bluuebunny/crossref_metadata_2025 huggingface dataset:
An efficient soft switching buck converter scheme for charging lead acid battery from PV source
Authors: Seetharaman Veeralagureddy , Manoharan P. Subramanian
Published: June 2017

In this paper, a high efficiency soft switched two channel interleaved buck converter scheme for charging a lead acid battery bank is presented. This scheme uses the incremental conductance (INC) maximum power point tracking (MPPT). An internal model control system (IMC) is used for controlling the charging of the battery in the constant current mode, constant voltage mode, and trickle mode depending upon the state of charge (SOC) of the battery. Various subsystems of simulation and the results are presented. The simulation results are validated experimentally by using a 125 W photovoltaic (PV) panel unit and a 36 A H lead acid battery. The real time experiment is performed under climatic conditions of Madurai which is a city located in Tamil Nadu, India. The result of the proposed system has been compared against the Perturb and observe MPPT scheme. The results of both simulation and the experiment reveal that the proposed soft switched, internal model controller incorporated INC scheme of MPPT offers more close tracking of the PV power and is more efficient.
Thermal memristor and neuromorphic networks for manipulating heat flow
Authors: Ben-Abdallah Philippe
Published: June 2017

A memristor is one of four fundamental two-terminal solid elements in electronics. In addition with the resistor, the capacitor and the inductor, this passive element relates the electric charges to current in solid state elements. Here we report the existence of a thermal analog for this element made with metal-insulator transition materials. We demonstrate that these memristive systems can be used to create thermal neurons opening so the way to neuromorphic networks for smart thermal management and information treatment.
The new Moon
Authors: Denevi Brett
Published: June 2017

Recent findings are challenging much of what we thought we knew about Earth’s nearest neighbor.
Effects of ovarian disaggregation on adult murine follicle yield and viability
Authors: Young Fiona , Drummond John , Akers Emma , Bartle Louise , Kennedy David , Asaduzzaman Mohammad
Published: June 2017

Follicles are isolated from ovaries for numerous reasons, including IVM, but adult murine yields are <2 follicles mg−1. The aim of the present study was to optimise ovarian disaggregation and develop methods applicable to the rapid screening of follicle viability. Ovaries from adult mice (n = 7) were halved and disaggregated mechanically, or by using collagenase IV (Col-IV; 590 U mL−1) or animal origin-free collagenase IV (AOF) at 590 or 1180 U mL−1. Isolated follicles were stained with 4′,6′-diamidino-2-phenylindole (DAPI; nuclei), chloromethyl-X-rosamine (CMXRos; mitochondria) or fluorescein isothiocyanate-conjugated anti-α-tubulin antibody. Follicle diameters and staining were measured and analysed using ImageJ, and data analysed using GraphPad Prism. Col-IV disaggregation yielded the highest number of follicles (17 ± 10 follicles mg−1 ovarian tissue). All disaggregation methods released more secondary follicles (86 ± 20 per ovary; P < 0.05) than any other size cohort. Mechanical and Col-IV disaggregation yielded similar numbers of morphologically intact follicles, whereas AOF disaggregation caused more damage (P < 0.01). As the morphological disruption increased, DAPI and CMXRos staining decreased (P < 0.05), and tubulin localisation became more heterogeneous. Col-IV disaggregation gave the best yield of morphologically intact follicles containing viable granulosa cells. In conclusion, we improved adult murine follicle yields and applied molecular markers to assess follicle morphology, cellular cytoskeleton and mitochondrial function.
Parotid and mandibular gland secretion by red kangaroos, Macropus rufus, in response to heat stress
Authors: Beal A. M.
Published: June 2017

Salivary flow rates from ipsilateral parotid and mandibular glands were measured in conscious red kangaroos over a 70–90-min period during episodes of saliva spreading induced by heat stress. At the onset of saliva spreading, mandibular flow rose rapidly to plateau at 1.12 ± 0.10 mL min–1 for the collection intervals after the first 10 min of licking. Parotid flow increased more slowly and progressively, reaching secretion rates similar to those of the mandibular gland after 40 min of saliva spreading, exceeding mandibular flow after 70 min and showing no indication that it had reached maximum secretion at 90 min of saliva spreading. The ion concentrations of both parotid and mandibular salivas during saliva spreading were similar to those previously reported for parasympathomimetic stimulation. The low osmotic concentration of mandibular saliva relative to plasma (40%) makes it a functionally better evaporative coolant than parotid saliva, which was nearly isosmotic with plasma. The increased production of hydrogen ions associated with the increased secretion of bicarbonate by the parotid gland would tend to offset the respiratory alkalosis due to panting thereby helping to maintain acid/base balance during periods of prolonged heat stress.
Constructions, grammatical status and morphologization
Authors: Popova Gergana
Published: June 2017

This paper critically explores the question of what it means for a construction to be grammatical. The paper engages with some of the observations made in the grammaticalization literature, that elements in grammatical constructions undergo morphologization, and aims to show that grammatical status and morphologization need not be aligned. A number of parameters along which the grammatical status of a multiword expression can vary are proposed and data illustrating different aspects of these parameters are discussed in detail. The data are used to argue that grammatical status is complex and multifaceted and linked not only to the formal properties of a construction, but also to its semantics and the relationship it has with other grammatical forms (e.g. inflected forms) in a given language.
Microstructure and mechanical properties of Sn–Cu alloys for detonating and explosive cords
Authors: Liu Guangyu , Ji Shouxun , Grechcini Luke , Bentley Andrew , Fan Zhongyun
Published: June 2017

To develop alloys as the substitute of Pb-based alloys for cladding materials in detonating and explosive cords, the materials requirement was analysed and Sn–Cu based alloys were selected as potential candidates. Four alloys including Sn–0.3 wt-%Cu, Sn–0.5 wt-%Cu, Sn–0.7 wt-%Cu, and Sn–1.0 wt-%Cu were prepared by casting and rolling. Microstructures of as-cast Sn–Cu alloys comprised Sn solutions with Cu6Sn5 intermetallic in the matrix. The as-rolled hypoeutectic Sn–Cu alloys (0.3–0.5 wt-%Cu) offered the yield strength from 26.1 to 31.9 MPa, UTS from 30.1 to 34 MPa and elongation from 86.4 to 87.5%, which were found to be appropriate for detonating and explosive cords. Particularly, the Sn–Cu alloys exhibited strain softening behaviour under tensile stress, which will benefit cladding manufacture and subsequent processing after assembly with high-energy explosive materials.
Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
Authors: Ivanovska Irena L. , Swift Joe , Spinler Kyle , Dingal Dave , Cho Sangkyun , Discher Dennis E.
Published: June 2017

Synergistic cues from extracellular matrix and soluble factors are often obscure in differentiation. Here the rigidity of cross-linked collagen synergizes with retinoids in the osteogenesis of human marrow mesenchymal stem cells (MSCs). Collagen nanofilms serve as a model matrix that MSCs can easily deform unless the film is enzymatically cross-linked, which promotes the spreading of cells and the stiffening of nuclei as both actomyosin assembly and nucleoskeletal lamin-A increase. Expression of lamin-A is known to be controlled by retinoic acid receptor (RAR) transcription factors, but soft matrix prevents any response to any retinoids. Rigid matrix is needed to induce rapid nuclear accumulation of the RARG isoform and for RARG-specific antagonist to increase or maintain expression of lamin-A as well as for RARG-agonist to repress expression. A progerin allele of lamin-A is regulated in the same manner in iPSC-derived MSCs. Rigid matrices are further required for eventual expression of osteogenic markers, and RARG-antagonist strongly drives lamin-A–dependent osteogenesis on rigid substrates, with pretreated xenografts calcifying in vivo to a similar extent as native bone. Proteomics-detected targets of mechanosensitive lamin-A and retinoids underscore the convergent synergy of insoluble and soluble cues in differentiation.
Embedding in the city? Locating civil society in the philanthropy of place
Authors: Pill Madeleine C
Published: June 2017

Philanthropic foundations have become increasingly important actors in the governance of cities in decline in the United States. The relationships between foundation and other actors within city governance are illuminated via contrasting interpretations of state-society power relationships which highlight the mutability of ‘civil society’ as an oppositional or integrated part of the state. After detailing a typology of philanthropy of place, the twofold role played by foundations in the governance of neighbourhood revitalization in the cities in which they are embedded is explored: not only as an important source of funding and support for neighbourhood-based organizations, but as contributors to the creation of neighbourhood revitalization policy agendas. Considering the cities of Baltimore and Cleveland reveals that the policy approaches adopted have tended to align with the predominant neoliberal policy agenda rather than revealing foundation actors as activists who assist the organizations they support in exerting agency to contest or seek to transform the prevailing hegemony. This makes clear the need for rigour in defining what constitutes civil society, and points to the importance of embedded philanthropic practices in enabling civil society agency.
Surgical Outcomes of Posterior Spinal Fusion Alone Using Cervical Pedicle Screw Constructs for Cervical Disorders Associated With Athetoid Cerebral Palsy
Authors: Watanabe Kei , Hirano Toru , Katsumi Keiichi , Ohashi Masayuki , Shoji Hirokazu , Yamazaki Akiyoshi , Izumi Tomohiro , Hasegawa Kazuhiro , Ito Takui , Endo Naoto
Published: June 2017

Study Design.

Retrospective case series.

Objective.

The aim of this study was to investigate clinical outcomes after posterior spinal fusion (PSF) using cervical pedicle screw (CPS) constructs for cervical disorders associated with athetoid cerebral palsy (CP).

Summary of Background Data.

Traditionally, most patients with cervical myelopathy associated with CP have required combined anterior and posterior fusion to achieve solid stability against severe involuntary movement.

Methods.

Thirty-one CP patients with cervical disorders who underwent PSF alone with a minimum 2-year follow-up (mean 58 months) were analyzed. All patients were treated with PSF using CPS constructs with or without decompression procedures. The average number of fused segments was 5.1 (range, 1–10 segments), and a halo jacket was applied in 16 patients for at least 2 months after surgery. Clinical outcomes using the Japanese Orthoedic Association scoring system (JOA score) and walking ability, radiographic sagittal alignment, fusion status, and surgery-related complications were evaluated.

Results.

The JOA score improved from 8.3 points preoperatively to 10.9 points at the final follow-up (P < 0.05). Although no patients experienced deterioration in their walking ability postoperatively, 10 patients were unable to walk at the final follow-up. Sagittal alignment, including C0-2 angle, C2-7 angle, and local alignment in fused segments, was maintained postoperatively. Twenty-five patients achieved fusion at the final follow-up (fusion rate: 81%), and fivepatients with nonunion required additional surgery. With regard to complications, 5 patients encountered postoperative upper extremity palsy.

Conclusion.

The CPS construct is amenable to achieve a relatively high fusion rate without correction loss, and good clinical outcomes can be achieved with a posterior single approach for CP patients. In the future, efforts should be made to make appropriate decisions regarding the fusion area, take preventative measures against postoperative upper extremity palsy, and simplify external orthoses after surgery, especially with the use of a halo jacket.

Level of Evidence: 4
Evaluation of completeness of case ascertainment in Swiss cancer registration
Authors: Lorez Matthias , Bordoni Andrea , Bouchardy Christine , Bulliard Jean-Luc , Camey Bertrand , Dehler Silvia , Frick Harald , Konzelmann Isabelle , Maspoli Manuela , Mousavi Seyed M. , Rohrmann Sabine , Arndt Volker
Published: June 2017

This is the first comprehensive evaluation of completeness of case ascertainment in Swiss cancer registration. There is currently no method available that is considered to be the gold standard. Apart from simple measures such as the proportion of cases where registration was initiated by a death certificate and the proportion of diagnoses on the basis of histology or cytology/haematology, we applied two dedicated approaches: (i) the semiquantitative method of comparing the mortality to incidence rate ratio with relative survival (MI-Surv method) and (ii) the Flow method, which provides a quantitative estimate for the completeness depending on time since diagnosis. All 10 Swiss cancer registries in operation since at least 2006 and providing the required parameters were included. Simple and dedicated methods showed high completeness across all cancer registries and for most cancer types tested, with the notable exception of lymphoid leukaemia.
A population-based approach to compare patient-reported outcomes of long-term Hodgkin’s lymphoma survivors according to trial participation: a joint study from the Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship registry and European Organisation for Research and Treatment of Cancer
Authors: Thong Melissa S.Y. , Kicinski Michal , Coens Corneel , Giusti Francesco , van de Poll-Franse Lonneke , Bogaerts Jan , Liu Lifang
Published: June 2017

Survival discrepancy between patients treated in a clinical trial and routine practice is well recognized. No study has assessed the health-related quality of life (HRQL) of long-term Hodgkin’s lymphoma survivors (HLS) according to trial participation. We applied a population-based approach to examine the differences in HRQL, healthcare utilization, and satisfaction with healthcare among long-term HLS who had participated in a trial (tHLS) and those treated in routine care (rHLS). All HLS diagnosed during the period 1989–1998 and living in southern Netherlands were selected from the Netherlands Cancer Registry in 2004 to participate in the Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry study. Data linkage with the European Organisation for Research and Treatment of Cancer was performed in 2015 to identify trial participation. The 65 tHLS and 67 rHLS had comparable demographic and clinical characteristics. Unadjusted and adjusted models indicated no association between trial participation and HRQL. There was no evidence of differences in healthcare satisfaction. Trial participation was associated with 48% more visits to specialists in the past year (adjusted 95% confidence interval: 10–99). No association of trial participation with cancer-related contacts was observed. tHLS and rHLS had comparable long-term HRQL. Although trial participation was associated with more specialist visits, there was no evidence of an association with healthcare satisfaction and the number of cancer-related visits. Identification of trial participation in population-based cancer registry through data linkage with clinical trials enables a population-based approach to examine patient-reported outcomes differences between tHLS and rHLS.
Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the behavioral effects of quinpirole
Authors: Hernandez-Casner Caroline , Ramos Jeremiah , Serafine Katherine M.
Published: June 2017

Eating a diet high in fat can lead to negative health consequences, including obesity and insulin resistance. Omega-3 polyunsaturated fatty acids (such as those found in fish oil) prevent high fat diet-induced obesity and insulin resistance in rats. Eating a high fat diet also enhances sensitivity of rats to the behavioral effects of drugs that act on dopamine systems (e.g. quinpirole, a dopamine D2/D3 receptor agonist). To test the hypothesis that dietary supplementation with fish oil prevents high fat diet-induced enhanced sensitivity to the behavioral effects of quinpirole (0.0032–0.32 mg/kg), male rats ate standard laboratory chow, high fat chow, standard chow with fish oil, or high fat chow with fish oil (20% w/w). After 5 weeks, rats eating high fat chow were more sensitive (e.g. leftward shift of the quinpirole dose–response curve) than rats eating standard chow to yawning induced by quinpirole. Dietary supplementation with fish oil prevented this effect. That is, quinpirole dose–response curves were not different between rats eating high fat chow supplemented with fish oil and standard chow fed controls. These data add to a growing literature showing the complex relationship between diet and dopamine systems, and the health benefits of fish oil.
IKK/NF-κB-dependent satellite glia activation induces spinal cord microglia activation and neuropathic pain after nerve injury
Authors: Lim Hyoungsub , Lee Hyunkyoung , Noh Kyungchul , Lee Sung Joong
Published: June 2017

Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generatedIkkβconditional knockout mice (Cnp-Cre+/−/Ikkβf/f;cIkkβ−/−) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury–induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice. In addition, nerve injury–induced proinflammatory gene expression and macrophage infiltration into the dorsal root ganglion (DRG) were severely compromised. However, macrophages recruited into the DRG had minimal effects on spinal cord microglia activation, suggesting a causal effect for SGC activation on spinal cord microglia activation. In an effort to elucidate the molecular mechanisms, we measuredCsf1expression in the DRG, which is implicated in spinal cord microglia activation after nerve injury. IncIkkβ−/−mice, nerve injury–inducedCsf1upregulation was ameliorated indicating that IKK/NF-κΒ-dependent SGC activation inducedCsf1expression in sensory neurons. Taken together, our data suggest that nerve injury–induced SGC activation triggersCsf1induction in sensory neurons, spinal cord microglia activation, and subsequent central pain sensitization.
Sensitization of C-fiber nociceptors in mice with sickle cell disease is decreased by local inhibition of anandamide hydrolysis
Authors: Uhelski Megan L. , Gupta Kalpna , Simone Donald A.
Published: June 2017

Chronic pain and hyperalgesia, as well as pain resulting from episodes of vaso-occlusion, are characteristic features of sickle cell disease (SCD) and are difficult to treat. Since there is growing evidence that increasing local levels of endocannabinoids can decrease hyperalgesia, we examined the effects of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, which blocks the hydrolysis of the endogenous cannabinoid anandamide, on hyperalgesia and sensitization of cutaneous nociceptors in a humanized mouse model of SCD. Using homozygous HbSS-BERK sickle mice, we determined the effects of URB597 on mechanical hyperalgesia and on sensitization of C-fiber nociceptors in vivo. Intraplantar administration of URB597 (10 μg in 10 μL) decreased the frequency of withdrawal responses evoked by a von Frey monofilament (3.9 mN bending force) applied to the plantar hind paw. This was blocked by the CB1 receptor antagonist AM281 but not by the CB2 receptor antagonist AM630. Also, URB597 decreased hyperalgesia in HbSS-BERK/CB2R−/− sickle mice, further confirming the role of CB1 receptors in the effects produced by URB597. Electrophysiological recordings were made from primary afferent fibers of the tibial nerve in anesthetized mice. The proportion of Aδ- and C-fiber nociceptors that exhibited spontaneous activity and responses of C-fibers to mechanical and thermal stimuli were greater in HbSS-BERK sickle mice as compared to control HbAA-BERK mice. Spontaneous activity and evoked responses of nociceptors were decreased by URB597 via CB1 receptors. It is suggested that enhanced endocannabinoid activity in the periphery may be beneficial in alleviating chronic pain associated with SCD.
The Lived Experience of Midlife Women With Major Depression
Authors: Li Ching-Chu , Shu Bih-Ching , Wang Yu-Ming , Li Shih-Ming
Published: June 2017

Background:

Midlife, a significant developmental phase for women, is a period of biological, psychological, and social role changes. However, not all women transition smoothly into middle age, with those who experience depression typically bearing significantly greater physical and psychological discomforts in midlife. Despite the expanding body of research on women and depression, little is understood about how depressed women handle the midlife transition.

Purpose:

The aim of this study was to gain a deeper understanding about the lived experience of middle-aged women with major depression.

Methods:

This study used a phenomenological design. Four women between 43 and 55 years old with a diagnosis of major depression were interviewed. There were seven transcripts in total. A 62-year-old depressed woman was also interviewed to verify the results.

Results:

After data analysis, “a harder life” emerged as the core of these women’s experiences. Two themes with two respective subthemes were identified. The theme “struggling to redefine the self” was associated with the subthemes “taking pills in the dump” and “the inane life.” The theme “swinging to develop new social interactions” was associated with the subthemes “being alienated from former social contacts” and “starting new social interactions.” Results indicate that the participants encountered greater challenges in adapting to middle age than their nondepressed peers.

Conclusions:

Much adaptation and help are needed for depressed women to experience a smooth transition into midlife. In caring for these women, their interpersonal relationships with others should be the main target. Meanwhile, nurses must understand what challenges depressed women typically encounter in midlife based on the developmental perspective and then assess how pharmaceutical treatments impact the view of self of women.
Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Kronlage Moritz , Pitarokoili Kalliopi , Schwarz Daniel , Godel Tim , Heiland Sabine , Yoon Min-Suk , Bendszus Martin , Bäumer Philipp
Published: June 2017

Purpose

The aims of this study were to assess diagnostic accuracy of diffusion tensor imaging (DTI) in chronic inflammatory demyelinating polyneuropathy (CIDP), to correlate DTI with electrophysiological parameters, and to evaluate whether radial diffusivity (RD) and axial diffusivity (AD) might serve as specific biomarkers of demyelinating and axonal pathology.

Materials and Methods

This prospective study was approved by the institutional ethics committee, and written informed consent was obtained from all participants. Magnetic resonance neurography of upper and lower extremity nerves (median, ulnar, radial, sciatic, tibial) was performed by single-shot DTI sequences at 3.0 T in 18 patients with a diagnosis of CIDP and 18 healthy controls, matched to age and sex. The scalar readout parameters nerve fractional anisotropy (FA), mean diffusivity (MD), RD, and AD were obtained after manual segmentation and postprocessing and compared between patients and controls. Diagnostic accuracy was assessed by receiver operating characteristic analysis, and cutoff values were calculated by maximizing the Youden index. All patients underwent a complementary electroneurography and correlation of electrophysiological markers and DTI parameters was analyzed and described by Pearson and Spearman coefficients.

Results

Nerve FA was decreased to a mean of 0.42 ± 0.08 in patients compared with 0.52 ± 0.04 in healthy controls (P < 0.001). This decrease in FA was a result of an increase of RD (P = 0.02), whereas AD did not differ between the two groups. Of all DTI parameters, FA showed best diagnostic accuracy with a receiver operating characteristic area under the curve of 0.90. Optimal cutoff for an average FA of all analyzed nerves was 0.47, yielding a sensitivity of 0.83 and a specificity of 0.94. Fractional anisotropy and RD correlated strongly with electrophysiological markers of demyelination, whereas AD did not correlate with markers of axonal neuropathy.

Conclusions

Diffusion tensor imaging yields valid quantitative biomarkers in CIDP and might aid in diagnosis with high diagnostic accuracy. Fractional anisotropy and RD may serve as parameters of myelin sheath integrity, but AD is unable to reflect axonal damage in CIDP.
Concurrent Electroconvulsive Therapy and Bupropion Treatment
Authors: Takala Christopher R. , Leung Jonathan G. , Murphy Lauren L. , Geske Jennifer R. , Palmer Brian A.
Published: June 2017

Background

Bupropion is associated with a dose-dependent increased risk of seizures. Use of concomitant bupropion and electroconvulsive therapy (ECT) remains controversial because of an increased risk of prolonged seizures. This is the first systematic evaluation of the effect of bupropion on ECT.

Methods

A case group (n = 119), patients treated with concomitant ECT and bupropion, was compared with an age and gender frequency–matched control group (n = 261), treated with only ECT. Electroconvulsive therapy treatment data including seizure length, number of treatments, and concurrent medications were extracted. Longitudinal mixed models examined ECT versus ECT + bupropion group differences over the course of treatments measured by seizure duration (electroencephalogram [EEG] and motor). Multivariable models examined the total number of treatments and first and last seizure duration. All models considered group differences with ECT treatment measures adjusted for age, gender, benzodiazepine treatment, lead placement, and setting.

Results

Electroconvulsive therapy treatment with bupropion led to shorter motor seizure duration (0.047) and EEG seizure duration (P = 0.001). The number of ECT treatments (7.3 vs 7.0 treatments; P = 0.23), respectively, or the probability of a prolonged seizure (P = 0.15) was not significantly different. Benzodiazepine use was significantly more common in control subjects (P = 0.01).

Limitations

This is a retrospective analysis limited in part by unavailable variables (seizure threshold, nature of EEG and motor seizure monitoring, type of ECT device, dosing and formulation of bupropion, and duration of the current depressive illness).

Conclusions

This study revealed a significantly shorter duration in seizure length with ECT + concomitant bupropion, but not in the number of required treatments in those treated compared with ECT without bupropion. There remains a critical need to reevaluate the efficacy of concomitant use of psychotropic medications + ECT.
Image-based modelling of lateral magma flow: the Basement Sill, Antarctica
Authors: Petford Nick , Mirhadizadeh Seyed
Published: June 2017

The McMurdo Dry Valleys magmatic system, Antarctica, provides a world-class example of pervasive lateral magma flow on a continental scale. The lowermost intrusion (Basement Sill) offers detailed sections through the now frozen particle microstructure of a congested magma slurry. We simulated the flow regime in two and three dimensions using numerical models built on a finite-element mesh derived from field data. The model captures the flow behaviour of the Basement Sill magma over a viscosity range of 1–10
4
 Pa s where the higher end (greater than or equal to 10
2
 Pa s) corresponds to a magmatic slurry with crystal fractions varying between 30 and 70%. A novel feature of the model is the discovery of transient, low viscosity (less than or equal to 50 Pa s) high Reynolds number eddies formed along undulating contacts at the floor and roof of the intrusion. Numerical tracing of particle orbits implies crystals trapped in eddies segregate according to their mass density. Recovered shear strain rates (10
−3
–10
−5
 s
−1
) at viscosities equating to high particle concentrations (around more than 40%) in the Sill interior point to shear-thinning as an explanation for some types of magmatic layering there. Model transport rates for the Sill magmas imply a maximum emplacement time of
ca
10
5
years, consistent with geochemical evidence for long-range lateral flow. It is a theoretically possibility that fast-flowing magma on a continental scale will be susceptible to planetary-scale rotational forces.
Oldest skeleton of a plesiadapiform provides additional evidence for an exclusively arboreal radiation of stem primates in the Palaeocene
Authors: Chester Stephen G. B. , Williamson Thomas E. , Bloch Jonathan I. , Silcox Mary T. , Sargis Eric J.
Published: June 2017

Palaechthonid plesiadapiforms from the Palaeocene of western North America have long been recognized as among the oldest and most primitive euarchontan mammals, a group that includes extant primates, colugos and treeshrews. Despite their relatively sparse fossil record, palaechthonids have played an important role in discussions surrounding adaptive scenarios for primate origins for nearly a half-century. Likewise, palaechthonids have been considered important for understanding relationships among plesiadapiforms, with members of the group proposed as plausible ancestors of Paromomyidae and Microsyopidae. Here, we describe a dentally associated partial skeleton of
Torrejonia wilsoni
from the early Palaeocene (approx. 62 Ma) of New Mexico, which is the oldest known plesiadapiform skeleton and the first postcranial elements recovered for a palaechthonid. Results from a cladistic analysis that includes new data from this skeleton suggest that palaechthonids are a paraphyletic group of stem primates, and that
T. wilsoni
is most closely related to paromomyids. New evidence from the appendicular skeleton of
T. wilsoni
fails to support an influential hypothesis based on inferences from craniodental morphology that palaechthonids were terrestrial. Instead, the postcranium of
T. wilsoni
indicates that it was similar to that of all other plesiadapiforms for which skeletons have been recovered in having distinct specializations consistent with arboreality.
Activin Signaling Regulates Autophagy and Cardiac Aging through mTORC2
Authors: Chang Kai , Kang Ping , Liu Ying , Huang Kerui , Taylor Erika , Sagona Antonia P. , Nezis Ioannis P. , Bodmer Rolf , Ocorr Karen , Bai Hua
Published: June 2017

Age-dependent loss of cardiac tissue homeostasis largely impacts heart performance and contributes significantly to cardiovascular diseases later in life. Cellular quality control machinery, such as autophagy/lysosome system, plays a crucial role in maintaining cardiac health and preventing age-induced cardiomyopathy and heart failure. However, how aging alters the autophagy/lysosome system to impact cardiac function remains largely unknown. Here usingDrosophilaheart as a model system, we show that activin signaling, a member of TGF-beta superfamily, negatively regulates cardiac autophagy and cardiac health during aging. We found that cardiac-specific knockdown ofDaw, an activin-like protein inDrosophila, increased cardiac autophagy and prevented age-related cardiac dysfunction, including arrhythmia and bradycardia (slow heart rate). Inhibition of autophagy blockedDawknockdown-mediated cardioprotection. Consistently, cardiac-specific expression of constitutively activated activin type I receptorBabodisrupted cardiac function at young ages. Intriguingly, the key autophagy regulator, mechanistic target of rapamycin complex 1 (mTORC1), was not involved in activin-mediated autophagy. Instead, activin signaling genetically interacted with Rictor, the key subunit of mTORC2, to regulate autophagy and cardiac aging. Knockdown ofDawincreased the mRNA expression of Rictor and the phosphorylation of AKT in fly hearts. Finally, cardiac-specific silencing ofDawnot only improved cardiac health, but also prolonged lifespan. Thus, our findings highlight an emerging role of activin signaling and mTORC2 in the regulation of autophagy and cardiac aging.
Moderate nucleotide diversity in the Atlantic herring is associated with a low mutation rate
Authors: Feng Chungang , Pettersson Mats , Lamichhaney Sangeet , Rubin Carl-Johan , Rafati Nima , Casini Michele , Folkvord Arild , Andersson Leif
Published: June 2017

The Atlantic herring (Clupea harengus) is one of the most abundant vertebrates on earth but its nucleotide diversity is moderate (π=0.3%), only three-fold higher than in human. The expected nucleotide diversity for selectively neutral alleles is a function of population size and the mutation rate, and it is strongly affected by demographic history. Here, we present a pedigree-based estimation of the mutation rate in the Atlantic herring. Based on whole-genome sequencing of four parents and 12 offspring, the estimated mutation rate is 1.7 × 10−9per base per generation. There was no significant difference in the frequency of paternal and maternal mutations (8 and 7, respectively). Furthermore, we observed a high degree of parental mosaicism indicating that a large fraction of thesede novomutations occurred during early germ cell development when we do not expect a strong gender effect. The now estimated mutation rate – the lowest among vertebrates analyzed to date – partially explains the discrepancy between the rather low nucleotide diversity in herring and its huge census population size (>1011). But our analysis indicates that a species like the herring will never reach its expected nucleotide diversity for selectively neutral alleles primarily because of fluctuations in population size due to climate variation during the millions of years it takes to build up a high nucleotide diversity. In addition, background selection and selective sweeps lead to reductions in nucleotide diversity at linked neutral sites.
A Model-Free Approach for Detecting Genomic Regions of Deep Divergence Using the Distribution of Haplotype Distances
Authors: Pettersson Mats E. , Kierczak Marcin , Almén Markus Sällman , Lamichhaney Sangeet , Andersson Leif
Published: June 2017

Recent advances in comparative genomics have revealed that divergence between populations is not necessarily uniform across all parts of the genome. There are examples of regions with divergent haplotypes that are substantially more different from each other that the genomic average.

Typically, these regions are of interest, as their persistence over long periods of time may reflect balancing selection. However, they are hard to detect unless the divergent sub-populations are known prior to analysis.

Here, we introduce HaploDistScan, an R-package implementing model-free detection of deep-divergence genomic regions based on the distribution of pair-wise haplotype distances, and show that it can detect such regions without use ofa prioriinformation about population sub-division. We apply the method to real-world data sets, from ruff and Darwin’s finches, and show that we are able to recover known instances of balancing selection – originally identified in studies reliant on detailed phenotyping – using only genotype data. Furthermore, in addition to replicating previously known divergent haplotypes as a proof-of-concept, we identify novel regions of interest in the Darwin’s finch genome and propose a plausible, data-driven evolutionary history for each novel locus individually.

In conclusion, HaploDistScan requires neither phenotypic nor demographic input data, thus filling a gap in the existing set of methods for genome scanning, and provides a useful tool for identification of regions under balancing selection or similar evolutionary processes.
A standard operating procedure for outlier removal in large-sample epidemiological transcriptomics datasets
Authors: Bøvelstad Hege Marie , Holsbø Einar , Bongo Lars Ailo , Lund Eiliv
Published: June 2017

Transcriptome measurements and other –omics type data are increasingly more used in epidemiological studies. Most of omics studies to date are small with samples sizes in the tens, or sometimes low hundreds, but this is changing. Our Norwegian Woman and Cancer (NOWAC) datasets are to date one or two orders of magnitude larger. The NOWAC biobank contains about 50000 blood samples from a prospective study. Around 125 breast cancer cases occur in this cohort each year. The large biological variation in gene expression means that many observations are needed to draw scientific conclusions. This is true for both microarray and RNA-seq type data. Hence, larger datasets are likely to become more common soon.

Technical outliers are observations that somehow were distorted at the lab or during sampling. If not removed these observations add bias and variance in later statistical analyses, and may skew the results. Hence, quality assessment and data cleaning are important. We find common quality assessment libraries difficult to work with for large datasets for two reasons: slow execution speed and unsuitable visualizations.

In this paper, we present our standard operating procedure (SOP) for large-sample transcriptomics datasets. Our SOP combines automatic outlier detection with manual evaluation to avoid removing valuable observations. We use laboratory quality measures and statistical measures of deviation to aid the analyst. These are available in thenowacleanR package, currently available on GitHub (https://github.com/3inar/nowaclean). Finally, we evaluate our SOP on one of our larger datasets with 832 observations.
Medial frontal theta is entrained to rewarded actions
Authors: Amarante Linda M. , Caetano Marcelo S. , Laubach Mark
Published: June 2017

Rodents lick to consume fluids. The reward value of ingested fluids is likely to be encoded by neuronal activity entrained to the lick cycle. Here, we investigated relationships between licking and reward signaling by the medial frontal cortex [MFC], a key cortical region for reward-guided learning and decision-making. Multi-electrode recordings of spike activity and field potentials were made in male rats as they performed an incentive contrast licking task. Rats received access to higher and lower value sucrose rewards over alternating 30 sec periods. They learned to lick persistently when higher value rewards were available and to suppress licking when lower value rewards were available. Spectral analysis of spikes and fields revealed evidence for reward value being encoded by the strength of phase-locking of a 6-12 Hz theta rhythm to the rats’ lick cycle. Recordings during the initial acquisition of the task found that the strength of phase-locking to the lick cycle was strengthened with experience. A modification of the task, with a temporal gap of 2 sec added between reward deliveries, found that the rhythmic signals persisted during periods of dry licking, a finding that suggests the MFC encodes either the value of the currently available reward or the vigor with which rats act to consume it. Finally, we found that reversible inactivations of the MFC in the opposite hemisphere eliminated the encoding of reward information. Together, our findings establish that a 6-12 Hz theta rhythm, generated by the rodent medial frontal cortex, is synchronized to rewarded actions.

Significance Statement

The cellular and behavioral mechanisms of reward signaling by the medial frontal cortex [MFC] have not been resolved. We report evidence for a 6-12 Hz theta rhythm that is generated by the MFC and synchronized with ongoing consummatory actions. Previous studies of MFC reward signaling have inferred value coding upon temporally sustained activity during the period of reward consumption. Our findings suggest that MFC activity is temporally sustained due to the consumption of the rewarding fluids, and not necessarily the abstract properties of the rewarding fluid. Two other major findings were that the MFC reward signals persist beyond the period of fluid delivery and are generated by neurons within the MFC.
Genome-enabled insights into the ecophysiology of the comammox bacteriumCandidatusNitrospira nitrosa
Authors: Camejo Pamela Y. , Domingo Jorge Santo , McMahon Katherine D. , Noguera Daniel R.
Published: June 2017

The recently discovered comammox bacteria have the potential to completely oxidize ammonia to nitrate. These microorganisms are part of theNitrospiragenus and are present in a variety of environments, including Biological Nutrient Removal (BNR) systems. However, the physiological traits within and between comammox- and nitrite oxidizing bacteria (NOB)-likeNitrospiraspecies have not been analyzed in these ecosystems. In this study, we identifiedNitrospirastrains dominating the nitrifying community of a sequencing batch reactor (SBR) performing BNR under micro-aerobic conditions. We recovered metagenomes-derived draft genomes from twoNitrospirastrains: (1)Nitrospirasp. UW-LDO-01, a comammox-like organism classified asCandidatusNitrospira nitrosa, and (2)Nitrospirasp. UW-LDO-02, a nitrite oxidizing strain belonging to theNitrospira defluviispecies. A comparative genomic analysis of these strains with otherNitrospira-likegenomes identified genomic differences inCa.Nitrospira nitrosa mainly attributed to each strains’ niche adaptation. Traits associated with energy metabolism also differentiate comammox from NOB-like genomes. We also identified several transcriptionally regulated adaptive traits, including stress tolerance, biofilm formation and micro-aerobic metabolism, which might explain survival ofNitrospiraunder multiple environmental conditions. Overall, our analysis expanded our understanding of the genetic functional features ofCa.Nitrospira nitrosa, and identified genomic traits that further illuminate the phylogenetic diversity and metabolic plasticity of theNitrospiragenus.
Pantothenate auxotrophy inZymomonas mobilisZM4 is due to a lack of aspartate decarboxylase activity
Authors: Gliessman J. R. , Kremer T. A. , Sangani A. A. , Jones-Burrage S. E. , McKinlay J. B.
Published: June 2017

The bacteriumZymomonas mobilisnaturally produces ethanol at near theoretical maximum yields, making it of interest for industrial ethanol production.Z. mobilisrequires the vitamin pantothenate for growth. Here we characterized the genetic basis for theZ. mobilispantothenate auxotrophy. We found that this auxotrophy is due to the absence of a single gene,panD, encoding aspartate-decarboxylase. Heterologous expression ofEscherichia coliPanD inZ. mobilisor supplementation of the growth medium with the product of PanD activity, β-alanine, eliminated the need for exogenous pantothenate. We also determined that IlvC, an enzyme better known for branched-chain amino acid synthesis, is required for pantothenate synthesis inZ. mobilis, as it compensates for the absence of PanE, another pantothenate synthesis pathway enzyme. In addition to contributing to an understanding of the nutritional requirements ofZ. mobilis, our results have led to the design of a more cost-effective growth medium.
Crystallographic and optical study of LiNb1 − xTaxO3
Authors: Huband S. , Keeble D. S. , Zhang N. , Glazer A. M. , Bartasyte A. , Thomas P. A.
Published: June 2017

Powders of lithium niobate-tantalate across the full compositional range have been made and crystals grown using a lithium vanadate flux growth technique. The Li-content of a lithium tantalate crystal has been determined using the zero-birefringence temperature and Curie measurements, confirming the Li content is between that of congruent and stoichiometric crystals. X-ray diffraction measurements show the Nb/Ta displacement and octahedral tilt both decrease as the Ta content is increased. This also results in a decrease in the lattice parameters from lithium niobate to lithium tantalate. Birefringence measurements on the crystals as a function of temperature have been used to determine the point that the crystals become zero-birefringent, and by comparison with the structural studies have confirmed that it is not related to a phase transition and the structures remain polar through the zero-birefringence points.
High-resolution cryo-EM proteasome structures in drug development
Authors: Morris Edward P. , da Fonseca Paula C. A.
Published: June 2017

With the recent advances in biological structural electron microscopy (EM), protein structures can now be obtained by cryo-EM and single-particle analysis at resolutions that used to be achievable only by crystallographic or NMR methods. We have explored their application to study protein–ligand interactions using the human 20S proteasome, a well established target for cancer therapy that is also being investigated as a target for an increasing range of other medical conditions. The map of a ligand-bound human 20S proteasome served as a proof of principle that cryo-EM is emerging as a realistic approach for more general structural studies of protein–ligand interactions, with the potential benefits of extending such studies to complexes that are unfavourable to other methods and allowing structure determination under conditions that are closer to physiological, preserving ligand specificity towards closely related binding sites. Subsequently, the cryo-EM structure of thePlasmodium falciparum20S proteasome, with a new prototype specific inhibitor bound, revealed the molecular basis for the ligand specificity towards the parasite complex, which provides a framework to guide the development of highly needed new-generation antimalarials. Here, the cryo-EM analysis of the ligand-bound human andP. falciparum20S proteasomes is reviewed, and a complete description of the methods used for structure determination is provided, including the strategy to overcome the bias orientation of the human 20S proteasome on electron-microscope grids and details of theicr3dsoftware used for three-dimensional reconstruction.
Modelling competitive advantage of nation: a literature review
Authors: Hanafi Muhammad , Wibisono Dermawan , Mangkusubroto Kuntoro , Siallagan Manahan , Badriyah Mila Jamilah Khatun
Published: June 2017

Purpose

This paper aims to create a mapping of competitive advantage of nations (CAN) from research using some previous studies and recommend future research.

Design/methodology/approach

This paper applies a systematic literature review on the most recent studies of CAN. The research gap is analysed based on several categories: implication (strategy and policy, portrait); general characteristics (fundamental issues, indicators and patterns); solution methodology and strategic level (nation and industry). Then, the state-of-the-art analysis is used to develop future research.

Findings

The results of this study recommend future research of CAN based on the following CAN categories: implication (strategy and policy, portrait); general characteristics (fundamental issues, indicators and patterns); solution methodology and strategic level (nation and industry).

Research limitations/implications

This literature review has important implications and gives direction for research and teaching, as well as for further investigation of CAN. The limitation lies in the classification of patterns, which requires further study to avoid the ambiguity of grouping.

Originality/value

This is the first literature review about CAN using categories. It is of value in building future research of CAN in different industries and nations.