bluuebunny/crossref_metadata_2025 huggingface dataset:
The H, H2+, and HeH2+ systems confined by an impenetrable spheroidal cavity: Revisited study via the Lagrange‐mesh approach
Authors: Olivares‐Pilón Horacio , Cruz Salvador A.
Published: May 2017

The one electron systems H, H
, and HeH
confined by an impenetrable spheroidal cavity are revisited in the frame of the Lagrange‐mesh method. The Born–Oppenheimer approximation where the nuclei are clamped at the foci is considered. Benchmark results of the total energy are obtained as a function of the interfocal distance R and the eccentricity of the cavity
. Dipole oscillator strengths are calculated for the molecular ions H
and HeH
.
Bone Marrow Endothelial Progenitor Cells Are the Cellular Mediators of Pulmonary Hypertension in the Murine Monocrotaline Injury Model
Authors: Aliotta Jason M. , Pereira Mandy , Wen Sicheng , Dooner Mark S. , Del Tatto Michael , Papa Elaine , Cheng Yan , Goldberg Laura , Ventetuolo Corey E. , Liang Olin , Klinger James R. , Quesenberry Peter J.
Published: May 2017

The role of bone marrow (BM) cells in modulating pulmonary hypertensive responses is not well understood. Determine if BM-derived endothelial progenitor cells (EPCs) induce pulmonary hypertension (PH) and if this is attenuated by mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Three BM populations were studied: (a) BM from vehicle and monocrotaline (MCT)-treated mice (PH induction), (b) BM from vehicle-, MCT-treated mice that received MSC-EV infusion after vehicle, MCT treatment (PH reversal, in vivo), (c) BM from vehicle-, MCT-treated mice cultured with MSC-EVs (PH reversal, in vitro). BM was separated into EPCs (sca-1+/c-kit+/VEGFR2+) and non-EPCs (sca-1-/c-kit-/VEGFR2-) and transplanted into healthy mice. Right ventricular (RV) hypertrophy was assessed by RV-to-left ventricle+septum (RV/LV+S) ratio and pulmonary vascular remodeling by blood vessel wall thickness-to-diameter (WT/D) ratio. EPCs but not non-EPCs from mice with MCT-induced PH (MCT-PH) increased RV/LV+S, WT/D ratios in healthy mice (PH induction). EPCs from MCT-PH mice treated with MSC-EVs did not increase RV/LV+S, WT/D ratios in healthy mice (PH reversal, in vivo). Similarly, EPCs from MCT-PH mice treated with MSC-EVs pre-transplantation did not increase RV/LV+S, WT/D ratios in healthy mice (PH reversal, in vitro). MSC-EV infusion reversed increases in BM-EPCs and increased lung tissue expression of EPC genes and their receptors/ligands in MCT-PH mice. These findings suggest that the pulmonary hypertensive effects of BM are mediated by EPCs and those MSC-EVs attenuate these effects. These findings provide new insights into the pathogenesis of PH and offer a potential target for development of novel PH therapies.
Connective Tissue Growth Factor Promotes Efficient Generation of Human Induced Pluripotent Stem Cell-Derived Choroidal Endothelium
Authors: Songstad Allison E. , Worthington Kristan S. , Chirco Kathleen R. , Giacalone Joseph C. , Whitmore S. Scott , Anfinson Kristin R. , Ochoa Dalyz , Cranston Cathryn M. , Riker Megan J. , Neiman Maurine , Stone Edwin M. , Mullins Robert F. , Tucker Budd A.
Published: May 2017

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, the majority of stem cell research to date has focused on production of retinal pigment epithelial (RPE) and photoreceptor cells for the purpose of evaluating disease pathophysiology and cell replacement, there is strong evidence that the choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first to be lost in this disease. As such, to accurately evaluate disease pathophysiology and develop an effective treatment, production of patient-specific, stem cell-derived CECs will be required. In this study, we report for the first time a stepwise differentiation protocol suitable for generating human iPSC-derived CEC-like cells. RNA-seq analysis of the monkey CEC line, RF/6A, combined with two statistical screens allowed us to develop media comprised of various protein combinations. In both screens, connective tissue growth factor (CTGF) was identified as the key component required for driving CEC development. A second factor tumor necrosis factor (TNF)-related weak inducer of apoptosis receptor was also found to promote iPSC to CEC differentiation by inducing endogenous CTGF secretion. CTGF-driven iPSC-derived CEC-like cells formed capillary tube-like vascular networks, and expressed the EC-specific markers CD31, ICAM1, PLVAP, vWF, and the CEC-restricted marker CA4. In combination with RPE and photoreceptor cells, patient-specific iPSC derived CEC-like cells will enable scientists to accurately evaluate AMD pathophysiology and develop effective cell replacement therapies.
Tailoring of Hetero–oligophenylene Stabilized Nanohybrid Materials: Potential Tandem Photo‐Promoted Systems for C–C and C–X Bond Formation Reactions via C‐H Activation
Authors: Walia Preet Kamal , Kumar Manoj , Bhalla Vandana
Published: May 2017

Supramolecular assemblies of the hetero‐oligophenylene derivative 3 served as reactors for the facile synthesis of ZnO and Pd NPs in mixed aqueous media. Unprecendentally, these assemblies provided a common platform for the generation of bimetallic Pd‐ZnO nanohybrid materials in aqueous media which served as efficient catalytic systems in C−C/C−X bond forming reactions. The freshly prepared zinc oxide nanoparticles showed high efficiency in (i) single pot three (in situ five) component reactions for the synthesis of tetrahydropyridine derivatives ii) photo‐promoted synthesis of propargylamines via A3‐coupling reaction. On the other hand, freshly prepared bimetallic Pd‐ZnO nanohybrid materials enabled efficient harvesting of visible light radiation to catalyze biaryl coupling and “green” Sonogashira coupling in aqueous media. Additionally, ZnO NPs and Pd NPs in combination with bimetallic Pd‐ZnO nanohybrid materials efficiently photocatalyzed the “one‐pot two‐step reactions” comprising Sonogashira cross coupling, reduction and three component reaction for the synthesis of tetrahydropyridine derivative in good yield.
Synthesis and Characterization of a New Class of Triazoles Containing Bicyclic Silaheterocycles
Authors: Wang Tengjiao , Cho Hyeon Mo , Lee Myong Euy
Published: May 2017

A new class of bicyclic silaheterocycles, 6,6‐dimethyl‐2‐aryl‐6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3,5]thiazasilines, which could be developed as potential sila‐drugs. The reactions of several 3‐aryl‐5‐mercapto‐1,2,4‐triazoles with bis(chloromethyl)dimethylsilane under basic conditions gave high yields of bicyclic products. Reaction, product workup and isolation were streamlined without requiring an anhydrous solvent, inert gas or chromatographic purification. The products were structurally characterized by single‐crystal X‐ray diffraction.
Metal‐Free Alkyl(Aryl) Transfer‐Aromatization‐Alkylation Domino Approach: Facile Synthesis of Branched Hydroquinones from p‐Quinols and Diaryl Carbinols
Authors: Singh Pallavi , Peddinti Rama Krishna
Published: May 2017

Simple but effective and eco‐friendly metal‐free alkyl(aryl) transfer‐aromatization‐alkylation domino (ATAAD) approach was demonstrated to synthesize branched hydroquinones in good to excellent yields. This high atom economy approach proceeded through molecular iodine‐catalyzed aromatization of p‐quinols followed by C–C bond formation with diaryl carbinols. The use of inexpensive catalyst and easily accessible starting materials rendered this clean method more exciting for wide substrate scope to afford symmetrical and unsymmetrical branched hydroquinones. Short reaction time, easy workup and gram‐scale preparation are the significant features of this hitherto unknown synthesis of the title compounds.
N‐Arylsulfonimides as Photoinitiators for Cationic Polymerization of Epoxy Sol‐Gel Materials
Authors: Torti Edoardo , Protti Stefano , Fagnoni Maurizio , Della Giustina Gioia
Published: May 2017

N‐arylsulfonimides, a new class of non‐ionic photoacid generators (PAGs) able to release two equivalents of strong sulfonic acids per equivalent of PAG are employed in solid state polymerization within an epoxy based hybrid sol‐gel system. Thus, epoxy ring opening reactions were successfully induced by UV light exposure of sol‐gel films and the organic network progression was followed by infrared spectroscopy. Polymerization degrees reached with N‐arylsulfonimides were close to that obtained with a commercial PAG (4‐phenylthiophenyl)diphenylsulfonium triflate, DPST). Different micrometric patterns with satisfactory pattern definition were achieved by UV lithography of sol‐gel films containing a N‐arylsulfonimide. These new PAGs are therefore promising photoinitiators to be applied in photopolymerization processes and microelectronics.
Bulky 2,6‐Dibenzhydryl‐4‐methylaniline Derived Schiff Base Complexes of Pd(II), Cu(II) and Co(II) as Efficient Catalysts for Suzuki Coupling and Alcohol Oxidation Reactions
Authors: Saxena Priya , Murugavel Ramaswamy
Published: May 2017

Bulky 2,6‐dibenzhydryl‐4‐methylaniline reacts with 2‐hydroxybenzaldehyde or 2‐pyridinecaboxyaldehyde to form [N,O‐] and [N,N] donor ligands, 2‐(((2,6‐dibenzhydryl‐4‐methylphenyl)imino)methyl)phenol (L1) and N‐(2,6‐dibenzhydryl‐4‐methylphenyl)‐1‐(pyridin‐2‐yl)methanimine (L2), respectively. Schiff bases, L1 and L2 on treatment with metal precursors, MCl2 (M = Pd, Cu or Co) in toluene under reflux conditions afford mono‐ or dinuclear complexes [(L1‐H)2M] (M= Pd (1) and Cu (2)) or [L2(μ‐Cl)M]2 (M= Cu (3) and Co (4)). The ligands and complexes were structurally characterized through single crystal X‐ray diffraction and depending upon the type of compound, further characterized by spectroscopic (IR, Mass, NMR, EPR, UV‐Vis), mircroanalytical (CHN), thermal (TGA) and electrochemical (CV) techniques. Complex 1 was employed in Suzuki‐Miyaura coupling whereas complexes 2‐4 were studied for the oxidation of secondary alcohols. These were found to be efficient catalysts for the respective reaction systems.
Cellulose‐Derived Hollow Carbonaceous Nanospheres from Rice Husks as Anode for Lithium‐Ion Batteries with Enhanced Reversible Capacity and Cyclic Performance
Authors: Yu Kaifeng , Li Jian , Qi Hui , Liang Ce
Published: May 2017

Disordered carbons are widely used as anode materials for lithium‐ion batteries due to their stable cycle performance, high specific capacity and negative redox potentials. Among them, as an environmental friendly renewable source, biomass has attracted much attention for its application in the preparation of disordered carbon. We report a novel carbonaceous material with interconnected hollow nanosphere structure which used cellulose extracted from rice husk (RH) as a precursor and prepared through hydrothermal carbonization and high temperature calcination. When used as anodes for lithium‐ion batteries, the first discharge specific capacity is as high as 1040 mAhg−1 at a rate of 0.2 C and the reversible specific capacity stabilized at 489 mAhg−1 after 100 cycles. The novel disordered nanostructure material displays superior Lithium‐ion battery performance with large reversible capacities, excellent cyclic performance, and outstanding rate capability, highlighting the importance of hollow interconnected structure for maximum utilization of electrochemically active for energy storage applications in high‐performance lithium‐ion batteries.
About P‐glycoprotein: a new drugable domain is emerging from structural data
Authors: Ferreira Ricardo J. , Bonito Cátia A. , Ferreira Maria José U. , dos Santos Daniel J.V.A.
Published: May 2017

P‐glycoprotein (P‐gp) has been considered an important molecular target in the reversal of multidrug resistance (MDR). As such, the development of P‐gp modulators able to restore drug sensitivity in resistant cells is still considered one of the most promising strategies for overcoming MDR. Since the identification of the P‐gp's role in MDR, several studies have been performed in order to develop effective P‐gp modulators and understand the efflux mechanism. However, no efflux modulator is still clinically available for treating multidrug‐resistant cancers. Nevertheless, recent experimental studies suggest that MDR can be surpassed by targeting a specific region within the ABC transporter structure rather than the polyspecific drug‐binding pocket. This article will focus on the information available about this new target region and on a brief overview of which scaffolds would be suitable for modulating P‐gp at this new location. WIREs Comput Mol Sci 2017, 7:e1316. doi: 10.1002/wcms.1316

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics
Quantification of epithelial cell proliferation, cell dynamics, and cell kinetics in vivo
Authors: Goodlad Robert A.
Published: May 2017

The measurement of cell proliferation in vivo is usually carried out by the examination of static measures. These comprise the mitotic index or labeling indices using incorporation of DNA synthesis markers such as bromodeoxyuridine or tritiated thymidine, or intrinsic markers, such as Ki67 and proliferative cell nuclear antigen (PCNA). But static measures only provide a ‘snapshot’ of cell proliferation. Rate measures, including double labeling methods and the metaphase arrest method, can actually measure cell production rates but they are far less utilized at present. Transit times and migration rates can also be measured using pulse and chase labeling or by following the transit of labeled cells through the tissue. Simple indices of cell division can easily be confounded by concomitant changes in the compartment size and many alleged markers of proliferation have serious shortcomings, as the markers may be involved in multiple aspects of cell regulation. The complexities of studying proliferation in vivo are illustrated here with a focus on the gastrointestinal tract. Some of these methods can help elucidate the role of the stem cells and their relationship to label retaining cells. WIREs Dev Biol 2017, 6:e274. doi: 10.1002/wdev.274

This article is categorized under:

Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models
Linking mitochondrial dysfunction to neurodegeneration in lysosomal storage diseases
Authors: Saffari Afshin , Kölker Stefan , Hoffmann Georg F. , Ebrahimi‐Fakhari Darius
Published: May 2017

Lysosomal storage diseases (LSD) are inborn errors of metabolism resulting in multisystem disease. Central nervous system involvement, often with progressive neurodegeneration, accounts for a large portion of the morbidity and mortality seen in many LSD. Available treatments fail to prevent or correct neurologic symptoms and decline. Emerging evidence points to an important role for mitochondrial dysfunction in the pathogenesis and progression of LSD‐associated neurodegeneration. Mitochondrial dysfunction in LSD is characterized by alterations in mitochondrial mass, morphology and function. Disturbed mitochondrial metabolism in the CNS may lead to excessive production of mitochondrial reactive oxygen species and dysregulated calcium homeostasis. These metabolic disturbances ultimately result in mitochondria‐induced apoptosis and neuronal degeneration. Here, we review the current evidence for mitochondrial dysfunction in neuronal models of seven LSD, including GM1‐gangliosidosis, mucopolysaccharidosis IIIC, multiple sulfatase deficiency, Krabbe disease, Gaucher disease, Niemann Pick disease type C and the neural ceroid lipofuscinoses and outline current experimental therapies aimed at restoring mitochondrial function and neuroprotection in LSD.
Occurrence and risk assessment of trace metals and metalloids in sediments and benthic invertebrates from Dianshan Lake, China
Authors: Wu Yan , Zhou Yihui , Qiu Yanling , Chen Da , Zhu Zhiliang , Zhao Jianfu , Bergman Ǻke
Published: May 2017

The present study measured concentrations of Cr, Ni, Cu, Zn, As, Cd, Sb, and Pb in surface sediments and two benthic invertebrate species (Anodonta woodiana and Bellamya aeruginosa) collected from Dianshan Lake, located in the Yangtze River Delta. The Dianshan Lake acts as one of the most important drinking water sources to Shanghai, the biggest city in China. Concentrations of trace metals and metalloids ranged from 0.04 mg/kg for Cd to 288.0 mg/kg for Zn. Substantial bioaccumulation in invertebrates was observed for Zn and Cu based on the biota-sediment accumulation factor (BSAF) measurements. The results revealed that concentrations of metals and metalloids in sediments from Dianshan Lake were at the lower end of the range of levels found in other regions of China. The assessment of three significantly inter-related evaluation indices, including the geo-accumulation Index (Igeo), potential ecological risk factor (Eri), and mean probable effect concentration quotients (Qm-PEC), suggested that sediment-associated trace elements exhibited no considerable ecological risks in the studied watershed. However, the target hazard quotient and hazard index analysis suggested that selected elements (particularly As) accumulation in edible tissues of benthic invertebrates could pose potential health risks to local populations, especially fishermen. Given that wild aquatic organisms (e.g., fish and bivalves) constitute the diet of local populations as popular food/protein choices, further investigations are needed to better elucidate human health risks from metal and metalloid exposure via edible freshwater organisms.
Femoral and Lumbar Fractures During Rehabilitation for a Traumatic Spinal Cord Injury in Osteogenesis Imperfecta: A Case Presentation
Authors: Ross Brendon S. , Ripley David , Ho Anna M. , Rydberg Leslie
Published: May 2017

Osteogenesis imperfecta (OI) is one of the most common inherited bone disorders. These individuals are high‐risk for developing fractures during their lifetime secondary to bone fragility. This case presents a female with type I OI involved in a high speed motor vehicle accident resulting in a traumatic spinal cord injury (SCI) and paraplegia. Inpatient rehabilitation was complicated by fractures of the femur and lumbar spine which impacted her level of independence upon discharge to prevent additional fractures and maintain safety. OI coupled with SCI creates a difficult combination for the rehabilitation team. This case highlights the complexity of this challenge to bring awareness to the rehabilitation team in order to safely maximize independence and minimize and prevent unnecessary injury when designing an interdisciplinary treatment plan.

Level of Evidence

V
Interfang Distances of Rattlesnakes: Sexual, Interspecific, and Body Size-related Variation, and Implications for Snakebite Research and Management
Authors: Hayes William K. , Corbit Aaron G. , Cardwell Michael D. , Herbert Shelton S.
Published: May 2017

Objectives

Snakebite severity corresponds to size of snake because the amount of venom a snake injects is positively associated with snake size. Because fang marks are often present on snakebite patients, we tested whether the relationship between snake length and distance between fang puncture wounds can be generalized for rattlesnakes of genus Crotalus.

Methods

We measured 2 interfang distances from 79 rattlesnakes of both sexes, 5 species, and varying body length: 1) distance between fang bases in anesthetized snakes, and 2) distance between fang punctures in a membrane-covered beaker bitten defensively.

Results

Statistical analyses supported our 2 hypotheses, that 1) body size-related fang divergence during fang protraction (ie, anterolateral movement during fang erection), and 2) the relationship between snake length and interfang distance are similar between the sexes and among different rattlesnake species. We therefore derived a general equation to estimate snake length based on distance between fang marks, and recommended 5 snake size categories: very small (<10 mm), small (10–15 mm), medium (15–20 mm), large (20–25 mm), and very large (>25 mm).

Conclusions

The distance between fang marks on a snakebite patient may be used to estimate the size or size category of the offending snake, which in some cases may have predictive value for overall clinical severity of a given envenomation. Assessing interfang distance from puncture wounds can improve snakebite research and anticipation of snakebite severity.
Battlefield Trauma-Induced Hypothermia: Transitioning the Preferred Method of Casualty Rewarming
Authors: Bennett Brad L. , Holcomb John B.
Published: May 2017

For centuries, cold and wet weather has affected military combat operations leading to tremendous loss of manpower caused by cold–weather-related injuries including trench foot, frostbite, and hypothermia. The initial battlefield management of hypothermia in military personnel had not advanced significantly following many wars and conflicts until 2006. The aim of this review is to: 1) provide an overview of trauma-induced hypothermia (TIH); 2) highlight the Department of Defense strategy for the implementation of a hypothermia clinical management program for battlefield (prehospital) casualties; 3) highlight the research and development of the Hypothermia Prevention and Management Kit (HPMK) as the preferred field rewarming system for battlefield TIH; and 4) emphasize how the HPMK can be easily transitioned to the civilian sector for active rewarming of both accidental and TIH patients. The HPMK is ideal for those working in civilian Emergency Medical Services and austere prehospital care environments. This kit is a low cost, lightweight, small dimension commercial product that can provide effective passive management or active rewarming for both accidental (primary) and trauma-induced (secondary) hypothermia patients.
Tiltrotor CFD Part II - aerodynamic optimisation of tiltrotor blades
Authors: Jimenez-Garcia A. , Biava M. , Barakos G.N. , Baverstock K.D. , Gates S. , Mullen P.
Published: May 2017

This paper presents aerodynamic optimisation of tiltrotor blades with high-fidelity computational fluid dynamics. The employed optimisation framework is based on a quasi-Newton method, and the required high-fidelity flow gradients were computed using a discrete adjoint solver. Single-point optimisations were first performed to highlight the contrasting requirements of the helicopter and aeroplane flight regimes. It is then shown how a trade-off blade design can be obtained using a multi-point optimisation strategy. The parametrisation of the blade shape allowed the twist and chord distributions to be modified and a swept tip to be introduced. The work shows how these main blade shape parameters influence the optimal performance of the tiltrotor in helicopter and aeroplane modes, and how an optimised blade shape can increase the overall tiltrotor performance. Moreover, in all the presented cases, the accuracy of the adjoint gradients resulted in a small number of flow evaluations for finding the optimal solution, thus indicating gradient-based optimisation as a viable tool for modern tiltrotor design.
Inclined gravity currents filling basins: the impact of peeling detrainment on transport and vertical structure
Authors: Hogg Charlie A. R. , Dalziel Stuart B. , Huppert Herbert E. , Imberger Jörg
Published: May 2017

Transport of dense fluid by an inclined gravity current can control the vertical density structure of the receiving basin in many natural and industrial settings. A case familiar to many is a lake fed by river water that is dense relative to the lake water. In laboratory experiments, we pulsed dye into the basin inflow to visualise the transport pathway of the inflow fluid through the basin. We also measured the evolving density profile as the basin filled. The experiments confirmed previous observations that when the turbulent gravity current travelled through ambient fluid of uniform density, only entrainment into the dense current occurred. When the gravity current travelled through the stratified part of the ambient fluid, however, the outer layers of the gravity current outflowed from the current by a peeling detrainment mechanism and moved directly into the ambient fluid over a large range of depths. The prevailing model of a filling box flow assumes that a persistently entraining gravity current entrains fluid from the basin as the current descends to the deepest point in the basin. This model, however, is inconsistent with the transport pathway observed in visualisations and poorly matches the stratifications measured in basin experiments. The main contribution of the present work is to extend the prevailing filling box model by incorporating the observed peeling detrainment. The analytical expressions given by the peeling detrainment model match the experimental observations of the density profiles more closely than the persistently entraining model. Incorporating peeling detrainment into multiprocess models of geophysical systems, such as lakes, will lead to models that better describe inflow behaviour.
Coriolis effect and the attachment of the leading edge vortex
Authors: Jardin T.
Published: May 2017

The role of the Coriolis effect on the attachment of the leading edge vortex (LEV) is investigated. Toward that end, the Navier–Stokes equations are solved in the non-inertial reference frame of a high angle of attack $\unicode[STIX]{x1D6FC}$ rotating wing with the Coriolis term being artificially tuned. Reynolds numbers in the range $Re\in [100;750]$ are considered to identify the interplay between Coriolis and viscous effects. Similarly, artificial tuning of the centrifugal term is achieved to identify the interplay between Coriolis and centrifugal effects. It is shown that (i) the Coriolis effect is the key element in LEV stability for $Re>200$, (ii) viscous effects are the key element for $Re<200$ and (iii) centrifugal effects have a marginal role. The Coriolis effect is found to promote spanwise flow in the core and behind the LEV, which is known to promote outboard vorticity transport and presumably contributes to stabilizing the aft boundary layer. These mechanisms of LEV stabilization have increased authority as $\unicode[STIX]{x1D6FC}$ decreases.
Legal Issues Arising from the Brexit Referendum: A UK and EU Constitutional Analysis
Authors: Markakis Menelaos
Published: May 2017

The dust has not yet settled after the referendum on Britain's relationship with the EU, which took place on 23 June 2016. UK voted to leave the EU by 51.9% to 48.1%, which is a winning margin of almost 1.3 million votes. However, it is not yet clear what ‘Brexit’ means or how it will come about – legally and constitutionally. This article seeks to answer the latter question from the standpoint of UK and EU law. The discussion begins with the domestic process before beginning the initial withdrawal negotiations, which is governed by UK constitutional law. The focus then shifts to the process of withdrawing from the EU, which is set out in Article 50 TEU. This article further examines whether ‘Brexit’ can be stopped once Article 50 has been triggered. The penultimate section of the article looks at the legal nature and substantive content of the agreements that might be concluded between the UK and the EU if ‘Brexit’ were to become a reality. The final section of the article examines the UK rules on ratification of such international agreements.
Free, Open, and Re-Usable Access to Legal Information – The Australian Experience
Authors: Kinder Petal
Published: May 2017

Several years ago, the Australian Information Commissioner decided that, subject to security and privacy and so forth, all of its public-sector information should be, “free, easily discoverable, machine readable and re-useable.”
Data Protection and the ‘Right to be Forgotten’ in Practice: A UK Perspective
Authors: Townend Judith
Published: May 2017

We are in an uncertain and complex period for data protection and privacy in Europe, and especially so in the UK, following the result of the ‘Brexit’ referendum on 23 June 2016. Information law, and data protection in particular, are of increasing concern for those in the business of knowledge sharing and information dissemination: media organizations, academic institutions and libraries. The notion of the ‘right to be forgotten’ is particularly troublesome, as lawyers, archivists, historians and philosophers grapple with the theoretical and practical implications. This article presents a selection of recent European and British policy and legal developments, and discusses how they are changing social practice and citizens’ engagement with information rights.
First reported actinopterygian from the Navajo Sandstone (Lower Jurassic, Glen Canyon Group) of southern Utah, USA
Authors: Frederickson Joseph A. , Davis Brian M.
Published: May 2017

We report the first occurrence of an actinopterygian fish from the Lower Jurassic Navajo Sandstone, discovered in the Grand Staircase-Escalante National Monument in southern Utah, U.S.A. The site contains multiple individuals, preserved within an interdune deposit, possessing the elongate modified dorsal scales usually characterizing semionotiform fishes. The presence of moderately sized fish provides further evidence that interdune oases were occasionally persistent environmental habitats within the greater Navajo dune system, and that the paleobiota is still woefully undersampled. Additionally, this site could help fill a gap in the actinopterygian fossil record between the patchy Lower Jurassic and better-known Middle Jurassic documentation of western North America.
Teaching the Digital Natives
Authors: Moustafa Laila Hussein
Published: May 2017

The goals of the Middle East history survey course are to introduce students to the major events in the history of the Middle East and to show the diversity of Middle Eastern civilization. In this paper, I discuss how instructors can use the Internet to enrich their teaching of the Middle East history survey course for students known as “digital natives.”
The cardiovascular system: Mathematical modelling, numerical algorithms and clinical applications
Authors: Quarteroni A. , Manzoni A. , Vergara C.
Published: May 2017

Mathematical and numerical modelling of the cardiovascular system is a research topic that has attracted remarkable interest from the mathematical community because of its intrinsic mathematical difficulty and the increasing impact of cardiovascular diseases worldwide. In this review article we will address the two principal components of the cardiovascular system: arterial circulation and heart function. We will systematically describe all aspects of the problem, ranging from data imaging acquisition, stating the basic physical principles, analysing the associated mathematical models that comprise PDE and ODE systems, proposing sound and efficient numerical methods for their approximation, and simulating both benchmark problems and clinically inspired problems. Mathematical modelling itself imposes tremendous challenges, due to the amazing complexity of the cardiocirculatory system, the multiscale nature of the physiological processes involved, and the need to devise computational methods that are stable, reliable and efficient. Critical issues involve filtering the data, identifying the parameters of mathematical models, devising optimal treatments and accounting for uncertainties. For this reason, we will devote the last part of the paper to control and inverse problems, including parameter estimation, uncertainty quantification and the development of reduced-order models that are of paramount importance when solving problems with high complexity, which would otherwise be out of reach.
Numerical analysis of strongly nonlinear PDEs
Authors: Neilan Michael , Salgado Abner J. , Zhang Wujun
Published: May 2017

We review the construction and analysis of numerical methods for strongly nonlinear PDEs, with an emphasis on convex and non-convex fully nonlinear equations and the convergence to viscosity solutions. We begin by describing a fundamental result in this area which states that stable, consistent and monotone schemes converge as the discretization parameter tends to zero. We review methodologies to construct finite difference, finite element and semi-Lagrangian schemes that satisfy these criteria, and, in addition, discuss some rather novel tools that have paved the way to derive rates of convergence within this framework.
THE VICTORIAN VERSE NOVEL AS BESTSELLER: OWEN MEREDITH'SLUCILE
Authors: Addison Catherine
Published: May 2017

By the 1860s, the versenovel had become a significant feature of the Victorian literary landscape. According to Dino Felluga, this hybrid was a “perverse” and even “subversive” genre, firstly, because it undermined the “‘high’ autotelic” status of poetry by mixing it with the “heteroglot, carnivalesque, and polyphonic novel” and, secondly, because its specific fictions tended to oppose or parody the “middle-class heterosexual, domestic ideology” upheld by the prose novel of the period. In support of his argument, Felluga discusses a handful of texts that are normally regarded as “high” literature: Elizabeth Barrett Browning'sAurora Leigh, Arthur Hugh Clough'sAmours de Voyage, George Meredith'sModern Loveand Robert Browning'sThe Ring and the Book(Felluga, “Verse Novel” 171–74; “Novel Poetry” 491–96).
MADEIRA ANDJANE EYRE’S COLONIAL INHERITANCE
Authors: Valint Alexandra
Published: May 2017

The denouement of Charlotte Brontë’sJane Eyrecontains multiple happy rewards for its heroine: a fortune, strangers turned friends turned cousins, the self-elimination of Bertha, and a Rochester still alive, still in England, and now free to marry. The hefty twenty-thousand-pound legacy (of which Jane only keeps one-fourth) bequeathed to her by her late uncle John Eyre allows Jane to return to the maimed Rochester and gleefully proclaim, “I am an independent woman now” (Brontë 501; ch. 37). Citing such financial independence, Sandra Gilbert and Susan Gubar briefly mention Jane's inheritance as the event that allows Jane to “follow her own will” and marry Rochester on terms of equality (367). Similarly, Nancy Armstrong writes that “[m]ore so perhaps than her virtue or passion, it is an endowment from Jane's wealthy uncle that makes her happiness possible” (47). Other critics, such as Elaine Freedgood and Susan Meyer, focus on the origin of the fortune – Madeira – and suggest that such a colonially associated locale implicates Jane in the finances of colonialism and even of slavery. Unlike those critics, however, I will claim that Jane's complicated relationship to the inheritance distances her from the problematic taint of the money's colonial associations and marks her non-conformity with and resistance to the economic practices of the British Empire.
MISTRESS AND MAID: HOMOEROTICISM, CROSS-CLASS DESIRE, AND DISGUISE IN NINETEENTH-CENTURY FICTION
Authors: Bohata Kirsti
Published: May 2017

The relationship between mistress andmaid is curiously intimate yet bounded by class. Employers and their servants are caught in a dynamic of dominance and submission, in which they practice mutual surveillance. Yet the relationship may also evoke models of loyalty, devotion, and the possibility, in fiction at least, of female alliance. On the comparatively rare occasions that servants feature at all in Victorian fiction, these dynamics lend a homoerotic dimension to the cross-class relationship between mistress and maid. The positions of mistress and maid bring two women together under the same roof while separating them by class, thus providing a framework for a fictional exploration for yearning, desire, unrequited love, or sometimes union. Alternatively, a queer relationship may be obscured by the guise of employer and servant. Indeed, the mistress-maid stories discussed here often involve masquerade in some form, including cross-class and cross-gender disguises.
GIVING BIRTH TO A NEW NATION: FEMALE MEDIATION AND THE SPREAD OF TEXTUAL KNOWLEDGE IN DRACULA
Authors: Straight Alyssa
Published: May 2017

After his harrowing escape from Castle Dracula, Jonathan Harker entrusts his journal, and the secret of his traumatic experiences with the vampire Count contained therein, to his new wife, Mina Harker (née Murray). “Here is the book,” he urges; “Take it and keep it, read it if you will, but never let me know; unless, indeed, some solemn duty should come upon me to go back to the bitter hours, asleep or awake, sane or mad, recorded here” (Stoker 100; ch. 9). Mina clasps the book, sealing it with a kiss, as she replies, “it would be an outward and visible sign for us all our lives that we trusted each other.” This scene from Bram Stoker's Dracula (1897) catalyzes the novel's concern with how knowledge transfer and technology intersect with women's bodies and labor. Not only is Mina the one trusted with the diary, but she is also the only person within the novel who has the required skills to translate its shorthand into a typed and readable document. In this solemn scene, which precedes and resembles their marriage vows, Mina both gains access to private information and is charged with deciding who else should have access to that knowledge and under what circumstances. This “trust” secures Mina as the mediator of knowledge and the curator of what will become an increasingly expansive imperial archive within the novel.
Reconstructing Past Sea Level Change to Understand the Future
Authors: Steponaitis Elena , Yanchilina Anastasia , Bervid Heather
Published: May 2017

PALSEA2 2016 Workshop: Sea-Level Budgets at Decadal to Millennial Time Scales to Bridge the Paleo and Instrumental Records; Mount Hood, Oregon, 19–21 September 2016
Reinterpreting the Age and Origins of Taiwan’s Yuli Belt Terrane
Authors: Cook Terri
Published: May 2017

Uranium-lead dating of zircons from Taiwan’s east central metamorphic belt offers robust evidence that this uplifted terrane is some 90 million years younger than previously thought.
What’s the Average Methane Isotope Signature in Arctic Wetlands?
Authors: Cook Terri
Published: May 2017

Aircraft measurements confirm that methane emissions from northern European wetlands exhibit a uniform regional carbon isotopic signature, despite considerable ground-level heterogeneity.
Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH
Authors: Boatz Jennifer C. , Whitley Matthew J. , Li Mingyue , Gronenborn Angela M. , van der Wel Patrick C. A.
Published: May 2017

Cataracts cause vision loss through the large-scale aggregation of eye lens proteins as a result of ageing or congenital mutations. The development of new treatments is hindered by uncertainty about the nature of the aggregates and their mechanism of formation. We describe the structure and morphology of aggregates formed by the P23T human γD-crystallin mutant associated with congenital cataracts. At physiological pH, the protein forms aggregates that look amorphous and disordered by electron microscopy, reminiscent of the reported formation of amorphous deposits by other crystallin mutants. Surprisingly, solid-state NMR reveals that these amorphous deposits have a high degree of structural homogeneity at the atomic level and that the aggregated protein retains a native-like conformation, with no evidence for large-scale misfolding. Non-physiological destabilizing conditions used in many in vitro aggregation studies are shown to yield qualitatively different, highly misfolded amyloid-like fibrils.
Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy
Authors: Wang Fang , Xu Cheng , Reece E. Albert , Li Xuezheng , Wu Yanqing , Harman Christopher , Yu Jingwen , Dong Daoyin , Wang Cheng , Yang Penghua , Zhong Jianxiang , Yang Peixin
Published: May 2017

Gene deletion-induced autophagy deficiency leads to neural tube defects (NTDs), similar to those in diabetic pregnancy. Here we report the key autophagy regulators modulated by diabetes in the murine developing neuroepithelium. Diabetes predominantly leads to exencephaly, induces neuroepithelial cell apoptosis and suppresses autophagy in the forebrain and midbrain of NTD embryos. Deleting thePrkcagene, which encodes PKCα, reverses diabetes-induced autophagy impairment, cellular organelle stress and apoptosis, leading to an NTD reduction. PKCα increases the expression of miR-129-2, which is a negative regulator of autophagy. miR-129-2 represses autophagy by directly targeting PGC-1α, a positive regulator for mitochondrial function, which is disturbed by maternal diabetes. PGC-1α supports neurulation by stimulating autophagy in neuroepithelial cells. These findings identify two negative autophagy regulators, PKCα and miR-129-2, which mediate the teratogenicity of hyperglycaemia leading to NTDs. We also reveal a function for PGC-1α in embryonic development through promoting autophagy and ameliorating hyperglycaemia-induced NTDs.
Menin enhances c-Myc-mediated transcription to promote cancer progression
Authors: Wu Gongwei , Yuan Mengqiu , Shen Shengqi , Ma Xiaoyu , Fang Jingwen , Zhu Lianbang , Sun Linchong , Liu Zhaoji , He Xiaoping , Huang De , Li Tingting , Li Chenchen , Wu Jun , Hu Xin , Li Zhaoyong , Song Libing , Qu Kun , Zhang Huafeng , Gao Ping
Published: May 2017

Menin is an enigmatic protein that displays unique ability to either suppress or promote tumorigenesis in a context-dependent manner. The role for Menin to promote oncogenic functions has been largely attributed to its essential role in forming the MLL methyltransferase complex, which mediates H3K4me3. Here, we identify an unexpected role of Menin in enhancing the transactivity of oncogene MYC in a way independent of H3K4me3 activity. Intriguingly, we find that Menin interacts directly with the TAD domain of MYC and co-localizes with MYC to E-Box to enhance the transcription of MYC target genes in a P-TEFb-dependent manner. We further demonstrate that, by transcriptionally promoting the expression of MYC target genes in cancer cells, Menin stimulates cell proliferation and cellular metabolism both in vitro and in vivo. Our results uncover a previously unappreciated mechanism by which Menin functions as an oncogenic regulatory factor that is critical for MYC-mediated gene transcription.
Exploring nonlinear topological states of matter with exciton-polaritons: Edge solitons in kagome lattice
Authors: Gulevich D. R. , Yudin D. , Skryabin D. V. , Iorsh I. V. , Shelykh I. A.
Published: May 2017

Matter in nontrivial topological phase possesses unique properties, such as support of unidirectional edge modes on its interface. It is the existence of such modes which is responsible for the wonderful properties of a topological insulator – material which is insulating in the bulk but conducting on its surface, along with many of its recently proposed photonic and polaritonic analogues. We show that exciton-polariton fluid in a nontrivial topological phase in kagome lattice, supports nonlinear excitations in the form of solitons built up from wavepackets of topological edge modes – topological edge solitons. Our theoretical and numerical results indicate the appearance of bright, dark and grey solitons dwelling in the vicinity of the boundary of a lattice strip. In a parabolic region of the dispersion the solitons can be described by envelope functions satisfying the nonlinear Schrödinger equation. Upon collision, multiple topological edge solitons emerge undistorted, which proves them to be true solitons as opposed to solitary waves for which such requirement is waived. Importantly, kagome lattice supports topological edge mode with zero group velocity unlike other types of truncated lattices. This gives a finer control over soliton velocity which can take both positive and negative values depending on the choice of forming it topological edge modes.
Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery
Authors: Thean D. , Ebo J. S. , Luxton T. , Lee Xue’Er Cheryl , Yuen T. Y. , Ferrer F. J. , Johannes C. W. , Lane D. P. , Brown C. J.
Published: May 2017

Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53. A lead peptide was identified that activated intracellular p53 with negligible nonspecific cytotoxicity, however it still bound serum avidly and only showed a marginal improvement in cellular potency. These hurdles were overcome by successfully identifying a pyridinium-based cationic lipid formulation, which significantly improved the activity of the stapled peptide in a p53 reporter cell line, principally through increased vesicular escape. These studies underscore that stapled peptides, which are cell permeable and target specific, can be identified with rigorous experimental design and that these properties can be improved through use with lipid based formulations. This work should facilitate the clinical translation of stapled peptides.
Tumor suppressor menin is required for subunit-specific nAChR α5 transcription and nAChR-dependent presynaptic facilitation in cultured mouse hippocampal neurons
Authors: Getz Angela M. , Xu Fenglian , Visser Frank , Persson Roger , Syed Naweed I.
Published: May 2017

In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to determine whether an analogous cholinergic mechanism underlies menin’s synaptogenic function in the vertebrate CNS. Our data from mouse primary hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal fragment (C-menin) regulate the subunit-specific transcription and synaptic clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR α5 subunit expression, the clustering of α7 subunit-containing nAChRs at glutamatergic presynaptic terminals, and nicotine-induced presynaptic facilitation. Moreover, the number and function of glutamatergic synapses was unaffected by MEN1 knockdown, indicating that the synaptogenic actions of menin are specific to cholinergic regulation. Taken together, our results suggest that the influence of menin on synapse formation and synaptic plasticity occur via modulation of nAChR channel subunit composition and functional clustering.