bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of the total sub-debris ablation from point-scale ablation data on a debris-covered glacier
Authors: Shah Sunil Singh , Banerjee Argha , Nainwal Harish Chandra , Shankar R.
Published: August 2019

Glaciological ablation is computed from point-scale data at a few ablation stakes that are usually regressed as a function of elevation and averaged over the area-elevation distribution of a glacier. This method is contingent on a tight control of elevation on local ablation. However, in debris-covered glaciers, systematic and random spatial variations of debris thickness modify the ablation rates. We propose and test a method to compute sub-debris ablation where stake data are interpolated as a function of debris-thickness alone and averaged over the debris-thickness distribution at different parts of the glacier. We apply this method on Satopanth Glacier located in Central Himalaya utilising ~1000 ablation measurements obtained from a network of up to 56 stakes during 2015–2017. The estimated mean sub-debris ablation ranges between 1.5±0.2 to 1.7±0.3 cm d−1. We show that the debris-thickness-dependent regression describes the spatial variability of the sub-debris ablation better than the elevation dependent regression. The uncertainties in ablation estimates due to the corresponding uncertainties in the measurement of ablation and debris-thickness distribution, and those due to interpolation procedures are estimated using Monte Carlo methods. Possible biases due to a finite number of stakes used are also investigated.
Interpersonal Violence as an Intrinsic Part of The Civilizing Process
Authors: Braun Andreas
Published: August 2019

Even though Elias himself does not focus on an explicit theory on violence inThe Civilizing Process, due to his research question on pacific social processes, violence is not generally theoretically excluded. Against this backdrop, and contrary to criticisms regarding a general loss as well as a biological rather than a sociological explanation of violence, and besides theories that explain meso and macro-level violence within Elias’s framework, this article considers interpersonal micro-level violence as an intrinsic part of the civilizing process. Especially by supplementing Elias’s assumptions of drive control and self-constraint with recent neuroscientific findings, it is possible to conceptualize interpersonal micro-level violence as situational exceedance of a subjective threshold of pain. Here, despite a normative civilized frame of behavior, aggression, as a (neuro)biologically-based reactive drive, is no longer controlled by socially learned self-constraint, leading to violence as a subjectively perceived rewarding behavior and socially performed action.
On Populists and Demagogues
Authors: Patapan Haig
Published: August 2019

The article seeks to understand what is specifically modern about populists, why we have difficulty in agreeing on who and what they are, and—importantly—how we can address the formidable challenge they present to contemporary democratic politics. It does so by detailing the classical conception of the demagogue and by showing how modernity, in its liberal and counter-liberal aspects, sought to solve conclusively the problem of the demagogue. It argues that modern populists face significant obstacles to their ambitions in the form of modern constitutionalism, yet are also armed with new weapons, including new concepts or “ideologies” for manipulation (such as “the people,” nation, race and class) and new rhetorical techniques (such as propaganda that exploits modern technology and mass media).
“EVERY SPERM IS SACRED”: PALESTINIAN PRISONERS, SMUGGLED SEMEN, AND DERRIDA'S PROPHECY
Authors: Hamdan Mohammed
Published: August 2019

This paper investigates the contemporary phenomenon of smuggling sperm from within Israeli jails, which I treat as a biopolitical act of resistance. Palestinian prisoners who have been sentenced to life-imprisonment have recently resorted to delivering their sperm to their distant wives in the West Bank and Gaza where it is then used for artificial insemination. On the level of theory, my analysis of this practice benefits from Jacques Derrida's commentary inThe Post Cardon imaginative postal delivery of sperm to distant lovers. I use Derrida's heteronormative implication to examine how Palestinian prisoners defy the Israeli carceral system via the revolutionary act of sperm smuggling. The article then argues that smuggling sperm challenges the conventional gender codes in Palestinian society that see women in passive roles. Drawing on Derrida's metaphorical connection between masturbation and writing, I problematize the perception of speech/orality as primary in traditional Palestinian culture. Women, who mostly act as smugglers, become social agents whose written stories of bionational resistance emerge as a dominant mode of representation.
How can schistosome circulating antigen assays be best applied for diagnosing male genital schistosomiasis (MGS): an appraisal using exemplar MGS cases from a longitudinal cohort study among fishermen on the south shoreline of Lake Malawi
Authors: Kayuni S. A. , Corstjens P. L. A. M. , LaCourse E. J. , Bartlett K. E. , Fawcett J. , Shaw A. , Makaula P. , Lampiao F. , Juziwelo L. , de Dood C. J. , Hoekstra P. T. , Verweij J. J. , Leutscher P. D. C. , van Dam G. J. , van Lieshout L. , Stothard J. R.
Published: August 2019

We provide an update on diagnostic methods for the detection of urogenital schistosomiasis (UGS) in men and highlight that satisfactory urine-antigen diagnostics for UGS lag much behind that for intestinal schistosomiasis, where application of a urine-based point-of-care strip assay, the circulating cathodic antigen (CCA) test, is now advocated. Making specific reference to male genital schistosomiasis (MGS), we place greater emphasis on parasitological detection methods and clinical assessment of internal genitalia with ultrasonography. Unlike the advances made in defining a clinical standard protocol for female genital schistosomiasis, MGS remains inadequately defined. Whilst urine filtration with microscopic examination for ova of Schistosoma haematobium is a convenient but error-prone proxy of MGS, we describe a novel low-cost sampling and direct visualization method for the enumeration of ova in semen. Using exemplar clinical cases of MGS from our longitudinal cohort study among fishermen along the shoreline of Lake Malawi, the portfolio of diagnostic needs is appraised including: the use of symptomatology questionnaires, urine analysis (egg count and CCA measurement), semen analysis (egg count, circulating anodic antigen measurement and real-time polymerase chain reaction analysis) alongside clinical assessment with portable ultrasonography.
Promastigote secretory gel from natural and unnatural sand fly vectors exacerbateLeishmania majorandLeishmania tropicacutaneous leishmaniasis in mice
Authors: Giraud E. , Svobodová M. , Müller I. , Volf P. , Rogers M. E.
Published: August 2019

Leishmaniarely heavily on glycans to complete their digenetic life cycle in both mammalian and phlebotomine sand fly hosts.Leishmaniapromastigotes secrete a proteophosphoglycan-rich gel (Promastigote Secretory Gel, PSG) that is regurgitated during transmission and can exacerbate infection in the skin. Here we explored the role of PSG from naturalLeishmania-sand fly vector combinations by obtaining PSG fromLeishmania (L.) major-infectedPhlebotomus (P.) papatasiandP. duboscqiandL. tropica-infectedP. arabicus. We found that, in addition to the vector's saliva, the PSG fromL. majorandL. tropicapotently exacerbated cutaneous infection in BALB/c mice, improved the probability of developing a patent cutaneous lesion, parasite growth and the evolution of the lesion. Of note, the presence of PSG in the inoculum more than halved the prepatent period of cutaneousL. tropicainfection from an average of 32 weeks to 13 weeks. In addition,L. majorandL. tropicaPSG extracted from the permissive experimental vector,Lutzomyia (Lu.) longipalpis, also exacerbated infections in mice. These results reinforce and extend the hypothesis that PSG is an important and evolutionarily conserved component ofLeishmaniainfection that can be used to facilitate experimental infection for drug and vaccine screening.
Vote Brokers, Clientelist Appeals, and Voter Turnout: Evidence from Russia and Venezuela
Authors: Frye Timothy , Reuter Ora John , Szakonyi David
Published: August 2019

Modern clientelist exchange is typically carried out by intermediaries—party activists, employers, local strongmen, traditional leaders, and the like. Politicians use such brokers to mobilize voters, yet little about their relative effectiveness is known. The authors argue that broker effectiveness depends on their leverage over clients and their ability to monitor voters. They apply their theoretical framework to compare two of the most common brokers worldwide, party activists and employers, arguing the latter enjoy numerous advantages along both dimensions. Using survey-based framing experiments in Venezuela and Russia, the authors find voters respond more strongly to turnout appeals from employers than from party activists. To demonstrate mechanisms, the article shows that vulnerability to job loss and embeddedness in workplace social networks make voters more responsive to clientelist mobilization by their bosses. The results shed light on the conditions most conducive to effective clientelism and highlight broker type as important for understanding why clientelism is prevalent in some countries but not others.
Imperial Rule, the Imposition of Bureaucratic Institutions, and their Long-Term Legacies
Authors: Vogler Jan P.
Published: August 2019

Significant variation in the institutions and efficiency of public bureaucracies across countries and regions are observed. These differences could be partially responsible for divergence in the effectiveness of policy implementation, corruption levels, and economic development. Do imperial legacies contribute to the observed variation in the organization of public administrations? Historical foreign rule and colonization have been shown to have lasting effects on legal systems, political institutions, and trade in former controlled territories. Imperial legacies could also explain variations in the performance of public administrations. The author uses the case of Poland to investigate the long-term effects of foreign rule on bureaucratic systems. Historically, Poland was split between three imperial powers with very different public administrations: Prussia, Austria, and Russia. Statistical analyses of original data collected through a survey of more than 650 Polish public administrations suggest that some present-day differences in the organization and efficiency of bureaucracies are due to imperial legacies.
A TALE OF TWO CHURCHES: ‘PROTESTANT’ ARCHITECTURE AND THE POLITICS OF RELIGION IN LATE NINETEENTH-CENTURY ROME
Authors: Bremner G.A.
Published: August 2019

The two Anglican churches in Rome by the distinguished nineteenth-century English architect George Edmund Street — St Paul's Within-the-Walls (1872–6), Via Nazionale, and All Saints’ (1880–7), Via del Babuino — are notable examples of High Victorian design. Yet little scholarly attention has been afforded either church, especially All Saints’. This article considers both these buildings not so much as works of architecture but as markers of cultural intent in an environment (and age) fraught with political and religious tension and conflict. It seeks to understand them in the difficult and often fluid context of Risorgimento Italy out of which they emerged, including the city of Rome immediately following its capture by Italian national forces on 20 September 1870. The aim is to establish an interpretation of the two buildings that pays due attention to their political and religious agency. In so doing this article considers closely how architecture was understood as a mediating force in the struggle over politics and identity in the late nineteenth century. In taking a fresh look at the extant archival documentation, alternative possibilities are offered (and revealed) as to how we might further decode the significance of these beguiling if still largely misunderstood works of architecture.
The maximal current carried by a normal–superconducting interface in the absence of magnetic field
Authors: HART L. K. , ALMOG Y.
Published: August 2019

Modelling a normal–superconducting interface, we consider a semi-infinite wire whose edge is adjacent to a normal magnetic metal, assuming asymptotic convergence, away from the boundary, to the purely superconducting state. We obtain that the maximal current which can be carried by the interface diminishes in the small normal conductivity limit.
Anethole improves blastocysts rates together with antioxidant capacity when added during bovine embryo culture rather than in the in vitro maturation medium
Authors: Anjos J.C. , Aguiar F.L.N. , Sá N.A.R. , Souza J.F. , Cibin F.W.S. , Alves B.G. , Santos R.R. , Figueiredo J.R.
Published: August 2019

We performed the exposure of bovine oocytes to anethole during in vitro maturation (0 or 300 µg/ml), during in vitro embryo production (0, 30, 300 or 2000 µg/ml), or during both periods to determine the rates of 2−4 cells embryos, blastocysts rates and cells numbers, as well as the production of reactive oxygen species (ROS). Bovine ovaries (n = 240) were collected from a local abattoir after slaughter and cumulus–oocyte complexes (COCs) with homogeneous and non-dark cytoplasm, surrounded by two or more compact layers of cumulus cells, and an intact zona pellucida were selected for in vitro maturatuion (IVM). Mature oocytes were then submitted to in vitro fertilization (IVF) and in vitro embryo production (IVP) in culture medium supplemented or not with different concentrations of anethole, as described above. Although IVM medium supplementation with 300 µg/ml anethole improved the rates of bovine blastocysts formation, we demonstrated that IVP medium supplementation with 30 µg/ml anethole, regardless of IVM medium enrichment, considerably enhanced blastocysts rates. Furthermore, ROS levels were decreased only when anethole was added to the IVP medium without previous IVM medium supplementation.
Incidental finding of type A aortic dissection in a paediatric heart transplant recipient
Authors: D’Addese Laura , Komarlu Rukmini , Zahka Kenneth
Published: August 2019

Aortic dissection causes significant morbidity and mortality in adults and treatment guidelines are based on well-documented risk factors. Conversely, dissection after orthotopic heart transplantation is very rare, especially in the absence of infection, hypertension, or donor–recipient aortic size mismatch. Several forms of CHD are associated with aortic dilatation, but the incidence of aortic dissection and aneurysm in children is also low, which makes use of adult guidelines in children challenging. We present a 17-year-old Amish female with a homozygous gene mutation in the MYBPC3 gene known to cause lethal, infantile hypertrophic cardiomyopathy. She underwent orthotopic heart transplantation and then developed an asymptomatic aortic dissection despite no known risk factors.
Motivating residents to change communication: the role of a brief motivational interviewing didactic
Authors: Miller-Matero Lisa Renee , Tobin Erin T. , Fleagle Elizabeth , Coleman Joseph P. , Nair Anupama
Published: August 2019

Introduction:

Motivational interviewing (MI) is a patient-centered approach that encourages patients to change behaviors. MI training programs have increased residents’ knowledge and use of MI skills; however, many residency programs may not have the time to dedicate to lengthy MI programs. The purpose of this study was to evaluate the benefits of a brief MI didactic for residents in an academic internal medicine patient-centered medical home.

Methods:

Thirty-two residents completed a 1-h MI training between October 2016 and June 2017 and completed measures on their knowledge of, confidence using, and utilization of MI skills prior to the training, immediately after the training, and at a 1-month follow-up.

Results:

The residents’ knowledge of and confidence using MI skills increased from pre-test to post-test and also increased from pre-test to the 1-month follow-up.

Conclusion:

The utilization of MI skills increased from pre-test to the 1-month follow-up. A 1-h didactic offers benefits to residents.
Risk of dementia and cognitive dysfunction in individuals with diabetes or elevated blood glucose
Authors: Wium-Andersen I K , Rungby J , Jørgensen M B , Sandbæk A , Osler M , Wium-Andersen M K
Published: August 2019

Aims

To determine the risk of dementia in patients with type 1 or type 2 diabetes and in individuals with glycosylated haemoglobin, type A1C (HbA1c) of ⩾48 mmol/mol, which is the diagnostic limit for diabetes.

Methods

We included the following cohorts: all incident diabetes cases aged 15 or above registered in the National Diabetes Registry (NDR) from January 2000 through December 2012 (n= 148 036) and a reference population, adult participants from the Glostrup cohort (n= 16 801), the ADDITION Study (n= 26 586) and Copenhagen Aging and Midlife Biobank (CAMB) (n= 5408). Using these cohorts, we analysed if a diagnosis of type 1 or type 2 diabetes in the NDR or HbA1c level of ⩾ 6.5% (48 mmol/mol) in the cohorts increased risk of dementia in the Danish National Patient Registry or cognitive performance assessed by the Intelligenz-Struktur-Test 2000R (IST2000R).

Results

A diagnosis of type 1 or type 2 diabetes in the NDR was associated with increased risk of dementia diagnosed both before or after age 65 as well as across different subtypes of dementia. Self-reported diabetes or high HbA1c levels were associated with lower cognitive performance (p= 0.004), while high HbA1c was associated with increased risk of dementia (HR 1.94 (1.10–3.44) in the Glostrup cohort but not in the ADDITION Study (HR 0.96 (0.57–1.61)).

Conclusions

Both type 1 and type 2 diabetes are associated with an increased risk of dementia, while the importance of screening-detected elevated HbA1c remains less clear.
Reduced herbicide rates for control of living mulch and weeds in fresh market tomato
Authors: Bhaskar Vinay , Bellinder Robin R. , Reiners Stephen , DiTommaso Antonio
Published: August 2019

Living mulches can provide many sustainability benefits. However, living mulch–cash crop competition and unreliable weed control are major challenges in living mulch systems. In this study, we evaluated the potential of herbicides used at reduced rates in combination with living mulch to suppress weeds, while simultaneously reducing living mulch vigor. Herbicide treatments were a combination of two POST applications, each consisting of a single, different herbicide. Field trials were conducted in Freeville, NY, USA, using: fresh market field tomato as cash crop; sesbania and sunn hemp as living mulch; and the herbicides fomesafen, halosulfuron, metribuzin, and rimsulfuron. In 2015, when water was not limiting, tomato yield and living mulch biomass were positively correlated. This relationship was negative in 2016, likely because of drought during the growing season. Compared with the untreated living mulch check, using the herbicide treatments in combination with living mulch reduced tomato yield losses by up to 71% in 2015 and 51% in 2016. In these herbicide plus living mulch plots, weed biomass was reduced by up to 97%, compared with the weedy check. Living mulch in herbicide treatments generated up to 2500 kg ha−1 of dry matter during both 2015 and 2016, with an average ground cover of 63% in 2015 and 85% in 2016. A predominantly PRE herbicide with residual soil activity (metribuzin), followed by a herbicide with greater POST activity (halosulfuron/rimsulfuron) was the most effective herbicide application sequence. Results from our study indicate that well-designed herbicide applications may enhance the practicability of living mulch systems.
Extended U.S. Tornado Outbreak During Late May 2019: A Forecast of Opportunity
Authors: Gensini Vittorio A. , Gold David , Allen John T. , Barrett Bradford S.
Published: August 2019

The second half of May 2019 was an unusually active period for tornadic thunderstorms across the U.S. Great Plains, Midwest, and lower Great Lakes. While this period typically coincides with the peak climatological frequency of tornadoes, preliminary reports of tornadoes were over triple the expected 30‐year average. Multiple‐day outbreaks of tornadoes are not unprecedented in the United States; however, this event was perhaps the first to be forecast at subseasonal lead times (3–4 weeks) by the Extended Range Tornado Activity Forecast team. This forecast of opportunity was driven, in part, by anomalous convective forcing in portions of the tropical Indian and Pacific Oceans, causing subsequent changes in Northern Hemisphere atmospheric angular momentum. This manuscript analyzes the evolution of hemispheric‐scale circulation features leading up to the event, examines teleconnection processes known to influence U.S. tornadoes, and provides insights into the forecast process at subseasonal lead times.
Lunar Tide in the F Region Ionosphere
Authors: Forbes Jeffrey M. , Zhang Xiaoli
Published: August 2019

In this paper the magnetic latitude (±50°) and longitude, local solar time (LST), and month‐to‐month variability of the M2 lunar semidiurnal tide in the ionosphere is revealed through analysis of topside F region electron density measurements by the Planar Langmuir Probe instrument on the CHAMP satellite during the two 5‐year periods 2001–2005 and 2005–2009. The local time precession rate of CHAMP is such that 5 years is required to obtain full LST coverage for every month of the year at each latitude of interest. Thus, each 5‐year period is compressed into one equivalent year. M2 amplitudes, expressed in terms of percent residuals from a background value, range between about 3% and 20% and vary considerably with LST and magnetic longitude. Longitude variations in principle arise from zonal asymmetries in lunar tidal forcing due to Earth and ocean tides, as well as magnitude of Earth's magnetic field. The O1 diurnal tide is also discussed in the context of CHAMP and other measurements of the F region ionosphere.
Nighttime Magnetic Perturbation Events Observed in Arctic Canada: 1. Survey and Statistical Analysis
Authors: Engebretson M. J. , Pilipenko V. A. , Ahmed L. Y. , Posch J. L. , Steinmetz E. S. , Moldwin M. B. , Connors M. G. , Weygand J. M. , Mann I. R. , Boteler D. H. , Russell C. T. , Vorobev A. V.
Published: August 2019

The rapid changes of magnetic fields associated with large, isolated magnetic perturbations with amplitudes |ΔB| of hundreds of nanotesla and 5‐ to 10‐min periods can induce bursts of geomagnetically induced currents that can harm technological systems. This paper presents statistical summaries of the characteristics of nightside magnetic perturbation events observed in Eastern Arctic Canada from 2014 through 2017 using data from stations that are part of four magnetometer arrays: MACCS, AUTUMNX, CANMOS, and CARISMA, covering a range of magnetic latitudes from 68 to 78°. Most but not all of the magnetic perturbation events were associated with substorms: roughly two thirds occurred between 5 and 30 min after onset. The association of intense nighttime magnetic perturbation events with magnetic storms was significantly reduced at latitudes above 73°, presumably above the nominal auroral oval. A superposed epoch study of 21 strong events at Cape Dorset showed that the largest |dB/dt| values appeared within an ~275‐km radius that was associated with a region of shear between upward and downward field‐aligned currents. The statistical distributions of impulse amplitudes of both |ΔB| and |dB/dt| fit well the log‐normal distribution at all stations. The |ΔB| distributions are similar over the magnetic latitude range studied, but the kurtosis and skewness of the |dB/dt| distributions show a slight increase with latitude. Knowledge of the statistical characteristics of these events has enabled us to estimate the occurrence probability of extreme impulsive disturbances using the approximation of a log‐normal distribution.
Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity
Authors: van Baak Marleen A. , Vink Roel G. , Roumans Nadia J. T. , Cheng Christine C. , Adams Andrew C. , Mariman Edwin C. M.
Published: August 2019

Fibroblast growth factor 21 (FGF21) is an important regulator of energy metabolism. FGF21 is inactivated by fibroblast activation protein (FAP). We investigated whether FGF21 and/or FAP are secreted from human white adipose tissue of individuals with obesity by measuring total FGF21, active FGF21, and FAP concentrations in arterialized blood and venous blood draining the subcutaneous abdominal adipose tissue (scAT). Measurements were performed under fasting conditions and after a high fat meal before and after diet-induced weight loss in 16 adults with BMI 27–35 kg/m2. FGF21 was not released from scAT, neither before nor after weight loss in agreement with an undetectable gene expression of FGF21 in this tissue. Although scAT showed significant gene expression of FAP, no release of FAP from the tissue could be detected. The high fat meal increased postprandial circulating FGF21 but not FAP. Circulating levels of FAP but not FGF21 were significantly reduced after weight loss. On the other hand, FAP expression in scAT was increased. In conclusion, release from scAT does not appear to contribute to circulating concentrations of FGF21 and FAP and their responses to ingestion of a high fat meal or weight loss, respectively, in individuals with obesity.
Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies
Authors: Kourelis Taxiarchis V. , Villasboas Jose C. , Jessen Erik , Dasari Surendra , Dispenzieri Angela , Jevremovic Dragan , Kumar Shaji
Published: August 2019

Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with the development of a progressively more “permissive” immune tumor microenvironment (iTME). Novel multiparametric cytometry approaches, such as cytometry by time-of-flight (CyTOF) combined with novel gating algorithms can rapidly characterize previously unknown phenotypes in the iTME of tumors and better capture its heterogeneity. Here, we used a 33-marker CyTOF panel to characterize the iTME of dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, and AL amyloidosis) at diagnosis and after standard of care first line therapies (triplet induction chemotherapy and autologous stem cell transplant—ASCT). We identify novel subsets, some of which are unique to the iTME and absent from matched peripheral blood samples, with potential roles in tumor immunosurveillance as well as tumor immune escape. We find that AL amyloidosis has a distinct iTME compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. We show that T cell immune senescence might be implicated in disease pathogenesis in patients with trisomies. Finally, we demonstrate that the early post-ASCT period is associated with an increase of senescent and exhausted subsets, which might have implications for the rational selection of post-ASCT therapies.
ERα-mediated alterations in circ_0023642 and miR-490-5p signaling suppress bladder cancer invasion
Authors: Wu Longxiang , Zhang Mengda , Qi Lin , Zu Xiongbing , Li Yuan , Liu Longfei , Chen Minfeng , Li Yangle , He Wei , Hu Xiheng , Mo Miao , Ou Zhenyu , Wang Long
Published: August 2019

Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we explored the mechanisms by which ERα inhibits BCa invasion by modulating circRNA levels. ERα suppressed BCa invasion by decreasing circ_0023642 expression. Chromatin immunoprecipitation (ChIP) and luciferase assays revealed that ERα reduced circ_0023642 expression by regulating the expression of its host gene, UVRAG, at the transcriptional level. ERα decreased circ_0023642 levels and subsequently increased miR-490-5p expression, resulting in decreased EGFR expression to suppress BCa cell invasion. Circ_0023642 was demonstrated to directly bind to miR-490-5p. Notably, miR-490-5p regulated EGFR expression by binding to the miR-490-5p-binding site located in the 3′-untranslated region (UTR) of the EGFR mRNA. Preclinical studies using an in vivo mouse model also confirmed that this ERα/circ_0023642/miR-490-5p/EGFR signaling pathway suppressed BCa progression. Altogether, this newly identified pathway may serve as the basis for developing novel therapeutic strategies to treat BCa.
GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling
Authors: Matsumoto Shinji , Yamamichi Taku , Shinzawa Koei , Kasahara Yuuya , Nojima Satoshi , Kodama Takahiro , Obika Satoshi , Takehara Tetsuo , Morii Eiichi , Okuyama Hiroomi , Kikuchi Akira
Published: August 2019

The β-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/β-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/β-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of β-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFβ signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/β-catenin signaling and required for HB progression.
A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8+ T-cell response and effective tumor control
Authors: Sun Zhichen , Ren Zhenhua , Yang Kaiting , Liu Zhida , Cao Shuaishuai , Deng Sisi , Xu Lily , Liang Yong , Guo Jingya , Bian Yingjie , Xu Hairong , Shi Jiyun , Wang Fan , Fu Yang-Xin , Peng Hua
Published: August 2019

While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies.
High-performance silk-based hybrid membranes employed for osmotic energy conversion
Authors: Xin Weiwen , Zhang Zhen , Huang Xiaodong , Hu Yuhao , Zhou Teng , Zhu Congcong , Kong Xiang-Yu , Jiang Lei , Wen Liping
Published: August 2019

The salinity gradient between seawater and river water is a clean energy source and an alternative solution for the increasing energy demands. A membrane-based reverse electrodialysis technique is a promising strategy to convert osmotic energy to electricity. To overcome the limits of traditional membranes with low efficiency and high resistance, nanofluidic is an emerging technique to promote osmotic energy harvesting. Here, we engineer a high-performance nanofluidic device with a hybrid membrane composed of a silk nanofibril membrane and an anodic aluminum oxide membrane. The silk nanofibril membrane, as a screening layer with condensed negative surface and nanochannels, dominates the ion transport; the anodic aluminum oxide membrane, as a supporting substrate, offers tunable channels and amphoteric groups. Thus, a nanofluidic membrane with asymmetric geometry and charge polarity is established, showing low resistance, high-performance energy conversion, and long-term stability. The system paves avenues for sustainable power generation, water purification, and desalination.
Catalytic amidation of natural and synthetic polyol esters with sulfonamides
Authors: Liu Hua , Zhu Yi-Ling , Li Zhi
Published: August 2019

Triacylglycerides are naturally abundant and renewable feedstock for biofuels and chemicals. In this report, these seemingly stable compounds are shown to be reactive toward a variety of sulfonamides under Lewis acid catalysis. In these reactions, alkyl C(sp3)–O bonds are cleaved and C–N bonds constructed, providing functionalized value-added products directly from renewables. Mechanistic and scope study demonstrate that the origin of the reactivity could be the synergy of Lewis acid catalysis and neighboring group participation by the 2- or 3-acyloxy or acylamido group with respect to the reactive site. Since poly(ethylene terephthalate) (PET), a widely available consumer polyester, also contains 1,2-diol diester group as the repeating unit in the main chain, this chemistry can also be applied to efficient depolymerization of PET.
Revisiting the genetic diversity of emerging hantaviruses circulating in Europe using a pan-viral resequencing microarray
Authors: Filippone Claudia , Castel Guillaume , Murri Séverine , Ermonval Myriam , Korva Misa , Avšič-Županc Tatjana , Sironen Tarja , Vapalahati Olli , McElhinney Lorraine M. , Ulrich Rainer G. , Groschup Martin H. , Caro Valérie , Sauvage Frank , van der Werf Sylvie , Manuguerra Jean-Claude , Gessain Antoine , Marianneau Philippe , Tordo Noël
Published: August 2019

Hantaviruses are zoonotic agents transmitted from small mammals, mainly rodents, to humans, where they provoke diseases such as Hemorrhagic fever with Renal Syndrome (HFRS) and its mild form, Nephropathia Epidemica (NE), or Hantavirus Cardio-Pulmonary Syndrome (HCPS). Hantaviruses are spread worldwide and monitoring animal reservoirs is of primary importance to control the zoonotic risk. Here, we describe the development of a pan-viral resequencing microarray (PathogenID v3.0) able to explore the genetic diversity of rodent-borne hantaviruses endemic in Europe. Among about 800 sequences tiled on the microarray, 52 correspond to a tight molecular sieve of hantavirus probes covering a large genetic landscape. RNAs from infected animal tissues or from laboratory strains have been reverse transcribed, amplified, then hybridized to the microarray. A classical BLASTN analysis applied to the sequence delivered through the microarray allows to identify the hantavirus species up to the exact geographical variant present in the tested samples. Geographical variants of the most common European hantaviruses from France, Germany, Slovenia and Finland, such as Puumala virus, Dobrava virus and Tula virus, were genetically discriminated. Furthermore, we precisely characterized geographical variants still unknown when the chip was conceived, such as Seoul virus isolates, recently emerged in France and the United Kingdom.
Non-Contact Universal Sample Presentation for Room Temperature Macromolecular Crystallography Using Acoustic Levitation
Authors: Morris R. H. , Dye E. R. , Axford D. , Newton M. I. , Beale J. H. , Docker P. T.
Published: August 2019

Macromolecular Crystallography is a powerful and valuable technique to assess protein structures. Samples are commonly cryogenically cooled to minimise radiation damage effects from the X-ray beam, but low temperatures hinder normal protein functions and this procedure can introduce structural artefacts. Previous experiments utilising acoustic levitation for beamline science have focused on Langevin horns which deliver significant power to the confined droplet and are complex to set up accurately. In this work, the low power, portable TinyLev acoustic levitation system is used in combination with an approach to dispense and contain droplets, free of physical sample support to aid protein crystallography experiments. This method facilitates efficient X-ray data acquisition in ambient conditions compatible with dynamic studies. Levitated samples remain free of interference from fixed sample mounts, receive negligible heating, do not suffer significant evaporation and since the system occupies a small volume, can be readily installed at other light sources.
Complex Susceptibilities and Chiroptical Effects of Collagen Measured with Polarimetric Second-Harmonic Generation Microscopy
Authors: Golaraei Ahmad , Kontenis Lukas , Mirsanaye Kamdin , Krouglov Serguei , Akens Margarete K. , Wilson Brian C. , Barzda Virginijus
Published: August 2019

Nonlinear optical properties of collagen type-I are investigated in thin tissue sections of pig tendon as a research model using a complete polarimetric second-harmonic generation (P-SHG) microscopy technique called double Stokes-Mueller polarimetry (DSMP). Three complex-valued molecular susceptibility tensor component ratios are extracted. A significant retardance is observed between the chiral susceptibility component and the achiral components, while the achiral components appear to be in phase with each other. The DSMP formalism and microscopy measurements are further used to explain and experimentally validate the conditions required for SHG circular dichroism (SHG-CD) of collagen to occur. The SHG-CD can be observed with the microscope when: (i) the chiral second-order susceptibility tensor component has a non-zero value, (ii) a phase retardance is present between the chiral and achiral components of the second-order susceptibility tensor and (iii) the collagen fibres are tilted out of the image plane. Both positive and negative areas of SHG-CD are observed in microscopy images, which relates to the anti-parallel arrangement of collagen fibres in different fascicles of the tendon. The theoretical formalism and experimental validation of DSMP imaging technique opens new opportunities for ultrastructural characterisation of chiral molecules, in particular collagen, and provides basis for the interpretation of SHG-CD signals. The nonlinear imaging of chiroptical parameters offers new possibilities to further improve the diagnostic sensitivity and/or specificity of nonlinear label-free histopathology.
Long-term isolation at a low effective population size greatly reduced genetic diversity in Gulf of California fin whales
Authors: Rivera-León Vania E. , Urbán Jorge , Mizroch Sally , Brownell Robert L. , Oosting Tom , Hao Wensi , Palsbøll Per J. , Bérubé Martine
Published: August 2019

The Gulf of California, Mexico is home to many cetacean species, including a presumed resident population of fin whales,Balaenoptera physalus. Past studies reported very low levels of genetic diversity among Gulf of California fin whales and a significant level of genetic differentiation from con-specifics in the eastern North Pacific. The aim of the present study was to assess the degree and timing of the isolation of Gulf of California fin whales in a population genetic analysis of 18 nuclear microsatellite genotypes from 402 samples and 565 mitochondrial control region DNA sequences (including mitochondrial sequences retrieved from NCBI). The analyses revealed that the Gulf of California fin whale population was founded ~2.3 thousand years ago and has since remained at a low effective population size (~360) and isolated from the eastern North Pacific (Nembetween 0.89–1.4). The low effective population size and high degree of isolation implied that Gulf of California fin whales are vulnerable to the negative effects of genetic drift, human-caused mortality and habitat change.
Differentiating cervical metastatic lymphadenopathy and lymphoma by shear wave elastography
Authors: Chae Soo Young , Jung Hye Na , Ryoo Inseon , Suh Sangil
Published: August 2019

Shear wave elastography (SWE) is a recent technological advance of ultrasonography (US) to assess tissue stiffness. The purpose of this study is to assess tissue stiffness of malignant cervical lymph nodes (LN) with SWE, to reveal diagnostic performance of SWE in differentiating metastatic LN from lymphoma, and to assess inter-observer agreement of SWE. We assessed 62 malignant LN (24 lymphomas and 38 metastatic LN) and their median speed was 6.34 m/s and median elasticity was 69.7 kPa. Add of SWE with conventional US improved diagnostic accuracy of differentiating metastasis from lymphoma (16.13, 8.07 and 11.3% for three radiologists). Kendall’s Coefficient of Concordance of three readers for analyzing SWE patterns was 0.86. SWE can be a useful tool to discriminate metastatic cervical LN from lymphoma with improvement of diagnostic accuracy when using with conventional US.
Phylogenetic characterization of bacterial endophytes from four Pinus species and their nematicidal activity against the pine wood nematode
Authors: Ponpandian Lakshmi Narayanan , Rim Soon Ok , Shanmugam Gnanendra , Jeon Junhyun , Park Young-Hwan , Lee Sun-Keun , Bae Hanhong
Published: August 2019

Recently, bacterial endophytes (BEs) have gained importance in the agricultural sector for their use as biocontrol agents to manage plant pathogens. Outbreak of the pine wilt disease (PWD) in Korea has led researchers to test the feasibility of BEs in controlling the pine wood nematode (PWN)Bursaphelenchus xylophilus. In this study, we have reported the diversity and biocontrol activity of BEs against the PWN. By employing a culture-dependent approach, 1,622 BEs were isolated from the needle, stem, and root tissues ofP.densiflora,P.rigida,P.thunbergii, andP.koraiensisacross 18 sampling sites in Korea. We classified 389 members based on 16S rDNA analysis and taxonomic binning, of which, 215 operational taxonomic units (OTUs) were determined. Using Shannon’s indices, diversity across thePinusspecies and tissues was estimated to reveal the composition of BEs and their tissue-specific preferences. When their ethyl acetate crude extracts were analysed for biocontrol activity, 44 candidates with nematicidal activity were obtained. Among these,StenotrophomonasandBacillussp. exhibited significant inhibitory activity against PWN during their developmental stages. Altogether, our study furnishes a basic comprehension of bacterial communities found in thePinusspecies and highlights the potential of BEs as biocontrol agents to combat PWD.
PIDD interaction with KEAP1 as a new mutation-independent mechanism to promote NRF2 stabilization and chemoresistance in NSCLC
Authors: Ji Lili , Zhang Rui , Chen Jie , Xue Qun , Moghal Nadeem , Tsao Ming-Sound
Published: August 2019

Chemotherapy resistance is a major problem in non-small cell lung cancer (NSCLC) treatment. A major mechanism of chemoresistance involves stabilization of the NRF2 transcription factor. NRF2 levels are normally tightly regulated through interaction with KEAP1, an adaptor that targets NRF2 to the CUL3 E3 ubiquitin ligase for proteolysis. In NSCLC, aberrant NRF2 stabilization is best understood through mutations in NRF2, KEAP1, or CUL3 that disrupt their interaction. Biochemical studies, however, have revealed that NRF2 can also be stabilized through expression of KEAP1-interacting proteins that competitively sequester KEAP1 away from NRF2. Here, we have identified PIDD, as a novel KEAP1-interactor in NSCLC that regulates NRF2. We show that this interaction allows PIDD to reduce NRF2 ubiquitination and increase its stability. We also demonstrate that PIDD promotes chemoresistance in NSCLC cells both in vitro and in vivo, and that this effect is dependent on NRF2. Finally, we report that NRF2 protein expression in a NSCLC cohort exceeds the typical incidence of combined NRF2, KEAP1, and CUL3 mutations, and that NRF2 expression in this cohort is correlated with PIDD levels. Our data identify PIDD as a new NRF2 regulator, and suggest that variations in PIDD levels contribute to differential chemosensitivities among NSCLC patients.
Dynamical decoration of stabilized-microtubules by Tau-proteins
Authors: Hervy Jordan , Bicout Dominique J.
Published: August 2019

Tau is a microtubule-associated protein that regulates axonal transport, stabilizes and spatially organizes microtubules in parallel networks. The Tau-microtubule pair is crucial for maintaining the architecture and integrity of axons. Therefore, it is essential to understand how these two entities interact to ensure and modulate the normal axonal functions. Based on evidence from several published experiments, we have developed a two-dimensional model that describes the interaction between a population of Tau proteins and a stabilized microtubule at the scale of the tubulin dimers (binding sites) as an adsorption-desorption dynamical process in which Tau can bind on the microtubule outer surface via two distinct modes: a longitudinal (along a protofilament) and lateral (across adjacent protofilaments) modes. Such a process yields a dynamical distribution of Tau molecules on the microtubule surface referred to as microtubule decoration that we have characterized at the equilibrium using two observables: the total microtubule surface coverage with Tau’s and the distribution of nearest neighbors Tau’s. Using both analytical and numerical approaches, we have derived expressions and computed these observables as a function of key parameters controlling the binding reaction: the stoichiometries of the Taus in the two binding modes, the associated dissociation constants and the ratio of the Tau concentration to that of microtubule tubulin dimers.
The Single-molecule long-read sequencing of Scylla paramamosain
Authors: Wan Haifu , Jia Xiwei , Zou Pengfei , Zhang Ziping , Wang Yilei
Published: August 2019

Scylla paramamosain is an important aquaculture crab, which has great economical and nutritional value. To the best of our knowledge, few full-length crab transcriptomes are available. In this study, a library composed of 12 different tissues including gill, hepatopancreas, muscle, cerebral ganglion, eyestalk, thoracic ganglia, intestine, heart, testis, ovary, sperm reservoir, and hemocyte was constructed and sequenced using Pacific Biosciences single-molecule real-time (SMRT) long-read sequencing technology. A total of 284803 full-length non-chimeric reads were obtained, from which 79005 high-quality unique transcripts were obtained after error correction and sequence clustering and redundant. Additionally, a total of 52544 transcripts were annotated against protein database (NCBI nonredundant, Swiss-Prot, KOG, and KEGG database). A total of 23644 long non-coding RNAs (lncRNAs) and 131561 simple sequence repeats (SSRs) were identified. Meanwhile, the isoforms of many genes were also identified in this study. Our study provides a rich set of full-length cDNA sequences for S. paramamosain, which will greatly facilitate S. paramamosain research.