bluuebunny/crossref_metadata_2025 huggingface dataset:
Elliptic symbol calculus: from elliptic polylogarithms to iterated integrals of Eisenstein series
Authors: Broedel Johannes , Duhr Claude , Dulat Falko , Penante Brenda , Tancredi Lorenzo
Published: August 2018

Abstract

We present a generalization of the symbol calculus from ordinary multiple polylogarithms to their elliptic counterparts. Our formalism is based on a special case of a coaction on large classes of periods that is applied in particular to elliptic polylogarithms and iterated integrals of modular forms. We illustrate how to use our formalism to derive relations among elliptic polylogarithms, in complete analogy with the non-elliptic case. We then analyze the symbol alphabet of elliptic polylogarithms evaluated at rational points, and we observe that it is given by Eisenstein series for a certain congruence subgroup. We apply our formalism to hypergeometric functions that can be expressed in terms of elliptic polylogarithms and show that they can equally be written in terms of iterated integrals of Eisenstein series. Finally, we present the symbol of the equal-mass sunrise integral in two space-time dimensions. The symbol alphabet involves Eisenstein series of level six and weight three, and we can easily integrate the symbol in terms of iterated integrals of Eisenstein series.
A note on entanglement edge modes in Chern Simons theory
Authors: Wong Gabriel
Published: August 2018

Abstract

We elaborate on the extended Hilbert space factorization of Chern Simons theory and show how this arises naturally from a proper regularization of the entangling surface in the Euclidean path integral. The regularization amounts to stretching the entangling surface into a co-dimension one surface which hosts edge modes of the Chern Simons theory when quantized on a spatial subregion. The factorized state is a regularized Ishibashi state and reproduces the well known topological entanglement entropies. We illustrate how the same factorization arises from the gluing of two spatial subregions via the entangling product defined by Donnelly and Freidel [1].
Effects of Genetic Counselor Self‐Disclosure: an Experimental Analog Study
Authors: Volz Brianna , Valverde Kathleen D. , Robbins Steven J.
Published: August 2018

The complex nature of self‐disclosure poses challenges for genetic counselors in clinical practice. We examined the impact of genetic counselor self‐disclosure on observer perceptions of the counselor. In an online analog study, 123 participants watched a 3‐minute video of a simulated genetic counseling session. For half the participants, the video showed the counselor disclosing that she had a family medical history similar to the patient (direct personal disclosure). For half the participants, the counselor revealed her experience with other patients (direct professional disclosure). Half the participants in each video condition read that the patient had discovered personal information about the counselor during a pre‐session web search (indirect personal disclosure); half read that the patient learned of the counselor's FAQ webpage for prospective patients (indirect professional disclosure). Participants in the direct personal disclosure conditions gave higher ratings to the counseling relationship on an abbreviated version of the Barrett‐Lennard Relationship Inventory and rated themselves more likely to see the counselor compared to those in the direct professional disclosure conditions. The content of the indirect disclosure conditions (personal or professional) had no effect. Brief, direct, verbal disclosure of session‐relevant personal information by a genetic counselor appears to enhance the counselor‐patient relationship and increase the likelihood of patients returning to the counselor.
Fluence quickly secures contracts in China for Aspiral following its launch in May
Authors: Atkinson Simon
Published: August 2018

Immediately after unveiling Aspiral™, Fluence Corp Ltd secured a series of contracts in China during May and June for various models that are part of this family of wastewater treatment systems. The details of these contracts are summarised here – in the first of this month's news focus articles.
Best Practices in Social and Behavioral Research: A multisite pilot evaluation of the good clinical practice online training course
Authors: Murphy Susan L. , Samuels Elias M. , Kolb H. Robert , Behar-Horenstein Linda S. , Champagne Ellen , Byks-Jazayeri Christine , Hahn Jordan , Roth Mary-Tara , Ennever Fanny , Bajwa Wajeeh , Singh Meher , Homish Gregory G. , Dubocovich Margarita L.
Published: August 2018

Introduction

The Best Practices in Social and Behavioral Research Course was developed to provide instruction on good clinical practice for social and behavioral trials. This study evaluated the new course.

Methods

Participants across 4 universities took the course (n=294) and were sent surveys following course completion and 2 months later. Outcomes included relevance, how engaging the course was, and working differently because of the course. Open-ended questions were posed to understand how work was impacted.

Results

Participants rated the course as relevant and engaging (6.4 and 5.8/7 points) and reported working differently (4.7/7 points). Participants with less experience in social and behavioral trials were most likely to report working differently 2 months later.

Discussion

The course was perceived as relevant and engaging. Participants described actions taken to improve rigor in implementing trials. Future studies with a larger sample and additional participating sites are recommended.
Lessons learned from developing and sustaining a community-research collaborative through translational research
Authors: LeClair Amy , Lim Jean J. , Rubin Carolyn
Published: August 2018

Introduction

The goal of this project was to document the current state of a community-academic partnership, identifying early successes and lessons learned.

Methods

We employed qualitative methods, semi-structured interviews and document analysis, from 2 data sources to (1) show how the principles of community-based participatory research are enacted through the activities of Addressing Disparities in Asian Populations through Translational Research (ADAPT) and (2) elucidate the barriers and facilitators to adhering to those principles from the perspectives of the members themselves.

Results

In addition to established community-based participatory research values, understanding individuals’ motivations for participation, the challenges aligning the priorities of community organizations and academic partners, and definitions of success are themes that emerged as key to the process of maintaining this partnership.

Conclusion

As the emphasis on community-academic partnerships grows, there is potential for clinical and translational science awards to use community engagement to facilitate translational research beyond the traditional medical spheres of influence and to forge relationships with affected communities.
Insight Into Health Care Services: A Characterization of Emergency Room Visits and Economic Hazards in the United States
Authors: Hamadi Hanadi , Apatu Emma , Osagiede Osayande , Spaulding Aaron
Published: August 2018

Objective

This study explores the impact of economic hazard areas on hospital-based emergency departments to determine whether economically hazardous environments, characterized by the change of population, income per capita, and unemployment rate, experience a higher number of emergency room visits than areas of lower rated economic hazard risk in the United States.

Method

A cross-sectional design was used of a nationally constructed data set of hospital-based emergency departments of over 6,000 hospitals in the United States. We identified our quality outcome measure as the emergency room visits rate within a hospital service area. We created the variable by dividing the number of emergency room visits by the population of the hospital services area in which the emergency room was located.

Results

Results indicate that there is a difference in the incident rate ratio of emergency room visits between environments considered to be experiencing greater amounts of hazard, compared to lower amounts of hazard.

Conclusion

Hospital administrators and health policy-makers need to work in conjunction to focus efforts on public safety as a key objective in the delivery of emergency medical care. One crucial effort that hospital administrators need to focus on is improving emergency room capacity and efficiency as part of the disaster preparedness plan (Disaster Med Public Health Prep. 2019;13:470-475)
Assessing the environmental impact of the dairy processing industry in the Republic of Ireland
Authors: Finnegan William , Goggins Jamie , Zhan Xinmin
Published: August 2018

This Research Communication describes the methodology used and the subsequent results obtained for an assessment of the environmental impact associated with the manufacture of dairy products in the Republic of Ireland. As the Irish dairy industry changes and grows, it is necessary to have a benchmark of the environmental performance of the sector if it is to remain sustainable in the future. In order to estimate the environmental impact, life cycle assessment has been implemented, which has been structured in accordance with the International Organisation for Standardisation guidelines. In this study, the environmental impact categories assessed are terrestrial acidification potential, cumulative energy demand, freshwater eutrophication potential, global warming potential, marine eutrophication potential and water depletion. The main Irish dairy products have been compared across these environmental impact categories in order to derive meaningful results. It is identified that packaging materials, particularly for infant formula, and energy usage, across each of the life cycle stages, should be targeted as these are the most significant contributors to the overall environmental impact.
Dominance of the genus Polaromonas in the microbial ecology of an Intermittently Aerated Sequencing Batch Reactor (IASBR) treating dairy processing wastewater under varying aeration rates
Authors: Gil-Pulido Beatriz , Tarpey Emma , Finnegan William , Zhan Xinmin , Dobson Alan DW , O'Leary Niall
Published: August 2018

In this Research Communication we investigate potential correlations between key bacterial groups and nutrient removal efficiency in an Intermittently Aerated Sequencing Batch Reactor (IASBR) treating synthetic dairy processing wastewater. Reactor aeration rates of 0·6 and 0·4 litre per minute (LPM) were applied to an 8 l laboratory scale system and the relative impacts on IASBR microbial community structure and orthophosphate (PO4-P) and ammonium (NH4-N) removal efficiencies compared. Aeration at 0·6 LPM over several sludge retention times (SRTs) resulted in approximately 92% removal efficiencies for both PO4-P and NH4-N. Biomass samples subjected to next-generation sequencing (NGS), 16S rRNA profiling revealed a concomitant enrichment of Polaromonas under 0·6 LPM conditions, up to ~50% relative abundance within the reactor biomass. The subsequent shift in reactor aeration to 0·4 LPM, over a period of 3 SRTs, resulted in markedly reduced nutrient removal efficiencies for PO4-P (50%) and NH4-N (45%). An 85·7% reduction in the genus level relative abundance of Polaromonas was observed under 0·4 LPM aeration conditions over the same period.
DairyWater: striving for sustainability within the dairy processing industry in the Republic of Ireland
Authors: Finnegan William , Clifford Eoghan , Goggins Jamie , O'Leary Niall , Dobson Alan , Rowan Neil , Xiao Liwen , Miao Song , Fitzhenry Kelly , Leonard Peter , Tarpey Emma , Gil-Pulido Beatriz , Gao Fei , Zhan Xinmin
Published: August 2018

This Review describes the objectives and methodology of the DairyWater project as it aims to aid the Irish dairy processing industry in achieving sustainability as it expands. With the abolition of European milk quotas in March 2015, the Republic of Ireland saw a surge in milk production. The DairyWater project was established in anticipation of this expansion of the Irish dairy sector in order to develop innovative solutions for the efficient management of water consumption, wastewater treatment and the resulting energy use within the country's dairy processing industry. Therefore, the project can be divided into three main thematic areas: dairy wastewater treatment technologies and microbial analysis, water re-use and rainwater harvesting and environmental assessment. In order to ensure the project remains as relevant as possible to the industry, a project advisory board containing key industry stakeholders has been established. To date, a number of large scale studies, using data obtained directly from the Irish dairy industry, have been performed. Additionally, pilot-scale wastewater treatment (intermittently aerated sequencing batch reactor) and tertiary treatment (flow-through pulsed ultraviolet system) technologies have been demonstrated within the project. Further details on selected aspects of the project are discussed in greater detail in the subsequent cluster of research communications.
A Day in the Life: Aryanization Before the Swedish Supreme Court 1941–42
Authors: Wallerman Anna
Published: August 2018

This article examines the jurisprudence of the Swedish Supreme Court during WW2 in disputes between exiled Jewish business owners and the Nazi-appointed administrators of their companies over the rights to the enterprises’ assets in Sweden. Contrary to assertions in previous scholarship, this article argues that the judgments of the Supreme Court were dictated neither by moral indignation in the face of the treatment of Jews in the Third Reich, nor by political considerations in a time of war. Instead, they were based on principles of private international law that predated, and outlived, the Third Reich. The outcome of the cases hinged upon whether the claim to Swedish assets arose before or after the date when the enterprise was placed under forced administration. If before, the claims of the Jewish owners were in principle successful; if after, they were not. This reasoning was well in line with both previous and subsequent case law on confiscations effected abroad. The article therefore concludes that the Swedish Supreme Court's judgments on Jewish assets in Sweden should be viewed not as outflows of extrajudicial considerations, but rather as failures to recognize political or ethical responsibility.
Pathways between food insecurity and glycaemic control in individuals with type 2 diabetes
Authors: Walker Rebekah J , Williams Joni Strom , Egede Leonard E
Published: August 2018

Objective

Food insecurity is reported in approximately 28 % of individuals with diabetes in the USA and is associated with poor glycaemic and lipid control. The present study aimed to understand the direct and indirect pathways through which food insecurity impacts glycaemic control in individuals with diabetes.

Design/Setting/Subjects

Adults (n 615) with type 2 diabetes completed validated questionnaires after recruitment from two primary care clinics. Structural equation modelling was used to investigate mechanisms through which food insecurity influences diabetes self-care behaviours and glycaemic control, including investigation into possible direct and indirect effects of perceived stress and social support.

Results

The final model showed that higher food insecurity was directly significantly related to increased stress (r=0·14, P<0·001) and increased glycosylated Hb (r=0·66, P=0·03). Higher stress was significantly related to poorer self-care (r=−0·54, P<0·001) and lower social support (r=−0·41, P<0·001). There was no significant direct association between food insecurity and self-care, or between perceived stress and glycaemic control.

Conclusions

Food insecurity had both a direct effect on glycaemic control and an indirect effect on self-care through stress. The indirect pathway suggests that efforts to address stress may influence the ability of individuals to perform diabetes self-care behaviours. The direct effect on glycaemic control suggests that pathways independent of self-care behaviours may also be necessary to improve diabetes outcomes. Results from the study suggest a multipronged approach is necessary to address food insecurity in individuals with diabetes.
U.S. Households' Perception of Drinking Water as Unsafe and its Consequences: Examining Alternative Choices to the Tap
Authors: Javidi Ariana , Pierce Gregory
Published: August 2018

Using 2015 American Housing Survey data, this study generates the first national estimates of the use of drinking water alternatives among households who perceive their tap water to be unsafe. Multivariate regression models examine factors influencing both perception of tap water and the choice of tap alternatives. We find that minority households more commonly perceive their tap water to be unsafe and choose bottled water when they perceive the tap as unsafe. While perception of unsafe tap water is most prevalent among Hispanic households, among the population perceiving their tap to be unsafe, Black households more commonly buy bottled water. We estimate the minimum annual expenditure by all U.S. households who perceive the tap as unsafe and buy bottled water to meet necessary consumption standards at $5.65 billion annually. Novel secondary treatment interventions and education campaigns are needed to address the perception of tap water as unsafe and consequent alternative source reliance, while additional research is needed to document the active trade‐offs households make to manage their water sources, and to better understand determinants of the perception of tap water as unsafe within minority groups.
Variability of the Iceland‐Scotland Overflow Water Transport Through the Charlie‐Gibbs Fracture Zone: Results From an Eddying Simulation and Observations
Authors: Xu Xiaobiao , Bower Amy , Furey Heather , Chassignet Eric P.
Published: August 2018

Observations show that the westward transport of the Iceland‐Scotland overflow water (ISOW) through the Charlie‐Gibbs Fracture Zone (CGFZ) is highly variable. This study examines (a) where this variability comes from and (b) how it is related to the variability of ISOW transport at upstream locations in the Iceland Basin and other ISOW flow pathways. The analyses are based on a 35‐year 1/12° eddying Atlantic simulation that represents well the main features of the observed ISOW in the area of interest, in particular, the transport variability through the CGFZ. The results show that (a) the variability of the ISOW transport is closely correlated with that of the barotropic transports in the CGFZ associated with the meridional displacement of the North Atlantic Current front and is possibly induced by fluctuations of large‐scale zonal wind stress in the Western European Basin east of the CGFZ; (b) the variability of the ISOW transport is increased by a factor of 3 from the northern part of the Iceland Basin to the CGFZ region and transport time series at these two locations are not correlated, further suggesting that the variability at the CGFZ does not come from the upstream source; and (c) the variability of the ISOW transport at the CGFZ is strongly anticorrelated to that of the southward ISOW transport along the eastern flank of the Mid‐Atlantic Ridge, suggesting an out‐of‐phase covarying transport between these two ISOW pathways.
Joint Effects of Extrinsic Biophysical Fluxes and Intrinsic Hydrodynamics on the Formation of Hypoxia West off the Pearl River Estuary
Authors: Lu Zhongming , Gan Jianping , Dai Minhan , Liu Hongbin , Zhao Xiaozheng
Published: August 2018

Using field measurements and a process‐oriented three‐dimensional coupled physical‐biogeochemical numerical model, we investigated the physical and biogeochemical processes governing the bottom hypoxic zone west off the Pearl River estuary. The intensity and area of the hypoxia grew with increasing total nutrient input from the Pearl River that has increased continuously in recent decades. The hypoxic zone was formed and maintained largely associated with the stable water column where the stability was provided simultaneously by wind stress and freshwater discharge, favorable local hydrodynamics for flow convergence, and westward organic matter transport. Wind stress altered the stratification, while freshwater discharge changed the stratification and baroclinic velocity shear simultaneously. Two‐layered flow with a cyclonically rotating current around a coastal salient edge of the western shelf off the estuary hydrodynamically enhanced the local convergence, allowing sufficient residence time in the bottom for the remineralization of organic matter produced in the hypoxic zone and organic matter transported into the region. Our results suggest that a combination of unique local hydrodynamic feature and decomposition of organic matter in water column (and possibly in the sediment) are the cause of the formation and maintenance of the bottom hypoxia on the western shelf of the estuary during summer.
Longitudinal and Seasonal Variability of Equatorial Ionospheric Irregularities and Electrodynamics
Authors: Yizengaw Endawoke , Groves Keith M.
Published: August 2018

Over the past decades significant progresses have been done to understand the origin of seeding mechanisms of ionospheric irregularities. However, characterization of the global ionospheric irregularities as a function of local time, longitude, and season is still a challenge for the modeling community. In this review paper, using multiinstrument observations, we investigated the global irregularity distribution and its possible drivers that control the longitudinal and seasonal dependences. We demonstrated that forcing from lower thermosphere, like the localized tropospheric gravity waves seeding, may be responsible for the formation of strong longitudinal dependence of irregularity distribution. The location of Intertropical Convergence Zone that generate forceful thunderstorms and become favorable location for the launch of localized gravity waves may play an important role in the longitudinal dependence of irregularity distribution. Hence, incorporating the Intertropical Convergence Zone location into density irregularity modeling effort may provide important information to understand and characterize the longitudinal variability of irregularity distributions.
Revealing circadian mechanisms of integration and resilience by visualizing clock proteins working in real time
Authors: Mori Tetsuya , Sugiyama Shogo , Byrne Mark , Johnson Carl Hirschie , Uchihashi Takayuki , Ando Toshio
Published: August 2018

The circadian clock proteins KaiA, KaiB, and KaiC reconstitute a remarkable circa-24 h oscillation of KaiC phosphorylation that persists for many days in vitro. Here we use high-speed atomic force microscopy (HS-AFM) to visualize in real time and quantify the dynamic interactions of KaiA with KaiC on sub-second timescales. KaiA transiently interacts with KaiC, thereby stimulating KaiC autokinase activity. As KaiC becomes progressively more phosphorylated, KaiA’s affinity for KaiC weakens, revealing a feedback of KaiC phosphostatus back onto the KaiA-binding events. These non-equilibrium interactions integrate high-frequency binding and unbinding events, thereby refining the period of the longer term oscillations. Moreover, this differential affinity phenomenon broadens the range of Kai protein stoichiometries that allow rhythmicity, explaining how the oscillation is resilient in an in vivo milieu that includes noise. Therefore, robustness of rhythmicity on a 24-h scale is explainable by molecular events occurring on a scale of sub-seconds.
Diverse Cretaceous larvae reveal the evolutionary and behavioural history of antlions and lacewings
Authors: Badano Davide , Engel Michael S. , Basso Andrea , Wang Bo , Cerretti Pierfilippo
Published: August 2018

Myrmeleontiformia are an ancient group of lacewing insects characterized by predatory larvae with unusual morphologies and behaviours. Mostly soil dwellers with a soft cuticle, their larvae fossilize only as amber inclusions, and thus their fossil record is remarkably sparse. Here, we document a disparate assemblage of myrmeleontiform larvae from the mid-Cretaceous amber (99 Ma) of Myanmar, evidence of a considerable diversification. Our cladistic analysis integrating extant and extinct taxa resolves the fossils as both stem- and crown-groups. Similarities between extinct and extant species permit inferences of larval ethology of the fossil species through statistical correlation analyses with high support, implying that morphological disparity matched behavioural diversity. An improved understanding of the evolutionary history of antlions and relatives supports the conclusion that hunting strategies, such as camouflage and fossoriality, were acquired early within the lineage.
Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16 scramblase
Authors: Lee Byoung-Cheol , Khelashvili George , Falzone Maria , Menon Anant K. , Weinstein Harel , Accardi Alessio
Published: August 2018

Members of the TMEM16/ANO family of membrane proteins are Ca2+-activated phospholipid scramblases and/or Cl− channels. A membrane-exposed hydrophilic groove in these proteins serves as a shared translocation pathway for ions and lipids. However, the mechanism by which lipids gain access to and permeate through the groove remains poorly understood. Here, we combine quantitative scrambling assays and molecular dynamic simulations to identify the key steps regulating lipid movement through the groove. Lipid scrambling is limited by two constrictions defined by evolutionarily conserved charged and polar residues, one extracellular and the other near the membrane mid-point. The region between these constrictions is inaccessible to lipids and water molecules, suggesting that the groove is in a non-conductive conformation. A sequence of lipid-triggered reorganizations of interactions between these residues and the permeating lipids propagates from the extracellular entryway to the central constriction, allowing the groove to open and coordinate the headgroups of transiting lipids.
Spatially similar surface energy flux perturbations due to greenhouse gases and aerosols
Authors: Persad Geeta G. , Ming Yi , Shen Zhaoyi , Ramaswamy V.
Published: August 2018

Despite distinct geographic distributions of top-of-the-atmosphere radiative forcing, anthropogenic greenhouse gases and aerosols have been found to produce similar patterns of climate response in atmosphere-and-ocean coupled climate model simulations. Understanding surface energy flux changes, a crucial pathway by which atmospheric forcing is communicated to the ocean, is a vital bridge to explaining the similar full atmosphere-and-ocean responses to these disparate forcings. Here we analyze the fast, atmosphere-driven change in surface energy flux caused by present-day greenhouse gases vs aerosols to elucidate its role in shaping the subsequent slow, coupled response. We find that the surface energy flux response patterns achieve roughly two-thirds of the anti-correlation seen in the fully coupled response, driven by Rossby waves excited by symmetric changes to the land–sea contrast. Our results suggest that atmosphere and land surface processes are capable of achieving substantial within-hemisphere homogenization in the climate response to disparate forcers on fast, societally-relevant timescales.
Confined small-sized cobalt catalysts stimulate carbon-chain growth reversely by modifying ASF law of Fischer–Tropsch synthesis
Authors: Cheng Qingpeng , Tian Ye , Lyu Shuaishuai , Zhao Na , Ma Kui , Ding Tong , Jiang Zheng , Wang Lihua , Zhang Jing , Zheng Lirong , Gao Fei , Dong Lin , Tsubaki Noritatsu , Li Xingang
Published: August 2018

Fischer–Tropsch synthesis (FTS) is a promising technology to convert syngas derived from non-petroleum-based resources to valuable chemicals or fuels. Selectively producing target products will bring great economic benefits, but unfortunately it is theoretically limited by Anderson–Schulz–Flory (ASF) law. Herein, we synthesize size-uniformed cobalt nanocrystals embedded into mesoporous SiO2 supports, which is likely the structure of water-melon seeds inside pulps. We successfully tune the selectivity of products from diesel-range hydrocarbons (66.2%) to gasoline-range hydrocarbons (62.4%) by controlling the crystallite sizes of confined cobalt from 7.2 to 11.4 nm, and modify the ASF law. Generally, larger Co crystallites increase carbon-chain growth, producing heavier hydrocarbons. But here, we interestingly observe a reverse phenomenon: the uniformly small-sized cobalt crystallites can strongly adsorb active C* species, and the confined structure will inhibit aggregation of cobalt crystallites and escape of reaction intermediates in FTS, inducing the higher selectivity towards heavier hydrocarbons.
The tyrosine phosphatase SHP2 controls TGFβ-induced STAT3 signaling to regulate fibroblast activation and fibrosis
Authors: Zehender Ariella , Huang Jingang , Györfi Andrea-Hermina , Matei Alexandru-Emil , Trinh-Minh Thuong , Xu Xiaohan , Li Yi-Nan , Chen Chih-Wei , Lin Jianping , Dees Clara , Beyer Christian , Gelse Kolja , Zhang Zhong-Yin , Bergmann Christina , Ramming Andreas , Birchmeier Walter , Distler Oliver , Schett Georg , Distler Jörg H. W.
Published: August 2018

Uncontrolled activation of TGFβ signaling is a common denominator of fibrotic tissue remodeling. Here we characterize the tyrosine phosphatase SHP2 as a molecular checkpoint for TGFβ-induced JAK2/STAT3 signaling and as a potential target for the treatment of fibrosis. TGFβ stimulates the phosphatase activity of SHP2, although this effect is in part counterbalanced by inhibitory effects on SHP2 expression. Stimulation with TGFβ promotes recruitment of SHP2 to JAK2 in fibroblasts with subsequent dephosphorylation of JAK2 at Y570 and activation of STAT3. The effects of SHP2 on STAT3 activation translate into major regulatory effects of SHP2 on fibroblast activation and tissue fibrosis. Genetic or pharmacologic inactivation of SHP2 promotes accumulation of JAK2 phosphorylated at Y570, reduces JAK2/STAT3 signaling, inhibits TGFβ-induced fibroblast activation and ameliorates dermal and pulmonary fibrosis. Given the availability of potent SHP2 inhibitors, SHP2 might thus be a potential target for the treatment of fibrosis.
The Streptococcus pyogenes fibronectin/tenascin-binding protein PrtF.2 contributes to virulence in an influenza superinfection
Authors: Herrera Andrea L. , Faal Haddy , Moss Danielle , Addengast Leslie , Fanta Lauren , Eyster Kathleen , Huber Victor C. , Chaussee Michael S.
Published: August 2018

Influenza A virus (IAV) and Streptococcus pyogenes (the group A Streptococcus; GAS) are important contributors to viral-bacterial superinfections, which result from incompletely defined mechanisms. We identified changes in gene expression following IAV infection of A549 cells. Changes included an increase in transcripts encoding proteins with fibronectin-type III (FnIII) domains, such as fibronectin (Fn), tenascin N (TNN), and tenascin C (TNC). We tested the idea that increased expression of TNC may affect the outcome of an IAV-GAS superinfection. To do so, we created a GAS strain that lacked the Fn-binding protein PrtF.2. We found that the wild-type GAS strain, but not the mutant, co-localized with TNC and bound to purified TNC. In addition, adherence of the wild-type strain to IAV-infected A549 cells was greater compared to the prtF.2 mutant. The wild-type strain was also more abundant in the lungs of mice 24 hours after superinfection compared to the mutant strain. Finally, all mice infected with IAV and the prtF.2 mutant strain survived superinfection compared to only 42% infected with IAV and the parental GAS strain, indicating that PrtF.2 contributes to virulence in a murine model of IAV-GAS superinfection.
A rock physics modelling algorithm for simulating the elastic parameters of shale using well logging data
Authors: Wang Bing , Chen Yurong , Lu Jing , Jin Wujun
Published: August 2018

As a high-resolution geophysical method employed by the oil and gas industry, well logging can be used to accurately investigate reservoirs. Challenges associated with shale gas reservoir exploration increase the importance of applying elastic parameters or velocity at the logging scale. An efficient shale rock physics model is the foundation for the successful application of this method. We propose a procedure for modelling shale rock physics in which an appropriate modelling method is applied for different compositions of shale rock. The stiffnesses of the kerogen and fluid (oil, gas or water) mixture are obtained with the Kuster-Toksöz model, which assumes that the fluid is included in the kerogen matrix. A self-consistent approximation method is used to model clay, where the clay pores are filled with formation water. The Backus averaging model is then used to simulate the influence of laminated clay and laminated kerogen. Elastic parameter simulations using well logging data show the importance of treating the volume fractions of laminated clay and kerogen carefully. A comparison of the measured compressional slowness and modelled compressional slowness shows the efficiency of the proposed modelling procedure.
Electrochemical metallization cell with solid phase tunable Ge2Sb2Te5 electrolyte
Authors: Zhang Ziyang , Wang Yaoyuan , Wang Guanghan , Mu Jiaming , Ma Mingyuan , He Yuhan , Yang Rongrong , Li Huanglong
Published: August 2018

Electrochemical metallization (ECM) cell kinetics are strongly determined by the electrolyte and can hardly be altered after the cell has been fabricated. Solid-state property tunable electrolytes in response to external stimuli are therefore desirable to introduce additional operational degree of freedom to the ECM cells, enabling novel applications such as multistate memory and reconfigurable computation. In this work, we use Ge2Sb2Te5(GST) as the electrolyte material whose solid state is switched from the amorphous(a) to the crystalline(c) phase thermally. Electrical heating too is readily achievable. The resistive switching characteristics of the cells with different GST phases are examined. The magnitude of the high resistance, the SET voltage and the on/off ratio are found to be considerably affected by the solid phase of GST, whereas the magnitude of the low resistance is least affected. Moreover, a transition from volatile to nonvolatile SET switching is only observed for c-GST based cell under prolonged voltage sweep, but not for a-GST based cell. This work provides a springboard for more studies on the manipulation of the ECM cell kinetics by tunable electrolyte and the resulting unprecedented device functionalities.
Multi-marker metabarcoding approach to study mesozooplankton at basin scale
Authors: Stefanni Sergio , Stanković David , Borme Diego , de Olazabal Alessandra , Juretić Tea , Pallavicini Alberto , Tirelli Valentina
Published: August 2018

Zooplankton plays a pivotal role in marine ecosystems and the characterisation of its biodiversity still represents a challenge for marine ecologists. In this study, mesozooplankton composition from 46 samples collected in summer along the western Adriatic Sea, was retrieved by DNA metabarcoding analysis. For the first time, the highly variable fragments of the mtDNA COI and the V9 region of 18S rRNA genes were used in a combined matrix to compile an inventory of mesozooplankton at basin scale. The number of sequences retrieved after quality filtering were 824,148 and 223,273 for COI and 18S (V9), respectively. The taxonomical assignment against reference sequences, using 95% (for COI) and 97% (for 18S) similarity thresholds, recovered 234 taxa. NMDS plots and cluster analysis divided coastal from offshore samples and the most representative species of these clusters were distributed according to the dominant surface current pattern of the Adriatic for the summer period. For selected sampling sites, mesozooplankton species were also identified under a stereo microscope providing insights on the strength and weakness of the two approaches. In addition, DNA metabarcoding was shown to be helpful for the monitoring of non-indigenous marine metazoans and spawning areas of commercial fish species. We defined pros and cons of applying this approach at basin scale and the benefits of combining the datasets from two genetic markers.
Laplace-domain diffuse optical measurement
Authors: Hasnain Ali , Mehta Kalpesh , Zhou Xiaowei , Li Hongsheng , Chen Nanguang
Published: August 2018

Time-domain diffuse optical measurement systems determine depth-resolved absorption changes by using the time of flight distribution of the detected photons. It is well known that certain feature data, such as the Laplace transform of the temporal point spread function, is sufficient for image reconstruction and diffuse optical sensing. Conventional time-domain systems require the acquisition of full temporal profiles of diffusive photons and then numerically compute the feature dataset, for example, Laplace transformed intensities for imaging applications. We have proposed a novel method for directly obtaining the Laplace transform data. Our approach can significantly improve the data acquisition speed for time-domain diffuse optical imaging. We also demonstrated that the use of negative Laplace parameters can provide enhanced sensitivity to perturbations located in deep regions.
A cancer vaccine approach for personalized treatment of Lynch Syndrome
Authors: Majumder Snigdha , Shah Rakshit , Elias Jisha , Manoharan Malini , Shah Priyanka , Kumari Anjali , Chakraborty Papia , Kode Vasumathi , Mistry Yogesh , Coral Karunakaran , Mittal Bharti , SM Sakthivel Murugan , Mahadevan Lakshmi , Gupta Ravi , Chaudhuri Amitabha , Khanna-Gupta Arati
Published: August 2018

Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70–80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients. To this end we performed whole-exome and RNA seq analysis on the blood and tumour samples from an LS-CRC patient, and used our proprietary neoepitope prioritization pipeline OncoPeptVAC to select peptides, and confirm their immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes derived from the tumour of this patient elicited a potent CD8+ T cell response. Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T cells expressing low levels of activation markers, suggesting mechanisms of immune suppression at play in this relapsed tumour. Taken together, our study paves the way towards development of a cancer vaccine to treat or delay the onset/relapse of LS-CRC.
Immunoproteomic Identification and Characterization of Leishmania Membrane Proteins as Non-Invasive Diagnostic Candidates for Clinical Visceral Leishmaniasis
Authors: Ejazi Sarfaraz Ahmad , Bhattacharyya Anirban , Choudhury Somsubhra Thakur , Ghosh Sneha , Sabur Abdus , Pandey Krishna , Das Vidya Nand Ravi , Das Pradeep , Rahaman Mehebubar , Goswami Rama Prosad , Ali Nahid
Published: August 2018

Visceral leishmaniasis (VL), a potentially fatal disease is an outcome of infection caused by the parasiteLeishmania donovani. The clinical diagnostic tests for this disease are still related to invasive tissue aspiration or serological immunochromatography. Advancements in immunoproteomics such as two-dimensional gel electrophoresis, mass spectrometry, B cell epitope prediction, and peptide synthesis have enabled researchers to discover newer biomarkers for disease diagnosis. In this study, we have screened several urine-reactive leishmanial membrane proteins as potential biomarker candidates. In the immunoblot assay, three proteins 51, 55 and 63 kDa showed 100% reactivity to the urine of 47 VL patients and nonreactive to 18 healthy and other diseases. Mass spectrometry revealed the identity of 51, 55 and 63 kDa proteins as elongation factor 1α (EF1-α), α-tubulin, and glycoprotein 63, respectively. B cell reactive epitopes of these proteins were mapped through bioinformatic tools and one epitope from each protein that had the highest score were synthesized. All the three native electroeluted proteins and their corresponding synthetic peptides were tested through ELISA for reactivity with VL and control urine samples. While all three demonstrated good reactivity, the diagnostic performance of EF1-α was the best. Our findings illustrate the use of urine-based proteomic approach for biomarker discovery in non-invasive clinical diagnosis of VL.
Statistical Evidence for the Role of Southwestern Indian Ocean Heat Content in the Indian Summer Monsoon Rainfall
Authors: Venugopal T. , Ali M. M. , Bourassa M. A. , Zheng Y. , Goni G. J. , Foltz G. R. , Rajeevan M.
Published: August 2018

This study examines the benefit of using Ocean Mean Temperature (OMT) to aid in the prediction of the sign of Indian Summer Monsoon Rainfall (ISMR) anomalies. This is a statistical examination, rather than a process study. The thermal energy needed for maintaining and intensifying hurricanes and monsoons comes from the upper ocean, not just from the thin layer represented by sea surface temperature (SST) alone. Here, we show that the southwestern Indian OMT down to the depth of the 26 °C isotherm during January–March is a better qualitative predictor of the ISMR than SST. The success rate in predicting above- or below-average ISMR is 80% for OMT compared to 60% for SST. Other January–March mean climate indices (e.g., NINO3.4, Indian Ocean Dipole Mode Index, El Niño Southern Oscillation Modoki Index) have less predictability (52%, 48%, and 56%, respectively) than OMT percentage deviation (PD) (80%). Thus, OMT PD in the southwestern Indian Ocean provides a better qualitative prediction of ISMR by the end of March and indicates whether the ISMR will be above or below the climatological mean value.
Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice
Authors: Wadduwage Dushan N. , Kay Jennifer , Singh Vijay Raj , Kiraly Orsolya , Sukup-Jackson Michelle R. , Rajapakse Jagath , Engelward Bevin P. , So Peter T. C.
Published: August 2018

Homologous recombination (HR) events are key drivers of cancer-promoting mutations, and the ability to visualize these events in situ provides important information regarding mutant cell type, location, and clonal expansion. We have previously created the Rosa26Direct Repeat (RaDR) mouse model wherein HR at an integrated substrate gives rise to a fluorescent cell. To fully leverage this in situ approach, we need better ways to quantify rare fluorescent cells deep within tissues. Here, we present a robust, automated event quantification algorithm that uses image intensity and gradient features to detect fluorescent cells in deep tissue specimens. To analyze the performance of our algorithm, we simulate fluorescence behavior in tissue using Monte Carlo methods. Importantly, this approach reduces the potential for bias in manual counting and enables quantification of samples with highly dense HR events. Using this approach, we measured the relative frequency of HR within a chromosome and between chromosomes and found that HR within a chromosome is more frequent, which is consistent with the close proximity of sister chromatids. Our approach is both objective and highly rapid, providing a powerful tool, not only to researchers interested in HR, but also to many other researchers who are similarly using fluorescence as a marker for understanding mammalian biology in tissues.
A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes
Authors: Engelmann Brett W. , Hsiao Chiaowen Joyce , Blischak John D. , Fourne Yannick , Khan Zia , Ford Michael , Gilad Yoav
Published: August 2018

Phosphorylation of proteins on serine, threonine, and tyrosine residues is a ubiquitous post-translational modification that plays a key part of essentially every cell signaling process. It is reasonable to assume that inter-individual variation in protein phosphorylation may underlie phenotypic differences, as has been observed for practically any other molecular regulatory phenotype. However, we do not know much about the extent of inter-individual variation in phosphorylation because it is quite challenging to perform a quantitative high throughput study to assess inter-individual variation in any post-translational modification. To test our ability to address this challenge with SILAC-based mass spectrometry, we quantified phosphorylation levels for three genotyped human cell lines within a nested experimental framework, and found that genetic background is the primary determinant of phosphoproteome variation. We uncovered multiple functional, biophysical, and genetic associations with germline driven phosphopeptide variation. Variants affecting protein levels or structure were among these associations, with the latter presenting, on average, a stronger effect. Interestingly, we found evidence that is consistent with a phosphopeptide variability buffering effect endowed from properties enriched within longer proteins. Because the small sample size in this ‘pilot’ study may limit the applicability of our genetic observations, we also undertook a thorough technical assessment of our experimental workflow to aid further efforts. Taken together, these results provide the foundation for future work to characterize inter-individual variation in post-translational modification levels and reveal novel insights into the nature of inter-individual variation in phosphorylation.
Lake sediment fecal and biomass burning biomarkers provide direct evidence for prehistoric human-lit fires in New Zealand
Authors: Argiriadis E. , Battistel D. , McWethy D. B. , Vecchiato M. , Kirchgeorg T. , Kehrwald N. M. , Whitlock C. , Wilmshurst J. M. , Barbante C.
Published: August 2018

Deforestation associated with the initial settlement of New Zealand is a dramatic example of how humans can alter landscapes through fire. However, evidence linking early human presence and land-cover change is inferential in most continental sites. We employed a multi-proxy approach to reconstruct anthropogenic land use in New Zealand’s South Island over the last millennium using fecal and plant sterols as indicators of human activity and monosaccharide anhydrides, polycyclic aromatic hydrocarbons, charcoal and pollen as tracers of fire and vegetation change in lake-sediment cores. Our data provide a direct record of local human presence in Lake Kirkpatrick and Lake Diamond watersheds at the time of deforestation and a new and stronger case of human agency linked with forest clearance. The first detection of human presence matches charcoal and biomarker evidence for initial burning at c. AD 1350. Sterols decreased shortly after to values suggesting the sporadic presence of people and then rose to unprecedented levels after the European settlement. Our results confirm that initial human arrival in New Zealand was associated with brief and intense burning activities. Testing our approach in a context of well-established fire history provides a new tool for understanding cause-effect relationships in more complex continental reconstructions.