupling. In a concurrent TMS-electroencephalography study, we therefore examined the technique’s influence on theta-gamma, alpha-gamma and beta-gamma phase-amplitude coupling by delivering single-pulse TMS (sTMS) and repetitive TMS (rTMS) over the left motor cortex and right visual cortex of healthy participants. The rTMS pulse trains were of 5 Hz, 11 Hz and 23 Hz for the three coupling variations, respectively. Relative to sham stimulation, all conditions showed transient but significant increases in phase-amplitude coupling at the stimulation site. In addition, we observed enhanced coupling over various other cortical sites, with a more extensive propagation during rTMS than during sTMS. By indicating that scalp-recorded phase-amplitude coupling can be effectively probed with TMS, these findings open the door to the technique’s application in manipulative dissections of such coupling during human cognition and behaviour in healthy and pathological conditions.
Assessment and refinement of sample preparation methods for deep and quantitative plant proteome profiling
Authors: Song Gaoyuan , Yingshan Hsu Polly Y , Walley Justin W.
Published: March 2018

A major challenge in the field of proteomics is obtaining high quality peptides for comprehensive proteome profiling by liquid chromatography mass spectrometry for many organisms. Here we evaluate and modify a range of sample preparation methods using photosynthetically active Arabidopsis leaf tissues from several developmental timepoints. We find that inclusion of FASP-based on filter digestion improves all protein extraction methods tested. Ultimately, we show that a detergent-free urea-FASP approach enables deep and robust quantification of leaf proteomes. For example, from 4-day-old leaf tissue we profiled up to 11,690 proteins from a single sample replicate. This method should be broadly applicable to researchers working on difficult to process samples from a range of plant and non-plant organisms.

Abbreviations

Chloro

Methanol/Chloroform Extraction

FASP

Filter Aided Sample Prep

GO

Gene Ontology

IAA

Iodoacetamide

LFQ

Label Free Quantification

MS/MS

Tandem mass spectrometry

TF

Transcription Factor

UA

Urea Extraction

1D

1 Dimensional

2D

2 Dimensional
A new function for Prokineticin 2: recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury
Authors: Mundim Mayara Vieira , Zamproni Laura Nicoleti , Sardinha Pinto Agnes Araújo , Galindo Layla Testa , Xavier André Machado , Glezer Isaias , Porcionatto Marimélia
Published: March 2018

Traumatic brain injury is an important cause of mortality and morbidity all over the world. After the initial injury there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim not only to counteract these mechanisms but also to replenish the lost cell population in order to achieve a better recovery. The adult mammal brain in not as plastic as the postnatal, but it has at least two neurogenic regions that maintains physiological functions in the brain; the subgranular zone of the dentate gyrus of the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) of the lateral ventricles, that produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that SVZ cells migrate to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis by promoting the directional migration of neuroblasts, is induced in the injured cortex. Using PROK2 receptor antagonist and recombinant PROK2 we show for the first time that PROK2 can directionally attract SVZ cells in vitro and in vivo. The data we present here links one more element of the inflammatory process, PROK2 secreted by microglia, to the attempt to regenerate an acutely injured mammalian cortex.

Abbreviations

SGZ

subgranular zone

SVZ

subventricular zone

RMS

rostral migratory stream

PROK2

Prokineticin 2
Molecular dynamics ensemble refinement of the heterogeneous native state of NCBD using chemical shifts and NOEs
Authors: Papaleo Elena , Camilloni Carlo , Teilum Kaare , Vendruscolo Michele , Lindorff-Larsen Kresten
Published: March 2018

Many proteins display complex dynamical properties that are often intimately linked to their biological functions. As the native state of a protein is best described as an ensemble of confor-mations, it is important to be able to generate models of native state ensembles with high accuracy. Due to limitations in sampling efficiency and force field accuracy it is, however, challenging to obtain accurate ensembles of protein conformations by the use of molecular simulations alone. Here we show that dynamic ensemble refinement, which combines an accurate atomistic force field with commonly available nuclear magnetic resonance (NMR) chemical shifts and NOEs, can provide a detailed and accurate description of the conformational ensemble of the native state of a highly dynamic protein. As both NOEs and chemical shifts are averaged on timescales up to milliseconds, the resulting ensembles reflect the structural heterogeneity that goes beyond that probed e.g. by NMR relaxation order parameters. We selected the small protein domain NCBD as object of our study since this protein, which has been characterized experimentally in substantial detail, displays a rich and complex dynamical behaviour. In particular, the protein has been described as having a molten-globule like structure, but with a relatively rigid core. Our approach allowed us to describe the conformational dynamics of NCBD in solution, and to probe the structural heterogeneity resulting from both short- and long-time-scale dynamics by the calculation of order parameters on different time scales. These results illustrate the usefulness of our approach since they show that NCBD is rather rigid on the nanosecond timescale, but interconverts within a broader ensemble on longer timescales, thus enabling the derivation of a coherent set of conclusions from various NMR experiments on this protein, which could otherwise appear in contradiction with each other.
Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism inDrosophila
Authors: Obniski Rebecca , Sieber Matthew , Spradling Allan C.
Published: March 2018

Tissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with developmental pathways. Using the Drosophila midgut as a model we found that during the first four days of adult life, dietary lipids including cholesterol, determine how many enteroendocrine (ee) cells differentiate and persist in the posterior midgut where lipids are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, and utilization, is required for sterol-mediated changes in ee number. Dietary cholesterol influences new intestinal epithelial cell differentiation from stem cells by altering the level and persistance of Notch signaling. Exogenous lipids modulate signaling by changing the stability of the Delta ligand and Notch intracellular domain and their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues such as the ovary, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in ee number in young animals contribute to a metabolic program adapted to the prevailing nutrient environment that persists after the diet changes. A low sterol diet also slows the proliferation of enteroendocrine tumors initiated by disruptions in the Notch pathway. These studies show that a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.
An Array of Gut-on-a-Chips for Drug Development
Authors: Ashammakhi Nureddin , Elmusrati Mohammed
Published: March 2018

Drug development is a time and cost-consuming long process. Conventionally, this involves the use of two-dimensional (2D) cell culture and animal testing. However, these methods often fail to mimic normal human physiology and drug metabolism, and sometimes complications may occur later because they do not appear in preclinical studies. With recent development of organ-on-a-chip devices, these biomimetic systems try to recapitulate human physiology more than other methods, and promise to largely replace animal studies and reduce costs and complications. Because gut is an important route for drug administration and absorption, gut-on-a-chip platform was developed. To develop a high throughput system, a recent work reported on using a multiplication array of several chip devices, demonstrating the efficiency in studying drug effect on gut barrier function as compared to conventional methods. Huge data was generated, and thus new multidisciplinary approach is needed where data collection, communication and analysis platforms need to be developed. This will enable validation of organ-on-a-chip approach and lay basis for its establishment as efficient and cost-effective tool in drug development. Because of the importance of the work, this commentary highlights important aspects of the topic and try to stimulate new the development of innovations in the field.

Disclosure

No conflict of interest.
Genomic Exploration of Within-Host Microevolution Reveals a Distinctive Molecular Signature of PersistentStaphylococcus aureusBacteraemia
Authors: Giulieri Stefano G. , Baines Sarah L. , Guerillot Romain , Seemann Torsten , da Silva Anders Gonçalves , Schultz Mark , Massey Ruth C. , Holmes Natasha E. , Stinear Timothy P. , Howden Benjamin P.
Published: March 2018

Background

Large-scale genomic studies of within-host evolution duringStaphylococcus aureusbacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in management of SAB. However, available comparative genomic studies of sequential SAB isolates have tended to focus on selected cases of unusually prolonged bacteraemia, where secondary antimicrobial resistance has developed. To understand the bacterial genomic evolution during SAB more broadly, we applied whole genome sequencing to a large collection of sequential isolates obtained from patients with persistent or relapsing bacteraemia.

Results

We show that, while adapation pathways are heterogenous and episode-specific, isolates from persistent bacteraemia have a distinctive molecular signature, characterised by a low mutation frequency and high proportion of non-silent mutations. By performing an extensive analysis of structural genomic variants in addition to point mutations, we found that these often overlooked genetic events are commonly acquired during SAB. We discovered that IS256insertion may represent the most effective driver of within-host microevolution in selected lineages, with up to three new insertion events per isolate even in the absence of other mutations. Genetic mechanisms resulting in significant phenotypic changes, such as increases in vancomycin resistance, development of small colony phenotypes, and decreases in cytotoxicity, included mutations in key genes (rpoB, stp, agrA) and anIS256insertion upstream of thewalKRoperon.

Conclusions

This study provides for the first time a large-scale analysis of within-host evolution during invasiveS. aureusinfection and describes specific patterns of adaptation that will be informative for both understandingS. aureuspathoadaptation and utilising genomics for management of complicatedS. aureusinfections.