bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Tide and Wind on the Propagation of Fronts in a Shallow River Plume
Authors: Rijnsburger Sabine , Flores Raúl P. , Pietrzak Julie D. , Horner‐Devine Alexander R. , Souza Alejandro J.
Published: June 2018

In this study we used field data and radar images to investigate the influence of winds and tides on the propagation of tidal plume fronts. The measurements were collected in a shallow shelf region off the Dutch coast, 10 km north of the Rhine River mouth, and they clearly show the passage of distinct freshwater lenses and associated fronts at the surface that propagate all the way to the coastline. These fronts are observed as a sudden drop in near‐surface salinity, accompanied by high cross‐shore shear with onshore velocities at the surface. We determined the arrival time to our measurement site, frontal propagation speed, and structure of the fronts by combining the in situ data and radar images. Frontal Froude numbers show a wide range of values, with an average of 0.44. Our results show that fronts during spring tides are thinner, more mixed, and move faster relative to the ground during calm spring tides when compared to calm neap tides. Downwelling winds during spring tides result in thicker and faster fronts; however, the intrinsic frontal propagation speed indicates that the wind and tide control the frontal propagation mainly due to advection rather than by changing the frontal structure. Strong return currents in the near‐bed layer resulting from fast and thick fronts increase near‐bed turbulence and bed stresses. These high stresses suggest that the passage of fronts in shallow coastal areas can initiate sediment resuspension and contribute to transport processes.
Ensemble Prediction of a Halo Coronal Mass Ejection Using Heliospheric Imagers
Authors: Amerstorfer T. , Möstl C. , Hess P. , Temmer M. , Mays M. L. , Reiss M. A. , Lowrance P. , Bourdin P.‐A.
Published: June 2018

The Solar TErrestrial RElations Observatory (STEREO) and its heliospheric imagers (HIs) have provided us the possibility to enhance our understanding of the interplanetary propagation of coronal mass ejections (CMEs). HI‐based methods are able to forecast arrival times and speeds at any target and use the advantage of tracing a CME's path of propagation up to 1 AU and beyond. In our study, we use the ELEvoHI model for CME arrival prediction together with an ensemble approach to derive uncertainties in the modeled arrival time and impact speed. The CME from 3 November 2010 is analyzed by performing 339 model runs that are compared to in situ measurements from lined‐up spacecraft MErcury Surface, Space ENvironment, GEochemistry, and Ranging and STEREO‐B. Remote data from STEREO‐B showed the CME as halo event, which is comparable to an HI observer situated at L1 and observing an Earth‐directed CME. A promising and easy approach is found by using the frequency distributions of four ELEvoHI output parameters, drag parameter, background solar wind speed, initial distance, and speed. In this case study, the most frequent values of these outputs lead to the predictions with the smallest errors. Restricting the ensemble to those runs, we are able to reduce the mean absolute arrival time error from 3.5 ± 2.6 to 1.6 ± 1.1 hr at 1 AU. Our study suggests that L1 may provide a sufficient vantage point for an Earth‐directed CME, when observed by HI, and that ensemble modeling could be a feasible approach to use ELEvoHI operationally.
Quantifying Uncertainty About Earth’s Resources
Authors: Caers Jef
Published: June 2018

A new book explores how uncertainty quantification can enable optimal decisions in the exploration, appraisal, and development of subsurface resources.
Strong Mixing and Recirculation in the Northwestern Argentine Basin
Authors: Valla Daniel , Piola Alberto R. , Meinen Christopher S. , Campos Edmo
Published: June 2018

The Atlantic component of the Meridional Overturning Circulation (AMOC) is a key contributor to the global meridional transport of volume, salt, and heat, and thus plays a central role in global climate. As part of ongoing efforts to monitor the intensity and variability of the AMOC in the South Atlantic, hydrographic sections have been regularly occupied since 2009 near the western boundary along a zonal line at 34.5°S. Here this high‐quality, high‐resolution data set is analyzed to establish the average hydrographic conditions of the northwestern Argentine Basin and the water mass spatial and temporal variability. The water mass analysis also reveals the pathways of the flow in this region, which are further corroborated by full‐depth direct velocity measurements. The repeated hydrographic sections capture an extremely rich vertical structure, characterized by seven distinct water mass layers of northern and southern origin, each with unique property signatures. Almost all of these layers exhibit a sharp zonally banded structure, which is indicative of recirculation cells offshore from the western boundary. The circulation at intermediate levels includes a previously undetected recirculation cell confined very close to the western boundary and superimposed on the classical intermediate water pathway beneath the South Atlantic subtropical gyre. The deep level flow is characterized by the Deep Western Boundary Current (DWBC) and a northward recirculation ~500 km east from the slope.
Infragravity Wave Radiation Across the Shelf Break
Authors: Smit P. B. , Janssen T. T. , Herbers T. H. C. , Taira T. , Romanowicz B. A.
Published: June 2018

Observations collected as part of the Cascadia Amphibious Array (Oregon‐Washington coast) show that ocean surface infragravity (IG) waves (periods from 30 to 250 s) in the Pacific Ocean originate from the coastal zone. With the deepest observations at 1909 m, we identify tidal modulation and a dramatic reduction in energy as IG waves cross the shelf break. Observations are consistent with radiation from an isotropic, nearshore source, and provide quantitative verification linking oceanic IG fluctuations with nearshore motions. Our analysis demonstrates that trapping of IG waves on the shelf break strongly reduces energy radiation into ocean basins. Further, for narrow continental shelves (U.S. West Coast), energy levels past the shelf break depend only weakly on shelf geometry. Consequently, oceanic energy levels can be related to coastal sources by scaling relations predicted by geometric optics, simplifying the effort to estimate the impact of radiated IG‐waves on remote sites (e.g., to estimate seismic noise levels or impact on ice shelves).
Retrieval of Atmospheric Profiles in the New York State Mesonet Using One‐Dimensional Variational Algorithm
Authors: Yang Jun , Min Qilong
Published: June 2018

A one‐dimensional variational (1DVAR) algorithm was developed, which combines measurements taken by the ground‐based microwave radiometer profiler (MWRP) with the Rapid Refresh (RAP) model to retrieve a more accurate temperature and humidity profiles under clear sky. The passive and active microwave‐vector radiative transfer model was used to simulate brightness temperatures and calculate weighting functions for 22 channels of the MWRP. As MWRP measurements are mainly weighted in the lower atmosphere, a measurement adjustment is performed to reduce the contribution from above 10 km. The results of the 1DVAR algorithm have been compared with the MWRP built‐in neural network (NN) retrievals and radiosonde observations, which show that the 1DVAR method outperforms the NN retrieval both in temperature and water vapor. Our statistical study further shows that the water vapor profiles from RAP are biased higher than the radiosonde observations, while the 1DVAR‐retrieved humidity values show significant improvements throughout the entire 10‐km range. The improvements in temperature profiles occur mainly within the lowest 4‐km atmosphere, while upper level retrievals are mostly influenced by initial values. This is consistent with the characteristics of the Jacobian matrix and the background error covariance matrix. The outcomes of 44 clear‐sky cases show that the maximum mean retrieval error of the 1DVAR algorithm is less than 0.2 K for temperature below 4 km and less than 0.15 g/m3 in water vapor density. These results are shown to be significantly better than the NN retrieval (3.0 K and 1.25 g/m3) and also superior to the RAP reanalysis (0.3 K and 0.5 g/m3).
Predicting Health Care Utilization and Charges Using a Risk Score for Poor Adherence in Pediatric Kidney Transplant Recipients
Authors: Rich Kristin Loiselle , Modi Avani C. , Mara Constance , Pai Ahna L. H. , Varnell Charles D. , Turnier Luke , Huber John , Hooper David K.
Published: June 2018

Pediatric kidney transplant recipients must follow a complicated regimen of timely adherence to immunosuppressant medication, routine blood work, and medical follow-up visits. Failure to adhere to the recommended regimen can result in medical complications and costly treatment. We developed a novel risk score to identify patients at risk for poor adherence behaviors and evaluated whether it would predict future health care utilization and charges. Our risk stratification score combined three simple pass/fail metrics of adherence derived directly from the electronic health record including standard deviation of immunosuppression drug levels, timely laboratory monitoring, and timely clinic visits as indicated by our clinical protocol. Risk for poor adherence was assessed over a three-month period. Linear regression was used to predict subsequent health care charges and utilization. Greater than 75% of patients had some degree of nonadherence risk during the study period, but there were no significant differences found on any outcomes for the overall score. However, when the individual components of the overall risk score were evaluated independently, patients with tacrolimus drug level standard deviation ≥2 (e.g., a marker of poor adherence) had greater health care utilization (e.g., hospitalizations) and increased total charges. Additionally, patients who did not follow up in clinic at least every 4 months had more ED visits and ED-related charges, but fewer hospitalizations. Regular clinic visits and minimizing drug level variation may deter future costly ED visits and hospitalizations.

Implications for Impact Statement

Nonadherence to immunosuppression medication is costly in terms of impact on health and financially. Having an easy-to-use system to quickly identify patients at risk for nonadherence at the point of care has clinical utility. Intervening on kidney transplant recipients who have high drug level variation or miss clinic visits may deter future costly medical care.
Single (Aim)-Minded Strategies for Demonstrating Value to Payers for Youth With Medical Complexity
Authors: Harris Michael A. , Teplitsky Lena , Nagra Harpreet , Spiro Kim , Wagner David V.
Published: June 2018

In the current financial climate, health care institutions and providers experience substantial challenges in achieving the Triple Aim in health care reform (i.e., reducing costs, improving health, improving care). The present study describes the successes and challenges of garnering payment for a population health program, Novel Interventions in Children’s Health care (NICH), for youth with both medical and social vulnerability. Using 4 real patient scenarios, this study provides examples of how to use economic data to demonstrate program value to key stakeholders (i.e., insurance providers, hospital administrators) and obtain authorization and payment for services. Health care utilization and cost data were retrieved through retrospective review of patient medical records and hospital financial records. NICH utilized distinct strategies to overcome systemic barriers, demonstrate value, and show need for intervention to key stakeholders. Strategies included highlighting patients’: (a) history of utilization, (b) accumulated medical expenditures, (c) projected costs for anticipated procedures, and (d) social risk linked to poor health and high utilization. We describe each effort using real patient scenarios that feature varied medical conditions including Type 1 diabetes, chronic pain, and failure-to-thrive. Economic data can be a useful tool in garnering support for behavioral health interventions. And while these data offer programs like NICH the opportunity to make the case for investing in an alternative intervention, the strategies utilized by NICH to advocate for services can be applied by pediatric psychologists working with youth with medical complexity and social vulnerability.

Implications for Impact Statement

In order to increase service access for individuals, families, and medical teams in an ever-changing fiscal environment, psychologists and other behavioral health providers should be prepared to highlight the financial value of their efforts to health care systems and payers. This article provides (a) an example of how a behavioral health program can identify and collect economically relevant data and (b) strategies that use economic data to convince payers to authorize and evaluate the services of such programs. For each of these strategies, we provide real patient scenarios to better illustrate how behavioral health providers can make a compelling case for intervention programs through the strategic presentation of medical, social, and economic data.
Early Childhood Behavioral Health Integration Activities and HealthySteps: Sustaining Practice, Averting Costs
Authors: Buchholz Melissa , Burnett Bridget , Margolis Kathryn L. , Millar Amanda , Talmi Ayelet
Published: June 2018

The practice of early childhood behavioral health (ECBH) integration in primary care settings promotes optimal care for families with young children while simultaneously improving health care utilization and averting unnecessary health care expenditures. Implementing ECBH integration activities across four domains—screening processes, prevention and health promotion, case-based consultation and intervention, and care coordination—has the potential to enhance the lifelong health and well-being of children and families. Unfortunately, billing and reimbursement for activities focused on prevention, early identification, and early childhood intervention in primary care settings presents challenges. The current article describes a financial analysis of a grant-funded project focused on ECBH activities delivered by pediatric psychologists and psychology fellows. A business case for HealthySteps (HS), an evidence-based intervention to enhance primary care in early childhood, was applied in a site serving a high risk pediatric population. Delivering HS in this pediatric primary care setting yielded significant cost aversion across both maternal and child level interventions. Estimated costs averted exceeded the program operating costs of HS implementation in this setting. In a changing health care landscape that is shifting away from volume-based, fee-for-service models to value-based, cost-control models, optimizing the potential of primary care for early childhood populations is necessary to improve health outcomes and reduce the total cost of care across the life span.

Implications for Impact Statement

This paper describes concrete mechanisms for assessing potential reduction in total cost of care to the health care system by implementing early childhood behavioral health strategies into primary care settings. Financial analysis of these interventions could be replicated to demonstrate value and make a case for sustainability of integrated ECBH activities in primary care settings.
Real-time beam shaping without additional optical elements
Authors: Fries Felix , Fröbel Markus , Ang Pen Yiao , Lenk Simone , Reineke Sebastian
Published: June 2018

Providing artificial light and enhancing the quality of the respective light sources is of continued interest in the fields of solid state, condensed matter, and semiconductor physics. Much research has been carried out to increase the luminous efficiency, lifetime and colour stability of such devices. However, the emission characteristics of a given light source do not necessarily comply with today’s often sophisticated applications. Here, beam shaping addresses the transformation of a given light distribution into a customized form. This is typically achieved by secondary optical elements often sporting elaborate designs, where the actual light source takes up only a small fraction of the system’s volume. Such designs limit the final light source to a single permanent operation mode, which can only be overcome by employing mechanically adjustable optical elements. Here we show that organic light-emitting diodes (OLEDs) can enable real-time regulation of a beam shape without relying on secondary optical elements and without using any mechanical adjustment. For a red light-emitting two-unit OLED architecture, we demonstrate the ability to continuously tune between strongly forward and strongly sideward emission, where the device efficiency is maintained at an application-relevant level ranging between 6 and 8% of external quantum efficiency for any chosen setting. In combination with additional optical elements, customizable and tuneable systems are possible, whereby the tuning stems from the light source itself rather than from the use of secondary optics.
Phylogenetic-scale disparities in the soil microbial diversity–ecosystem functioning relationship
Authors: Goberna Marta , Verdú Miguel
Published: June 2018

The historical conditions under which bacterial lineages evolve determine their functional traits, and consequently their contribution to ecosystem functions (EFs). Under significant trait conservatism, which is common in prokaryotes, phylogeny may track the evolutionary history of species and predict their functionality. Productive communities can arise from: (i) the coexistence of functional, and therefore phylogenetically distant lineages, producing high EF rates at large phylogenetic diversity (PD); (ii) the dominance of productive lineages that outcompete other clades, generating high EF at low PD. Community composition will modulate the PD–EF relationship: The effects of anciently divergent lineages, whose deeply conserved functions determine the occupancy of major niches, may differ from that of recently divergent lineages showing adaptations to current conditions. We hypothesized that, in our model Mediterranean ecosystem, EF can be explained both by competitive superiority of ancient lineages and functional complementarity of recent lineages. To test this hypothesis, we sequenced a phylogenetic marker targeting bacteria across 28 soil plots and quantified EF related to microbial productivity, decomposition and nutrient cycling. Plots accumulating recently divergent lineages consistently showed higher EF levels that were slightly modified by the accumulation of ancient lineages. We discuss the assembly processes behind these phylogenetic-scale disparities and the final outcome in terms of ecosystem functioning.
Phylogenetic conservatism of thermal traits explains dispersal limitation and genomic differentiation of Streptomyces sister-taxa
Authors: Choudoir Mallory J , Buckley Daniel H
Published: June 2018

The latitudinal diversity gradient is a pattern of biogeography observed broadly in plants and animals but largely undocumented in terrestrial microbial systems. Although patterns of microbial biogeography across broad taxonomic scales have been described in a range of contexts, the mechanisms that generate biogeographic patterns between closely related taxa remain incompletely characterized. Adaptive processes are a major driver of microbial biogeography, but there is less understanding of how microbial biogeography and diversification are shaped by dispersal limitation and drift. We recently described a latitudinal diversity gradient of species richness and intraspecific genetic diversity in Streptomyces by using a geographically explicit culture collection. Within this geographically explicit culture collection, we have identified Streptomyces sister-taxa whose geographic distribution is delimited by latitude. These sister-taxa differ in geographic distribution, genomic diversity, and ecological traits despite having nearly identical SSU rRNA gene sequences. Comparative genomic analysis reveals genomic differentiation of these sister-taxa consistent with restricted gene flow across latitude. Furthermore, we show phylogenetic conservatism of thermal traits between the sister-taxa suggesting that thermal trait adaptation limits dispersal and gene flow across climate regimes as defined by latitude. Such phylogenetic conservatism of thermal traits is commonly associated with latitudinal diversity gradients for plants and animals. These data provide further support for the hypothesis that the Streptomyces latitudinal diversity gradient was formed as a result of historical demographic processes defined by dispersal limitation and driven by paleoclimate dynamics.
miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3
Authors: Zhang Hongliang , Yang Kang , Ren Tingting , Huang Yi , Tang Xiaodong , Guo Wei
Published: June 2018

Aberrantly expressed miRNAs play a crucial role in the development of multiple cancer types, including chordoma. However, the detailed molecular mechanisms are unclear and need to be elucidated. In this study, miRNAs were screened by miRNA array analysis and then confirmed by real-time PCR analysis. We found that miR-16-5p was significantly downregulated in chordoma, and overexpression of miR-16-5p suppressed chordoma cell proliferation, invasion and migration in vitro and in vivo and correlated with the upregulated expression of E-cadherin and downregulated expression of N-cadherin and vimentin. Furthermore, Smad3 was identified as a target of miR-16-5p, and Smad3 was highly expressed in chordoma tissues. Further research showed that knockdown of Smad3 had an effect similar to that of overexpression of miR-16-5p in chordoma cells. Our findings demonstrate that miR-16-5p plays a tumor suppressor role in chordoma progression by targeting Smad3, which could provide a promising prognostic and therapeutic strategy for chordoma treatment.
Hypoxia restrains the expression of complement component 9 in tumor-associated macrophages promoting non-small cell lung cancer progression
Authors: Li Lei , Yang Hong , Li Yan , Li Xiao-Dong , Zeng Ting-Ting , Lin Su-Xia , Zhu Ying-Hui , Guan Xin-Yuan
Published: June 2018

The tumor microenvironment, including stroma cells, signaling molecules, and the extracellular matrix, critically regulates the growth and survival of cancer cells. Dissecting the active molecules in tumor microenvironment may uncover the key factors that can impact cancer progression. Human NSCLC tumor tissue-conditioned medium (TCM) and adjacent nontumor tissue-conditioned medium (NCM) were used to treat two NSCLC cells LSC1 and LAC1, respectively. Cell growth and foci formation assays were applied to assess the effects of TCM and NCM on cancer cells. The active factors were identified by protein mass spectrometry. Cell growth and foci formation assays showed that 8 of 26 NCM and none of TCM could effectively lead to tumor cell lysis, which was known as tumoricidal activity. And then protein mass spectrometry analysis and functional verifications confirmed that complement component 9 (C9) played a crucial role in the complement-dependent cytotoxicity (CDC)-mediated tumoricidal activity in vitro. Furthermore, immunofluorescent staining revealed that C9 specifically expressed in most alveolar macrophages (AMs) in adjacent lung tissues and a small fraction of tumor-associated macrophages (TAMs) in NSCLC tissues. Most importantly, the percentage of C9-positive cells in AMs or TAMs was responsible for the tumoricidal activity of NCM and TCM. Herein, we found that high expression of C9 in TAMs was a significant independent prognostic factor (P = 0.029), and associated with beneficial overall survival (P = 0.012) and disease-free survival (P = 0.016) for patients with NSCLC. Finally, we unveiled that hypoxic tumor microenvironment could switch the phenotype of macrophages from M1 to M2 forms, accompanying with the downregulation of C9 in TAMs. Collectively, our findings elucidated a novel role of TAMs expressing C9 in the prognosis of NSCLC patients, which provided a promising strategy in the development of anticancer treatments based on the CDC-mediated tumoricidal activity.
Hot-electron transfer in quantum-dot heterojunction films
Authors: Grimaldi Gianluca , Crisp Ryan W. , ten Brinck Stephanie , Zapata Felipe , van Ouwendorp Michiko , Renaud Nicolas , Kirkwood Nicholas , Evers Wiel H. , Kinge Sachin , Infante Ivan , Siebbeles Laurens D. A. , Houtepen Arjan J.
Published: June 2018

Thermalization losses limit the photon-to-power conversion of solar cells at the high-energy side of the solar spectrum, as electrons quickly lose their energy relaxing to the band edge. Hot-electron transfer could reduce these losses. Here, we demonstrate fast and efficient hot-electron transfer between lead selenide and cadmium selenide quantum dots assembled in a quantum-dot heterojunction solid. In this system, the energy structure of the absorber material and of the electron extracting material can be easily tuned via a variation of quantum-dot size, allowing us to tailor the energetics of the transfer process for device applications. The efficiency of the transfer process increases with excitation energy as a result of the more favorable competition between hot-electron transfer and electron cooling. The experimental picture is supported by time-domain density functional theory calculations, showing that electron density is transferred from lead selenide to cadmium selenide quantum dots on the sub-picosecond timescale.
Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin
Authors: Torres-Ayuso Pedro , Sahoo Sudhakar , Ashton Garry , An Elvira , Simms Nicole , Galvin Melanie , Leong Hui Sun , Frese Kristopher K , Simpson Kathryn , Cook Natalie , Hughes Andrew , Miller Crispin J , Marais Richard , Dive Caroline , Krebs Matthew G , Brognard John
Published: June 2018

Precision medicine aims to tailor cancer therapies to target specific tumor-promoting aberrations. For tumors that lack actionable drivers, which occurs frequently in the clinic, extensive molecular characterization and pre-clinical drug efficacy studies will be required. A cell line maintained at low passage and a patient- derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient’s DNA. However, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. We then conducted pathway analysis, which revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis will significantly aid in identifying actionable alterations in rare tumors and guide patient stratification into early-phase clinical trials.
Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii
Authors: Solanki Vandana , Tiwari Vishvanath
Published: June 2018

The emergence of drug-resistant Acinetobacter baumannii is the global health problem associated with high mortality and morbidity. Therefore it is high time to find a suitable therapeutics for this pathogen. In the present study, subtractive proteomics along with reverse vaccinology approaches were used to predict suitable therapeutics against A. baumannii. Using subtractive proteomics, we have identified promiscuous antigenic membrane proteins that contain the virulence factors, resistance factors and essentiality factor for this pathogenic bacteria. Selected promiscuous targeted membrane proteins were used for the design of chimeric-subunit vaccine with the help of reverse vaccinology. Available best tools and servers were used for the identification of MHC class I, II and B cell epitopes. All selected epitopes were further shortlisted computationally to know their immunogenicity, antigenicity, allergenicity, conservancy and toxicity potentials. Immunogenic predicted promiscuous peptides used for the development of chimeric subunit vaccine with immune-modulating adjuvants, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequence. Designed vaccine construct V4 also interact with the MHC, and TLR4/MD2 complex as confirm by docking and molecular dynamics simulation studies. Therefore designed vaccine construct V4 can be developed to control the host-pathogen interaction or infection caused by A. baumannii.
The Radiated Deep-frozen Xenogenic Meniscal Tissue Regenerated the Total Meniscus with Chondroprotection
Authors: Jiang Dong , Zhang Zheng-Zheng , Zhao Feng , Wang Shao-Jie , Qi Yan-Song , Zhao Li-Heng , Zhang Ji-Ying , Yu Jia-Kuo
Published: June 2018

Meniscal allograft transplantation yields good and excellent results but is limited by donor availability. The purpose of the study was to evaluate the effectiveness of radiated deep-frozen xenogenic meniscal tissue (RDF-X) as an alternative graft choice in meniscal transplantation. The xenogenic meniscal tissues were harvested from the inner 1/3 part of the porcine meniscus and then irradiated and deeply frozen. The medial menisci of rabbits were replaced by the RDF-X. Meniscal allograft transplantation, meniscectomy and sham operation served as controls. Only a particular kind of rabbit-anti-pig antibody (molecular ranging 60–80 kD) was detected in the blood serum at week 2. The menisci of the group RDF-X grossly resembled the native tissue and the allograft meniscus with fibrocartilage regeneration at postoperative 1 year. Cell incorporation and the extracellular matrix were mostly observed at the surface and the inner 1/3 part of the newly regenerated RDF-X, which was different from the allograft. The biomechanical properties of the group RDF-X were also approximate to those of the native meniscus except for the compressive creep. In addition, chondroprotection was achieved after the RDF-X transplantation although the joint degeneration was not completely prevented. To conclude, the RDF-X could be a promising alternative for meniscal transplantation with similar tissue regeneration capacity to allograft transplantation and superior chondroprotection. The potential minor immunological rejection should be further studied before its clinical application.
Immunome differences between porcine ileal and jejunal Peyer’s patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues
Authors: Maroilley T. , Berri M. , Lemonnier G. , Esquerré D. , Chevaleyre C. , Mélo S. , Meurens F. , Coville J. L. , Leplat J. J. , Rau A. , Bed’hom B. , Vincent-Naulleau S. , Mercat M. J. , Billon Y. , Lepage P. , Rogel-Gaillard C. , Estellé J.
Published: June 2018

The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer’s patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genesFOXP3,GATA3,STAT4,TBX21andRORCwere less expressed in IPPs compared to JPPs, whereas the transcription factorBCL6was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specificcis-genetic control of gene expression.
Dispersion engineering with plasmonic nano structures for enhanced surface plasmon resonance sensing
Authors: Arora Pankaj , Talker Eliran , Mazurski Noa , Levy Uriel
Published: June 2018

We demonstrate numerically and experimentally the enhancement of Surface Plasmon Resonance (SPR) sensing via dispersion engineering of the plasmonic response using plasmonic nanograting. Following their design and optimization, the plasmonic nanograting structures are fabricated using e-beam lithography and lift-off process and integrated into conventional prism based Kretschmann configuration. The presence of absorptive nanograting near the metal film, provides strong field enhancement with localization and allows to control the dispersion relation which was originally dictated by a conventional SPR structure. This contributes to the enhancement in Q factor which is found to be 3–4 times higher as compared to the conventional Kretschmann configuration. The influence of the incident angle on resonance wavelength is also demonstrated both numerically and experimentally, where, only a negligible wavelength shift is observed with increasing the incident angles for plasmonic nanograting configuration. This surprising feature may be helpful for studying and utilizing light-matter interaction between plasmons and narrow linewidth media (e.g. Rb atom or molecule) having nonlocalities in their susceptibility-momentum relation. Finally, we analyze the role of plasmonic nanograting in enhancing the performance of an SPR sensor. Our results indicate that the integrated SPR-nanograting device shows a great promise as a sensor for various types of analytes.
A single cell high content assay detects mitochondrial dysfunction in iPSC-derived neurons with mutations in SNCA
Authors: Little Daniel , Luft Christin , Mosaku Olukunbi , Lorvellec Maëlle , Yao Zhi , Paillusson Sébastien , Kriston-Vizi Janos , Gandhi Sonia , Abramov Andrey Y. , Ketteler Robin , Devine Michael J. , Gissen Paul
Published: June 2018

Mitochondrial dysfunction is implicated in many neurodegenerative diseases including Parkinson’s disease (PD). Induced pluripotent stem cells (iPSCs) provide a unique cell model for studying neurological diseases. We have established a high-content assay that can simultaneously measure mitochondrial function, morphology and cell viability in iPSC-derived dopaminergic neurons. iPSCs from PD patients with mutations in SNCA and unaffected controls were differentiated into dopaminergic neurons, seeded in 384-well plates and stained with the mitochondrial membrane potential dependent dye TMRM, alongside Hoechst-33342 and Calcein-AM. Images were acquired using an automated confocal screening microscope and single cells were analysed using automated image analysis software. PD neurons displayed reduced mitochondrial membrane potential and altered mitochondrial morphology compared to control neurons. This assay demonstrates that high content screening techniques can be applied to the analysis of mitochondria in iPSC-derived neurons. This technique could form part of a drug discovery platform to test potential new therapeutics for PD and other neurodegenerative diseases.
Year-to-year Variability in Arctic Minimum Sea Ice Extent and its Preconditions in Observations and the CESM Large Ensemble Simulations
Authors: Yang Wenchang , Magnusdottir Gudrun
Published: June 2018

Arctic sea ice extent (SIE) achieves its minimum in September each year and this value has been observed to decline steeply over the satellite era of the past three decades. Yet large year-to-year fluctuations are also present in the September SIE and the mechanisms for this variability are still not clear. Here we address this issue by examining the preconditions in meteorological fields in the previous spring and summer from observations and a large ensemble of historical climate model simulations. The focus of this study is on the impact of anomalous moisture transport into the Arctic and the associated surface energy fluxes on the September SIE. We find that the below-normal September SIE is associated with enhanced moisture transport into the Arctic in spring, which induces downward thermal radiation at the surface. However, in summer, the anomalous moisture transport over the Arctic is divergent due to an anticyclonic atmospheric flow pattern and the ice albedo feedback plays a leading role in sea ice loss.
Assigning biological function using hidden signatures in cystine-stabilized peptide sequences
Authors: Islam S. M. Ashiqul , Kearney Christopher Michel , Baker Erich J.
Published: June 2018

Cystine-stabilized peptides have great utility as they naturally block ion channels, inhibit acetylcholine receptors, or inactivate microbes. However, only a tiny fraction of these peptides has been characterized. Exploration for novel peptides most efficiently starts with the identification of candidates from genome sequence data. Unfortunately, though cystine-stabilized peptides have shared structures, they have low DNA sequence similarity, restricting the utility of BLAST and even more powerful sequence alignment-based annotation algorithms, such as PSI-BLAST and HMMER. In contrast, a supervised machine learning approach may improve discovery and function assignment of these peptides. To this end, we employed our previously described m-NGSG algorithm, which utilizes hidden signatures embedded in peptide primary sequences that define and categorize structural or functional classes of peptides. From the generalized m-NGSG framework, we derived five specific models that categorize cystine-stabilized peptide sequences into specific functional classes. When compared with PSI-BLAST, HMMER and existing function-specific models, our novel approach (named CSPred) consistently demonstrates superior performance in discovery and function-assignment. We also report an interactive version of CSPred, available through download (https://bitbucket.org/sm_islam/cystine-stabilized-proteins/src) or web interface (watson.ecs.baylor.edu/cspred), for the discovery of cystine-stabilized peptides of specific function from genomic datasets and for genome annotation. We fully describe, in the Availability section following the Discussion, the quick and simple usage of the CsPred website to automatically deliver function assignments for batch submissions of peptide sequences.
Touch-induced face conditioning is mediated by genetic variation in opioid but not oxytocin receptors
Authors: Fu Yu , Selcuk Emre , Moore Sarah R. , Depue Richard A.
Published: June 2018

Soft touch possesses strong prosocial effects that facilitate social bonding and group cohesion in animals. Touch activates opioids (OP) and oxytocin (OXT), two neuromodulators involved in affiliative behaviors and social bonding. We examined whether touch serves as an unconditioned reward in affective conditioning of human faces, a basic process in social bonding, and whether this process is mediated by variation in mu-OP (OPRM1) and OXT (rs53576) receptor genes. Participants viewed affectively-neutral human faces, half of which were paired with a brief soft brushing on the forearm as an unconditioned stimulus (US). Paired and unpaired faces were rated for positive affective and sensory features of touch. Variation inOPRM1but notrs53576significantly modulated strength and development of conditioning, indicating that touch-induced mu-OP but not OXT activity provides rewarding properties of a US in conditioning. Implications for touch-inducedmu-OP activity in normal and disordered conditioned social bonding are discussed.
Super Resolution Network Analysis Defines the Molecular Architecture of Caveolae and Caveolin-1 Scaffolds
Authors: Khater Ismail M. , Meng Fanrui , Wong Timothy H. , Nabi Ivan Robert , Hamarneh Ghassan
Published: June 2018

Quantitative approaches to analyze the large data sets generated by single molecule localization super-resolution microscopy (SMLM) are limited. We developed a computational pipeline and applied it to analyzing 3D point clouds of SMLM localizations (event lists) of the caveolar coat protein, caveolin-1 (Cav1), in prostate cancer cells differentially expressing CAVIN1 (also known as PTRF), that is also required for caveolae formation. High degree (strongly-interacting) points were removed by an iterative blink merging algorithm and Cav1 network properties were compared with randomly generated networks to retain a sub-network of geometric structures (or blobs). Machine-learning based classification extracted 28 quantitative features describing the size, shape, topology and network characteristics of ∼80,000 blobs. Unsupervised clustering identified small S1A scaffolds corresponding to SDS-resistant Cav1 oligomers, as yet undescribed larger hemi-spherical S2 scaffolds and, only in CAVIN1-expressing cells, spherical, hollow caveolae. Multi-threshold modularity analysis suggests that S1A scaffolds interact to form larger scaffolds and that S1A dimers group together, in the presence of CAVIN1, to form the caveolae coat.
Triple-negative invasive breast carcinoma: the association between the sonographic appearances with clinicopathological feature
Authors: Li Jia-wei , Zhang Kai , Shi Zhao-ting , Zhang Xun , Xie Juan , Liu Jun-ying , Chang Cai
Published: June 2018

In this study, we aimed to evaluate the clinical and pathological factors that associated with sonographic appearances of triple-negative (TN) invasive breast carcinoma. With the ethical approval, 560 patients who were pathologically confirmed as invasive breast carcinoma were reviewed for ultrasound, clinical, and pathological data. Logistic regression analysis was used to identify the typical sonographic features for TN invasive breast carcinomas. The effect of clinical and pathological factors on the sonographic features of TN invasive breast carcinoma was studied. There were 104 cases of TN invasive breast carcinoma. The independent sonographic features for the TN subgroup included regular shape (odds ratio, OR = 1.73, p = 0.033), no spiculated/angular margin (OR = 2.09, p = 0.01), posterior acoustic enhancement (OR = 2.09, p = 0.004), and no calcifications (OR = 2.11, p = 0.005). Higher pathological grade was significantly associated with regular tumor shape of TN breast cancer (p = 0.012). Higher Ki67 level was significantly associated with regular tumor shape (p = 0.023) and absence of angular/spiculated margin (p = 0.005). Higher human epidermal growth factor receptor 2 (HER2) score was significantly associated with the presence of calcifications (p = 0.033). We conclude that four sonographic features are associated with TN invasive breast carcinoma. Heterogeneity of sonographic features was associated with the pathological grade, Ki67 proliferation level and HER2 score of TN breast cancers.
Glutamine 89 is a key residue in the allosteric modulation of human serine racemase activity by ATP
Authors: Canosa Andrea V. , Faggiano Serena , Marchetti Marialaura , Armao Stefano , Bettati Stefano , Bruno Stefano , Percudani Riccardo , Campanini Barbara , Mozzarelli Andrea
Published: June 2018

Serine racemase (SR) catalyses two reactions: the reversible racemisation of L-serine and the irreversible dehydration of L- and D-serine to pyruvate and ammonia. SRs are evolutionarily related to serine dehydratases (SDH) and degradative threonine deaminases (TdcB). Most SRs and TdcBs – but not SDHs – are regulated by nucleotides. SR binds ATP cooperatively and the nucleotide allosterically stimulates the serine dehydratase activity of the enzyme. A H-bond network comprising five residues (T52, N86, Q89, E283 and N316) and water molecules connects the active site with the ATP-binding site. Conservation analysis points to Q89 as a key residue for the allosteric communication, since its mutation to either Met or Ala is linked to the loss of control of activity by nucleotides. We verified this hypothesis by introducing the Q89M and Q89A point mutations in the human SR sequence. The allosteric communication between the active site and the allosteric site in both mutants is almost completely abolished. Indeed, the stimulation of the dehydratase activity by ATP is severely diminished and the binding of the nucleotide is no more cooperative. Ancestral state reconstruction suggests that the allosteric control by nucleotides established early in SR evolution and has been maintained in most eukaryotic lineages.
Preliminary Investigation of Focused Ultrasound-Facilitated Drug Delivery for the Treatment of Leptomeningeal Metastases
Authors: O’Reilly Meaghan A. , Chinnery Tricia , Yee My-Linh , Wu Sheng-Kai , Hynynen Kullervo , Kerbel Robert S. , Czarnota Gregory J. , Pritchard Kathleen I. , Sahgal Arjun
Published: June 2018

Leptomeningeal metastases (LM) are a serious complication of cancer in the central nervous system (CNS) and are diagnosed in approximately 5% of patients with solid tumors. Effective treatment using systemically administered therapeutics is hindered by the barriers of the CNS. Ultrasound can mediate delivery of drugs through these barriers. The goal of this study was to test the feasibility of using ultrasound-mediated drug delivery to improve the treatment of LM. LM was induced in the spinal cord of athymic rats by injecting HER2-expressing breast cancer cells into the subarachnoid space of the thoracic spine. Animals were divided into three groups: no treatment (n = 5), trastuzumab only (n = 6) or trastuzumab + focused ultrasound + microbubbles (FUS + MBs) (n = 7). Animals in groups 2 and 3 were treated weekly with intravenous trastuzumab +/− FUS + MBs for three weeks. Suppression in tumor growth was qualitatively observed by MRI in the group receiving ultrasound, and was confirmed by a significant difference in the tumor volume measured from the histology data (25 ± 17 mm3 vs 8 ± 5 mm3, p = 0.04 in the trastuzumab-only vs trastuzumab + FUS + MBs). This pilot study demonstrates the potential of ultrasound-mediated drug delivery as a novel treatment for LM. Future studies will extend this work to larger cohorts and the investigation of LM arising from other cancers.