bluuebunny/crossref_metadata_2025 huggingface dataset:
Deinstitutionalization and other factors in the criminalization of persons with serious mental illness and how it is being addressed
Authors: Lamb H. Richard , Weinberger Linda E.
Published: October 2019

One of the major concerns in present-day psychiatry is the criminalization of persons with serious mental illness (SMI). This trend began in the late 1960s when deinstitutionalization was implemented throughout the United States. The intent was to release patients in state hospitals and place them into the community where they and other persons with SMI would be treated. Although community treatment was effective for many, there was a large minority who did not adapt successfully and who presented challenges in treatment. Consequently, some of these individuals’ mental condition and behavior brought them to the attention of law enforcement personnel, whereupon they would be subsequently arrested and incarcerated. The failure of the mental health system to provide a sufficient range of treatment interventions, including an adequate number of psychiatric inpatient beds, has contributed greatly to persons with SMI entering the criminal justice system. A discussion of the many issues and factors related to the criminalization of persons with SMI as well as how the mental health and criminal justice systems are developing strategies and programs to address them is presented.
A Comparative Study of Some Central Notions of ASPIC+ and DeLP
Authors: GARCÍA ALEJANDRO J. , PRAKKEN HENRY , SIMARI GUILLERMO R.
Published: October 2019

This paper formally compares some central notions from two well-known formalisms for rule-based argumentation, DeLP and ASPIC+. The comparisons especially focus on intuitive adequacy and inter-translatability, consistency, and closure properties. As for differences in the definitions of arguments and attack, it turns out that DeLP’s definitions are intuitively appealing but that they may not fully comply with Caminada and Amgoud’s rationality postulates of strict closure and indirect consistency. For some special cases, the DeLP definitions are shown to fare better than ASPIC+. Next, it is argued that there are reasons to consider a variant of DeLP with grounded semantics, since in some examples its current notion of warrant arguably has counterintuitive consequences and may lead to sets of warranted arguments that are not admissible. Finally, under some minimality and consistency assumptions on ASPIC+ arguments, a one-to-many correspondence between ASPIC+ arguments and DeLP arguments is identified in such a way that if the DeLP warranting procedure is changed to grounded semantics, then ’s DeLP notion of warrant and ASPIC+ ’s notion of justification are equivalent. This result is proven for three alternative definitions of attack.
War, trauma and culture: working with Tamil refugees and asylum seekers using culturally adapted CBT
Authors: Bahu Meera
Published: October 2019

This study explores the mental health difficulties associated with severe trauma as experienced by refugees and asylum seekers, and issues related to psychological treatments. An evaluation was conducted of a culturally adapted cognitive therapy group programme for Tamil refugees and asylum seekers in the Wandsworth IAPT (Improving Access to Psychological Therapies) service. Data were examined from 16 Tamil participants who accessed the service between 2014 and 2015 and subsequently engaged in the group programme between 2015 and 2016. The IAPT minimum data set (PHQ9, GAD-7, Phobia scale and WSAS) and IES-R (Impact of Events Scale Revised) were used as quantitative measures. Qualitative feedback about the programme was also obtained. A positive change in the wellbeing of participants was indicated by a reduction in the severity of negative symptoms for all metrics and qualitative feedback provided additional evidence that participants had benefited from the programme. The implications of these findings are discussed.

Key learning aims

(1)

To examine the difficulties experienced by refugees and asylum seekers and to provide a shared understanding of these themes for CBT practitioners.

(2)

To assist CBT practitioners to develop their confidence in using culturally adapted CBT treatment programmes for refugees and asylum seekers.

(3)

To inform service providers how culturally adapted CBT models can be used in developing specialist services for refugees and asylum seekers.
Life after Work: The Impact of Basic Income on Nonemployment Activities
Authors: Calnitsky David , Latner Jonathan P. , Forget Evelyn L.
Published: October 2019

Basic income experiments tend to show some decline in work hours, but less is known about how that nonwork time is spent. This article uses data from a randomized controlled trial of a guaranteed annual income to examine the activities of recipients who left the labor force for some amount of time. In particular, we analyze the reasons respondents gave for not working. We find that the intervention led to growth in care work activities and education, especially among women, moderate growth in self-employment, relatively strong growth in the portion of men and women simply reporting that they did not want to work, and the strongest growth in nonemployment connected to dissatisfaction with work/job conditions. Finally, the sole nonemployment category that declines as a result of the experiment is health-related reasons for not working.
Distinct Frontal Ablation Processes Drive Heterogeneous Submarine Terminus Morphology
Authors: Fried M. J. , Carroll D. , Catania G. A. , Sutherland D. A. , Stearns L. A. , Shroyer E. L. , Nash J. D.
Published: October 2019

Calving and submarine melt drive frontal ablation and sculpt the ice face of marine‐terminating glaciers. However, there are sparse observations of submarine termini, which limit estimates of spatially varying submarine melt. Here we present a detailed survey of a west Greenland glacier to reveal heterogeneity in submarine terminus morphology. We find that the majority of the terminus (~77%) is undercut, driven by calving in the upper water column and submarine melting at depth. The remaining ~23% of the terminus is overcut, driven by calving alone. We use observations of six subglacial discharge outlets, combined with a plume model, to estimate spatially varying discharge fluxes. While small discharge fluxes (<43 m3/s) feed numerous, deeply undercut outlets with subsurface plumes, ~70% of the net subglacial flux emerges at the terminus center, producing a vigorous, surface‐reaching plume. This primary outlet drives large, localized seasonal retreat that exceeds calving rates at secondary outlets.
Statistical Study of Auroral/Resonant‐Scattering 427.8‐nm Emission Observed at Subauroral Latitudes Over 14 Years
Authors: Shiokawa K. , Otsuka Y. , Connors M.
Published: October 2019

Auroral emission at 427.8‐nm from N2+ ions is caused by precipitation of energetic electrons, or by resonant scattering of sunlight by auroral N2+ ions. The latter often causes impressive purple aurora at high altitudes. However, statistical characteristics of auroral 427.8‐nm emission have not been well studied. In this paper we report occurrence characteristics of high 427.8‐nm emission intensities (more than 100 R) at subauroral latitudes, based on measurements by a filter‐tilting photometer over 14 years (2005–2018) at Athabasca, Canada (magnetic latitude: ~62°). We divided the data set into solar elevation angles (θs) more than and less than −24° (shadow height of sunlight: 600 km) to separate the 427.8‐nm emissions caused by resonant scattering of sunlight and those excited by auroral electrons, respectively. The occurrence rate of 427.8‐nm emissions of more than 100 R is 10.6% and 7.65% for θs more than and less than −24°, respectively, confirming that resonant scattering of sunlight by N2+ ions is a cause of the strong 427.8‐nm emissions of more than 100 R in the sunlit ionosphere. The occurrence rate is high in the postmidnight sector and increases with increasing geomagnetic activity, solar wind speed, and density. The occurrence rate is lowest in winter. A high occurrence rate was observed in 2015–2018, during the declining phase of the 11‐year solar activity. Superposed epoch analysis indicates that the 427.8‐nm emission exceeds 100 R when solar wind speed increases and solar wind density concurrently decreases, though the standard deviation of the data is rather large.
Direct Comparison Between Magnetospheric Plasma Waves and Polar Mesosphere Winter Echoes in Both Hemispheres
Authors: Tanaka Y.‐M. , Nishiyama T. , Kadokura A. , Ozaki M. , Miyoshi Y. , Shiokawa K. , Oyama S.‐I. , Kataoka R. , Tsutsumi M. , Nishimura K. , Sato K. , Kasahara Y. , Kumamoto A. , Tsuchiya F. , Fukizawa M. , Hikishima M. , Matsuda S. , Matsuoka A. , Shinohara I. , Nosé M. , Nagatsuma T. , Shinohara M. , Fujimoto A. , Teramoto M. , Nomura R. , Yukimatu A. Sessai , Hosokawa K. , Shoji M. , Latteck R.
Published: October 2019

We present the first and direct comparison between magnetospheric plasma waves and polar mesosphere winter echoes (PMWE) simultaneously observed by the conjugate observation with Arase satellite and high‐power atmospheric radars in both hemispheres, namely, the Program of the Antarctic Syowa Mesosphere, Stratosphere, and Troposphere/Incoherent Scatter Radar at Syowa Station (SYO; −69.00°S, 39.58°E), Antarctica, and the Middle Atmosphere Alomar Radar System at Andøya (AND; 69.30°N, 16.04°E), Norway. The PMWE were observed during 03–07 UT on 21 March 2017, just after the arrival of corotating interaction region in front of high‐speed solar wind stream. An isolated substorm occurred at 04 UT during this interval. Electromagnetic ion cyclotron (EMIC) waves and whistler mode chorus waves were simultaneously observed near the magnetic equator and showed similar temporal variations to that of the PMWE. These results indicate that chorus waves as well as EMIC waves are drivers of precipitation of energetic electrons, including relativistic electrons, which make PMWE detectable at 55‐ to 80‐km altitude. Cosmic noise absorption measured with a 38.2‐MHz imaging riometer and low‐altitude echoes at 55–70 km measured with an medium‐frequency radar at SYO also support the relativistic electron precipitation. We suggest a possible scenario in which the various phenomena observed in near‐Earth space, such as magnetospheric plasma waves (EMIC waves and chorus waves), pulsating auroras, cosmic noise absorption, and PMWE, can be explained by the interaction between the high‐speed solar wind containing corotating interaction regions and the magnetosphere.
Energetic Electron Patterns in the New SLS5 Longitude System
Authors: Carbary J. F. , Mitchell D. G. , Ye Shengyi
Published: October 2019

Energetic electron (110–300 keV) fluxes collected during the entire 13‐year Cassini mission are organized in the new Saturn longitude system (SLS5). This system is based on Saturn radio emissions, varies slowly in time and has a north and a south branch. When the fluxes are organized in SLS5 longitudes and magnetodisk coordinates, they display an m=1 wave pattern that is quasi‐linear in longitude‐range maps. These spiral patterns are easily recognized in energetic electrons and have positive slopes a few degrees of longitude per RS (1 RS =60,268 km), similar to that observed in both particles and magnetic fields earlier in the mission. The patterns are most prominent at elevations +2 RS (SLS5 north) or −2 RS (SLS5 south) relative to the magnetodisk center. The results indicate the persistence of this pattern for essentially half a Saturnian year, suggesting that this pattern is a quasi‐permanent feature of the magnetosphere, much the same as its plasma sheet or magnetopause.
A Survey of Plasma Waves Appearing Near Dayside Magnetopause Electron Diffusion Region Events
Authors: Wilder F. D. , Ergun R. E. , Hoilijoki S. , Webster J. , Argall M. R. , Ahmadi N. , Eriksson S. , Burch J. L. , Torbert R. B. , Le Contel O. , Strangeway R. J. , Giles B. L.
Published: October 2019

One of the major unresolved questions regarding the magnetic reconnection phenomenon is how plasma waves impact the process. In 2015, the National Aeronautics and Space Administration launched the four‐satellite Magnetospheric Multiscale Mission to study magnetic reconnection, especially on the electron scale. Since launch, it has identified several wave modes below the electron plasma frequency that occur near the dayside reconnection X‐line. These include large‐amplitude parallel electrostatic waves, whistler mode waves, lower hybrid waves, and turbulence associated with a corrugated current structure. We survey 23 electron diffusion region events observed by Magnetospheric Multiscale Mission at the dayside magnetopause to help understand how these wave modes impact the reconnection process. Common wave modes are identified, as well as their typical location within the reconnection layer (e.g., electron diffusion region, ion diffusion region, separatrix, and inflow and outflow jets). We find that, with a few exceptions, electromagnetic whistlers are most commonly confined to the separatrices of the exhaust boundary. Lower hybrid waves are found on the magnetosphere side of the current layer and do not make it to the X‐line. The wave modes that typically occur closest to the dissipation region are the corrugated current structures and large‐amplitude parallel electrostatic waves.
The High‐Latitude Trough in the Southern Hemisphere Observed by Swarm‐A Satellite
Authors: Yang Na , Yu Tao , Le Huijun , Liu Libo , Sun Yang‐Yi , Xia Chunliang , Zuo Xiaomin , Yan Xiangxiang , Wang Jin
Published: October 2019

Based on the electron density, field‐aligned currents (FACs) and ion drift velocity data from the Swarm‐A satellite during 2013–2018, we investigate the features of the high‐latitude trough in the Southern Hemisphere. The results show that the high‐latitude trough in the Southern Hemisphere is a persistent postmidnight feature in winter. It is observed mainly in the eastern longitudes under low solar activity conditions and in a smaller longitudinal range under high solar activity conditions. The high‐latitude trough moves to higher latitudes at later local times, which is more obvious under low solar activity conditions. We also find that the features of FACs and ion drift velocity distribution in the high‐latitude trough region depend on longitude. In the longitude sector of 0°–70°E, the high‐latitude trough positions are always located at the poleward boundary of the downward FAC region, and collocated with the convection reversal boundary in the postmidnight region. In the longitude sector of 80°–130°E, the high‐latitude trough positions are located at the poleward boundary of the downward FAC region in the midnight region and at the strong westward or antisunward ion flow region in the postmidnight region. It is suggested that the high‐latitude trough formation and evolution is possibly associated with downward FACs, flow stagnation in the convection reversal boundary, and westward or antisunward ion flow.
The Role of Clouds and Surface Heat Fluxes in the Maintenance of the 2013–2016 Northeast Pacific Marine Heatwave
Authors: Schmeisser Lauren , Bond Nicholas A. , Siedlecki Samantha A. , Ackerman Thomas P.
Published: October 2019

Starting in late 2013, the Northeast (NE) Pacific Ocean experienced anomalously warm sea surface temperatures (SSTs) that persisted for over 2 years. This marine heatwave, known as “the Blob,” produced many devastating ecological impacts with socioeconomic implications for coastal communities. The warm waters observed during the NE Pacific 2013/2016 marine heatwave altered the surface energy balance and disrupted ocean–atmosphere interactions in the region. In principle, ocean–atmosphere interactions following the formation of the marine heatwave could have perpetuated warm SSTs through a positive SST‐cloud feedback. The actual situation was more complicated. While reanalysis data show a decrease in boundary layer cloud fraction and an increase in downward shortwave radiative flux at the surface coincident with warm SSTs, this was accompanied by an increase in longwave radiative fluxes at the surface, as well as an increase in sensible and latent heat fluxes out of the ocean mixed layer. The result is a small negative net heat flux anomaly (compared to the anomalies of the individual terms contributing to the net heat flux). This provides new information about the midlatitude ocean–atmosphere system while it was in a perturbed state. More specifically, a mixed layer heat budget reveals that anomalies in both the atmospheric and oceanic processes offset each other such that the anomalously warm SSTs persisted for multiple years. The results show how the atmosphere–ocean system in the NE Pacific is able to maintain itself in an anomalous state for an extended period of time.
Role of the Tenax® Adsorbent in the Interpretation of the EGA and GC‐MS Analyses Performed With the Sample Analysis at Mars in Gale Crater
Authors: Buch A. , Belmahdi I. , Szopa C. , Freissinet C. , Glavin D.P. , Millan M. , Summons R. , Coscia D. , Teinturier S. , Bonnet J.‐Y. , He Y. , Cabane M. , Navarro‐Gonzalez R. , Malespin C.A. , Stern J. , Eigenbrode J. , Mahaffy P.R. , Johnson S.S.
Published: October 2019

The Sample Analysis at Mars (SAM) experiment on the National Aeronautics and Space Administration Curiosity rover seeks evidence of organic compounds on the surface of Mars. Since the beginning of the mission, various organic molecules have been detected and identified. While several have been demonstrated to be indigenous to the Martian soil and rocks analyzed, others appear to have been produced from sources internal to the experiment. The objective of this study is to build an exhaustive molecular database to support the interpretation of SAM results by identifying all the chemical species produced from Tenax® adsorbents, by determining (1) the thermal degradation by‐products of Tenax®, (2) the effect of Tenax® conditioning on the formation of Tenax® by‐products, (3) the impact of MTBSTFA or a mixture of MTBSTFA and DMF on Tenax® decomposition, and (4) the reaction between Tenax® and calcium perchlorate. Our results indicate that the by‐products of the SAM trap are due to the impact of trap heating, the impact of the derivatization reagent (MTBSTFA) and the presence of perchlorate in Martian soil. Some of these by‐products are observed in the SAM gas chromatograph mass spectrometer data from Mars.
Ensemble Streamflow Forecasting Using an Energy Balance Snowmelt Model Coupled to a Distributed Hydrologic Model with Assimilation of Snow and Streamflow Observations
Authors: Gichamo Tseganeh Z. , Tarboton David G.
Published: October 2019

In many river basins across the world, snowmelt is an important source of streamflow. However, detailed snowmelt modeling is hampered by limited input data and uncertainty arising from inadequate model structure and parametrization. Data assimilation that updates model states based on observations, reduces uncertainty and improves streamflow forecasts. In this study, we evaluated the Utah Energy Balance (UEB) snowmelt model coupled to the Sacramento Soil Moisture Accounting (SAC‐SMA) and rutpix7 stream routing models, integrated within the Research Distributed Hydrologic Model (RDHM) framework for streamflow forecasting. We implemented an ensemble Kalman filter for assimilation of snow water equivalent (SWE) observations in UEB and a particle filter for assimilation of streamflow to update the SAC‐SMA and rutpix7 states. Using leave one out validation, it was shown that the modeled SWE at a location where observations were excluded from data assimilation was improved through assimilation of data from other stations, suggesting that assimilation of sparse observations of SWE has the potential to improve the distributed modeling of SWE over watershed grid cells. In addition, the spatially distributed snow data assimilation improved streamflow forecasts and the forecast volume error was reduced. On the other hand, the assimilation of streamflow observations did not provide additional forecast improvement over that achieved by the SWE assimilation for seasonal forecast volume likely due to there being little information content in streamflow at the forecast date prior to its rising during the melt period and this application of particle filter being better suited for shorter timescales.
Assessing the Feasibility of Satellite‐Based Thresholds for Hydrologically Driven Landsliding
Authors: Thomas Matthew A. , Collins Brian D. , Mirus Benjamin B.
Published: October 2019

Elevated soil moisture and heavy precipitation contribute to landslides worldwide. These environmental variables are now being resolved with satellites at spatiotemporal scales that could offer new perspectives on the development of landslide warning systems. However, the application of these data to hydrometeorological thresholds (which account for antecedent soil moisture and rainfall) first needs to be evaluated with respect to proven, direct measurement‐based thresholds that use rain gages and in situ soil moisture sensors. Here we compare ground‐based hydrologic data to overlapping satellite‐based data before, during, and after a recent season of widespread shallow landsliding in the San Francisco Bay Area (California, USA). We then explore how the remotely sensed information could be used to empirically define hypothetical thresholds for shallow landsliding. We find that the ground‐based thresholds developed with a single monitoring station show superior performance because the in situ soil saturation data better reflect the gravity‐dominated subsurface flow conditions that are characteristic of hillslopes during the rainy season. Although the satellite‐based thresholds can identify most of the landslide days, they include a greater number of false alarms due to overestimates of soil moisture between major storm events. To avoid the type of false alarms that are characteristic of our satellite‐based thresholds, further postprocessing of the near‐surface hydrologic response data should be integrated into satellite‐based model outputs to better reflect gravity‐dominated drainage. Our results encourage further deployment of ground stations in landslide‐prone terrain and cautious exploration of satellite‐based hydrometeorological thresholds where in situ networks are nonexistent.
Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells
Authors: Wang Baiyao , Zheng Jieling , Li Rong , Tian Yunhong , Lin Jie , Liang Yingying , Sun Quanquan , Xu Anan , Zheng Ronghui , Liu Mengzhong , Ji Aimin , Bu Junguo , Yuan Yawei
Published: October 2019

Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.
Correction: APR-246 reactivates mutant p53 by targeting cysteines 124 and 277
Authors: Zhang Qiang , Bykov Vladimir J. N. , Wiman Klas G. , Zawacka-Pankau Joanna
Published: October 2019

Since publication of this article, the authors have noticed that there was an error in Fig. 1d, third panel from left, “R273H + 200 μM MQ-H” should be “R273H + 200 μM MQ”. Our corrections do not affect the original conclusions of this paper.
Heat shock protein 60 regulates yolk sac erythropoiesis in mice
Authors: Duan Yaoyun , Wang Hong , Mitchell-silbaugh Kalia , Cai Shangbin , Fan Feifei , Li Yali , Tang Huayuan , Wang Gang , Fang Xi , Liu Jie , Jia Nan , Jing Ran , Ouyang Kunfu
Published: October 2019

The yolk sac is the first site of blood-cell production during embryonic development in both murine and human. Heat shock proteins (HSPs), including HSP70 and HSP27, have been shown to play regulatory roles during erythropoiesis. However, it remains unknown whether HSP60, a molecular chaperone that resides mainly in mitochondria, could also regulate early erythropoiesis. In this study, we used Tie2-Cre to deactivate the Hspd1 gene in both hematopoietic and vascular endothelial cells, and found that Tie2-Cre+Hspd1f/f (HSP60CKO) mice were embryonic lethal between the embryonic day 10.5 (E10.5) and E11.5, exhibiting growth retardation, anemia, and vascular defects. Of these, anemia was observed first, independently of vascular and growth phenotypes. Reduced numbers of erythrocytes, as well as an increase in cell apoptosis, were found in the HSP60CKO yolk sac as early as E9.0, indicating that deletion of HSP60 led to abnormality in yolk sac erythropoiesis. Deletion of HSP60 was also able to reduce mitochondrial membrane potential and the expression of the voltage-dependent anion channel (VDAC) in yolk sac erythrocytes. Furthermore, cyclosporine A (CsA), which is a well-recognized modulator in regulating the opening of the mitochondrial permeability transition pore (mPTP) by interacting with Cyclophilin D (CypD), could significantly decrease cell apoptosis and partially restore VDAC expression in mutant yolk sac erythrocytes. Taken together, we demonstrated an essential role of HSP60 in regulating yolk sac cell survival partially via a mPTP-dependent mechanism.
Progress in laser cooling semiconductor nanocrystals and nanostructures
Authors: Zhang Shubin , Zhukovskyi Maksym , Jankó Boldizsár , Kuno Masaru
Published: October 2019

Over the past two decades, there have been sizable efforts to realize condensed phase optical cooling. To date, however, there have been no verifiable demonstrations of semiconductor-based laser cooling. Recently, advances in the synthesis of semiconductor nanostructures have led to the availability of high-quality semiconductor nanocrystals, which possess superior optical properties relative to their bulk counterparts. In this review, we describe how these nanostructures can be used to demonstrate condensed phase laser cooling. We begin with a description of charge carrier dynamics in semiconductor nanocrystals and nanostructures under both above gap and below-gap excitation. Two critical parameters for realizing laser cooling are identified: emission quantum yield and upconversion efficiency. We report the literature values of these two parameters for different nanocrystal/nanostructure systems as well as the measurement approaches used to estimate them. We identify CsPbBr3 nanocrystals as a potential system by which to demonstrate verifiable laser cooling given their ease of synthesis, near-unity emission quantum yields and sizable upconversion efficiencies. Feasibility is further demonstrated through numerical simulations of CsPbBr3 nanocrystals embedded in an aerogel matrix. Our survey generally reveals that optimized semiconductor nanocrystals and nanostructures are poised to demonstrate condensed phase laser cooling in the near future.
In situ epitaxial engineering of graphene and h-BN lateral heterostructure with a tunable morphology comprising h-BN domains
Authors: Geng Dechao , Dong Jichen , Kee Ang Lay , Ding Feng , Yang Hui Ying
Published: October 2019

Graphene and hexagonal boron nitride (h-BN), as typical two-dimensional (2D) materials, have long attracted substantial attention due to their unique properties and promise in a wide range of applications. Although they have a rather large difference in their intrinsic bandgaps, they share a very similar atomic lattice; thus, there is great potential in constructing heterostructures by lateral stitching. Herein, we present the in situ growth of graphene and h-BN lateral heterostructures with tunable morphologies that range from a regular hexagon to highly symmetrical star-like structure on the surface of liquid Cu. The chemical vapor deposition (CVD) method is used, where the growth of the h-BN is demonstrated to be highly templated by the graphene. Furthermore, large-area production of lateral G-h-BN heterostructures at the centimeter scale with uniform orientation is realized by precisely tuning the CVD conditions. We found that the growth of h-BN is determined by the initial graphene and symmetrical features are produced that demonstrate heteroepitaxy. Simulations based on the phase field and density functional theories are carried out to elucidate the growth processes of G-h-BN flakes with various morphologies, and they have a striking consistency with experimental observations. The growth of a lateral G-h-BN heterostructure and an understanding of the growth mechanism can accelerate the construction of various heterostructures based on 2D materials.
Interplay between structural hierarchy and exciton diffusion in artificial light harvesting
Authors: Kriete Björn , Lüttig Julian , Kunsel Tenzin , Malý Pavel , Jansen Thomas L. C. , Knoester Jasper , Brixner Tobias , Pshenichnikov Maxim S.
Published: October 2019

Unraveling the nature of energy transport in multi-chromophoric photosynthetic complexes is essential to extract valuable design blueprints for light-harvesting applications. Long-range exciton transport in such systems is facilitated by a combination of delocalized excitation wavefunctions (excitons) and exciton diffusion. The unambiguous identification of the exciton transport is intrinsically challenging due to the system’s sheer complexity. Here we address this challenge by employing a spectroscopic lab-on-a-chip approach: ultrafast coherent two-dimensional spectroscopy and microfluidics working in tandem with theoretical modeling. We show that at low excitation fluences, the outer layer acts as an exciton antenna supplying excitons to the inner tube, while under high excitation fluences the former converts its functionality into an exciton annihilator which depletes the exciton population prior to any exciton transfer. Our findings shed light on the excitonic trajectories across different sub-units of a multi-layered artificial light-harvesting complex and underpin their great potential for directional excitation energy transport.
Engineering transferrable microvascular meshes for subcutaneous islet transplantation
Authors: Song Wei , Chiu Alan , Wang Long-Hai , Schwartz Robert E. , Li Bin , Bouklas Nikolaos , Bowers Daniel T. , An Duo , Cheong Soon Hon , Flanders James A. , Pardo Yehudah , Liu Qingsheng , Wang Xi , Lee Vivian K. , Dai Guohao , Ma Minglin
Published: October 2019

The success of engineered cell or tissue implants is dependent on vascular regeneration to meet adequate metabolic requirements. However, development of a broadly applicable strategy for stable and functional vascularization has remained challenging. We report here highly organized and resilient microvascular meshes fabricated through a controllable anchored self-assembly method. The microvascular meshes are scalable to centimeters, almost free of defects and transferrable to diverse substrates, ready for transplantation. They promote formation of functional blood vessels, with a density as high as ~220 vessels mm-2, in the poorly vascularized subcutaneous space of SCID-Beige mice. We further demonstrate the feasibility of fabricating microvascular meshes from human induced pluripotent stem cell-derived endothelial cells, opening a way to engineer patient-specific microvasculature. As a proof-of-concept for type 1 diabetes treatment, we combine microvascular meshes and subcutaneously transplanted rat islets and achieve correction of chemically induced diabetes in SCID-Beige mice for 3 months.
The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site
Authors: Horton John R. , Woodcock Clayton B. , Opot Sifa B. , Reich Norbert O. , Zhang Xing , Cheng Xiaodong
Published: October 2019

The Caulobacter crescentus cell cycle-regulated DNA methyltransferase (CcrM) methylates the adenine of hemimethylated GANTC after replication. Here we present the structure of CcrM in complex with double-stranded DNA containing the recognition sequence. CcrM contains an N-terminal methyltransferase domain and a C-terminal nonspecific DNA-binding domain. CcrM is a dimer, with each monomer contacting primarily one DNA strand: the methyltransferase domain of one molecule binds the target strand, recognizes the target sequence, and catalyzes methyl transfer, while the C-terminal domain of the second molecule binds the non-target strand. The DNA contacts at the 5-base pair recognition site results in dramatic DNA distortions including bending, unwinding and base flipping. The two DNA strands are pulled apart, creating a bubble comprising four recognized base pairs. The five bases of the target strand are recognized meticulously by stacking contacts, van der Waals interactions and specific Watson–Crick polar hydrogen bonds to ensure high enzymatic specificity.
A flexible high-performance simulator for verifying and benchmarking quantum circuits implemented on real hardware
Authors: Villalonga Benjamin , Boixo Sergio , Nelson Bron , Henze Christopher , Rieffel Eleanor , Biswas Rupak , Mandrà Salvatore
Published: October 2019

Here we present qFlex, a flexible tensor network-based quantum circuit simulator. qFlex can compute both the exact amplitudes, essential for the verification of the quantum hardware, as well as low-fidelity amplitudes, to mimic sampling from Noisy Intermediate-Scale Quantum (NISQ) devices. In this work, we focus on random quantum circuits (RQCs) in the range of sizes expected for supremacy experiments. Fidelity f simulations are performed at a cost that is 1/f lower than perfect fidelity ones. We also present a technique to eliminate the overhead introduced by rejection sampling in most tensor network approaches. We benchmark the simulation of square lattices and Google’s Bristlecone QPU. Our analysis is supported by extensive simulations on NASA HPC clusters Pleiades and Electra. For our most computationally demanding simulation, the two clusters combined reached a peak of 20 Peta Floating Point Operations per Second (PFLOPS) (single precision), i.e., 64% of their maximum achievable performance, which represents the largest numerical computation in terms of sustained FLOPs and the number of nodes utilized ever run on NASA HPC clusters. Finally, we introduce a novel multithreaded, cache-efficient tensor index permutation algorithm of general application.
Utility of a Smartphone Based System (cvrPhone) to Predict Short-term Arrhythmia Susceptibility
Authors: Sohn Kwanghyun , Dalvin Steven P. , Merchant Faisal M. , Kulkarni Kanchan , Sana Furrukh , Abohashem Shady , Singh Jagmeet P. , Heist E. Kevin , Owen Chris , Isselbacher Eric M. , Armoundas Antonis A.
Published: October 2019

Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. We developed a 12-lead, blue-tooth/Smart-Phone (Android) based electrocardiogram (ECG) acquisition and monitoring system (cvrPhone), and an application to estimate RA, in real-time. In in-vivo swine studies (N = 17), 12-lead ECG signals were recorded at baseline and following coronary artery occlusion. RA was estimated using the Fast Fourier Transform (FFT) method using a custom developed algorithm in JAVA. Underlying ischemia was detected using a custom developed ischemic index. RA from each lead showed a significant (p < 0.05) increase within 1 min of occlusion compared to baseline (n = 29). Following myocardial infarction, spontaneous ventricular tachycardia episodes (n = 4) were preceded by significant (p < 0.05) increase of RA prior to the onset of the tachy-arrhythmias. Similarly, the ischemic index exhibited a significant increase following myocardial infarction (p < 0.05) and preceding a tachy-arrhythmic event. In conclusion, RA can be effectively estimated using surface lead electrocardiograms by analyzing beat-to-beat variability in ECG morphology using a smartphone based platform. cvrPhone can be used to detect myocardial ischemia and arrhythmia susceptibility using a user-friendly, clinically acceptable, mobile platform.
Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption
Authors: Denzinger Maximilian , Staendker Ludger , Ehlers Keno , Schneider Julian M. , Schulz Tanja , Hein Tabea , Wiese Sebastian , Roecker Annika , Gross Ruediger , Münch Jan , Bracht Hendrik , Barth Eberhard , Weiss Manfred , Georgieff Michael , Schneider E. Marion
Published: October 2019

Hemoadsorption devices are used to treat septic shock by adsorbing inflammatory cytokines and as yet incompletely defined danger and pathogen associated molecular patterns. In an ideal case, hemoadsorption results in immediate recovery of microvascular endothelial cells’ (mEC) function and rapid recovery from catecholamine-dependency and septic shock. We here tested a single device, which consists of polystyrene-divinylbenzene core particles of 450 μm diameter with a high affinity for hydrophobic compounds. The current study aimed at the proof of concept that endothelial-specific damage mediators are adsorbed and can be recovered from hemoadsorption devices. Because of excellent clinical experience, we tested protein fractions released from a hemoadsorber in a novel endothelial bioassay. Video-based, long-term imaging of mEC proliferation and cell death were evaluated and combined with apoptosis and ATP measurements. Out of a total of 39 fractions recovered from column fractionation, we identified 3 fractions that caused i) inhibition of mEC proliferation, ii) increased cell death and iii) induction of apoptosis in mEC. When adding these 3 fractions to mEC, their ATP contents were reduced. These fractions contained proteins of approximately 15 kDa, and high amounts of nucleic acid, which was at least in part oxidized. The efficacy for endothelial cell damage prevention by hemoadsorption can be addressed by a novel endothelial bioassay and long-term video observation procedures. Protein fractionation of the hemoadsorption devices used is feasible to study and define endothelial damage ligands on a molecular level. The results suggest a significant effect by circulating nucleic acids – bound to an as yet undefined protein, which may constitute a major danger-associated molecular pattern (DAMP) in the exacerbation of inflammation when patients experience septic shock. Hemoadsorption devices may thus limit endothelial damage, through the binding of nucleic acid-bearing aggregates and thus contribute to improved endothelial barrier function.
Quantifying muscle glycosaminoglycan levels in patients with post-stroke muscle stiffness using T1ρ MRI
Authors: Menon Rajiv G. , Raghavan Preeti , Regatte Ravinder R.
Published: October 2019

The purpose of this study was to provide imaging evidence of increased glycosaminoglycan (GAG) content in patients with post-stroke muscle stiffness; and to determine the effect of hyaluronidase treatment on intramuscular GAG content. In this prospective study, we used 3D-T1ρ (T1rho) magnetic resonance (MR) mapping of the upper arm muscles to quantify GAG content in patients with post-stroke muscle stiffness before and after hyaluronidase injection treatment. For this study, healthy controls (n = 5), and patients with post-stroke muscle stiffness (n = 5) were recruited (March 2017–April 2018). T1ρ MR imaging and Dixon water-fat MR imaging of the affected upper arms were performed before and after off-label treatment with hyaluronidase injections. T1ρ mapping was done using a three-parameter non-linear mono-exponential fit. Wilcoxon Mann-Whitney test was used to compare patients’ vs controls and pre- vs post-treatment conditions. The T1ρ values in the biceps were significantly higher in patients before treatment (34.04 ± 4.39 ms) compared with controls (26.70 ± 0.54 ms; P = 0.006). Significant improvement was seen in the biceps of patients before (35.48 ± 3.38 ms) and after treatment (29.45 ± 1.23 ms; P = 0.077). Dixon water-fat distribution was not significantly different in the patients compared to the controls (biceps P = 0.063; triceps P = 0.190). These results suggest that T1ρ mapping can be used to quantify GAG content in the muscles of patients with post-stroke muscle stiffness, and that muscle hyaluronan content is increased in stiff muscles compared with controls, providing imaging corroboration for the hyaluronan hypothesis of muscle stiffness.
A Complex Interplay of Anionic Phospholipid Binding Regulates 3′-Phosphoinositide-Dependent-Kinase-1 Homodimer Activation
Authors: Heras-Martínez Gloria de las , Calleja Véronique , Bailly Remy , Dessolin Jean , Larijani Banafshé , Requejo-Isidro Jose
Published: October 2019

3′-Phosphoinositide-dependent-Kinase-1 (PDK1) is a master regulator whereby its PI3-kinase-dependent dysregulation in human pathologies is well documented. Understanding the direct role for PtdIns(3,4,5)P3 and other anionic phospholipids in the regulation of PDK1 conformational dynamics and its downstream activation remains incomplete. Using advanced quantitative-time-resolved imaging (Fluorescence Lifetime Imaging and Fluorescence Correlation Spectroscopy) and molecular modelling, we show an interplay of antagonistic binding effects of PtdIns(3,4,5)P3 and other anionic phospholipids, regulating activated PDK1 homodimers. We demonstrate that phosphatidylserine maintains PDK1 in an inactive conformation. The dysregulation of the PI3K pathway affects the spatio-temporal and conformational dynamics of PDK1 and the activation of its downstream substrates. We have established a new anionic-phospholipid-dependent model for PDK1 regulation, depicting the conformational dynamics of multiple homodimer states. We show that the dysregulation of the PI3K pathway perturbs equilibrium between the PDK1 homodimer conformations. Our findings provide a role for the PtdSer binding site and its previously unrewarding role in PDK1 downregulation, suggesting a possible therapeutic strategy where the constitutively active dimer conformer of PDK1 may be rendered inactive by small molecules that drive it to its PtdSer-bound conformer.
Reporter lines based on the gexp02 promoter enable early quantification of sexual conversion rates in the malaria parasite Plasmodium falciparum
Authors: Portugaliza Harvie P. , Llorà-Batlle Oriol , Rosanas-Urgell Anna , Cortés Alfred
Published: October 2019

Transmission of malaria parasites from humans to mosquito vectors requires that some asexual parasites differentiate into sexual forms termed gametocytes. The balance between proliferation in the same host and conversion into transmission forms can be altered by the conditions of the environment. The ability to accurately measure the rate of sexual conversion under different conditions is essential for research addressing the mechanisms underlying sexual conversion, and to assess the impact of environmental factors. Here we describe new Plasmodium falciparum transgenic lines with genome-integrated constructs in which a fluorescent reporter is expressed under the control of the promoter of the gexp02 gene. Using these parasite lines, we developed a sexual conversion assay that shortens considerably the time needed for an accurate determination of sexual conversion rates, and dispenses the need to add chemicals to inhibit parasite replication. Furthermore, we demonstrate that gexp02 is expressed specifically in sexual parasites, with expression starting as early as the sexual ring stage, which makes it a candidate marker for circulating sexual rings in epidemiological studies.
Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice
Authors: Fulop Daniel Balazs , Humli Viktoria , Szepesy Judit , Ott Virag , Reglodi Dora , Gaszner Balazs , Nemeth Adrienn , Szirmai Agnes , Tamas Laszlo , Hashimoto Hitoshi , Zelles Tibor , Tamas Andrea
Published: October 2019

Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.
Inhibition of dicer activity in lepidopteran and dipteran cells by baculovirus-mediated expression of Flock House virus B2
Authors: Hodgson Jeffrey J. , Wenger Luke W. , Clem Rollie J. , Passarelli A. Lorena
Published: October 2019

Prior studies have suggested that insect DNA viruses are negatively affected by dicer-2-mediated RNA interference (RNAi). To examine this further, we utilized an in vitro assay to measure dicer activity in lepidopteran and dipteran cells, combined with baculoviruses expressing the RNAi suppressor B2 from Flock House virus or Aedes aegypti dicer-2 (Aedicer-2) using a constitutive heat shock promoter. Addition of cell lysates containing baculovirus-expressed B2 to lysates from dipteran (S2, Aag2) or lepidopteran (Sf9) cells inhibited endogenous dicer activity in a dose-dependent manner, while expression of Aedicer-2 restored siRNA production in Ae. albopictus C6/36 cells, which are dicer-2 defective. However, B2 expression from the constitutive heat shock promoter had no impact on baculovirus replication or virulence in cell lines or larvae that were either highly permissive (Trichoplusia ni) or less susceptible (Spodoptera frugiperda) to infection. We determined that this constitutive level of B2 expression had little to no ability to suppress dicer activity in cell lysates, but higher expression of B2, following heat shock treatment, inhibited dicer activity in all cells tested. Thus, we cannot rule out the possibility that optimized expression of B2 or other RNAi suppressors may increase baculovirus replication and expression of heterologous proteins by baculoviruses.