bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated image processing method to quantify rotating detonation wave behavior
Authors: Bennewitz J. W. , Bigler B. R. , Schumaker S. A. , Hargus W. A.
Published: June 2019

An image processing technique is developed to automatically determine both average and instantaneous detonation wave properties within a rotating detonation rocket engine (RDRE) using high-speed imaging. This method entails segmenting the imaged RDRE annulus into 200 azimuthal bins and tracking integrated pixel intensity in each bin. By combining individual pixel intensity temporal histories across the azimuthal bins, this provides what is termed a detonation surface that visualizes the propagation of the individual detonation fronts azimuthally around the annulus. Average detonation modal properties including wave speed Ūwv, operational frequency fdet, and the number of waves m are determined automatically through a two-dimensional Fourier analysis of the detonation surface data. Also, instantaneous wave speeds Uwv for each individual detonation are determined by taking the numerical derivative of each waves’ angular position temporal history from the detonation surface. This provides useful insight into wave-to-wave variability for an operating condition, as well as denoting modal transitions and mode stability. For the flow conditions investigated, the number of waves ranges from 2 to 14, with Ūwv varying between 900 and 1700 m/s, corresponding to 33%–71% of the ideal Chapman-Jouguet detonation speed; these modes exhibit an operational frequency of 20–45 kHz, with an average of 40 kHz. Overall, these measurements advance the understanding of RDRE’s and may lead to performance gains above those achievable from constant pressure engines.
Unzipping DNA by a periodic force: Hysteresis loops, dynamical order parameter, correlations, and equilibrium curves
Authors: Kalyan M. Suman , Kapri Rajeev
Published: June 2019

The unzipping of a double stranded DNA whose ends are subjected to a time dependent periodic force with frequency ω and amplitude G is studied using Monte Carlo simulations. We obtain the dynamical order parameter, Q, defined as the time average extension between the end monomers of two strands of the DNA over a period, and its probability distributions P(Q) at various force amplitudes and frequencies. We also study the time autocorrelations of extension and the dynamical order parameter for various chain lengths. The equilibrium force-distance isotherms were also obtained at various frequencies by using nonequilibrium work measurements.
Accurate global potential energy surface for SiH2+(X2A1) and quantum dynamics of related reaction H(2S) + SiH+(X1Σ+)
Authors: Gao Feng , Zhang Lulu , Zhao Wenli , Meng Qingtian , Song Yuzhi
Published: June 2019

With the many-body expansion method, an accurate global potential energy surface (PES) is constructed for SiH2+(X2A1) by mapping 4762 ab initio energy points calculated on the multireference configuration interaction level including Davidson corrections with aug-cc-pV6Z Dunning’s basis set. The dissociation energies and equilibrium geometries of SiH+(X1Σ+) and H2(X1Σg+) agree well with the experimental results. The topographical characteristics of all stationary points for the SiH2+(X2A1) PES are discussed in detail and compared with other theoretical and experimental results. In order to verify the validity and usability of the present PES, the dynamics calculations based on the Chebyshev quantum wave packet method are performed for the H(S2)+SiH+(X1Σ+)→Si+(P2)+H2(X1Σg+) reaction. The probabilities, the total integral cross sections, and the rate constants are computed, and the analogies with the corresponding ones of reaction H(S2) + CH+(X1Σ+)→C+(P2) + H2(X1Σg+) are also made. The reasonable dynamical behavior throughout the entire configuration space indicates that the PES is suitable for relevant dynamics investigations and serves as a building block for constructing the PES of larger molecular systems containing Si+/H.
Dynamic susceptibility of modulated magnetic nanowires
Authors: Saavedra Eduardo , Saez Guidobeth , Díaz Pablo , Cisternas Eduardo , Vogel Eugenio E. , Escrig Juan
Published: June 2019

We have calculated the dynamic susceptibility of modulated permalloy nanowires of 1-µm long and 50 nm diameter using micromagnetic simulations. The resonance modes obtained from these simulations are investigated as functions of both the position of the modulation along the nanowire as well as the size of it. The results presented in this work are important in view of the possible realization of tunable frequency magnonic devices, since we showed that it is possible to adjust a set of frequencies by controlling the geometric parameters of the system.
Nanoscale capillarity for mitigating gas bubble adhesion on arrayed photoelectrode during photoelectrochemical water splitting
Authors: Chen Juanwen , Guo Liejin
Published: June 2019

One-dimensional (1D) arrayed photoelectrodes usually present superior performance in photoelectrochemical (PEC) water splitting. This superiority is known to be attributed to directional transport of photogenerated charge carriers. Herein, we show that in addition to this intrinsic charge transport property, a 1D arrayed structure introduces nanoscale capillary wetting, which is also believed to contribute to the improved PEC performance. Our theoretical model predicts that this morphology-dependent capillarity leads to the formation of a liquid film between the photoelectrode surface and the adhered bubble (the generated H2/O2 bubble), thus largely reducing the blockage of active sites at the bubble base. This prediction has been experimentally demonstrated by taking arrayed TiO2 nanorods as a model photoelectrode, with the observation of the PEC activity within the bubble base. This work extends our knowledge toward hydrodynamic functionality involved in morphology-controlled photoelectrodes for enhanced PEC performance.
Quantum size effect affecting environment assisted electron capture in quantum confinements
Authors: Molle Axel , Berikaa Essam R. , Pont Federico M. , Bande Annika
Published: June 2019

Ultrafast inter-Coulombic electron capture (ICEC) has been established as an important energy-transfer process in open paired-quantum-dot systems which can mediate between entrapment of free-moving electrons and release of trapped ones elsewhere by long-range electron-electron interaction within nanowires. Previous studies indicated ICEC enhancement through population and secondary decay of two-center resonance states, the latter known as inter-Coulombic decay (ICD). This study investigates the quantum-size effect of single- and double-electron states in an established model of a quasi-one-dimensional nanowire with two embedded confinement sites, represented by a pair of Gaussian wells. We analyze the ICEC related electron flux density as a function of confinement size and are able to clearly identify two distinct capture channels: a direct long-range electron-electron impulse and a conversion of kinetic energy to electron-electron correlation energy with consecutive ICD. The overlay of both channels makes ICEC extremely likely, while nanowires are a strong candidate for the next miniaturization step of integrated-circuit components.
Modified Paschen curves for pulsed breakdown
Authors: Levko Dmitry , Arslanbekov Robert R. , Kolobov Vladimir I.
Published: June 2019

The influence of the voltage rise time on the Paschen curves is analyzed using kinetic and fluid models. The Paschen curves, which describe the dependence of the breakdown voltage, Ubr, on the product pd of gas pressure p and the characteristic length d between the electrodes, have minima that correspond to optimal conditions for plasma generation. It is shown that both kinetic and fluid models predict the experimentally observed shift of the curves toward higher voltages and the shift of the Paschen minima toward higher values of pd with the decreasing voltage rise time τ. On the right branch of the Paschen curves, the agreement between both models is obtained for all τ. We confirm that the minimum of the Paschen curves corresponds to conditions of electron runaway. On the left branch, the electron velocity distribution function is nonlocal in space and also nonlocal in time.
Isolation and culture of epithelial cells from stored buffalo semen and their use for the production of cloned embryos
Authors: Saini Monika , Selokar Naresh L. , Rajendran Rasika , Kumar Dharmendra , Kumar Pradeep , Yadav Prem Singh
Published: June 2019

The aim of the present study was to isolate somatic cells from semen, a non-invasive source of donor somatic cells, for somatic cell nuclear transfer (SCNT) experiments. The study had two parts: (1) isolation and culture of somatic cells from semen, which was stored at 4°C; and (2) investigating the SCNT competence of semen-derived somatic cells. We successfully cultured somatic cells from freshly ejaculated semen, which was stored for different times (0, 4, 12, 24, 72 and 144h after semen collection) at 4°C, using a Percoll gradient method. Up to 24h storage, 100% cell attachment rates were observed; cell attachment rates of 66% were observed for the 72 and 144h storage groups. The attached cells observed in all groups examined were proliferated (100%). Cultured cells exhibited epithelial cell morphology and culture characteristics, which was further confirmed by positive expression of cytokeratin 18, an epithelial cell-type marker. We compared the SCNT competence of semen-derived epithelial cells and skin-derived fibroblasts. The cleavage rate, blastocyst production rate, total number of cells in blastocysts and the apoptotic index of blastocysts were similar for embryos produced from semen-derived epithelial cells and skin-derived fibroblasts, indicating that semen-derived epithelial cells can serve as donors for SCNT experiments. In conclusion, we demonstrate a method to culture epithelial cells from stored semen, which can be used to produce cloned embryos of breeding bulls, including remote bulls.
Cofilin drives rapid turnover and fluidization of entangled F-actin
Authors: McCall Patrick M. , MacKintosh Frederick C. , Kovar David R. , Gardel Margaret L.
Published: June 2019

Significance

When an animal cell moves or divides, a disordered network of actin filaments (F-actin) builds mechanical scaffolds to drive cell-shape changes. Actin filaments are undergoing continual cycles of assembly and disassembly, known as turnover, but it is unknown how these dynamics impact the mechanical properties of actin-filament-based networks. Here, we show that actin-filament turnover dynamics contribute to mechanical stress relaxation. Additionally, we identify the factors necessary to generate a nonequilibrium steady state of dynamic actin filaments that provides a picture of their regulation in vivo.
BMP controls dorsoventral and neural patterning in indirect-developing hemichordates providing insight into a possible origin of chordates
Authors: Su Yi-Hsien , Chen Yi-Chih , Ting Hsiu-Chi , Fan Tzu-Pei , Lin Ching-Yi , Wang Kuang-Tse , Yu Jr-Kai
Published: June 2019

A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling.
The tilted helix model of dynamin oligomers
Authors: Kadosh Avihay , Colom Adai , Yellin Ben , Roux Aurélien , Shemesh Tom
Published: June 2019

Significance

Hydrolysis of GTP leads to remodeling of dynamin helical collars and severing of the underlying membrane neck—a critical step in vesicle endocytosis. We use mathematical modeling to explore the mechanisms that regulate oligomer deformation. We find that orientation of dynamin’s pleckstrin homology domain relative to the membrane introduces tilt strain. Relaxation of this strain requires departure of the oligomer from its intrinsic helical shape. Nonuniform accumulation of strain along the length of the dynamin chain results in partial oligomer fragmentation. The results of our model are corroborated experimentally by atomic force microscopy measurements. Our analysis leads to a definition of the tilted helix: a surface curve that maintains a fixed angle between the curve normal and the surface normal.
Functional assembly of nitrous oxide reductase provides insights into copper site maturation
Authors: Zhang Lin , Wüst Anja , Prasser Benedikt , Müller Christoph , Einsle Oliver
Published: June 2019

The multicopper enzyme nitrous oxide reductase reduces the greenhouse gas N
2
O to uncritical N
2
as the final step of bacterial denitrification. Its two metal centers require an elaborate assembly machinery that so far has precluded heterologous production as a prerequisite for bioremediatory applications in agriculture and wastewater treatment. Here, we report on the production of active holoenzyme in
Escherichia coli
using a two-plasmid system to produce the entire biosynthetic machinery as well as the structural gene for the enzyme. Using this recombinant system to probe the role of individual maturation factors, we find that the ABC transporter NosFY and the accessory NosD protein are essential for the formation of the [4Cu:2S] site Cu
Z
, but not the electron transfer site Cu
A
. Depending on source organism, the heterologous host
E. coli
can, in some cases, compensate for the lack of the Cu chaperone NosL, while in others this protein is strictly required, underlining the case for designing a recombinant system to be entirely self-contained.
Evolution of sex ratio through gene loss
Authors: Yin Da , Haag Eric S.
Published: June 2019

Significance

Several species of
Caenorhabditis
nematodes, including
Caenorhabditis elegans
, have recently evolved self-fertile hermaphrodites from female/male ancestors. These hermaphrodites can either self-fertilize or mate with males, and the extent of outcrossing determines subsequent male frequency. Using experimental evolution, the authors show that a gene family with a historical role in sperm competition plays a large role in regulating male frequency after self-fertility evolves. By reducing, but not completely eliminating outcrossing, loss of the
mss
genes contributes to adaptive tuning of the sex ratio in a newly self-fertile species.
PRCD is essential for high-fidelity photoreceptor disc formation
Authors: Spencer William J. , Ding Jin-Dong , Lewis Tylor R. , Yu Chen , Phan Sebastien , Pearring Jillian N. , Kim Keun-Young , Thor Andrea , Mathew Rose , Kalnitsky Joan , Hao Ying , Travis Amanda M. , Biswas Sondip K. , Lo Woo-Kuen , Besharse Joseph C. , Ellisman Mark H. , Saban Daniel R. , Burns Marie E. , Arshavsky Vadim Y.
Published: June 2019

Significance

The function of progressive rod-cone degeneration (PRCD) protein has remained a mystery since its gene and associated mutation were discovered as one of the most common causes of retinal degeneration in dogs. Furthermore, numerous mutations in the protein have since been identified to cause retinal degeneration in human patients diagnosed with retinitis pigmentosa. Here, we generated a PRCD knockout mouse and found that PRCD functions at the site of photoreceptor disc morphogenesis where it is required to keep newly forming discs flat as they protrude from the plasma membrane. Without PRCD, the newly forming discs bulge and release extracellular vesicles, which accumulate in the extracellular space and ultimately lead to retinal pathology.
“Let me now answer, very directly, Marie’s question”
Authors: Bull Peter , Waddle Maurice
Published: June 2019

Prime Minister’s Questions (PMQs) in the UK attracts much criticism for the adversarial and occasional aggressive language on display. During his successful campaign for the leadership of the Labour Party, Jeremy Corbyn called for a “new kind of politics” (ITV 2015). One feature of his “new” approach, apparent during his early sessions as Leader of the Opposition, was to include questions to Prime Minister David Cameron sourced from members of the public. Although, subsequently, these “public questions” became less frequent, they provided an opportunity to compare their interactional effects with standard “non-public questions”. Arguably, the aim of this salient feature of corbyn’s approach to questioning Cameron was to redress the moral order of PMQs. We test this proposal via two measures of the PM’s responses: reply rate and personalisation. Results showed that Corbyn’s public questions did not enhance Cameron’s reply rate. However, whereas Cameron used significantly more personal attacks than Corbyn in response to non-public questions, the level of such attacks by the PM for public questions was as low as Corbyn’s, with no significant difference between them. In this latter regard, such an approach showed the potential to mitigate the ritualistic and customary verbal aggression of PMQs.
Moral impoliteness
Authors: Parvaresh Vahid
Published: June 2019

This study is concerned with the increasing use of impolite language that one observes during interactions which take place over the Internet. Drawing on a number ofInstagramposts uploaded by various socialites and public figures, this study proposes the notion of a ‘Basic Moral Perspective’ as being a window to an understanding of the nature of some impolite language witnessed on social media. I define ‘Basic Moral Perspective’ as the moral predisposition which interactants possess. As the study shows, in contexts in which there appears to be little relational history between interactants, the ‘Basic Moral Perspective’, amongst other factors, that interactants bring to an interaction can potentially result in impolite language. As will be shown throughout the study, the interactants’ Basic Moral Perspective can provide a clue as to how certain interactions are responded to.
General converbs in Andi
Authors: Verhees Samira
Published: June 2019

This paper describes the semantic and morphosyntactic properties of general converb constructions in Andi, a language of the Avar-Andic group of the East Caucasian language family. There are two general converbs in Andi, both of which are homophonous with a finite verb form (the aorist and the perfect, respectively). There is a considerable functional overlap between the two converbs. Both can be used to render the first stage of a complex event. The perfect / converb can also specify manner. An additive particlelooften accompanies the perfect as converb, while a specialised particlelodːuappears with the aorist as converb. The situation in Andi is unusual, because the two converbs are functionally very similar and not opposed in terms of aspect. In addition, Andi seems to be the only East Caucasian language where a specialised particle (i.e.lodːu) is found in this type of converbal clauses.
Flat as a wall or flat as a butcher’s hand
Authors: Tartakovsky Roi , Shen Yeshayahu
Published: June 2019

Foregrounding theory deals with the relation between deviant textual device (e.g., alliteration) and the effect on
readers (e.g., high aesthetic evaluation). While previous research has tended to look at an array of devices together in longer
stretches of text, we focus on an isolated, semantic foregrounding device, the closed simile. We introduce a distinction between
the standard and non-standard simile, representing first- and second-order foregrounding, respectively, and test the idea that the
more deviant version would yield higher ratings in terms of the aesthetic, cognitive, and emotive dimensions of text appreciation.
Our first finding is that experts prefer the more foregrounded version whereas novices opt for the less foregrounded one. However,
our second finding is that, when the novices are prompted to interpret the similes prior to rating them, the non-standard version
yields higher ratings. We conclude by discussing some implications of the present research for foregrounding theory.
What if two involving stories contradict each other?
Authors: Komori Megumi
Published: June 2019

This study investigated the relationship between individual differences in narrative transportation and attitude
robustness. A total of 840 respondents participated in a web survey. In the first phase of the survey, respondents indicated their
attitudes toward social issues after reading supporting or opposing texts with narrative and persuasive messages. After two weeks,
the same participants read another text expressing the opposite perspective on the same issue, and again indicated their
attitudes. Attitude robustness (i.e., degree of change in attitude between phases) was significantly predicted by transportability
and mediated by transportation-related concepts of situational involvement. Additionally, whereas situational involvement with
narrative text was predicted by transportability, situational involvement with persuasive text was consistently predicted by
self-involvement with the issues. Implications of the findings for narrative transportation and persuasion research and
limitations of the study are discussed.
Cantharidin decreased viable cell number in human osteosarcoma U-2 OS cells through G2/M phase arrest and induction of cell apoptosis
Authors: Chen Chia-Ching , Chueh Fu-Shin , Peng Shu-Fen , Huang Wen-Wen , Tsai Chang-Hai , Tsai Fuu-Jen , Huang Chih-Yang , Tang Chih-Hsin , Yang Jai-Sing , Hsu Yuan-Man , Yin Mei-Chin , Huang Yi-Ping , Chung Jing-Gung
Published: June 2019

Cantharidin (CTD), a sesquiterpenoid bioactive substance, has been reported to exhibit anticancer activity against various types of cancer cells. The aim of the present study was to investigate the apoptosis effects and the underlying mechanisms of CTD on osteosarcoma U-2 OS cells. Results showed that CTD induced cell morphologic changes, reduced total viable cells, induced DNA damage, and G2/M phase arrest. CTD increased the production of reactive oxygen species and Ca2+, and elevated the activities of caspase-3 and −9, but decreased the level of mitochondrial membrane potential. Furthermore, CTD increased the ROS- and ER stress-associated protein expressions and increased the levels of pro-apoptosis-associated proteins, but decreased that of anti-apoptosis-associated proteins. Based on these observations, we suggested that CTD decreased cell number through G2/M phase arrest and the induction of cell apoptosis in U-2 OS cells and CTD could be a potential candidate for osteosarcoma treatments.
The enemy of my enemy: PTEN and PLCXD collude to fight endosomal PtdIns(4,5)P2
Authors: Del Signore Steven J. , Rodal Avital A.
Published: June 2019

Loss of the phosphoinositide 5-phosphatase OCRL causes accumulation of PtdIns(4,5)P2 on membranes and, ultimately, Lowe syndrome. In this issue, Mondin et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201805155) discover that a surprising partnership between PTEN and the phospholipase PLCXD can compensate for OCRL to suppress endosomal PtdIns(4,5)P2 accumulation.
Modelling a laser plasma accelerator driven free electron laser
Authors: Alotaibi B M , Khalil Sh M , McNeil B W J , Traczykowski Piotr
Published: June 2019

Free-electron lasers (FEL) are the brightest, coherent sources of short wavelength radiation from the VUV into the x-ray. There is much research interest in reducing the cost and the size of FELs by utilising new accelerator techniques. Laser-plasma accelerator (LPA) are a promising accelerator for next generation compact FEL light sources with many potential advantages due to the high acceleration gradient and large peak currents they offer. The electron beams of a LPA typically have a smaller transverse emittance, a large energy spread and tend to be of shorter duration and higher current than conventional Radio Frequency (RF) accelerators. In this paper, a FEL driven by an electron beam from a typical LPA was simulated using the 3D FEL simulation code Puffin. It is shown that lowering the homogenous electron beam energy spread increases the radiation energy output in a short undulator and , as become less than the FEL, or Pierce parameter (

ρ

), then the peak radiation energy increases and the saturation length reduces significantly as expected.
Protecting Species through Legislation: The Case of Sea Turtles
Authors: Brei Michael , Pérez‐Barahona Agustín , Strobl Eric
Published: June 2019

We evaluate the effectiveness of legislation in reducing the negative impacts of beachfront lighting on sea turtle nesting activity, one of the main threats to the species. To this end we construct a time varying index of ordinance effectiveness across Florida counties and combine this with loggerhead nesting data to create a panel data set covering a twenty‐six year period. Our econometric findings show that such legislation can significantly increase nesting activity, where current levels of protection result in an additional 34%. Using our estimates within a calibrated population model we also demonstrate that legislation can reduce the time to the animals’ extinction. Finally, when considering estimates of local willingness to pay for sea turtle preservation, we show that alternatively raising sea turtles in captivity under a head start program may be prohibitively expensive.
Bitter melon juice-intake modulates glucose metabolism and lactate efflux in tumors in its efficacy against pancreatic cancer
Authors: Dhar Deepanshi , Raina Komal , Kant Rama , Wempe Michael F , Serkova Natalie J , Agarwal Chapla , Agarwal Rajesh
Published: June 2019

The established role of bitter melon juice (BMJ), a natural product, in activating master metabolic regulator adenosine monophosphate-activated protein kinase in pancreatic cancer (PanC) cells served as a basis for pursuing deeper investigation into the underlying metabolic alterations leading to BMJ efficacy in PanC. We investigated the comparative metabolic profiles of PanC cells with differential KRAS mutational status on BMJ exposure. Specifically, we employed nuclear magnetic resonance (NMR) metabolomics and in vivo imaging platforms to understand the relevance of altered metabolism in PanC management by BMJ. Multinuclear NMR metabolomics was performed, as a function of time, post-BMJ treatment followed by partial least square discriminant analysis assessments on the quantitative metabolic data sets to visualize the treatment group clustering; altered glucose uptake, lactate export and energy state were identified as the key components responsible for cell death induction. We next employed PANC1 xenograft model for assessing in vivo BMJ efficacy against PanC. Positron emission tomography ([18FDG]-PET) and magnetic resonance imaging on PANC1 tumor-bearing animals reiterated the in vitro results, with BMJ-associated significant changes in tumor volumes, tumor cellularity and glucose uptake. Additional studies in BMJ-treated PanC cells and xenografts displayed a strong decrease in the expression of glucose and lactate transporters GLUT1 and MCT4, respectively, supporting their role in metabolic changes by BMJ. Collectively, these results highlight BMJ-induced modification in PanC metabolomics phenotype and establish primarily lactate efflux and glucose metabolism, specifically GLUT1 and MCT4 transporters, as the potential metabolic targets underlying BMJ efficacy in PanC.
Evolutionary Algorithms For k-Anonymity In Social Networks Based On Clustering Approach
Authors: Yazdanjue Navid , Fathian Mohammad , Amiri Babak
Published: June 2019

The usage of social networks shows a growing trend in recent years. Due to a large number of online social networking users, there is a lot of data within these networks. Recently, advances in technology have made it possible to extract useful information about individuals and the interactions among them. In parallel, several methods and techniques were proposed to preserve the users’ privacy through the anonymization of social network graphs. In this regard, the utilization of the k-anonymity method, where k is the required threshold of structural anonymity, is among the most useful techniques. In this technique, the nodes are clustered together to form the super-nodes of size at least k. Our main idea in this paper is, initially, to optimize the clustering process in the k-anonymity method by means of the particle swarm optimization (PSO) algorithm in order to minimize the normalized structural information loss (NSIL), which is equal to maximizing 1-NSIL. Although the proposed PSO-based method shows a higher convergence rate than the previously introduced genetic algorithm (GA) method, it did not provide a lower NSIL value. Therefore, in order to achieve the NSIL value provided by GA optimization while preserving the high convergence rate obtained from the PSO algorithm, we present hybrid solutions based on the GA and PSO algorithms. Eventually, in order to achieve indistinguishable nodes, the edge generalization process is employed based on their relationships. The simulation results demonstrate the efficiency of the proposed model to balance the maximized 1-NSIL and the algorithm’s convergence rate.
Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54
Authors: Dellborg Mikael , Bonaca Marc P , Storey Robert F , Steg P Gabriel , Im Kyung A , Cohen Marc , Bhatt Deepak L , Oude Ophuis Ton , Budaj Andrezej , Hamm Christian , Spinar Jindrich , Kiss Robert G , Lopez-Sendon José , Kamensky Gabriel , Van de Werf Frans , Ardissino Diego , Kontny Frederic , Montalescot Gilles , Johanson Per , Bengtsson Olof , Himmelmann Anders , Braunwald Eugene , Sabatine Marc S
Published: June 2019

Aims

In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Methods and results

Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58).

Conclusion

In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.

Clinical trial registration

http://www.clinicaltrials.gov NCT01225562
The impact factor: implications for research policy, editorial rules and scholarly reputation
Authors: Argüelles Juan Carlos , Argüelles-Prieto Raquel
Published: June 2019

The assessment of scientific research is essentially based on several metric parameters, the so-termed Impact Factor perhaps being the predominant one. Despite well-founded criticisms and the wide opposition of reputed scientists, this procedure has become a tool of scientific policy, and is applied in editorial procedures for scientific publication, the evaluation of research groups, the concession of grants, fellowships or even academic positions. Indeed, cutting-edge research is today a competitive and exigent task, where the legitimacy and restrictions of such metric factors remain a preoccupation. However, whatever the policy of evaluation implemented, most breakthroughs are revolutionary, and involve a change in a given paradigm, usually being made by unorthodox scientists, whose scholarly reputation may be questioned by the establishment, and who may often be excluded as a result of the current system of highly productive research.
Do phenothiazines possess antimicrobial and efflux inhibitory properties?
Authors: Grimsey Elizabeth M , Piddock Laura J V
Published: June 2019

Antibiotic resistance is a global health concern; the rise of drug-resistant bacterial infections is compromising the medical advances that resulted from the introduction of antibiotics at the beginning of the 20th century. Considering that the presence of mutations within individuals in a bacterial population may allow a subsection to survive and propagate in response to selective pressure, as long as antibiotics are used in the treatment of bacterial infections, development of resistance is an inevitable evolutionary outcome. This, combined with the lack of novel antibiotics being released to the clinical market, means the need to develop alternative strategies to treat these resistant infections is critical. We discuss how the use of antibiotic adjuvants can minimise the appearance and impact of resistance. To this effect, several phenothiazine-derived drugs have been shown to potentiate the activities of antibiotics used to treat infections caused by Gram-positive and Gram-negative bacteria. Outside of their role as antipsychotic medications, we review the evidence to suggest that phenothiazines possess inherent antibacterial and efflux inhibitory properties enabling them to potentially combat drug resistance. We also discuss that understanding their mode of action is essential to facilitate the design of new phenothiazine derivatives or novel agents for use as antibiotic adjuvants.
Empty Institutions in Global Environmental Politics
Authors: Dimitrov Radoslav S
Published: June 2019

Why are some institutions without any policy powers or output? This study documents the efforts by governments to create empty international institutions whose mandates deprive them of any capacity for policy formulation or implementation. Examples include the United Nations Forum on Forests, the Copenhagen Accord on Climate Change, and the UN Commission on Sustainable Development. Research is based on participation in twenty-one rounds of negotiations over ten years and interviews with diplomats, policymakers, and observers. The article introduces the concept of empty institutions, provides evidence from three empirical cases, theorizes their political functions, and discusses theoretical implications and policy ramifications. Empty institutions are deliberately designed not to deliver and serve two purposes. First, they are political tools for hiding failure at negotiations, by creating a public impression of policy progress. Second, empty institutions are “decoys” that distract public scrutiny and legitimize collective inaction, by filling the institutional space in a given issue area and by neutralizing pressures for genuine policy. Contrary to conventional academic wisdom, institutions can be raised as obstacles that preempt governance rather than facilitate it.
Effectiveness of an intervention to improve antibiotic-prescribing behaviour in primary care: a controlled, interrupted time-series study
Authors: Teixeira Rodrigues António , Roque Fátima , Piñeiro-Lamas Maria , Falcão Amílcar , Figueiras Adolfo , Herdeiro Maria Teresa
Published: June 2019

Background

High rates of antibiotic misprescribing in primary care, with alarming clinical and economic consequences, highlight the urgent need for interventions to improve antibiotic prescribing in this setting.

Objectives

To assess the effectiveness on antibiotic prescribing quality indicators of a multifaceted intervention targeting health professionals’ and patients’ behaviour regarding antibiotic use.

Methods

We conducted a pragmatic cluster-randomized controlled trial in the catchment area covered by Portugal’s Central Regional Health Administration. The intervention consisted of a multidisciplinary, multifaceted programme involving physicians, pharmacists and patients, and comprising outreach visits for physicians and pharmacists, and educational materials for health professionals and patients. The following were assessed: relative ratios of prescription of penicillins sensitive to β-lactamase, penicillin combinations including β-lactamase inhibitors, third- and fourth-generation cephalosporins and fluoroquinolones; and the ratio of broad- to narrow-spectrum antibiotics. An interrupted time-series analysis for multiple-group comparisons was performed. The study protocol was registered on Clinical.trials.gov (NCT02173509).

Results

The participation rate in the educational intervention was 64% (197/309 GPs) in a total of 25 counties. Statistically significant improvements were obtained, not only in the relative prescription of penicillins sensitive to β-lactamase (overall relative change of +896%) and penicillin combinations including β-lactamase inhibitors (−161%), but also in the ratio of broad- to narrow-spectrum antibiotics (−200%). Statistically significant results were also obtained for third- and fourth-generation cephalosporins, though only in the immediate term.

Conclusions

This study showed that quality indicators of antibiotic prescribing can be improved by tackling influences on behaviour including knowledge and attitudes surrounding physicians’ clinical practice. Accordingly, these determinants must be considered when implementing interventions aimed at improving antibiotic prescribing.
Thrombolytic Salvage of Threatened Frostbitten Extremities and Digits: A Systematic Review
Authors: Drinane James , Kotamarti Vasanth S , O’Connor Casey , Nair Lakshmi , Divanyan Alex , Roth Malcolm Z , Patel Ashit , Ricci Joseph A
Published: June 2019

Frostbite is a cold injury that results in soft tissue loss and can lead to amputation. Vascular thrombosis following injury causes ischemic tissue damage. Despite understanding the pathology, its treatment has remained largely unchanged for over 30 years. Threatened extremities may be salvaged with thrombolytics to restore perfusion. The authors performed a systematic review to determine whether thrombolytic therapy is effective and to identify patients who may benefit from this treatment. The Pubmed, EBSCO, and Google Scholar databases were queried using the key words “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Studies written after 1990 in English met inclusion criteria. Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as administration of tPA, alteplase, urokinase, or streptokinase. Forty-two studies were identified and 17 included. Included were 1 randomized trial, 10 retrospective studies, 2 case series, and 4 case reports. One thousand eight hundred and forty-four limbs and digits in 325 patients were studied and 216 patients treated with thrombolytics and 346 amputations performed. The most common means of thrombolysis was intra-arterial tPA. The most common duration of therapy was 48 hours. Limb salvage rates ranged from 0% to 100% with a weighted average of 78.7%. Thrombolytics are a safe and effective treatment of severe frostbite. They represent the first significant advancement in frostbite treatment by preventing otherwise inevitable amputations warranting both greater utilization and further research to clarify the ideal thrombolytic protocol.
Serum Level of Musclin Is Elevated Following Severe Burn
Authors: Clark Audra , Huebinger Ryan M , Carlson Deborah L , Wolf Steven E , Song Juquan
Published: June 2019

Muscle wasting induced by severe burn worsens clinical outcomes is associated with hyperglycemia. A novel muscle-specific secretory factor, musclin, was reported to regulate glucose metabolism with a homologous sequence of natriuretic peptides. The purpose of the study was to investigate musclin expression in response to burn injury in both human and animal models. Serum was collected from 13 adult burn patients and circulating levels of musclin protein were measured via elisa. The cytokine profile was measured by Bio-Plex multiple immunoassay. Following the clinical study, we used a burn rat model with 40% TBSA to study the time course of musclin expression till day 14. Rat serum and muscle tissue sample were harvested. Finally, an in vitro study was applied to investigate whether the muscle cell C2C12 myoblast expressed musclin under 10% burn serum stimulation. Pearson analysis showed that there was a significant positive correlation of musclin expression to total body surface area of burn in patients (P &= .038). Musclin expression was significantly positively correlated with IL-4, IL-7, IL-12, and IL-13 in burn patients’ serum (P < .05). In the animal study, we found that the musclin level evaluated at 6 hours and 1 day in burn rat serum (P < .05). In vitro, musclin mRNA expression significantly increased with burn serum stimulation at 24 hours (P < .05). In conclusion, serum level of musclin elevated both in human patients and burn animals; musclin was correlated with the severity of burn injury as well as with an elevated cytokine profile in patients; burn serum-stimulated musclin expression in vitro further identified the resource of musclin expression after burn.
Interim results of a real-world observational study of eribulin in soft tissue sarcoma including rare subtypes
Authors: Kobayashi Eisuke , Naito Yoichi , Asano Naofumi , Maejima Aiko , Endo Makoto , Takahashi Shunji , Megumi Yasunori , Kawai Akira
Published: June 2019

Background

Although eribulin is used to treat soft tissue sarcomas (STSs), treatment data for rare subtypes are limited. We conducted a post-marketing surveillance study to assess safety and efficacy of eribulin in STS patients stratified by subtype.

Methods

Japanese patients (n = 256) with advanced or metastatic STS receiving eribulin treatment were monitored for treatment status, adverse events, diagnostic imaging, and clinical outcomes at 3 months and 1 year. Interim analysis was performed. Patients will be monitored up to 2 years.

Results

Interim analysis included 3-month (n = 255), imaging (n = 226), and 1-year (n = 105) data. STS subtype distribution was normal. Median number of eribulin cycles was 3.0 (range: 1–17 cycles). Among patients with imaging data, best overall tumor response (12 weeks) was partial response, 7.5% (n = 17); stable disease, 34.5% (n = 78); and stable disease ≥11 weeks, 10.2% (n = 23). Overall response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) for all patients were 7.5%, 42.0% and 17.7%, respectively. ORR, DCR, and CBR were 10.3%, 32.0% and 16.5%, respectively, for patients with STS subtypes other than liposarcoma and leiomyosarcoma and included responses from patients with rare STS subtypes. Adverse drug reactions (ADRs) occurred in 211 (82.7%) patients (42 [16.5%] patients had serious ADRs), and none led to death. ADRs leading to drug withdrawal and dose reduction occurred in 27 (10.6%) and 55 (21.6%) patients, respectively.

Conclusion

Eribulin was generally well tolerated and showed antitumor activity against STSs, including rare subtypes that currently have few treatment options.

Clinical trial number

NCT03058406 (ClinicalTrials.gov)
Single-arm confirmatory trial of postoperative concurrent chemoradiotherapy using intensity modulated radiation therapy for patients with high-risk uterine cervical cancer: Japan Clinical Oncology Group study (JCOG1402)
Authors: Murakami Naoya , Isohashi Fumiaki , Hasumi Yoko , Kasamatsu Takahiro , Okamoto Hiroyuki , Nakamura Kenichi , Shibata Taro , Ito Yoshinori , Ishikura Satoshi , Nishimura Yasumasa , Yaegashi Nobuo , Toita Takafumi
Published: June 2019

A single-arm confirmatory phase III clinical trial of postoperative concurrent chemoradiotherapy using intensity modulated radiation therapy for patients with high-risk uterine cervical cancer (JCOG1402)
Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis
Authors: Poonsombudlert Kittika , Kewcharoen Jakrin , Prueksapraopong Chattip , Limpruttidham Nath
Published: June 2019

Objectives

Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis.

Methods

We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups.

Results

We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57–0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02–1.95, I2=56.8%, and 1.77, 95% CI 1.1–2.87, I2=82.5%, respectively.

Conclusion

Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.