bluuebunny/crossref_metadata_2025 huggingface dataset:
High-fidelity measurements in channel flow with polymer wall injection
Authors: Elsnab John R. , Monty Jason P. , White Christopher M. , Koochesfahani Manoochehr M. , Klewicki Joseph C.
Published: November 2018

Streamwise velocity profiles and their wall-normal derivatives were used to investigate the properties of turbulent channel flow in the low polymer drag reduction$(DR)$regime ($DR=6.5\,\%$to$26\,\%$), as realized via polymer injection at the channel surface. Streamwise velocity data were obtained over a friction Reynolds number ranging from$650$to$1800$using the single-velocity-component version of molecular tagging velocimetry (1c-MTV). This adaptation of the MTV technique has the ability to accurately capture instantaneous profiles at very high spatial resolution (${\gtrsim}850$data points per wall-normal profile), and thus generate well-resolved derivative information as well. Owing to this ability, the present study is able to build upon and extend the recent numerical simulation analysis of Whiteet al. (J. Fluid Mech., vol. 834, 2018, pp. 409–433) that examined the mean dynamical structure of polymer drag-reduced channel flow at friction Reynolds numbers up to$1000$. Consistently, the present mean velocity profiles indicate that the extent of the logarithmic region diminishes with increasing polymer concentration, while statistically significant increases in the logarithmic profile slope begin to occur for drag reductions less than$15\,\%$. Profiles of the r.m.s. streamwise velocity indicate that the maximum moves farther from the wall and increases in magnitude with reductions in drag. Similarly, with increasing drag reduction, the profile of the combined Reynolds and polymer shear stress exhibits a decrease in its maximum value that also moves farther from the wall. Correlations are presented that estimate the location and value of the maximum r.m.s. streamwise velocity and combined Reynolds and polymer shear stress. Over the range of$DR$investigated, these effects consistently exhibit approximately linear trends as a function of$DR$. The present measurements allow reconstruction of the mean momentum balance (MMB) for channel flow, which provides further insights regarding the physics described in the study by Whiteet al. In particular, the present findings support a physical scenario in which the self-similar properties on the inertial domain identified from the leading-order structure of the MMB begin to detectably and continuously vary for drag reductions less than$10\,\%$.
‘Upliftment’, friends and finance: everyday exchange repertoires and mobile money transfer in Kenya
Authors: Johnson Susan , Krijtenburg Froukje
Published: November 2018

The rapid and massive adoption of mobile money transfer (MMT) services in East Africa, particularly in Kenya, stands in stark contrast to historically low use of formal financial systems on the continent. Its ‘fertile grounds’ therefore require in-depth analysis to understand the implications for African financial systems. This paper argues for the need to examine the underlying conceptual environment that enables low income and poor people's MMT adoption. It innovatively combines anthropological with ethnolinguistic analytical approaches to distinguish two repertoires around resource exchange. First, is a relational financial repertoire where relationships are developed and consolidated to create support and ‘upliftment’. A contrasting resource-focused repertoire is more like that of the formal financial sector. Identifying the conceptual features of relationality, the study offers a new perspective on the adoption and use of MMT in Africa and highlights the potential for disjunctures with policy efforts to increase financial inclusion.
Epidemics and intra-communal contestations: Ekeh, ‘les Guinéens’and Ebola in West Africa
Authors: Onoma Ato Kwamena
Published: November 2018

As the Ebola epidemic ravaged the Mano River Basin in 2014, there was concern in Senegal that the resident Peul community of Guinean origins will cause the spread of the disease to Senegal. These fears went unrealized as the Peul migrants embraced many of the epidemic control and prevention measures, which often distanced them from primordial publics in Guinea. While partly motivated by concern over the dangers of Ebola, Peul migrants embraced these measures also because the epidemic and measures advocated to curb it allowed them to assert greater autonomy in their often-fractious relations with primordial publics in their places of origin in Guinea. Their embrace of these measures suggests a rethink of the emphasis on intercommunal strife, intra-communal conviviality and trenchant state-society chasms, which pervades much work on the political economy of postcolonial Africa and which draws significant inspiration from the work of Peter Ekeh.
On annihilation of the relativistic electron vortex pair in collisionless plasmas
Authors: Lezhnin K. V. , Kamenets F. F. , Esirkepov T. Zh. , Bulanov S. V.
Published: November 2018

In contrast to hydrodynamic vortices, vortices in a plasma contain an electric current circulating around the centre of the vortex, which generates a magnetic field localized inside. Using computer simulations, we demonstrate that the magnetic field associated with the vortex gives rise to a mechanism of dissipation of the vortex pair in a collisionless plasma, leading to fast annihilation of the magnetic field with its energy transforming into the energy of fast electrons, secondary vortices and plasma waves. Two major contributors to the energy damping of a double vortex system, namely, magnetic field annihilation and secondary vortex formation, are regulated by the size of the vortex with respect to the electron skin depth, which scales with the electron$\unicode[STIX]{x1D6FE}$factor,$\unicode[STIX]{x1D6FE}_{e}$, as$R/d_{e}\propto \unicode[STIX]{x1D6FE}_{e}^{1/2}$. Magnetic field annihilation appears to be dominant in mildly relativistic vortices, while for the ultrarelativistic case, secondary vortex formation is the main channel for damping of the initial double vortex system.
Auditory and visual hallucination prevalence in Parkinson's disease and dementia with Lewy bodies: a systematic review and meta-analysis
Authors: Eversfield Charlotte Louise , Orton Llwyd David
Published: November 2018

Background

Non-motor features of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), such as auditory hallucinations (AH), contribute to disease burden but are not well understood.

Methods

Systematic review and random-effects meta-analyses of studies reporting AH associated with PD or DLB. Prevalence of visual hallucinations (VH) in identified studies meeting eligibility criteria were included in meta-analyses, facilitating comparison with AH. Synthesis of qualitative descriptions of AH was performed. PubMed, Web of Science and Scopus databases were searched for primary journal articles, written in English, published from 1970 to 2017. Studies reporting AH prevalence in PD or DLB were screened using PRISMA methods.

Results

Searches identified 4542 unique studies for consideration, of which, 26 met inclusion criteria. AH pooled prevalence in PD was estimated to be 8.9% [95% confidence interval (CI) 5.3–14.5], while in DLB was estimated to be 30.8% (±23.4 to 39.3). Verbal hallucinations, perceived as originating outside the head, were the most common form of AH. Non-verbal AH were also common while musical AH were rare. VH were more prevalent, with an estimated pooled prevalence in PD of 28.2% (±19.1 to 39.5), while in DLB they were estimated to be 61.8% (±49.1 to 73.0). Meta-regression determined that the use of validated methodologies to identify hallucinations produced higher prevalence estimates.

Conclusions

AH and VH present in a substantial proportion of PD and DLB cases, with VH reported more frequently in both conditions. Both AH and VH are more prevalent in DLB than PD. There is a need for standardised use of validated methods to detect and monitor hallucinations.
Pulmonary effects on exercise testing in tetralogy of Fallot patients repaired with a transannular patch
Authors: Powell Adam W. , Mays Wayne A. , Knecht Sandra K. , Chin Clifford
Published: November 2018

Background

A transannular patch is often used in the contemporary surgical repair of tetralogy of Fallot. This can lead to significant pulmonary insufficiency and increased right ventricular volumes and ultimately pulmonary valve replacement. Cardiopulmonary exercise testing is used to assess exercise capacity in tetralogy of Fallot patients before pulmonary valve replacement. There is only few published literatures on how lung function affects functional capacity in tetralogy of Fallot patients repaired with a transannular patch.

Methods

A retrospective chart review was done from 2015 to 2017 on patients with tetralogy of Fallot who underwent maximal effort cardiopulmonary exercise testing with cycle ergometry and with concurrent pulmonary function testing. Tetralogy of Fallot patients repaired with a transannular patch without pulmonary valve replacement were compared with age, gender, and size-matched normal controls.

Results

In the tetralogy of Fallot group, 24 out of 57 patients underwent primary repair with a transannular patch. When compared to the normal controls, they demonstrated abnormal predicted forced expiratory volume in one second (79 ± 23.1% versus 90.7 ± 14.1%, p<0.05), predicted maximal voluntary ventilation (74 ± 18% versus 90.5 ± 16.2%, p<0.05) while having low-normal predicted forced vital capacity (80.5 ± 17.2% versus 90.2 ± 12.4%, p<0.05) and normal breathing reserve percentage (50.3 ± 11.3% versus 47.5 ± 17.3%, p = 0.52). Cardiopulmonary exercise testing abnormalities included significantly lower percent predicted oxygen consumption (63.2 ± 12.2% versus 87 ± 12.1%, p<0.05), maximal heart rate (171.8 ± 18.9 versus 184.6 ± 13.6, p<0.05), and percent predicted maximum workload (61.7 ± 15.9% versus 88.3 ± 21.5%, p<0.05).

Conclusions

Tetralogy of Fallot patients repaired with a transannular patch can have abnormal pulmonary function testing with poor exercise capacity in addition to chronotropic incompetence and impaired muscular power.
Blockchain technology and the governance of foreign aid
Authors: Reinsberg Bernhard
Published: November 2018

Blockchain technology has been considered a vehicle to foster development in poor countries by promoting applications such as secure delivery of humanitarian aid, digital identity services, and proof of provenance. This article examines whether (and if so, how) blockchain technology can enhance the effectiveness and efficiency of foreign aid governance, thereby moving beyond completely anonymous contexts. Foreign aid governance is plagued by lack of credible commitments among states, which are further exacerbated by information asymmetries and which often undermine aid effectiveness. In this context, blockchain technology holds two promises. First, through the guaranteed execution of smart contracts, it can strengthen the credibility of state commitments, for example collective burden-sharing rules among a group of donors or recipient country compliance with policy conditionality in return for aid. Second, through leveraging prediction markets, blockchain technology can allay information problems related to the verification of real-world events along the entire aid delivery chain.
Toward Automatic Risk Assessment to Support Suicide Prevention
Authors: Adamou Marios , Antoniou Grigoris , Greasidou Elissavet , Lagani Vincenzo , Charonyktakis Paulos , Tsamardinos Ioannis , Doyle Michael
Published: November 2018

Abstract. Background: Suicide has been considered an important public health issue for years and is one of the main causes of death worldwide. Despite prevention strategies being applied, the rate of suicide has not changed substantially over the past decades. Suicide risk has proven extremely difficult to assess for medical specialists, and traditional methodologies deployed have been ineffective. Advances in machine learning make it possible to attempt to predict suicide with the analysis of relevant data aiming to inform clinical practice. Aims: We aimed to (a) test our artificial intelligence based, referral-centric methodology in the context of the National Health Service (NHS), (b) determine whether statistically relevant results can be derived from data related to previous suicides, and (c) develop ideas for various exploitation strategies. Method: The analysis used data of patients who died by suicide in the period 2013–2016 including both structured data and free-text medical notes, necessitating the deployment of state-of-the-art machine learning and text mining methods. Limitations: Sample size is a limiting factor for this study, along with the absence of non-suicide cases. Specific analytical solutions were adopted for addressing both issues. Results and Conclusion: The results of this pilot study indicate that machine learning shows promise for predicting within a specified period which people are most at risk of taking their own life at the time of referral to a mental health service.
Examining the Relationship Between Attitudes Toward Suicide and Suicide Attempt History
Authors: Hom Melanie A. , Stanley Ian H. , Duffy Mary E. , Davis Lisa , Joiner Thomas E.
Published: November 2018

Abstract. Background: Relatively little is known regarding the relationship between attitudes toward suicide, suicide attempt (SA) history, and future suicidal behaviors. Aims: Utilizing a sample of firefighters, this study compared attitudes toward suicide between individuals with/without a career SA history and evaluated whether certain attitudes toward suicide are associated with a greater self-reported likelihood of making a future SA. Method: US firefighters ( N = 818) completed self-report measures. One-way ANOVAs and linear regression analyses were utilized to address study aims. Results: Firefighters with a career SA reported significantly greater normalization/glorification of suicide – yet lower attributions of suicide to isolation/depression – than those without this history. More stigmatizing attitudes toward suicide and greater normalization/glorification of suicide were each significantly associated with greater self-reported future SA likelihood. Limitations: Data were cross-sectional and findings may not be generalizable. Conclusion: Firefighters who have made an SA during their firefighting careers may normalize and glorify suicide more than those who have not. These attitudes may be associated with greater self-perceived risk for future SAs. Research is needed to replicate findings and evaluate strategies for targeting potentially harmful beliefs about suicide among SA survivors.
In Search of the Prosocial Personality
Authors: Wertag Anja , Bratko Denis
Published: November 2018

Abstract. Prosocial behavior is intended to benefit others rather than oneself and is positively linked to personality traits such as Agreeableness and Honesty-Humility, and usually negatively to the Dark Triad traits (i.e., Machiavellianism, narcissism, and psychopathy). However, a significant proportion of the research in this area is conducted solely on self-report measures of prosocial behavior. Therefore, the aim of this study was to investigate the relationship between prosociality and the basic (i.e., HEXACO) and dark personality traits, comparing their contribution in predicting both self-reported prosociality and prosocial behavior. Results of the hierarchical regression analyses showed that the Dark Triad traits explain prosociality and prosocial behavior above and beyond the HEXACO traits, emphasizing the importance of the Dark Triad in the personality space.
Sex Differences in 32,347 Jordanian 4th Graders on the National Exam of Mathematics
Authors: Al-Bursan Ismael S. , Kirkegaard Emil O. W. , Fuerst John , Bakhiet Salaheldin Farah Attallah , Al Qudah Mohammad F. , Hassan Elsayed Mohammed Abu Hashem , Abduljabbar Adel S.
Published: November 2018

Abstract. Sex differences in mathematical ability were examined in a nation-wide sample of 32,346 Jordanian 4th graders (age 9–10 year) on a 40-item mathematics test. Overall, boys were found to perform slightly worse ( d = −0.12) but had slightly more variation in scores ( SD = 1.02 and SD = 0.98 for boys and girls, respectively). However, when results were disaggregated by school type, single-sex versus coed (i.e., coeducational), boys were found to perform better than girls in coed schools ( d = 0.27) but worse across single-sex schools ( d = −0.37). Two-parameter item response theory analysis showed that item difficulty was similar across sexes in the full sample. Item loadings exhibited substantial departure from measurement invariance with respect to boys and girls at single-sex schools, though. For boys and girls at coed schools, both the item difficulty and item loading correlations were highly similar, evincing that measurement invariance largely held in this case. Partially consistent with findings from other countries, a correlation between item difficulty and male advantage was observed, r = .57, such that the relative male advantage increased with increased item difficulty. Complicating interpretation, this association did not replicate within coed schools. Item content, Bloom’s cognitive taxonomy category, and item position showed no relation to sex differences.
Estimating Subseasonal Variability and Trends in Global Atmosphere Using Reanalysis Data
Authors: Žagar N. , Jelić D. , Alexander M. J. , Manzini E.
Published: November 2018

A new measure of subseasonal variability is introduced that provides a scale‐dependent estimation of vertically and meridionally integrated atmospheric variability in terms of the normal modes of linearized primitive equations. Applied to the ERA‐Interim data, the new measure shows that subseasonal variability decreases for larger zonal wave numbers. Most of variability is due to balanced (Rossby mode) dynamics but the portion associated with the inertio‐gravity (IG) modes increases as the scale reduces. Time series of globally integrated variability anomalies in ERA‐Interim show an increase in variability after year 2000. In recent years the anomalies have been about 2% above the 1981–2010 average. The relative increase in variability projecting on the IG modes is larger and more persistent than for the Rossby modes. Although the IG part is a small component of the subseasonal variability, it is an important effect likely reflecting the observed increase in the tropical precipitation variability.
Modification of Parametric Subharmonic Instability in the Presence of Background Geostrophic Currents
Authors: Yang Wei , Hibiya Toshiyuki , Tanaka Yuki , Zhao Liang , Wei Hao
Published: November 2018

Although various numerical experiments have been carried out to investigate the cascade of internal tide energy associated with parametric subharmonic instability (PSI), most of them assume idealized oceanic situations, ignoring the existence of background relative vorticity (ζ). Here we show, for the first time, that the existence of ζ can significantly modify the behavior of PSI by changing the local effective Coriolis frequency (
). A set of numerical experiments for 25.4°N show that the PSI efficiency significantly increases at the position where positive ζ shifts feff close to the M1 critical frequency (ω = ωM1). Furthermore, numerical experiments for 31°N, poleward of the M1 critical latitude, show that significant PSI energy transfer is possible when negative ζ is low enough. The presented results provide important implications for understanding the spatial distribution of diapycnal mixing in the ocean where background geostrophic currents prevail.
An Enhanced Pfafstetter Catchment Reference System
Authors: Stein J. L.
Published: November 2018

The Pfafstetter system delineates and codes hierarchically nested catchments. Its simple coding scheme denotes stream network position, enabling systematic analysis of the impacts of any activity on a river section without need for a GIS. However, widespread application has identified significant limitations. Issues raised include an inability to code complex drainage systems or large numbers of endorheic basins, the variability in both the levels of basin decomposition and subbasin sizes and main stem identification criteria not conforming to local understanding. To address these issues, the Pfafstetter system was modified to use an independent regionalization for the initial subdivision of the continent. New procedures were developed to code distributary drainage networks and endorheic basins and alternate criteria devised to identify the main stem and to produce a more even decomposition of a catchment. These modifications were successfully applied to the task of delineating and coding hierarchically nested catchments for the Australian continent including its complex distributary and anabranching drainage networks and large numbers of endorheic basins. The independent basin grouping produced initially smaller and more evenly sized subbasins and modeled estimates of flow identified the main stem correctly slightly more often than the original contributing area criterion. Enabling further subdivision of catchments with fewer than four tributaries produced the largest change in catchment delineations, doubling the number of subbasins and halving their size. Achieving the vision for a comprehensive basin reference system will require further development to include anthropogenic and other hydrological features not controlled by topography.
Multiresolution Large‐Eddy Simulation of an Array of Hydrokinetic Turbines in a Field‐Scale River: The Roosevelt Island Tidal Energy Project in New York City
Authors: Chawdhary Saurabh , Angelidis Dionysios , Colby Jonathan , Corren Dean , Shen Lian , Sotiropoulos Fotis
Published: November 2018

Marine hydrokinetic (MHK) power generation systems enable harvesting energy from waterways without the need for water impoundment. A major research challenge for numerical simulations of field‐scale MHK farms stems from the large disparity in scales between the size of waterway and the energy harvesting device. We propose a large‐eddy simulation (LES) framework to perform high‐fidelity, multiresolution simulations of MHK arrays in a real‐life marine environment using a novel unstructured Cartesian flow solver coupled with a sharp‐interface immersed boundary method. The potential of the method as a powerful engineering design tool is demonstrated by applying it to simulate a 30 turbine MHK array under development in the East River in New York City. A virtual model of the MHK power plant is reconstructed from high‐resolution bathymetry measurements in the East River and the 30 turbines placed in 10 TriFrame arrangements as designed by Verdant Power. A locally refined, near the individual turbines, background unstructured Cartesian grid enables LES across a range of geometric scales of relevance spanning approximately 5 orders of magnitude. The simulated flow field is compared with a baseline LES of the flow in the East River without turbines. While velocity deficits and increased levels of turbulence kinetic energy are observed in the vicinity of the turbine wakes, away from the turbines as well as on the water surface only a small increase in mean momentum is found. Therefore, our results point to the conclusion that MHK energy harvesting from large rivers is possible without a significant disruption of the river flow.
A 3‐D Semianalytical Solution for Density‐Driven Flow in Porous Media
Authors: Shao Qian , Fahs Marwan , Hoteit Hussein , Carrera Jesus , Ackerer Philippe , Younes Anis
Published: November 2018

Existing analytical and semianalytical solutions for density‐driven flow (DDF) in porous media are limited to 2‐D domains. In this work, we develop a semianalytical solution using the Fourier Galerkin method to describe DDF induced by salinity gradients in a 3‐D porous enclosure. The solution is constructed by deriving the vector potential form of the governing equations and changing variables to obtain periodic boundary conditions. Solving the 3‐D spectral system of equations can be computationally challenging. To alleviate computations, we develop an efficient approach, based on reducing the number of primary unknowns and simplifying the nonlinear terms, which allows us to simplify and solve the problem using only salt concentration as primary unknown. Test cases dealing with different Rayleigh numbers are solved to analyze the solution and gain physical insight into 3‐D DDF processes. In fact, the solution displays a 3‐D convective cell (actually a vortex) that resembles the quarter of a torus, which would not be possible in 2‐D. Results also show that 3‐D effects become more important at high Rayleigh number. We compare the semianalytical solution to research (Transport of RadioACtive Elements in Subsurface) and industrial (COMSOL Multiphysics®) codes. We show cases (high Raleigh number) where the numerical solution suffers from numerical artifacts, which highlight the worthiness of our semianalytical solution for code verification and benchmarking. In this context, we propose quantitative indicators based on several metrics characterizing the fluid flow and mass transfer processes and we provide open access to the source code of the semianalytical solution and to the corresponding numerical models.
Meandering Evolution and Width Variations: A Physics‐Statistics‐Based Modeling Approach
Authors: Lopez Dubon Sergio , Lanzoni Stefano
Published: November 2018

Many models have been so far proposed to simulate and understand the long‐term evolution of meandering rivers. Nevertheless, some modeling problems still need to be solved, for example, the physical soundness of long‐term simulations when width variations are accounted for. The present work proposes the use of statistical tools to capture the spatiotemporal variations of channel width and to embed their effect into a physics‐statistics‐based model that simulates the river bank evolution. Erosion and deposition processes are assumed to act independently, with a specific shear stress threshold for each of them. In addition, the width evolution is linked with a river‐specific probability density function. The analysis of a representative sample of meandering configurations, extracted from Landsat images, indicates that in many cases a generalized extreme value distribution nicely describes the along‐channel distribution of cross‐section width. For a given river, the parameters of this distribution keep almost constant in time. Significant variations are observed only after cutoff events that shorten the length of the river. The constraint of the river width based on the assumption of a generalized extreme value distribution ensures physically plausible configurations as the river moves throughout the floodplain, adapting continuously its local width. The application of the model to a reach of the Ucayali River appears to reasonably reproduce the planform river morphodynamics and yields realistic values of the cross‐section widths.
The combination of cantharidin and antiangiogenic therapeutics presents additive antitumor effects against pancreatic cancer
Authors: Xu Meng-Dan , Liu Lu , Wu Meng-Yao , Jiang Min , Shou Liu-Mei , Wang Wen-Jie , Wu Jing , Zhang Yan , Gong Fei-Ran , Chen Kai , Tao Min , Zhi Qiaoming , Li Wei
Published: November 2018

Cantharidin, one of the active components of mylabris, is believed to have antitumor activity. Cantharidin selectively inhibits protein phosphatase 2A (PP2A), which can repress multiple oncogenic kinases (ERK, JNK, PKC, and NF-κB). Researches in vitro have shown that cantharidin suppresses cell viability and metastasis in pancreatic cancer cells. This study aims to investigate the effects of cantharidin on pancreatic cancer xenografts in vivo. Xenograft models were established using cells stably expressing luciferase. Xenograft growth was evaluated by living imaging. Gene expression was determined using a microarray, real-time PCR, a RayBiotech antibody array, and the Milliplex assay. Surprisingly, cantharidin significantly accelerated xenograft growth. Living imaging showed a rapid distribution of D-luciferin in cantharidin-treated xenografts, suggesting a rich blood supply. Immunohistochemistry confirmed increased angiogenesis. Microarray and antibody array identified upregulated proangiogenic and downregulated antiangiogenic factors. The Milliplex assay suggested elevated secretion of IL-6, IL-8, TNF-α, and VEGF. Inhibitors of ERK, JNK, PKC, and NF-κB pathway attenuated the cantharidin-induced changes to proangiogenic gene expression. PKC pathway-inhibiting tamoxifen or antiangiogenic therapeutics, including Ginsenoside Rg3, bevacizumab, Apatinib, and Endostar, antagonized the proangiogenic effect of cantharidin or its derivatives. These regimens presented remarkable additive antitumor effects in vivo. Although cantharidin presents antitumor effects in vitro and has been applied in clinical practice, we revealed an unfavorable proangiogenic side effect. We recommend that the clinical application of cantharidin should be performed on the premise of antivascularization therapy.
RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation
Authors: Chen Xiao , Zhi Xin , Wang Jun , Su Jiacan
Published: November 2018

RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rankflox/flox: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
Authors: Li Yanyan , Gong Di , Zhang Le , Li Hongjiang , Zhang Shu , Zhang Jie , Li Kai , Zheng QianWen , Zhao Gang , Zhang Yue , Chen Yue , Guo Yafei , Xiang Rong , Lin Ping , Wei Yuquan
Published: November 2018

Breast cancer is one of the leading causes of death in women. Due to the existence of a small fraction of stem cell-like subpopulations, some breast cancer subtypes exhibit very high malignancy and resistance to multiple therapies. The underlying mechanisms of how these subtypes acquire stem cell-like properties and progress more aggressively remain largely unknown. Zinc finger protein 32 (ZNF32), a newly discovered transcription factor, has been reported to be associated with breast cancer progression. However, many questions remain about its target genes and its exact mechanisms in regulating stem cell-like properties and drug resistance. In the present study, we examined the relationship between ZNF32 and GPER, a membrane-associated estrogen receptor, and we addressed their roles in stemness regulation in human breast cancer cell lines. Our results showed that ZNF32 could induce expansion of stem cell-like subpopulations and increase drug resistance by upregulating GPER expression, in which ERK activation was also implicated. We also illustrated that ZNF32 induced GPER expression via a ZNF32 binding sequence located within the GPER promoter region. A correlation between ZNF32/GPER expression and increased tumor incidence and burden was observed in xenograft mouse models. We conclude that ZNF32 can engage GPER/ERK signalling and confer breast cancer stem cell-like properties, which may indicate poor prognosis of breast cancer patients. ZNF32 and GPER targeted therapies might provide new solutions for breast cancer treatment.
The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa
Authors: Park Se Eun , Pham Duy Thanh , Boinett Christine , Wong Vanessa K. , Pak Gi Deok , Panzner Ursula , Espinoza Ligia Maria Cruz , von Kalckreuth Vera , Im Justin , Schütt-Gerowitt Heidi , Crump John A. , Breiman Robert F. , Adu-Sarkodie Yaw , Owusu-Dabo Ellis , Rakotozandrindrainy Raphaël , Soura Abdramane Bassiahi , Aseffa Abraham , Gasmelseed Nagla , Keddy Karen H. , May Jürgen , Sow Amy Gassama , Aaby Peter , Biggs Holly M. , Hertz Julian T. , Montgomery Joel M. , Cosmas Leonard , Olack Beatrice , Fields Barry , Sarpong Nimako , Razafindrabe Tsiriniaina Jean Luco , Raminosoa Tiana Mirana , Kabore Leon Parfait , Sampo Emmanuel , Teferi Mekonnen , Yeshitela Biruk , El Tayeb Muna Ahmed , Sooka Arvinda , Meyer Christian G. , Krumkamp Ralf , Dekker Denise Myriam , Jaeger Anna , Poppert Sven , Tall Adama , Niang Aissatou , Bjerregaard-Andersen Morten , Løfberg Sandra Valborg , Seo Hye Jin , Jeon Hyon Jin , Deerin Jessica Fung , Park Jinkyung , Konings Frank , Ali Mohammad , Clemens John D. , Hughes Peter , Sendagala Juliet Nsimire , Vudriko Tobias , Downing Robert , Ikumapayi Usman N. , Mackenzie Grant A. , Obaro Stephen , Argimon Silvia , Aanensen David M. , Page Andrew , Keane Jacqueline A. , Duchene Sebastian , Dyson Zoe , Holt Kathryn E. , Dougan Gordon , Marks Florian , Baker Stephen
Published: November 2018

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.
Entangled polymer dynamics beyond reptation
Authors: Abadi Maram , Serag Maged F. , Habuchi Satoshi
Published: November 2018

Macroscopic properties of polymers arise from microscopic entanglement of polymer chains. Entangled polymer dynamics have been described theoretically by time- and space-averaged relaxation modes of single chains occurring at different time and length scales. However, theoretical and experimental studies along this framework provide oversimplified picture of spatiotemporally heterogeneous polymer dynamics. Characterization of entangled polymer dynamics beyond this paradigm requires a method that enables to capture motion and relaxation occurring in real space at different length and time scales. Here we develop new single-molecule characterization platform by combining super-resolution fluorescence imaging and recently developed single-molecule tracking method, cumulative-area tracking, which enables to quantify the chain motion in the length and time scale of nanometres to micrometres and milliseconds to minutes. Using linear and cyclic dsDNA molecules as model systems, our new method reveals chain-position-dependent motion of the entangled linear chains, which is beyond the scope of current theoretical framework.
Artificial optic-neural synapse for colored and color-mixed pattern recognition
Authors: Seo Seunghwan , Jo Seo-Hyeon , Kim Sungho , Shim Jaewoo , Oh Seyong , Kim Jeong-Hoon , Heo Keun , Choi Jae-Woong , Choi Changhwan , Oh Saeroonter , Kuzum Duygu , Wong H.-S. Philip , Park Jin-Hong
Published: November 2018

The priority of synaptic device researches has been given to prove the device potential for the emulation of synaptic dynamics and not to functionalize further synaptic devices for more complex learning. Here, we demonstrate an optic-neural synaptic device by implementing synaptic and optical-sensing functions together on h-BN/WSe2 heterostructure. This device mimics the colored and color-mixed pattern recognition capabilities of the human vision system when arranged in an optic-neural network. Our synaptic device demonstrates a close to linear weight update trajectory while providing a large number of stable conduction states with less than 1% variation per state. The device operates with low voltage spikes of 0.3 V and consumes only 66 fJ per spike. This consequently facilitates the demonstration of accurate and energy efficient colored and color-mixed pattern recognition. The work will be an important step toward neural networks that comprise neural sensing and training functions for more complex pattern recognition.
Determining molecular properties with differential mobility spectrometry and machine learning
Authors: Walker Stephen W. C. , Anwar Ahdia , Psutka Jarrod M. , Crouse Jeff , Liu Chang , Le Blanc J. C. Yves , Montgomery Justin , Goetz Gilles H. , Janiszewski John S. , Campbell J. Larry , Hopkins W. Scott
Published: November 2018

The fast and accurate determination of molecular properties is highly desirable for many facets of chemical research, particularly in drug discovery where pre-clinical assays play an important role in paring down large sets of drug candidates. Here, we present the use of supervised machine learning to treat differential mobility spectrometry – mass spectrometry data for ten topological classes of drug candidates. We demonstrate that the gas-phase clustering behavior probed in our experiments can be used to predict the candidates’ condensed phase molecular properties, such as cell permeability, solubility, polar surface area, and water/octanol distribution coefficient. All of these measurements are performed in minutes and require mere nanograms of each drug examined. Moreover, by tuning gas temperature within the differential mobility spectrometer, one can fine tune the extent of ion-solvent clustering to separate subtly different molecular geometries and to discriminate molecules of very similar physicochemical properties.
Efflux pump-mediated resistance to antifungal compounds can be prevented by conjugation with triphenylphosphonium cation
Authors: Chang Wenqiang , Liu Jun , Zhang Ming , Shi Hongzhuo , Zheng Sha , Jin Xueyang , Gao Yanhui , Wang Shuqi , Ji Aiguo , Lou Hongxiang
Published: November 2018

Antifungal resistance due to upregulation of efflux pumps is prevalent in clinical Candida isolates. Potential efflux pump substrates (PEPSs), which are active against strains deficient in efflux pumps but inactive against wild-type strains, are usually missed in routine antifungal screening. Here we present a method for identification of PEPSs, and show that conjugation with mitochondria-targeting triphenylphosphonium cation (TPP+) can enhance or restore the compounds’ antifungal activity. The screening method involves co-culturing a wild-type C. albicans strain and a Cdr efflux pump-deficient strain, labelled with different fluorescent proteins. We identify several PEPSs from a library of natural terpenes, and restore their antifungal activity against wild-type and azole-resistant C. albicans by conjugation with TPP+. The most active conjugate (IS-2-Pi-TPP) kills C. albicans cells, prevents biofilm formation and eliminates preformed biofilms, without inducing significant resistance. The antifungal activity is accompanied by mitochondrial dysfunction and increased levels of intracellular reactive oxygen species. In addition, IS-2-Pi-TPP is effective against C. albicans in a mouse model of skin infection.
Deep-learning-based inverse design model for intelligent discovery of organic molecules
Authors: Kim Kyungdoc , Kang Seokho , Yoo Jiho , Kwon Youngchun , Nam Youngmin , Lee Dongseon , Kim Inkoo , Choi Youn-Suk , Jung Yongsik , Kim Sangmo , Son Won-Joon , Son Jhunmo , Lee Hyo Sug , Kim Sunghan , Shin Jaikwang , Hwang Sungwoo
Published: November 2018

The discovery of high-performance functional materials is crucial for overcoming technical issues in modern industries. Extensive efforts have been devoted toward accelerating and facilitating this process, not only experimentally but also from the viewpoint of materials design. Recently, machine learning has attracted considerable attention, as it can provide rational guidelines for efficient material exploration without time-consuming iterations or prior human knowledge. In this regard, here we develop an inverse design model based on a deep encoder-decoder architecture for targeted molecular design. Inspired by neural machine language translation, the deep neural network encoder extracts hidden features between molecular structures and their material properties, while the recurrent neural network decoder reconstructs the extracted features into new molecular structures having the target properties. In material design tasks, the proposed fully data-driven methodology successfully learned design rules from the given databases and generated promising light-absorbing molecules and host materials for a phosphorescent organic light-emitting diode by creating new ligands and combinatorial rules.
The characteristic, antioxidative and multiple organ protective of acidic-extractable mycelium polysaccharides by Pleurotus eryngii var. tuoliensis on high-fat emulsion induced-hypertriglyceridemic mice
Authors: Gao Zheng , Lai Qiangqiang , Yang Qihang , Xu Nuo , Liu Wenbo , Zhao Fulan , Liu Xinchao , Zhang Chen , Zhang Jianjun , Jia Le
Published: November 2018

The antioxidant and multiple organ protection effects of acid- extracted mycelia polysaccharides (Ac-MPS) fromPleurotus eryngiivar. tuoliensison HFE-induced hypertriglyceridemic mice were investigated. The results showed that Ac-MPS have potential ability to relieve the hypertriglyceridemia and preventing oxidative stress by decreasing levels of TG, TC LDL-C, elevating contents of HDL-C in serum, increasing the activities of SOD, GSH-Px, CAT and T-AOC, and the down regulating MDA and LPO contents in liver, heart, kidney and spleen. And the histopathological observations also displayed that Ac-MPS could alleviate organ damage. Moreover, the GC, HPGPC, FT-IR and AFM analyses revealed the Ac-MPS possessed the typical polysaccharides structure with the molecular weights (Mw) of 2.712 × 105 Da. These conclusions indicated that the Ac-MPS had the potential to develop new drugs for hypertriglyceridemia-induced multiple organ failure.
MicroRNA cluster miR199a/214 are differentially expressed in female and male rats following nicotine self-administration
Authors: Pittenger Steven T. , Schaal Victoria L. , Moore Dalia , Guda Rahul S. , Koul Sneh , Yelamanchili Sowmya V. , Bevins Rick A. , Pendyala Gurudutt
Published: November 2018

Previous research has established sex differences associated with nicotine intake, however a significant gap in knowledge remains regarding the molecular mechanisms that govern these differences at the transcriptional level. One critical regulator of transcription are microRNAs (miRNAs). miRNAs are a family of non-coding RNAs that regulate an array of important biological functions altered in several disease states, including neuroadaptive changes within the brain associated with drug dependence. We examined the prefrontal cortex (PFC) from male and female Sprague-Dawley rats following self-administration (22 days) of nicotine or yoked saline controls using next generation RNA-Sequencing (RNA-Seq) technology and found an array of miRNAs to be significantly and differentially regulated by nicotine self-administration. Of these, we found the expression of miR-199a and 214, which are expressed on the same cluster of chromosome 1, to be upregulated in the female rats exposed to nicotine; upregulation in this group was further validated by real time polymerase chain reaction (RT-PCR). Bioinformatics analysis to assess common targets of miR-199/214 identified Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)- dependent deacetylase that plays a role in apoptosis, neuron survival, and stress resistance. Using western-blot, we confirmed downregulation of SIRT1 and increased cleaved caspase 3 expression in the brains of nicotine-exposed female rats and no change in expression levels in the other groups. Collectively, our findings highlight a miR-199/214 regulatory network that, through SIRT1, may be associated with nicotine seeking in females which may serve as a potential therapeutic target for sex-specific treatment approaches.
2nd-order random lasing in a multimode diode-pumped graded-index fiber
Authors: Evmenova Ekaterina A. , Kuznetsov Alexey G. , Nemov Ilya N. , Wolf Alexey A. , Dostovalov Alexandr V. , Kablukov Sergey I. , Babin Sergey A.
Published: November 2018

Raman lasing in a graded-index fiber (GIF) attracts now great deal of attention due to the opportunity to convert high-power multimode laser diode radiation into the Stokes wave with beam quality improvement based on the Raman clean-up effect. Here we report on the cascaded Raman generation of the 2nd Stokes order in the 1.1-km long GIF with 100-μm core directly pumped by 915-nm diodes. In the studied all-fiber scheme, the 1st Stokes order is generated at 950–954 nm in a linear cavity formed at GIF ends by two fiber Bragg gratings (FBGs) securing beam quality improvement from M2 ≈ 30 to M2 ≈ 2.3 due to special transverse structure of FBGs. The 2nd Stokes wave is generated either in linear (two FBGs) or half-open (one FBG) cavity with random distributed feedback via Rayleigh backscattering. Their comparison shows that the random lasing provides better beam quality and higher slope efficiency. Nearly diffraction limited beam (M2 ≈ 1.6) with power up to 27 W at maximum gain (996 nm), and 17 W at the detuned wavelength of 978 nm has been obtained, thus demonstrating that the 2nd-order random lasing in diode-pumped GIF with FBGs provides high-efficiency high-quality beam generation in a broad wavelength range within the Raman gain spectral profile.
3D microdevices that perform sample purification and multiplex qRT-PCR for early cancer detection with confirmation of specific RNAs
Authors: Kimura Yusuke , Ikeuchi Masashi , Inoue Yoshinori , Ikuta Koji
Published: November 2018

MicroRNA expression analysis is an important screening tool for the early detection of cancer. In this study, we developed two portable three-dimensional microdevices for multiple singleplex RNA expression analysis by microRNA purification and qRT-PCR as a prototype for point-of-care testing. These microdevices are composed of several types of modules termed ‘chemical IC chips’. We successfully reduced the heating area and fluorescence observation area, reduced the energy required for the reaction, and improved the portability of all systems in the devices. The purification microdevice could purify the microRNA from the sample using the FTA elute card system. The disposable reactor module mounted on both devices was easily fabricated by deforming a 100-μm-thick polypropylene film using an uncomplicated procedure. The qRT-PCR microdevice could perform reactions for samples of small volume. We purified microRNA from the HepG2 liver cancer cell line using the purification microdevice and confirmed the expression level of miR-224, which is a potential biomarker for liver cancer. Furthermore, we observed an increase in the fluorescence intensity when we performed qRT-PCR in the qRT-PCR microdevice. Therefore, the two developed microdevices show promise as a new portable tool for early cancer detection.