bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of magnetic field advection on turbulent magnetohydrodynamic flow in a square duct
Authors: Bandaru Vinodh , Boeck Thomas , Schumacher Jörg
Published: December 2018

In the field of magnetohydrodynamics, turbulent duct flows in a transverse magnetic field are of considerable interest. Their velocity fields exhibit electromagnetic boundary layers and anisotropy due to damping of turbulent fluctuations by the Lorentz force. The weak induced magnetic field is slaved to the velocity field (quasistatic limit) in laboratory experiments since the magnetic Reynolds number is small. Here we consider flow conditions with finite magnetic Reynolds number in direct numerical simulations, whereby the full induction equation needs to be solved. The modification of the imposed transverse field by the flow and other differences to the quasistatic results are briefly discussed.
Retarded potentials for wave propagation in elastic trusses
Authors: Pölz Dominik , Gfrerer Michael , Schanz Martin
Published: December 2018

A space‐time boundary element method for the dynamic simulation of simplified elastic truss systems is proposed. The considered truss systems consist of elastic rods whose dynamic behaviour is governed solely by the 1D wave equation. By using time domain boundary integral equations the problem reduces to the nodes of the truss system and therefore no spatial discretization is necessary. The discretization employs an adaptive mesh refinement scheme enabling the accurate resolution of non‐smooth solutions.
Investigation of the network topology of vitreous silica during cyclic tensile loading
Authors: Bamer Franz , Ebrahem Firaz , Markert Bernd
Published: December 2018

In this paper, we present visco‐plastic effects of vitreous silica. By introducing a stepwise loading‐relaxation procedure, we evaluate a quasi‐static hysteresis and observe permanent plastic deformation. The investigation of the medium‐range order of the sample at various deformation states provides new insights into the changes of the atomistic arrangements caused by the plastification.
Parametric model order reduction applied to thin‐walled structures modified by acoustic black holes
Authors: Rodríguez Sánchez Raúl , Miksch Matthias , Müller Gerhard
Published: December 2018

In thin walled structures a smooth reduction of the thickness results in a decreasing propagation speed and an increasing amplitude of the bending wave. Acoustic black holes (ABH) make use of this modulation to enhance the energy dissipation in the vicinity of the ABH. Modifying a thin walled structure with ABH can significantly influence the energy distribution in the structure. For large systems those investigations become computationally expensive. This contribution investigates the influence of the geometric parameter that defines the design of an ABH by using Model Order Reduction (MOR). Several numerical models are evaluated to assess the dependency between the geometric design parameters of the thickness variation and the energy distribution in the structure, the computational time and the quality of the approximation are compared with the solution obtained using the corresponding full‐scale FE model.
A mixed extended finite element formulation for the simulation of cracks in nearly incompressible materials
Authors: Loehnert Stefan
Published: December 2018

A low order mixed extended finite element for the simulation of cracks in nearly incompressible materials is presented. The finite element is based on a classical Q1P0 formulation in 3D including enrichment functions and corresponding degrees of freedom to account for the discontinuity in the displacement field. In addition, in the mixed formulation the volumetric stress field is enriched as well. The additional degrees of freedom can be eliminated on element level. The superior convergence behaviour of the presented formulation especially for nearly incompressible material behaviour is demonstrated by means of examples from linear elastic fracture mechanics.
On a Multi‐Scale and Multi‐Phase Model of Paracetamol‐induced Hepatotoxicity for Human Liver
Authors: Lambers Lena , Waschinsky Navina , Ricken Tim
Published: December 2018

More than 650 Million people worldwide suffer from a certain kind of liver disease. One of the most common disease is the non‐alcoholic fatty liver disease (NAFLD) which affects about 20‐30 % of the population in industrial countries. During a NAFLD fat is stored in liver cells causing tissue growth which impacts blood perfusion inside the liver. The liver is responsible for detoxification of drugs and toxins, e.g. the pain killer Paracetamol. However high dosages of toxic metabolites can harm the liver. The detoxification is perfusion‐dependent, due to the substances transported by the blood flow. To understand and predict the processes during a liver disease, we have developed a computational model using a multi‐scale and multi‐phase function‐perfusion approach basend on the Theory of Porous Media (TPM).
3‐D Numerical Simulation and Analysis of the Flow Pattern in the Shot Sleeve of the Cold Chamber HPDC Process
Authors: Laouar Roudouane
Published: December 2018

This work presents a 3d‐numerical study of the flow of molten metal in the shot sleeve of a horizontal high‐pressure die casting machine. The analysis of the flow pattern caused by the filling and the plunger motion can be of help in reducing porosity in manufactured parts caused by air entrapment. A particular attention has been paid to the flow and temperature field below the filling hole. The used numerical model is based on the conservation equations of mass, momentum and energy, and describes the free surface using the volume‐of‐fluid method.
Design and Optimization of Large‐Deformation Compliant Mechanisms
Authors: Humer Alexander
Published: December 2018

As compared to conventional mechanisms, compliant mechanisms exploit flexible deformation rather than rigid‐body motion of its components. The key advantage of jointless or monolithic structures lies in the absence of relative motion between the links. Besides the reduction in parts required to perform a task, compliant mechanisms typically show little friction, if any, and do not require lubrication to minimize wear. On the downside, design and synthesis of compliant mechanisms become much more involved than in rigid‐body linkages. In particular, optimization of compliant mechanisms relying on (sub‐)structures subjected to large flexible deformation is a challenging task, in which diverse aspects need to be considered. First and foremost, kinematic analysis of compliant mechanisms usually requires geometric non‐linearities to be accounted for. Further, limitations in actuation forces and torques impose constraints on the design. Depending on the application, the performance of compliant mechanisms may crucially depend on the natural frequencies and their change over the range of operation. In view of the diverse aspects, one typically has to deal with multi‐objective optimization problems in comparatively high‐dimensional parameter spaces.
Behaviour of Anionic and Cationic Hydrogels
Authors: Keller Karsten , Wallmersperger Thomas , Ricken Tim
Published: December 2018

Ionic polyelectrolytic gels in an aqueous solution, i.e. hydrogels – also known as smart materials – react to different kinds of environmental changes, e.g. chemical, electrical, mechanical, and thermal stimulation. As a reaction, they show enormous swelling capabilities resulting from the delivery or uptake of ions and solvent. These properties make them attractive for chemo‐electro‐mechanical energy converters and for the application as actuators or sensors. The applied multi‐field formulation consists of the chemical, electrical, and mechanical field and is capable of giving local concentrations, electric potential distributions and displacements. In this excerpt the reaction of a modelled hydrogel finger gripper under electrical stimulation is shown. The swelling ratio is assumed to be in the regime of small volume changes and corresponding displacements.
Diffusion under micro‐gravity: Mass transfer from rising bubble in a stagnant fluid column
Authors: Bari Md Ashfaqul , Akbulut Cemil , Münsch Manuel , Delgado Antonio
Published: December 2018

Numerical simulation of two‐phase flows using Volume of Fluid (VOF) method is known be to susceptible to parasitic currents, which arises due to erroneous interface curvature calculation to model the surface tension force. The interface curvature calculation scheme in OpenFoam has been modified according to the Sharp Surface Force (SSF) which reduced parasitic currents magnitude significantly. Alongside SSF method the Continuous Species Transfer (CST) equation is implemented in OpenFOAM 4.1 to simulate mass transfer from an Oxygen bubble to the surrounding stagnant water‐glycerol solution under micro‐gravity environment.
Fabrication, rheological analysis, and in vitro characterization of in situ chemically cross‐linkable thermogels as controlled and prolonged drug depot for localized and systemic delivery
Authors: Khan Samiullah , Akhtar Naveed , Minhas Muhammad Usman
Published: December 2018

5‐Fluorouracil (5‐FU) is widely used against many types of solid cancer in clinics. However, because of its limitations such as short half‐life, poor oral absorption and rapid clearance by dihydropyrimidine dehydrogenase have limited its applications. In current study, new in situ chemically grafted thermogels for prolonged drug release are formed on the basis of poloxamer 407 (PF127) and carboxymethyl chitosan (CMCS) using glutaraldehyde as cross‐linking agent. The phase transition from sol to gel state at body temperature was confirmed by tube titling, rheological analysis, and optical transmittance determinations. Swelling and drug release experiments conducted at various pH and temperature demonstrated that developed formulations are thermoresponsive with maximum swelling and release below critical gelation temperature (CGT) (pH 7.4, 25°C). Cells growth inhibition study confirmed the biocompatibility of thermogels against L929 cell lines. Methyl thiazolyl tetrazolium (MTT) assay confirmed that 5‐FU–loaded thermogels have the potential to cause cells death against HeLa and MCF‐7 cancer lines. The IC50values calculated for pure 5‐FU solution (27 ± 0.81 μg/mL for HeLa and 24 ± 0.58 μg/mL for MCF‐7) were found higher in comparison with 5‐FU–loaded thermogels, against HeLa (17 ± 0.39 μg/mL) and MCF‐7 (14 ± 0.67 μg/mL). Fourier transform infrared (FTIR) confirmed the new structure formation and chemical grafting between PF127 and CMCS. Thermogravimetric (TG) and differential scanning calorimetry (DSC) analyses proved the phase transition around physiologic temperature range, while scanning electron microscopy (SEM) analysis displayed the presence of connected pores in the cross section of thermogels facilitating the uptake of solvents and drug particles. Altogether, results concluded that developed chemically grafted thermogels can be used in vivo for prolonged drug release after subcutaneous administration.
Disseminated Bartonella henselae disease mimicking Langerhans’ cell histiocytosis
Authors: Apsemidou Athanasia , Rauwolf Kerstin , Tragiannidis Athanasios , Brentrup Angela , Schiborr Manfred , Becker Karsten , Ahlmann Martina , Groll Andreas H.
Published: December 2018

Bartonella henselae, the causative agent of cat‐scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation.
Surfactant Free Hydrothermal Synthesis of Zn2SnO4 Nanoparticles and Their Functional Properties
Authors: Singhal Anshu , Vishwanadh Bathula
Published: December 2018

A simple, low temperature, cost effective, surfactant free and scalable synthesis of technologically important Zn2SnO4 (ZTO) nanoparticles with controllable size and shape has been developed. X‐ray diffraction (XRD), transmission electron microscopy (TEM) and high‐resolution transmission electron microscopy (HRTEM) of the synthesized ZTO nanoparticles revealed the formation of highly pure crystalline ZTO phase with the spinel‐like structure. The Raman spectrum of the sample was dominated by the A1g vibration mode of pure ZTO phase. From UV–Vis absorption measurements, a band gap (Eg) of 3.78 eV was determined. The photocatalytic activity of the ZTO nanoparticles was evaluated for the photodegradation of methylene blue (MB) under UV‐Vis light irradiation. The ZTO‐assisted photocatalytic degradation of MB is complete in 25 minutes indicating good photocatalytic activity of ZTO. Mass spectrometric (MS) analysis of degradation intermediates isolated at regular time intervals reveals the presence of azure A, azure B and thionin which are demethylated products of the MB, indicating that the degradation is initiated by demethylation of the molecule.
Copper nanoparticle‐induced uterine injury in female rats
Authors: Hu Shifu , Yang Jing , Rao Meng , Wang Yingying , Zhou Fang , Cheng Guiping , Xia Wei , Zhu Changhong
Published: December 2018

Copper nanoparticles (Cu‐NPs) have been used increasingly in various products and applications. Although recent studies have reported that exposure to Cu‐NPs leads to organ accumulation and obvious toxicity, it remains unclear whether Cu‐NPs can be translocated to and cause damage in the uterus. In this study, we investigated the potential for uterine injury and gene expression patterns in female rats exposed to 3.12, 6.25, or 12.5 mg/kg/d Cu‐NPs via intraperitoneal injection for 14 consecutive days. The results indicated that exposure to Cu‐NPs led to significant decreases in the relative uterine weight coefficients and increases in inflammatory cell infiltration, mitochondrial swelling and vacuolization, shortened and reduced endometrial epithelial cell microvilli, and apoptosis. Furthermore, exposure to Cu‐NPs increased malondialdehyde (MDA) accumulation and decreased superoxide dismutase (SOD) levels. Signal transduction mechanism studies indicated that exposure to Cu‐NPs activated caspases 3, 8, and 9 and BH3 interacting domain death agonist (tBid), reduced B cell leukemia/lymphoma 2 (Bcl‐2) expression, and increased the expression of apoptotic peptidase activating factor 1 (Apaf‐1), BCL2‐associated X, apoptosis regulator (Bax), and cytochrome c. A microarray analysis revealed significant alterations in the expression of 963 genes; of these, 622 were upregulated and 341 were downregulated. The results of further evaluations of some altered genes, including matrix metallopeptidase 12 (Mmp12), using quantitative RT‐PCR agreed with the microarray findings. These results provide strong evidence that Cu‐NPs can trigger both intrinsic and extrinsic apoptotic pathways to mediate uterine injury, resulting in oxidative stress‐related changes in gene expression.
The testifying forensic discipline expert—A primer
Authors: Epstein Jules
Published: December 2018

Forensic service providers are not usually taught how to transition from the laboratory or workbench to the courtroom. The strictures of law, particularly the rules of evidence as applied to the threshold for and restrictions on expert testimony, are a far cry from intralab reporting and discussions. This primer will address the rudiments of evidence law to ensure that they are comprehensible to forensic service providers and to improve the quality of pretrial and trial presentation of forensic evidence.

This article is categorized under:

Jurisprudence and Regulatory Oversight > Expert Evidence and Narrative

Jurisprudence and Regulatory Oversight > Communication Across Science and Law
Interpretation continues to be the main weakness in criminal justice systems: Developing roles of the expert witness and court
Authors: Gill Peter
Published: December 2018

Interpretation of evidence continues to be the most difficult challenge that faces scientists, lawyers and judges. Despite advances, introduction into mainstream forensic science has been slow. Probabilistic software used to analyze complex DNA mixtures is gradually being implemented. With this software, allele probability databases are used to help calculate strength of evidence. Standardization is facilitated by software and databases, combined with training courses to teach the approach. This is the definition of the “knowledge‐base.” There is increasing interest in reporting at “activity level.” If the opinion is not based upon data, then it is subjective, especially if it is based purely upon personal experience. The aim must be to increase the objectivity of reporting to a similar standard to that currently used for mixture interpretation (with probabilistic software). To do this, a similar approach is required—construction of software and databases. However, compared to allele probability databases, there are currently no formalized collections that are available for scientists to use. Experimental designs are complex and require much more thought and effort. Consequently, knowledge‐bases to inform activity‐level propositions are poorly developed. It is important that courts focus on limitations of knowledge‐bases, otherwise miscarriages of justice may result, such as the Sally Clark case. It is important that courts develop as a forum that ensures that the consensus view prevails, and relies upon data‐informed opinion rather than opinion based upon experience. Relevant well‐informed defense commissioned experts are required as part of the system of checks and balances.

This article is categorized under:

Forensic Biology > Interpretation of Biological Evidence

Jurisprudence and Regulatory Oversight > Communication Across Science and Law

Forensic Biology > DNA Databases and Biometrics
Variant Logic Construction Under Permutation and Complementary Operations on Binary Logic
Authors: Zheng Jeffrey
Published: December 2018

This chapter presents a binary logic framework whose function elements are invariant under permutation and complementary operations. The entire framework is described using 4 levels of hierarchy: n variables, $$2^n$$

2
n

states, $$2^{2^n}$$

2

2
n

functions, and $$2^n! 2^{2^n}$$

2
n

!

2

2
n

logic functionals. Under the proposed framework, it is possible to determine higher level function complexity by analysing lower levels of organisation characteristics. These characteristics can be determined quite accurately because the symmetry conditions of variable and state organisations have invariant logic functions and a corresponding logic functional organisation. More symmetrical arrangement at state level creates more symmetrical permutations within the function space. Lower level properties are highly influential on the higher level properties of function components within a logic functional space. The proposed framework provides a logic foundation to describe complex binary systems using lower level properties, making analysis of systems more efficient and less calculation intensive. Different global coding schemes are discussed and typical two-variable cases of logic functionals are illustrated.
The nth Root of NOT Operators of Quantum Computers
Authors: Zheng Jeffrey
Published: December 2018

This chapter proposes a novel approach to resolve the nth root of NOT problem for quantum computers using (−1, 0, 1) permutation matrices. Only logic NOT and exchange operations are required. This result provides a complete solution to design and implement the nth root of NOT operators of quantum computers.
Visual Analysis of ECG Sequences on Variant Maps
Authors: Hou Zhihui , Zheng Jeffery
Published: December 2018

This chapter presents the variant measurement based on the variant logic, which uses the ECG sequence as the signal source, and outputs the variant maps of ECG sequences. It provides a supplementary study for ECG detection. Samples of ECG signal are collected from the First People’s Hospital of Yunnan Province. Under variant maps, main parameters of various interval values are checked and corresponding maps are illustrated.
Symmetric Clusters in Hierarchy with Cryptographic Properties
Authors: Zheng Jeffrey
Published: December 2018

Symmetric Boolean functions play a key role in stream ciphers. Symmetric constructions provide core components in cryptographic applications. In this chapter, four meta symmetric clustering schemes (combination, crossing, variant and rotation) are organized in a hierarchy for n variables of 0–1 vectors in measuring phase spaces. Local counting properties in a cluster and global counting properties in a given level are formulated. From selected symmetric clusters, a number of various symmetric Boolean functions are formulated. Counting properties on symmetric clusters, vectors in selected clusters and special symmetric Boolean functions are listed. Four sets of symmetric Boolean functions are compared. Properties of symmetric clusters and Boolean functions are discussed. Main results are expressed in theorems and tables. Among four meta schemes, the variant scheme presents novel properties approximately with $$O\left( n^2/4\right) $$

O

n
2

/
4

clusters on a 2D phase space different from other schemes: combinatorial $$O\left( n\right) $$

O

n

, crossing $$O\left( n/2\right) $$

O

n
/
2

and rotation $$O\left( 2^n/n\right) $$

O

2
n

/
n

on 1D measuring phase spaces, respectively. The variant pseudorandom number generator is a similar approach on RC4 and HC128 stream ciphers using word-oriented 0–1 vectors. Further advanced researches and explorations on relevant optimal configurations are required.
Independently parameterised momenta variables and Monte Carlo IR subtraction
Authors: Cox Peter , Melia Tom
Published: December 2018

Abstract

We introduce a system of parameters for the Monte Carlo generation of Lorentz invariant phase space that is particularly well-suited to the treatment of the infrared divergences that occur in the most singular, Born-like configurations of 1 → n QCD processes. A key feature is that particle momenta are generated independently of one another, leading to a simple parameterisation of all such IR limits. We exemplify the use of these variables in conjunction with the projection to Born subtraction technique at next-to-next-to-leading order. The geometric origins of this parameterisation lie in a coordinate chart on a Grassmannian manifold.
Semi-local quantum criticality and the instability of extremal planar horizons
Authors: Gralla Samuel E. , Ravishankar Arun , Zimmerman Peter
Published: December 2018

Abstract

We show that the Aretakis instability of compact extremal horizons persists in the planar case of interest to holography and discuss its connection with the emergence of “semi-local quantum criticality” in the field theory dual. In particular, the spatially localized power-law decay of this critical phase corresponds to spatially localized power-law growth of stress-energy on the horizon. For near-extremal black holes these phenomena occur transiently over times of order the inverse temperature. The boundary critical phase is characterized by an emergent temporal conformal symmetry, and the bulk instability seems to be essential to preserving the symmetry in the presence of interactions. We work primarily in the solvable example of charged scalar perturbations of five-dimensional (near-)extremal planar Reissner-Nordström anti-de Sitter spacetime and argue that the conclusions hold more generally.
Health Services and Infrastructure Recovery of a Major Public Hospital in Liberia During the 2014–2016 Ebola Epidemic
Authors: Ndede Paul Ochieng , Senkungu Jude Kimbowa , Shakpeh John K. , Jones Theresa E. , Sky Rebecca , McDonnell Sharon
Published: December 2018

During the 2014–2016 Ebola outbreak, health services in Liberia collapsed. Health care facilities could not support effective infection prevention and control (IPC) practices to prevent Ebola virus disease (EVD) transmission necessitating their closure. This report describes the process by which health services and infrastructure were recovered in the public hospital in Monrovia, Liberia. The authors conducted an assessment of the existing capacity for health care provision, including qualitative interviews with community members, record reviews in Ebola treatment units, and phone calls to health facilities. Assessment information was used to determine necessary actions to re-establish services, including building and environmental renovations, acquiring IPC supplies, changing health care practices, hiring additional staff, developing and using an EVD screening tool, and implementing psychosocial supports. On-site monitoring was continued for 2 years to assess what changes were sustained. Described in the report are 2 cases that highlight the challenge of safely re-establishing services with only a symptom-based screening tool and no laboratory tests available on-site. Despite fears among the public, health workers, and the international community, the actions taken enabled basic health care services to be provided during EVD transmission and led to sustainable improvements. This experience suggests that providing routine medical needs helps limit the morbidity and mortality during times of disease outbreak. (Disaster Med Public Health Preparedness. 2018;13:767–773)
The oldest sigmodontine rodent revisited and the age of the first South American cricetids
Authors: Barbière Franck , Ortiz Pablo E. , Pardiñas Ulyses F.J.
Published: December 2018

New fossil material ofAuliscomys formosusReig 1978 allows restudy of the oldest known South American representative of the subfamily Sigmodontinae. Description ofAuliscomys formosuswas based on a fragmentary dentary exhumed from the Monte Hermoso Formation of central Argentina. Previous studies allocatedA. formosusto the early Pliocene. A reevaluation of dental and cranial morphology, including for the first time the upper dentition, and the inclusion ofA. formosusin a phylogenetic analysis of the tribe Phyllotini indicate thatA. formosusrepresents a new genus,Kraglievichimys.Kraglievichimysshares a mosaic of characters with the livingAuliscomysOsgood, 1915 andLoxodontomysOsgood, 1947. The taxonomic reassignment ofA. formosusand the possibility that the Monte Hermoso Formation may be younger than early Pliocene in age provide a new understanding of cricetid diversification in South America. Estimates of sigmodontine ancestry by molecular approaches are biased toward older ages, whereas this new interpretation of the history ofK. formosussuggests that the South American history of sigmodontines spans less than 4 million years.

UUID:http://zoobank.org/49dd8f60-56b1-4e8a-a044-6cea3a1bd52b
Conflict and complementarity of paleontological and molecular chronologies?
Authors: Katz Ofir
Published: December 2018

Evolutionary history studies depend on having reliable chronologies of macroevolutionary processes. Construction of such chronologies often yields discrepancies between paleontological and molecular dates, which are sometimes viewed as conflicting. Nevertheless, each macroevolutionary process is composed of two main phases: emergence of a trait or clade and success of that trait or clade, which differ in mechanisms, drivers, and types of evidence. Moreover, emergence may be observed as gene divergence (which may be trait-coding or trait-unrelated genes), trait emergence, and clade emergence; whereas success can be observed as increase in abundance, diffusion, and/or diversity or as overall persistence over geologic time. Therefore, to fully and correctly understand any macroevolutionary process, it is of paramount importance to understand what event each date refers to, and how dates of various events and their integration reveal the complexity of macroevolutionary processes. I demonstrate this through three examples: the chronological gap between oxygenic photosynthesis emergence and the Great Oxidation Event, the chronological gap between paleontological and molecular dates of angiosperm emergence, and the evolution of plant silicon accumulation.
The Ethics of Interpretation in Political Theory and Intellectual History
Authors: Frazer Michael L.
Published: December 2018

Scholars studying classic political texts face an important decision: Should these texts be read as artifacts of history or as sources for still-valid insights about politics today? Competing historical and “presentist” approaches to political thought do not have a methodological dispute—that is, a disagreement about the most effective scholarly means to an agreed-upon end. They instead have an ethical dispute about the respective value of competing activities that aim at different purposes. This article examines six ethical arguments, drawn primarily from the work of Quentin Skinner, in favor of the historical approach. It concludes that while both intellectual history and presentist theory are ethically justifiable, the best justification of the former enterprise is that it can help us achieve the purposes of the latter.
Estimating surface melt and runoff on the Antarctic Peninsula using ERA-Interim reanalysis data
Authors: Costi Juliana , Arigony-Neto Jorge , Braun Matthias , Mavlyudov Bulat , Barrand Nicholas E. , da Silva Aline Barbosa , Marques Wiliam Correa , Simões Jefferson Cardia
Published: December 2018

Using the positive degree days approach and ERA-Interim reanalysis downscaled data, the researchers ran a melt model spatially gridded at 200 m with annual temporal resolution over 32 years and estimated surface melt (SM) and surface runoff (SR) on the Antarctic Peninsula. The model was calibrated and validated independently by field measurements. The maximum surface melt values occurred in 1985 (129 Gt), and the maximum runoff (40 Gt) occurred in 1993; both parameters showed minimum values in 2014 (26 Gt and 0.37 Gt, respectively). No significant trends are present. Two widespread positive anomalies occurred in 1993 and 2006. The results reveal that the floating ice areas produce an average of 68% of runoff and 61% of surface melt, emphasizing their importance to coastal hydrography. During the seven years preceding the Larsen B collapse, surface melt retention was higher than 95% on floating ice areas, and negative runoff anomalies persisted. Excluding the islands, the vicinity of this former ice shelf exhibits the highest specific surface melt and runoff across the studied area.
Retirement plans for contingent workers: issues and options
Authors: Gale William G. , Holmes Sarah E. , John David C.
Published: December 2018

This paper examines retirement saving policy for independent – or contingent – workers, a growing segment of the workforce. Because few of these workers are covered by employer-sponsored retirement plans, they often do not benefit from payroll deduction, employer matching contributions, automatic enrollment, and other provisions that encourage retirement saving. Better use of fintech, judicious changes to tax policy, and expanded Automatic IRAs would help independent workers save for retirement. In addition, we propose the creation of retirement saving accounts that attach to the worker as a supplement to, and possible replacement for, the current system of employer-sponsored accounts.
Informing Healthcare Team Performance: Integrating Data to Improve Quality and Safety
Authors: Ward Marie , McAuliffe Eilish , Fitzsimons John , O’Donovan Róisín
Published: December 2018

A worldwide rising demand for health care means increasing resource investment in health systems, with the concomitant requirement for greater accountability. Greater accountability requires the generation of more and more data and information. Health care is frequently described as fragmented or siloed, and this is reflected in how data is captured, managed, and shared throughout the system. Data relating to business performance, quality, and patient safety is extracted from different systems, and its primary use is to inform senior decision makers about organizational-level performance. Meanwhile, health care teams at a local level when asked if they are performing well in relation to quality and safety are often unable to answer this question. This policy brief summarizes the results of a study undertaken as part of the Collective Leadership for Safety Culture research program to codesign a suite of quality and safety performance indicators to assist acute hospital health care teams to monitor and improve their quality and safety performance. Recommendations are presented for senior decision makers in the acute hospital setting to inform policy on the gathering and management of Quality and Safety data.
RETRACTED ARTICLE: Exosome circRNA secreted from adipocytes promotes the growth of hepatocellular carcinoma by targeting deubiquitination-related USP7
Authors: Zhang Haiyang , Deng Ting , Ge Shaohua , Liu Ying , Bai Ming , Zhu Kegan , Fan Qian , Li Jialu , Ning Tao , Tian Fei , Li Hongli , Sun Wu , Ying Guoguang , Ba Yi
Published: December 2018

Hepatocellular carcinoma (HCC), the major form of liver cancer, has shown increasing incidence and poor prognosis. Adipose tissue is known to function in energy storage and metabolism regulation by the secretion of adipokines. Circular RNAs (circRNAs), a novel type of noncoding RNA, have recently been recognized as key factors in tumor development, but the role of exosome circRNAs derived from adipose tissues has not been defined yet. Here, adipose-secreted circRNAs were found to regulate deubiquitination in HCC, thus facilitating cell growth. It was observed that exosome circ-deubiquitination (circ-DB) is upregulated in HCC patients with higher body fat ratios. Moreover, in vitro and in vivo studies showed that exo-circ-DB promotes HCC growth and reduces DNA damage via the suppression of miR-34a and the activation of deubiquitination-related USP7. Finally, the results showed that the effects of adipose exosomes on HCC cells can be reversed by knockdown of circ-DB. These results indicate that exosome circRNAs secreted from adipocytes promote tumor growth and reduce DNA damage by suppressing miR-34a and activating the USP7/Cyclin A2 signaling pathway.
Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity
Authors: Zhitomirsky Benny , Yunaev Anna , Kreiserman Roman , Kaplan Ariel , Stark Michal , Assaraf Yehuda G.
Published: December 2018

Transcription factor EB (TFEB) is a master transcriptional regulator playing a key role in lysosomal biogenesis, autophagy and lysosomal exocytosis. TFEB activity is inhibited following its phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) on the surface of the lysosome. Phosphorylated TFEB is bound by 14-3-3 proteins, resulting in its cytoplasmic retention in an inactive state. It was suggested that the calcium-dependent phosphatase calcineurin is responsible for dephosphorylation and subsequent activation of TFEB under conditions of lysosomal stress. We have recently demonstrated that TFEB is activated following exposure of cancer cells to lysosomotropic anticancer drugs, resulting in lysosome-mediated cancer drug resistance via increased lysosomal biogenesis, lysosomal drug sequestration, and drug extrusion through lysosomal exocytosis. Herein, we studied the molecular mechanism underlying lysosomotropic-drug-induced activation of TFEB. We demonstrate that accumulation of lysosomotropic drugs results in membrane fluidization of lysosome-like liposomes, which is strictly dependent on the acidity of the liposomal lumen. Lysosomal accumulation of lysosomotropic drugs and the consequent fluidization of the lysosomal membrane, facilitated the dissociation of mTOR from the lysosomal membrane and inhibited the kinase activity of mTORC1, which is necessary and sufficient for the rapid translocation of TFEB to the nucleus. We further show that while lysosomotropic drug sequestration induces Ca2+ release into the cytoplasm, facilitating calcineurin activation, chelation of cytosolic Ca2+, or direct inhibition of calcineurin activity, do not interfere with drug-induced nuclear translocation of TFEB. We thus suggest that lysosomotropic drug-induced activation of TFEB is mediated by mTORC1 inhibition due to lysosomal membrane fluidization and not by calcineurin activation. We further postulate that apart from calcineurin, other constitutively active phosphatase(s) partake in TFEB dephosphorylation and consequent activation. Moreover, a rapid export of TFEB from the nucleus to the cytosol occurs upon relief of mTORC1 inhibition, suggesting that dephosphorylated TFEB constantly travels between the nucleus and the cytosol, acting as a rapidly responding sensor of mTORC1 activity.
Osteocalcin triggers Fas/FasL-mediated necroptosis in adipocytes via activation of p300
Authors: Otani Takahito , Matsuda Miho , Mizokami Akiko , Kitagawa Norio , Takeuchi Hiroshi , Jimi Eijiro , Inai Tetsuichiro , Hirata Masato
Published: December 2018

The uncarboxylated form of osteocalcin (GluOC) regulates glucose and lipid metabolism in mice. We previously showed that low-dose (≤10 ng/ml) GluOC induces the expression of adiponectin and peroxisome proliferator-activated receptor γ (PPARγ) via a cAMP–PKA–ERK–CREB signaling pathway in 3T3-L1 adipocytes. We also noticed that high-dose (≥20 ng/ml) GluOC inhibits the expression of adiponectin and PPARγ in these cells. We have here explored the mechanism underlying these effects of high-dose GluOC. High-dose GluOC triggered morphological changes in 3T3-L1 adipocytes suggestive of the induction of cell death. It activated the putative GluOC receptor GPRC6A and thereby induced the production of cAMP and activation of protein kinase A (PKA), similar to signaling by low-dose GluOC with the exception that the catalytic subunit of PKA also entered the nucleus. Cytosolic PKA induced phosphorylation of cAMP response element-binding protein (CREB) at serine-133 via extracellular signal-regulated kinase (ERK). Nuclear PKA appeared to mediate the inhibitory phosphorylation of salt-inducible kinase 2 (SIK2) at serine-358 and thereby to alleviate the inhibitory phosphorylation of the CREB co-activator p300 at serine-89. The activation of CREB and p300 resulted in increased expression of the transcription factor FoxO1 and consequent upregulation of Fas ligand (FasL) at the plasma membrane. The interaction of FasL with Fas on neighboring adipocytes triggered the phosphorylation at threonine-357/serine-358 and homotrimerization of mixed-lineage kinase domain-like protein (MLKL), a key regulator of necroptosis, as well as Ca2+ influx via transient receptor potential melastatin 7 (TRPM7), the generation of reactive oxygen species and lipid peroxides, and dephosphorylation of dynamin-related protein 1 (DRP1) at serine-637, resulting in mitochondrial fragmentation. Together, our results indicate that high-dose GluOC triggers necroptosis through upregulation of FasL at the plasma membrane in a manner dependent of activation of CREB-p300, followed by the activation of Fas signaling in neighboring adipocytes.
SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4
Authors: Tzelepis Konstantinos , De Braekeleer Etienne , Aspris Demetrios , Barbieri Isaia , Vijayabaskar M. S. , Liu Wen-Hsin , Gozdecka Malgorzata , Metzakopian Emmanouil , Toop Hamish D. , Dudek Monika , Robson Samuel C. , Hermida-Prado Francisco , Yang Yu Hsuen , Babaei-Jadidi Roya , Garyfallos Dimitrios A. , Ponstingl Hannes , Dias Joao M. L. , Gallipoli Paolo , Seiler Michael , Buonamici Silvia , Vick Binje , Bannister Andrew J. , Rad Roland , Prinjha Rab K. , Marioni John C. , Huntly Brian , Batson Jennifer , Morris Jonathan C. , Pina Cristina , Bradley Allan , Jeremias Irmela , Bates David O. , Yusa Kosuke , Kouzarides Tony , Vassiliou George S.
Published: December 2018

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.
Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans
Authors: Grant Emma J. , Josephs Tracy M. , Loh Liyen , Clemens E. Bridie , Sant Sneha , Bharadwaj Mandvi , Chen Weisan , Rossjohn Jamie , Gras Stephanie , Kedzierska Katherine
Published: December 2018

Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+T-cell epitopes, HLA-B*37:01-restricted NP338-346(B37-NP338) and HLA-A*01:01-restricted NP44-52(A1-NP44). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+T-cell-targeted vaccines could provide protection across different IAV strains.
Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells
Authors: Gannon Hugh S. , Zou Tao , Kiessling Michael K. , Gao Galen F. , Cai Diana , Choi Peter S. , Ivan Alexandru P. , Buchumenski Ilana , Berger Ashton C. , Goldstein Jonathan T. , Cherniack Andrew D. , Vazquez Francisca , Tsherniak Aviad , Levanon Erez Y. , Hahn William C. , Meyerson Matthew
Published: December 2018

Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers.
CRISPR/Cas9-mediated glycolate oxidase disruption is an efficacious and safe treatment for primary hyperoxaluria type I
Authors: Zabaleta Nerea , Barberia Miren , Martin-Higueras Cristina , Zapata-Linares Natalia , Betancor Isabel , Rodriguez Saray , Martinez-Turrillas Rebeca , Torella Laura , Vales Africa , Olagüe Cristina , Vilas-Zornoza Amaia , Castro-Labrador Laura , Lara-Astiaso David , Prosper Felipe , Salido Eduardo , Gonzalez-Aseguinolaza Gloria , Rodriguez-Madoz Juan R.
Published: December 2018

CRISPR/Cas9 technology offers novel approaches for the development of new therapies for many unmet clinical needs, including a significant number of inherited monogenic diseases. However, in vivo correction of disease-causing genes is still inefficient, especially for those diseases without selective advantage for corrected cells. We reasoned that substrate reduction therapies (SRT) targeting non-essential enzymes could provide an attractive alternative. Here we evaluate the therapeutic efficacy of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I (PH1), a rare inborn dysfunction in glyoxylate metabolism that results in excessive hepatic oxalate production causing end-stage renal disease. A single systemic administration of an AAV8-CRISPR/Cas9 vector targeting glycolate oxidase, prevents oxalate overproduction and kidney damage, with no signs of toxicity in Agxt1−/− mice. Our results reveal that CRISPR/Cas9-mediated SRT represents a promising therapeutic option for PH1 that can be potentially applied to other metabolic diseases caused by the accumulation of toxic metabolites.
Pressure-driven phase transitions and reduction of dimensionality in 2D silicon nanosheets
Authors: Hwang Gil Chan , Blom Douglas A. , Vogt Thomas , Lee Jaejun , Choi Heon-Jin , Shao Sen , Ma Yanming , Lee Yongjae
Published: December 2018

In-situ high-pressure synchrotron X-ray powder diffraction studies up to 21 GPa of CVD-grown silicon 2D-nanosheets establish that the structural phase transitions depend on size and shape. For sizes between 9.3(7) nm and 15.2(8) nm we observe an irreversible phase transition sequence from I (cubic) → II (tetragonal) → V (hexagonal) during pressure increase and during decompression below 8 GPa the emergence of an X-ray amorphous phase. High-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and atomic force microscopy (AFM) images of this X-ray amorphous phase reveal the formation of significant numbers of 1D nanowires with aspect ratios > 10, which are twinned and grow along the <111> direction. We discovered a reduction of dimensionality under pressure from a 2D morphology to a 1D wire in a material with a diamond structure. MD simulations indicate the reduction of thermal conductivity in such nanowires.
Nucleotide-dependent DNA gripping and an end-clamp mechanism regulate the bacteriophage T4 viral packaging motor
Authors: Ordyan Mariam , Alam Istiaq , Mahalingam Marthandan , Rao Venigalla B. , Smith Douglas E.
Published: December 2018

ATP-powered viral packaging motors are among the most powerful biomotors known. Motor subunits arranged in a ring repeatedly grip and translocate the DNA to package viral genomes into capsids. Here, we use single DNA manipulation and rapid solution exchange to quantify how nucleotide binding regulates interactions between the bacteriophage T4 motor and DNA substrate. With no nucleotides, there is virtually no gripping and rapid slipping occurs with only minimal friction resisting. In contrast, binding of an ATP analog engages nearly continuous gripping. Occasional slips occur due to dissociation of the analog from a gripping motor subunit, or force-induced rupture of grip, but multiple other analog-bound subunits exert high friction that limits slipping. ADP induces comparably infrequent gripping and variable friction. Independent of nucleotides, slipping arrests when the end of the DNA is about to exit the capsid. This end-clamp mechanism increases the efficiency of packaging by making it essentially irreversible.