bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Consistent Gyrus Formation: an Experimental and Computational Study
Authors: Zhang Tuo , Razavi Mir Jalil , Li Xiao , Chen Hanbo , Liu Tianming , Wang Xianqiao 
Published: November 2016

AbstractAs a significant type of cerebral cortical convolution pattern, the gyrus is widely preserved across species. Although many hypotheses have been proposed to study the underlying mechanisms of gyrus formation, it is currently still far from clear which factors contribute to the regulation of consistent gyrus formation. In this paper, we employ a joint analysis scheme of experimental data and computational modeling to investigate the fundamental mechanism of gyrus formation. Experimental data on mature human brains and fetal brains show that thicker cortices are consistently found in gyral regions and gyral cortices have higher growth rates. We hypothesize that gyral convolution patterns might stem from heterogeneous regional growth in the cortex. Our computational simulations show that gyral convex patterns may occur in locations where the cortical plate grows faster than the cortex of the brain. Global differential growth can only produce a random gyrification pattern, but it cannot guarantee gyrus formation at certain locations. Based on extensive computational modeling and simulations, it is suggested that a special area in the cerebral cortex with a relatively faster growth speed could consistently engender gyri.
Molecular analysis of the factorless internal ribosome entry site in Cricket Paralysis virus infection
Authors: Kerr Craig H. , Ma Zi Wang , Jang Christopher J. , Thompson Sunnie R. , Jan Eric 
Published: November 2016

AbstractThe dicistrovirus Cricket Paralysis virus contains a unique dicistronic RNA genome arrangement, encoding two main open reading frames that are driven by distinct internal ribosome entry sites (IRES). The intergenic region (IGR) IRES adopts an unusual structure that directly recruits the ribosome and drives translation of viral structural proteins in a factor-independent manner. While structural, biochemical, and biophysical approaches have provided mechanistic details into IGR IRES translation, these studies have been limited to in vitro systems and little is known about the behavior of these IRESs during infection. Here, we examined the role of previously characterized IGR IRES mutations on viral yield and translation in CrPV-infected Drosophila S2 cells. Using a recently generated infectious CrPV clone, introduction of a subset of mutations that are known to disrupt IRES activity failed to produce virus, demonstrating the physiological relevance of specific structural elements within the IRES for virus infection. However, a subset of mutations still led to virus production, thus revealing the key IRES-ribosome interactions for IGR IRES translation in infected cells, which highlights the importance of examining IRES activity in its physiological context. This is the first study to examine IGR IRES translation in its native context during virus infection.
Imprinting of cerebral cytochrome P450s in offsprings prenatally exposed to cypermethrin augments toxicity on rechallenge
Authors: Singh Anshuman , Agrahari Anita , Singh RadhaDutt , Yadav Sanjay , Srivastava Vikas , Parmar Devendra 
Published: November 2016

AbstractEpigenetic studies were carried in the rat offsprings, born to dams treated with cypermethrin (orally; 5.0 mg/kg) from gestation day (GD) 5 to 21 and rechallenged with cypermethrin (orally; 10 mg/kg for 6 days), at adulthood (12 weeks) to understand the mechanism underlying the overexpression of cerebral cytochrome P450s (CYPs) in exposed offsprings. The data revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of CYP1A- and 2B- isoenzymes in the brain isolated from rechallenged animals. Further, bisulphite sequencing revealed critical CpG methylation changes in BARBIE BOX (Barbiturate response element) and BTE (Basal transcription element) in promoter of CYP2B1 in the brain isolated from rechallenged animals. Western blotting and DNA laddering/fragmentation studies revealed a greater magnitude of increase in the signalling pathways associated with apoptosis in the rechallenged animals. The data have indicated that overexpression of cerebral CYPs could be due to the imprinting of CYPs. Further, increased apoptosis observed in the rechallenged offsprings has suggested that these epigenetic changes in CYPs may predispose the prenatally exposed offsprings to the neurotoxic effects of other centrally acting drugs and chemicals when subsequently rechallenged later at life.
Aβ42 oligomers modulate β-secretase through an XBP-1s-dependent pathway involving HRD1
Authors: Gerakis Yannis , Dunys Julie , Bauer Charlotte , Checler Fréderic 
Published: November 2016

AbstractThe aspartyl protease β-site APP cleaving enzyme, BACE1, is the rate-limiting enzyme involved in the production of amyloid-β peptide, which accumulates in both sporadic and familial cases of Alzheimer’s disease and is at the center of gravity of the amyloid cascade hypothesis. In this context, unravelling the molecular mechanisms controlling BACE1 expression and activity in both physiological and pathological conditions remains of major importance. We previously demonstrated that Aβ controlled BACE1 transcription in an NFκB-dependent manner. Here, we delineate an additional cellular pathway by which natural and synthetic Aβ42 oligomers enhance active X-box binding protein XBP-1s. XBP-1s lowers BACE1 expression and activity indirectly, via the up-regulation of the ubiquitin-ligase HRD1 that acts as an endogenous down-regulator of BACE1. Thus, we delineate a novel pathway by which cells could compensate for Aβ42 oligomers production and thus, associated toxicity, by triggering a compensatory mechanism aimed at lowering BACE-1-mediated Aβ production by a molecular cascade involving XBP-1s and HRD1. It thus identifies HRD1 as a potential target for a novel Aβ-centered therapeutic strategy.
14-Year Results of Bilateral versus Single Internal Thoracic Artery Grafts for Left-Sided Myocardial Revascularization in Young Diabetic Patients
Authors: Delalic Alem , Eszlari Edgar , Eichinger Walter , Gansera Brigitte 
Published: November 2016

Objectives Despite encouraging late outcomes, the use of bilateral internal thoracic artery (BITA) grafting for myocardial revascularization in diabetic patients remains controversial because of an increased risk of sternal wound complications. In the present study, early- and long-term outcomes of the use of left-sided BITA versus single internal thoracic artery (SITA) grafting in young (< 65 years of age) diabetic patients were reviewed retrospectively.
Methods A total of 250 propensity score pair-matched diabetic patients, operated on between February 2000 and December 2011, receiving either BITA (n = 125) or SITA (n = 125) grafting were analyzed retrospectively. In each group, 104 patients were males, and mean age was 60.1 ± 5.3 years. Follow-up was 2.1 to 14.8 years (mean, 9.3 ± 3.5 years) and complete for 100%.
Results Incidence of deep sternal wound infection was 2.4 versus 3.2% (p = 0.722). Rethoracotomy due to bleeding occurred in 4.8 versus 3.2% (p = 0.608). The 5-, 10-, and 14-year estimates of survival were 93.4, 76.6, and 67.5% (BITA) versus 89.5, 81.5, and 32.8% (SITA); p = 0.288. Freedom from reangiography/intervention (60.5 vs. 63.9%) during follow-up was comparable (p = 0.507) as well as infarction rate (93.8 vs. 95.1%, p = 0.833) and redoes (p = 0.672, exclusively valve surgery) were comparable. Freedom from thromboembolic or cerebrovascular events did not show any significant differences (94.0 vs. 94.0%, p = 0.78). Multivariate analysis identified poor ejection fraction as predictor for decreased long-term survival. Neither age nor gender or urgency had an influence on long-term mortality.
Conclusion Left-sided BITA grafting may be performed routinely even in diabetic patients without increased incidence of postoperative wound-healing complications. Survival rates after 5, 10, and 14 years were comparable for BITA and SITA grafting.
Damit ihr mich versteht
Authors: Maxeiner Sandra , Rühle Hedda 
Published: November 2016

SummaryViele Depressive fühlen sich wertlos und als Bürde für ihre Mitmenschen. Oft sehen sie Suizid als einzigen Ausweg. Kommunizieren Depressive ihre Erkrankung nach außen, stoßen sie häufig auf Unverständnis. Dies bestätigt ihr Gefühl, unverstanden zu sein. Mit unserer Logik als Maßstab lässt sich die innere Not von Betroffenen nicht begreifen. Urteilsfreies Zuhören dagegen hilft, ihre Situation nachzuempfinden.
Arabidopsis dehydroascorbate reductase 1 and 2 modulate redox states of ascorbate-glutathione cycle in the cytosol in response to photooxidative stress
Authors: Noshi Masahiro , Yamada Hiroki , Hatanaka Risa , Tanabe Noriaki , Tamoi Masahiro , Shigeoka Shigeru 
Published: November 2016

Abstract
Ascorbate and glutathione are indispensable cellular redox buffers and allow plants to acclimate stressful conditions. Arabidopsis contains three functional dehydroascorbate reductases (DHAR1-3), which catalyzes the conversion of dehydroascorbate into its reduced form using glutathione as a reductant. We herein attempted to elucidate the physiological role in DHAR1 and DHAR2 in stress responses. The total DHAR activities in DHAR knockout Arabidopsis plants, dhar1 and dhar2, were 22 and 92%, respectively, that in wild-type leaves. Under high light (HL), the levels of total ascorbate and dehydroascorbate were only reduced and increased, respectively, in dhar1. The oxidation of glutathione under HL was significantly inhibited in both dhar1 and dhar2, while glutathione contents were only enhanced in dhar1. The dhar1 showed stronger visible symptoms than the dhar2 under photooxidative stress conditions. Our results demonstrated a pivotal role of DHAR1 in the modulation of cellular redox states under photooxidative stress.
E×B

staircases and barrier permeability in magnetised plasmas
Authors: Hornung G. , Dif-Pradalier G. , Clairet F. , Sarazin Y. , Sabot R. , Hennequin P. , Verdoolaege G. 
Published: November 2016

Abstract
In-depth experimental characterisation of spontaneous shear flow patterning into a so-called

E

×

B

staircase—named after its planetary analogue—is shown in magnetised plasma turbulence, using ultrafast-sweeping reflectometry in the Tore Supra tokamak. Staircase signatures are found in a large variety of L-mode plasma conditions. Sensitivity to the dominant source of free energy is highlighted for the first time. A connection between staircase shear layer permeability and deviation from gyro-Bohm confinement scaling is strongly suggested, opening new routes to understanding confinement in drift-wave turbulence.
Determination of divertor stray light in high-resolution main chamber Hα spectroscopy in JET-ILW
Authors: Neverov V.S. , Kukushkin A.B. , Stamp M.F. , Alekseev A.G. , Brezinsek S. , von Hellermann M. 
Published: November 2016

Abstract
The theoretical model suggested for ITER main chamber H
α
spectroscopy is applied to the high-resolution spectroscopy (HRS) data of recent JET ITER-like wall (ILW) experiments. The model is aimed at reconstructing the neutral hydrogen isotope density in the SOL, as well as the isotope ratio, by solving a multi-parametric inverse problem with allowance for (i) the strong divertor stray light (DSL) on the main-chamber lines of sight (LoS), (ii) substantial deviation of the neutral atom velocity distribution function (VDF) from a Maxwellian in the SOL, and (iii) data for the direct observation of the divertor. The JET-ILW HRS data on resolving the power at the deuterium and hydrogen spectral lines of the Balmer-alpha series is analysed, with direct observation of the divertor from the top and with observation of the inner wall along the tangential and radial LoS from the equatorial ports. This data allows the spectrum of the DSL and the signal-to-background ratio for the Balmer-alpha light emitted from the far SOL and divertor in the JET-ILW to be evaluated. The results support the expectation of the strong impact of the DSL upon the ITER main chamber H
α
(and visible light) spectroscopy diagnostics.
Police Officers, Regular Soldiers, and Normative Institutional Analysis
Authors: Miller Seumas 
Published: November 2016

Abstract
In this chapter a normative, comparative institutional analysis of police officers and regular soldiers is provided. The roles of police officer and regular soldier are defined by recourse to normatively specified, empirically anchored, organizational roles. Two key theoretical notions employed are those of multilayered structures of joint action and collective goods. The moral rights and duties constitutive of institutional roles are derived in part from the collective goods that are the raison d’être of police and military organizations. These institutional moral rights and duties are special rights and duties.The institutional roles of police officers and regular soldiers are importantly different from one another.. For example, military forces, unlike police forces, do not have as a primary and overriding role to enforce the law, and soldiers use lethal force with less legal and moral constraints than police officers.
Military Use of Lethal Force
Authors: Miller Seumas 
Published: November 2016

Abstract
In this chapter, just war theory is outlined, including jus ad bellum and jus in bello, and a version provided that accommodates wars fought by and against nonstate actors (e.g., terrorist groups). The concept of war is framed in terms of such theoretical notions as joint actions, multilayered structures of joint action, and institutional roles. It is argued that (1) despite the moral difference between combatants fighting a just war and those fighting an unjust war, compliance with the doctrine of the moral equality of combatants is morally justified, but the institutional rights and duties constitutive of that doctrine are merely prima facie moral rights and duties; (2) the principle of military necessity is to be understood in terms of nested collective ends (e.g., the collective end of winning the war depends on winning various battles); and (3) the application of the principle of military necessity involvesthe rules of engagement.
Magnetohydrodynamics
Authors: Bers Abraham 
Published: November 2016

Abstract
This chapter discusses some basic aspects of magnetohydrodynamics (MHD) through two alternate presentations. The first describes a fluid physical of MHD based upon guiding-center particle motion, while the second is based on MHD from Braginskii's equation. In addition to MHD conservation equations and basic properties, a complete treatment is given of MHD wave dynamics in a uniform plasma. The chapter establishes an MHD model based on known dynamics of charged particles in equilibrium and slowly-varying dynamic fields, and obtains their fluid dynamic description from appropriate velocity space averages of the particles' distribution functions. The guiding center theory of charged-particle motions in slowly-varying EM fields, described in the previous chapter, provides a basis for this approach. It is an approach that allows the study of many interesting and relevant, stable and unstable, dynamics which are useful in understanding observed plasma dynamics phenomena.
Drift-free cold plasma, magnetized —III. Waves in arbitrary directions; nonlinear coupling
Authors: Bers Abraham 
Published: November 2016

Abstract
This chapter completes the task of describing linear natural modes in a homogeneous, drift-free cold-plasma and concludes with a brief look at the nonlinear coupling of linear modes. The linear wave analysis here follows the formulation and developments of the previous two chapters, and highlights the analysis of linear waves at any angle. Waves that propagate at an arbitrary angle are of a very large variety and their detailed description requires approximate analytical approaches for various applications. For propagation in infinitely-extended plasmas, it has been found useful to classify their description in a space of normalized magnetic field and density variables where the cutoff and resonance of the principal waves—this is referred to here as the Clemmow, Mullaly, Allis (CMA) diagram. The chapter also analyses approximate wave propagation treatments that have been found useful in various, more specific, wave applications in magnetized plasmas.
Linear coupling of modes—Amplifying and oscillating instabilities and devices—Appendix: Green’s functions in unstable LCOM interactions
Authors: Bers Abraham 
Published: November 2016

Abstract
This chapter presents the important application of the dynamic mode-perturbation theory developed in the previous chapter, namely, the linear coupling of modes (LCOM) in homogeneous, loss-free, and nearly-loss free systems. It traces the historical development of the theory of LCOM as it arose for the understanding of interactions between waves and e-beams in microwave amplifiers and oscillators. This was typically formulated as a phaseresonant LCOM in space at a given frequency of the waves. In particular, the distinction of LCOM that entails the coupling of stable and unstable waves in a loss-free system is analyzed. The chapter then illustrates the use of LCOM in space-time, in more general systems of plasmas and waves, and in particular to nonresonant and phase-resonant interactions. It concludes with the application of LCOM analysis to the cross-field magnetron amplifier which entails the coupling of an unstable e-beam mode—the diocotron instability—to a passive wave on an adjacent slow-wave structures (SWS).
Kinetic descriptions in inhomogeneous plasmas—Drift waves and instabilities
Authors: Bers Abraham 
Published: November 2016

Abstract
This chapter discusses the kinetic theory analysis of waves and instabilities in plasmas with nonuniform equilibria and, in particular, driftwave instabilities. In a stable inhomogeneous plasma, linear wave propagation in the vicinity of local propagation resonances and nearby cutoffs brings about a complex coupling of the natural wave modes of the homogeneous plasma. This coupling, generally called modeconversion (MC), is particularly important for analyzing the excitation of, or emission from, kinetic waves that exist only inside a hot plasma. In high-temperature plasmas, analysis of MC requires the solution of the full-wave kinetic Vlasov–Maxwell integro-partial differential equations. For a (DF) dissipation-free (MCR) modeconversion region in a plasma, the chapter derives the coupling symmetries that must be satisfied among the various wave energy flows into and out of such regions, without having to solve the full-wave kinetic equations. The general results are illustrated for cases of interest to heating and current drive in toroidally-confined high-temperature plasma.
EXPLOITING NEXT GENERATION SEQUENCING TO SOLVE THE HAPLOTYPING PUZZLE IN POLYPLOIDS: A SIMULATION STUDY
Authors: Motazedi Ehsan , Finkers Richard , Maliepaard Chris , de Ridder Dick 
Published: November 2016

AbstractHaplotypes are the units of inheritance in an organism, and many genetic analyses depend on their precise determination. Methods for haplotyping single individuals use the phasing information available in Next Generation sequencing reads, by matching overlapping sNPs while penalizing post hoc nucleotide corrections made. Haplotyping diploids is relatively easy, but the complexity of the problem increases drastically for polyploid genomes, which are found in both model organisms and in economically relevant plant and animal species. While a number of tools are available for haplotyping polyploids, the effects of the genomic makeup and the sequencing strategy followed on the accuracy of these methods have hitherto not been thoroughly evaluated.We developed the simulation pipelinehaplosimto evaluate the performance of haplotype estimation algorithms for polyploids: HapCompass, HapTree and SDhaP, in settings varying in sequencing approach, ploidy levels and genomic diversity, using tetraploid potato as the model. Our results show that sequencing depth is the major determinant of haplotype estimation quality, that 1kbPacBio CCS reads and Illumina reads with large insert-sizes are competitive, and that all methods fail to produce good haplotypes when ploidy levels increase. Comparing the three methods, HapTree produces the most accurate estimates, but also consumes the most resources. There is clearly room for improvement in polyploid haplotyping algorithms.
Computational evidence of a compound with nicotinic α4β2-Ach receptor partial agonist properties as possible coadjuvant for the treatment of obesity
Authors: den-Haan Helena , José Hernández Morante Juan , Pérez-Sánchez Horacio 
Published: November 2016

ABSTRACTBackgroundNowadays, the search for new anti-obesity drugs is oriented to the use of anti-addiction medications like bupropion and naltrexone. Other compounds like varenicline may be also useful to treat obesity. However, the low effectiveness of the former or the high number of adverse effects of the latter makes it necessary to search for new therapeutic agents.MethodsScreening database selected for the computational experiments was DrugBank. 3D global shape comparison with varenicline was performed by means of the Ligand Based Virtual Screening tool WEGA v2015. A pharmacophore model based in the structure of varenicline was created by means of LigandScout v4.08. The in-silico screening was performed using Relative Pharmacophore Fit (RPF) scoring function implemented in LigandScout. Up to 3 mismatches with varenicline pharmacophore model were allowed for hits retrieving.ResultsDrugbank database was screened in silico to find alternative molecules to varenicline, and the compound cevimeline was found to have strong similarity to varenicline in terms of 3D shape and pharmacophoric features. Thus, we propose this hit may interact with nicotinic α4β2-Ach receptor in the same mode as varenicline does.DiscussionThe functional activities of this compound and its validity as a drug therapy for obesity treatment must be confirmed in further in vitro, in vivo and preclinical studies; however, attending to our screening procedure, this compound should be a promising therapy for such a complex disorder such as obesity.
Phylogenomics-guided discovery of a novel conserved cassette of short linear motifs in BubR1 essential for the spindle checkpoint
Authors: Tromer Eelco , Bade Debora , Snel Berend , Kops Geert J.P.L. 
Published: November 2016

AbstractThe spindle assembly checkpoint (SAC) maintains genomic integrity by preventing progression of mitotic cell division until all chromosomes are stably attached to spindle microtubules. The SAC critically relies on the paralogs Bub1 and BubR1/Mad3, which integrate kinetochore-spindle attachment status with generation of the anaphase inhibitory complex MCC. We previously reported on the widespread occurrences of independent gene duplications of an ancestral ‘MadBub’ gene in eukaryotic evolution and the striking parallel subfunctionalization that lead to loss of kinase function in BubR1/Mad3-like paralogs. We now present an elaborate subfunctionalization analysis that includes all known motifs in Bub1 and BubR1, and show that ancestral features are consistently retained in the same functional paralog: GLEBS/CDI/CDII/kinase in the Bub1-like and KEN1/KEN2/D-Box in the BubR1/Mad3-like. The recently described ABBA motif can be found in either or both paralogs. We however discovered two additional ABBA motifs that flank KEN2. This cassette of ABBA1-KEN2-ABBA2 forms a strictly conserved module in all ancestral and BubR1/Mad3-like proteins, suggestive of a specific and crucial SAC function. Indeed, deletion of the ABBA motifs in human BUBR1 abrogates the SAC and affects APC/C-Cdc20 interactions. Our detailed comparative genomics analyses thus enabled discovery of a conserved cassette of motifs essential for the SAC and shows how this approach can be used to uncover hitherto unrecognized functional protein features.