bluuebunny/crossref_metadata_2025 huggingface dataset:
Unconscious reinforcement learning of hidden brain states supported by confidence
Authors: Cortese Aurelio , Lau Hakwan , Kawato Mitsuo
Published: August 2020

Can humans be trained to make strategic use of latent representations in their own brains? We investigate how human subjects can derive reward-maximizing choices from intrinsic high-dimensional information represented stochastically in neural activity. Reward contingencies are defined in real-time by fMRI multivoxel patterns; optimal action policies thereby depend on multidimensional brain activity taking place below the threshold of consciousness, by design. We find that subjects can solve the task within two hundred trials and errors, as their reinforcement learning processes interact with metacognitive functions (quantified as the meaningfulness of their decision confidence). Computational modelling and multivariate analyses identify a frontostriatal neural mechanism by which the brain may untangle the ‘curse of dimensionality’: synchronization of confidence representations in prefrontal cortex with reward prediction errors in basal ganglia support exploration of latent task representations. These results may provide an alternative starting point for future investigations into unconscious learning and functions of metacognition.
Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
Authors: Yamaguchi Toshihiro , Sumida Tomokazu S. , Nomura Seitaro , Satoh Masahiro , Higo Tomoaki , Ito Masamichi , Ko Toshiyuki , Fujita Kanna , Sweet Mary E. , Sanbe Atsushi , Yoshimi Kenji , Manabe Ichiro , Sasaoka Toshikuni , Taylor Matthew R. G. , Toko Haruhiro , Takimoto Eiki , Naito Atsuhiko T. , Komuro Issei
Published: August 2020

Pathophysiological roles of cardiac dopamine system remain unknown. Here, we show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Comprehensive single-cell resolution analysis identifies the presence of D1R-expressing CMs in both heart failure model mice and in heart failure patients with sustained ventricular tachycardia. Overexpression of D1R in CMs disturbs normal calcium handling while CM-specific deletion of D1R ameliorates heart failure-associated ventricular arrhythmia. Thus, cardiac D1R has the potential to become a therapeutic target for preventing heart failure-associated ventricular arrhythmia.
The effect of military training on the sense of agency and outcome processing
Authors: Caspar Emilie A. , Lo Bue Salvatore , Magalhães De Saldanha da Gama Pedro A. , Haggard Patrick , Cleeremans Axel
Published: August 2020

Armed forces often rely on strict hierarchical organization, where people are required to follow orders. In two cross-sectional studies, we investigate whether or not working in a military context influences the sense of agency and outcome processing, and how different durations (junior cadets vs senior cadets) and types (cadets vs privates) of military experience may modulate these effects. Participants could administer painful electrical shocks to a ‘victim’ in exchange for money, either by their own free choice, or following orders of the experimenter. Results indicate that working in a strictly hierarchical structure may have a generalized negative impact on one’s own sense of agency and outcome processing by reducing it, even when participants could freely decide their action. However, trained officers showed an enhanced sense of agency and outcome processing. This study offers insights on the potential for training the sense of agency and outcome processing.
Vital evidence: Change in the marine 14C reservoir around New Zealand (Aotearoa) and implications for the timing of Polynesian settlement
Authors: Petchey Fiona , Schmid Magdalena M. E.
Published: August 2020

Precise and accurate radiocarbon chronologies are essential to achieve tight chronological control for the ~ 750-years since Polynesian settlement of New Zealand. This goal has, however, been elusive. While radiocarbon datasets in the region are typically dominated by marine and estuarine shell dates, such chronological information has been ignored by those interpreting the timing of key events because a detailed regional calibration methodology for marine shell, comparable to the highly precise Southern Hemisphere calibration curve, is lacking. In this paper, we present the first temporal 14C marine offset (ΔR) model for New Zealand based on paired estuarine/marine and terrestrial radiocarbon dates from 52 archaeological contexts. Our dataset displays significant offsets between the measured New Zealand data and the modelled global marine radiocarbon curve. These shifts are associated with oceanographic fluctuation at the onset of the Little Ice Age ~ AD 1350–1450 (650–500 BP). The application of a regional and temporal correction to archaeological shell dates provides complimentary information to terrestrial radiocarbon production and has the potential to add structure to the blurred chronology that has plagued archaeological theories about the colonization of New Zealand, and other Pacific islands, for decades.
Functional skeletal muscle model derived from SOD1-mutant ALS patient iPSCs recapitulates hallmarks of disease progression
Authors: Badu-Mensah Agnes , Guo Xiufang , McAleer Christopher W. , Rumsey John W. , Hickman James J.
Published: August 2020

Recent findings suggest a pathologic role of skeletal muscle in amyotrophic lateral sclerosis (ALS) onset and progression. However, the exact mechanism by which this occurs remains elusive due to limited human-based studies. To this end, phenotypic ALS skeletal muscle models were developed from induced pluripotent stem cells (iPSCs) derived from healthy individuals (WT) and ALS patients harboring mutations in the superoxide dismutase 1 (SOD1) gene. Although proliferative, SOD1 myoblasts demonstrated delayed and reduced fusion efficiency compared to WT. Additionally, SOD1 myotubes exhibited significantly reduced length and cross-section. Also, SOD1 myotubes had loosely arranged myosin heavy chain and reduced acetylcholine receptor expression per immunocytochemical analysis. Functional analysis indicated considerably reduced contractile force and synchrony in SOD1 myotubes. Mitochondrial assessment indicated reduced inner mitochondrial membrane potential (ΔΨm) and metabolic plasticity in the SOD1-iPSC derived myotubes. This work presents the first well-characterized in vitro iPSC-derived muscle model that demonstrates SOD1 toxicity effects on human muscle regeneration, contractility and metabolic function in ALS. Current findings align with previous ALS patient biopsy studies and suggest an active contribution of skeletal muscle in NMJ dysfunction. Further, the results validate this model as a human-relevant platform for ALS research and drug discovery studies.
Demystifying biotrophs: FISHing for mRNAs to decipher plant and algal pathogen–host interaction at the single cell level
Authors: Badstöber Julia , Gachon Claire M. M. , Ludwig-Müller Jutta , Sandbichler Adolf M. , Neuhauser Sigrid
Published: August 2020

Plant-pathogen interactions follow spatial and temporal developmental dynamics where gene expression in pathogen and host undergo crucial changes. Therefore, it is of great interest to detect, quantify and localise where and when key genes are active to understand these processes. Many pathosystems are not accessible for genetic amendments or other spatially-resolved gene expression monitoring methods. Here, we adapt single molecule FISH techniques to demonstrate the presence and activity of mRNAs at the single-cell level using phytomyxids in their plant and algal host in lab and field material. This allowed us to monitor and quantify the expression of genes from the clubroot pathogen Plasmodiophora brassicae, several species of its Brassica hosts, and of several brown algae, including the genome model Ectocarpus siliculosus, infected with the phytomyxid Maullinia ectocarpii. We show that mRNAs are localised along a spatiotemporal gradient, thus providing a proof-of-concept of the usefulness of single-molecule FISH to increase knowledge about the interactions between plants, algae and phytomyxids. The methods used are easily applicable to any interaction between microbes and their algal or plant host, and have therefore the potential to rapidly increase our understanding of key, spatially- and temporally-resolved processes underpinning complex plant–microbe interactions.
Automatic prostate and prostate zones segmentation of magnetic resonance images using DenseNet-like U-net
Authors: Aldoj Nader , Biavati Federico , Michallek Florian , Stober Sebastian , Dewey Marc
Published: August 2020

Magnetic resonance imaging (MRI) provides detailed anatomical images of the prostate and its zones. It has a crucial role for many diagnostic applications. Automatic segmentation such as that of the prostate and prostate zones from MR images facilitates many diagnostic and therapeutic applications. However, the lack of a clear prostate boundary, prostate tissue heterogeneity, and the wide interindividual variety of prostate shapes make this a very challenging task. To address this problem, we propose a new neural network to automatically segment the prostate and its zones. We term this algorithm Dense U-net as it is inspired by the two existing state-of-the-art tools—DenseNet and U-net. We trained the algorithm on 141 patient datasets and tested it on 47 patient datasets using axial T2-weighted images in a four-fold cross-validation fashion. The networks were trained and tested on weakly and accurately annotated masks separately to test the hypothesis that the network can learn even when the labels are not accurate. The network successfully detects the prostate region and segments the gland and its zones. Compared with U-net, the second version of our algorithm, Dense-2 U-net, achieved an average Dice score for the whole prostate of 92.1± 0.8% vs. 90.7 ± 2%, for the central zone of$$89.5 \pm 2$$89.5±2% vs.$$89.1 \pm 2.2$$89.1±2.2%, and for the peripheral zone of 78.1± 2.5% vs.$$75 \pm 3$$75±3%. Our initial results show Dense-2 U-net to be more accurate than state-of-the-art U-net for automatic segmentation of the prostate and prostate zones.
Early warning climate indices for malaria and meningitis in tropical ecological zones
Authors: Ayanlade Ayansina , Nwayor Isioma J. , Sergi Consolato , Ayanlade Oluwatoyin S. , Di Carlo Paola , Jeje Olajumoke D. , Jegede Margaret O.
Published: August 2020

This study aims at assessing the impacts of climate indices on the spatiotemporal distribution of malaria and meningitis in Nigeria. The primary focus of the research is to develop an Early Warning System (EWS) for assessing climate variability implications on malaria and meningitis spread in the study area. Both climate and health data were used in the study to determine the relationship between climate variability and the occurrence of malaria and meningitis. The assessment was based on variations in different ecological zones in Nigeria. Two specific sample locations were randomly selected in each ecological zone for the analysis. The climatic data used in this study are dekadal precipitation, minimum and maximum temperature between 2000 and 2018, monthly aerosol optical depth between 2000 and 2018. The results show that temperature is relatively high throughout the year because the country is located in a tropical region. The significant findings of this study are that rainfall has much influence on the occurrence of malaria, while temperature and aerosol have more impact on meningitis. We found the degree of relationship between precipitation and malaria, there is a correlation coefficient R2 ≥ 70.0 in Rainforest, Freshwater, and Mangrove ecological zones. The relationship between temperature and meningitis is accompanied by R2 ≥ 72.0 in both Sahel and Sudan, while aerosol and meningitis harbour R2 = 77.33 in the Sahel. The assessment of this initial data seems to support the finding that the occurrences of meningitis are higher in the northern region, especially the Sahel and Sudan. In contrast, malaria occurrence is higher in the southern part of the study area. In all, the multiple linear regression results revealed that rainfall was directly associated with malaria with β = 0.64, p = 0.001 but aerosol was directly associated with meningitis with β = 0.59, p < 0.001. The study concludes that variability in climatic elements such as low precipitation, high temperature, and aerosol may be the major drivers of meningitis occurrence.
Tight security bounds for decoy-state quantum key distribution
Authors: Yin Hua-Lei , Zhou Min-Gang , Gu Jie , Xie Yuan-Mei , Lu Yu-Shuo , Chen Zeng-Bing
Published: August 2020

The BB84 quantum key distribution (QKD) combined with decoy-state method is currently the most practical protocol, which has been proved secure against general attacks in the finite-key regime. Thereinto, statistical fluctuation analysis methods are very important in dealing with finite-key effects, which directly affect secret key rate, secure transmission distance and most importantly, the security. There are two tasks of statistical fluctuation in decoy-state BB84 QKD. One is the deviation between expected value and observed value for a given expected value or observed value. The other is the deviation between phase error rate of computational basis and bit error rate of dual basis. Here, we provide the rigorous and optimal analytic formula to solve the above tasks, resulting to higher secret key rate and longer secure transmission distance. Our results can be widely applied to deal with statistical fluctuation in quantum cryptography protocols.
Reconciling yield gains in agronomic trials with returns under African smallholder conditions
Authors: Laajaj Rachid , Macours Karen , Masso Cargele , Thuita Moses , Vanlauwe Bernard
Published: August 2020

Increased adoption of improved agricultural technologies is considered an essential step to address global poverty and hunger, and agronomic trials suggest intensification in developing countries could result in large yield gains. Yet the promise of new technologies does not always carry over from trials to real-life conditions, and diffusion of many technologies remains limited. We show how parcel and farmer selection, together with behavioural responses in agronomic trials, can explain why yield gain estimates from trials may differ from the yield gains of smallholders using the same inputs under real-life conditions. We provide quantitative evidence by exploiting variation in farmer selection and detailed data collection from research trials in Western Kenya on which large yield increments were observed from improved input packages for maize and soybean. After adjusting for selection, behavioural responses, and other corrections, estimates of yield gains fall to being not significantly different from zero for the input package tested on one of the crops (soybean), but remain high for the other (maize). These results suggest that testing new agricultural technologies in real-world conditions and without researcher interference early in the agricultural research and development process might help with identifying which innovations are more likely to be taken up at scale.
Chemical signatures of femoral pore secretions in two syntopic but reproductively isolated species of Galápagos land iguanas (Conolophus marthae and C. subcristatus)
Authors: Colosimo Giuliano , Di Marco Gabriele , D’Agostino Alessia , Gismondi Angelo , Vera Carlos A. , Gerber Glenn P. , Scardi Michele , Canini Antonella , Gentile Gabriele
Published: August 2020

The only known population of Conolophus marthae (Reptilia, Iguanidae) and a population of C. subcristatus are syntopic on Wolf Volcano (Isabela Island, Galápagos). No gene flow occurs suggesting that effective reproductive isolating mechanisms exist between these two species. Chemical signature of femoral pore secretions is important for intra- and inter-specific chemical communication in squamates. As a first step towards testing the hypothesis that chemical signals could mediate reproductive isolation between C. marthae and C. subcristatus, we compared the chemical profiles of femoral gland exudate from adults caught on Wolf Volcano. We compared data from three different years and focused on two years in particular when femoral gland exudate was collected from adults during the reproductive season. Samples were processed using Gas Chromatography coupled with Mass Spectrometry (GC–MS). We identified over 100 different chemical compounds. Non-Metric Multidimensional Scaling (nMDS) was used to graphically represent the similarity among individuals based on their chemical profiles. Results from non-parametric statistical tests indicate that the separation between the two species is significant, suggesting that the chemical profile signatures of the two species may help prevent hybridization between C. marthae and C. subcristatus. Further investigation is needed to better resolve environmental influence and temporal reproductive patterns in determining the variation of biochemical profiles in both species.
Utilization of road dust chemical profiles for source identification and human health impact assessment
Authors: Kim Eun-Ah , Koh Byumseok
Published: August 2020

This study investigated the chemical profiles of fine urban road dust as a set of indicators for major air pollutants at sampling sites or as proxies for potential human health impacts. We examined the chemical compositions of fine particles (< 100 μm) or re-suspended ultrafine particles (< 2.5 μm) in the urban road dust collected from the cities with major emission sources of CO, NH3, NOx, PM2.5, SOx, and volatile organic compounds. The elemental compositions, including metal contents and volatile or semi-volatile organic compound species were determined to constitute comprehensive chemical profiles of the solid road dust samples. The water-extractable organic compounds and fluorescent species of the size-fractionated re-suspended fine particulate matter (RPM) were also incorporated in the chemical profiles. The metal content and aliphatic hydrocarbons could partly distinguish emission sources, and clearer distinctions were achieved with the inclusion of fluorescence excitation-emission matrix (EEM) results. The dose–response test results showed positive correlations between cytotoxicity and relative abundance of hydrocarbons or metal contents of urban road dust. The set of chemical profiles suggested in this study could be further utilized for site identification or human health impact assessment using urban road dust.
The influence of proline isomerization on potency and stability of anti-HIV antibody 10E8
Authors: Guttman Miklos , Padte Neal N. , Huang Yaoxing , Yu Jian , Rocklin Gabriel J. , Weitzner Brian D. , Scian Michele , Ho David D. , Lee Kelly K.
Published: August 2020

Monoclonal antibody (mAb) 10E8 recognizes a highly conserved epitope on HIV and is capable of neutralizing > 95% of circulating viral isolates making it one of the most promising Abs against HIV. Solution instability and biochemical heterogeneity of 10E8 has hampered its development for clinical use. We identify the source of 10E8 heterogeneity being linked to cis/trans isomerization at two prolines within the YPP motif in the CRD3 loop that exists as two predominant conformers that interconvert on a slow timescale. The YtransP conformation conformer can bind the HIV gp41 epitope, while the YcisP is not binding competent and shows a higher aggregation propensity. The high barrier of isomerization and propensity to adopt non-binding competent proline conformers provides novel insight into the slow binding kinetics, low potency, and poor solubility of 10E8. This study highlights how proline isomerization should be considered a critical quality attribute for biotherapeutics with paratopes containing potential cis proline amide bonds.
Effect of bilingualism on visual tracking attention and resistance to distraction
Authors: Janic Ana , Cavanagh Patrick , Rivest Josée
Published: August 2020

Speaking more than one language has been associated with enhanced cognitive capacities. Here we evaluated whether bilingual individuals have advantages in visual tracking attention. Adult bilingual (n = 35) and monolingual (n = 35) participants were tested in the Multiple Object Tracking task (MOT). In one condition, the MOT was performed by itself establishing the baseline performance of each group, and in the other condition, it was performed while participants counted backward out loud in their mother tongue. At baseline, the average speed tracking threshold of bilinguals was not better than that of the monolinguals. Importantly, for bilinguals, counting backward decreased their threshold by only 15%, but, for monolinguals, it decreased it three times as much. This result suggests that bilingualism confers advantages to visual tracking attention when dual tasking is required, extending the evidence that bilingualism affords cognitive benefits beyond verbal communication.
Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis
Authors: Shehadeh Fadi , Kalligeros Markos , Byrd Katrina , Shemin Douglas , Mylonakis Eleftherios , Martin Paul , D’Agata Erika M. C.
Published: August 2020

Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91–98%). The efficacy of the SOF-based regimen was 92% (95% CI 80–99%), 98% (95% CI 96–100%), and 100% (95% CI 95–100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5–29%), followed by anemia 15% (95% CI 3–31%), and nausea or vomiting 14% (95% CI 4–27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33–59%) compared to ribavirin-free regimens (3%, 95% CI 0–9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.
Exploring the genetic basis of fatty liver development in geese
Authors: Yang Yunzhou , Wang Huiying , Li Guangquan , Liu Yi , Wang Cui , He Daqian
Published: August 2020

Although geese possess an adaptive physiological capacity for lipid storage, few candidate genes contributing to this ability are characterised. By comparing the genomes of individuals with extremely high and low fatty liver weights (FLW), candidate genes were identified, includingARAP2,GABRE, andIL6. Single-nucleotide polymorphisms in or near these genes were significantly (p < 0.05) associated with carcass traits (FLW) and biochemical indexes (very-low-density lipoprotein and N-terminal procollagen III), suggesting contribution to trait variation. A common variant at the 5′-end ofLCORLexplained ~ 18% and ~ 26% of the phenotypic variance in body weight with/without overfeeding and had significant effects on FLW (p < 0.01).ZFF36L1,ARHGEF1andIQCJ,involved in bile acid metabolism, blood pressure, and lipid concentration modulation, were also identified. The presence of highly divergent haplotypes within these genes suggested involvement in protection against negative effects from excessive lipids in the liver or circulatory system. Based on this and transcriptomic data, we concluded that geese hepatosteatosis results from severe imbalance between lipid accumulation and secretion, comparable to human non-alcohol fatty liver disease but involving other genes. Our results provided valuable insights into the genesis of geese fatty liver and detected potential target genes for treatment of lipid-related diseases.
Visualization of lymphatic flow in laparoscopic colon cancer surgery using indocyanine green fluorescence imaging
Authors: Ushijima Hokuto , Kawamura Junichiro , Ueda Kazuki , Yane Yoshinori , Yoshioka Yasumasa , Daito Koji , Tokoro Tadao , Hida Jin-ichi , Okuno Kiyotaka
Published: August 2020

Intraoperative visualization of lymphatic flow could guide surgeons performing laparoscopic colon cancer surgery on the extent of intestinal resection required. The purpose of this study was to investigate indocyanine green fluorescence imaging for intraoperative detection of lymphatic flow and nodes in such patients. All patients undergoing elective laparoscopic surgery for colorectal cancer from October 2016 to July 2017 were included in this study. Indocyanine green was injected submucosally around the tumors via a colonoscope and lymphatic flow assessed with a laparoscopic near-infrared camera system intraoperatively. Lymphatic flow was visualized perioperatively in 43 of 57 patients (75.4%). The rate of visualized lymphatic flow was significantly higher in patients with a lower clinical stage than in those with a higher clinical stage (p = 0.0103). Among the 14 patients in whom lymphatic flow was not visualized, 10 (71.4%) had cStage III or IV cancer. Our results indicate the potential role of intraoperative navigation in colon cancer surgery in early-stage colon cancers. This method allows the surgeon to clearly identify lymphatic flow during surgery and allows the determination and individualization of the lymph node dissection range.
Metasurface sensing difference in waveforms at the same frequency with reduced power level
Authors: Tanikawa Mizuki , Ushikoshi Daiju , Asano Kosei , Sanji Kenichiro , Ikeda Masakazu , Anzai Daisuke , Wakatsuchi Hiroki
Published: August 2020

We numerically demonstrate a new type of waveform-selective metasurface that senses the difference in incoming waveforms or pulse widths at the same frequency. Importantly, the proposed structure contains precise rectifier circuits that, compared to ordinary schottky diodes used within old types of structures, rectify induced electric charges at a markedly reduced input power level depending on several design parameters but mostly on the gain of operational amplifiers. As a result, a waveform-selective absorbing mechanism related to this turn-on voltage appears even with a limited signal strength that is comparable to realistic wireless signal levels. In addition, the proposed structure exhibits a noticeably wide dynamic range from $${-}$$
-
 30 to 6 dBm, compared to a conventional structure that operated only around 0 dBm. Thus, our study opens up the door to apply the concept of waveform selectivity to a more practical field of wireless communications to control different small signals at the same frequency.
Genetic variation for resistance to the specific fly pathogen Entomophthora muscae
Authors: Wang Jonathan B. , Elya Carolyn , St. Leger Raymond J.
Published: August 2020

We found substantial variation in resistance to the fly-specific pathogen Entomophthora muscae 'Berkeley' (Entomophthoromycota), in 20 lines from the Drosophila melanogaster Genetic Reference Panel (DGRP). Resistance to E. muscae is positively (r = 0.55) correlated with resistance to the broad host range ascomycete entomopathogen Metarhizium anisopliae (Ma549), indicative of generalist (non-specific) defenses. Most of the lines showing above average resistance to Ma549 showed cross-resistance to E. muscae. However, lines that succumbed quickly to Ma549 exhibited the full range of resistance to E. muscae. This suggests fly populations differ in E. muscae-specific resistance mechanisms as well as generic defences effective against both Ma549 and E. muscae. We looked for trade-offs that could account for inter-line variation, but increases (decreases) in disease resistance to E. muscae are not consistently associated with increases (decreases) of resistance to oxidative stress, starvation stress and sleep indices. That these pathogens are dynamic agents of selection on hosts is reflected in this genetic variation for resistance in lines derived from wild populations.
Aging in the USA: similarities and disparities across time and space
Authors: Abeliansky Ana Lucia , Erel Devin , Strulik Holger
Published: August 2020

We study biological aging of elderly U.S. Americans born 1904–1966. We use thirteen waves of the Health and Retirement Study and construct a frailty index as the number of health deficits present in a person measured relative to the number of potential deficits. We find that, on average, Americans develop 5% more health deficits per year, that men age slightly faster than women, and that, at any age above 50, Caucasians display significantly fewer health deficits than African Americans. We also document a steady time trend of health improvements. For each year of later birth, health deficits decline on average by about 1%. This health trend is about the same across regions and for men and women, but significantly lower for African Americans compared to Caucasians. In non-linear regressions, we find that regional differences in aging follow a particular regularity, akin to the compensation effect of mortality. Health deficits converge for men and women and across American regions and suggest a life span of the American population of about 97 years.
Novel reassortant swine H3N2 influenza A viruses in Germany
Authors: Zell Roland , Groth Marco , Krumbholz Andi , Lange Jeannette , Philipps Anja , Dürrwald Ralf
Published: August 2020

Analysis of 228 H3N2 swine influenza A virus isolates collected between 2003 and 2015 in Germany revealed important changes in molecular epidemiology. The data indicate that a novel reassortant, Rietberg/2014-like swine H3N2, emerged in February 2014 in Northern Germany. It is comprised of a hemagglutinin gene of seasonal H3N2 (A/Denmark/129/2005-like), a neuraminidase gene of Emmelsbuell/2009-like swine H1N2 and the internal gene cassette of pandemic H1N1 viruses. Together with Danish swine H3N2 strains of 2013–2015 with identical genome layout, the Rietberg/2014-like viruses represent a second swine H3N2 lineage which cocirculates with a variant of the Gent/1984-like swine H3N2 lineage. This variant, named Gent1984/Diepholz-like swine H3N2, has a Gent/1984-like HA and a Diepholz/2008-like NA; the origin of the internal gene cassette likely derived from avian-like swine H1N1. The first isolate of the Gent1984/Diepholz reassortant emerged in Northern Germany in September 2011 whereas the last German Gent/1984-like isolate was collected in October 2011.
Elucidating the limiting factors for regeneration and successful establishment of the thermophilic tree Ziziphus spina-christi under a changing climate
Authors: Zait Yotam , Konsens Irit , Schwartz Amnon
Published: August 2020

Due to climate change, winter temperatures are predicted to increase worldwide. For thermophilic trees, highly sensitive to low temperatures, an increase in winter temperatures may be beneficial for survival and regeneration. Ziziphus spina-christi is a thermophilic tree that has recently become more abundant and widespread in the eastern Mediterranean, presumably due to a gradual increase in winter temperatures. We aim to define the temperature limitations for seed germination and the growth and survival of young seedlings to broaden our understanding of the future geographical distribution of this species. We studied effects of temperature on germination, growth, and photosynthesis in a controlled environment with four different day/night temperature regimes (34/28 °C, 28/22 °C, 22/16 °C and 16/10 °C). Effects of endocarp on germination and seed germination in the field were also studied. Results showed that germination has a lower thermal optimum (34–22 °C, 63.5–67.5% germination) than growth and photosynthesis (34–28 °C). Moderate cold stress (22/16 °C), did not affect germination capacity, but strongly reduced seedling growth (71%) and photosynthetic capacity (44.6%). Under severe cold stress (16/10 °C), germination still occurs (22%), but seedlings cannot perform growth and photosynthesis. We conclude that slow seedling growth, not germination, is the main barrier for successful establishment of Z. spina-christi under low temperature. Warmer winters could lead to earlier establishment of seedlings and increase their chance of survival the following summer. This may explain the recent increase in the tree’s relative abundance and further highlight the potential spread of this species at higher altitudes and latitudes across the Mediterranean.
Efficient harmonic oscillator chain energy harvester driven by colored noise
Authors: Romero-Bastida M. , López Juan M.
Published: August 2020

We study the performance of an electromechanical harmonic oscillator chain as an energy harvester to extract power from finite-bandwidth ambient random vibrations, which are modelled by colored noise. The proposed device is numerically simulated and its performance assessed by means of the net electrical power generated and its efficiency in converting the external noise-supplied power into electrical power. Our main result is a much enhanced performance, both in the net electrical power delivered and in efficiency, of the harmonic chain with respect to the popular single oscillator resonator. Our numerical findings are explained by means of an analytical approximation, in excellent agreement with numerics.
Tolerance to alkaline ambient pH in Aspergillus nidulans depends on the activity of ENA proteins
Authors: Markina-Iñarrairaegui Ane , Spielvogel Anja , Etxebeste Oier , Ugalde Unai , Espeso Eduardo A.
Published: August 2020

Tolerance of microorganisms to abiotic stress is enabled by regulatory mechanisms that coordinate the expression and activity of resistance genes. Alkalinity and high salt concentrations are major environmental physicochemical stresses. Here, we analyzed the roles of sodium-extrusion family (ENA) transporters EnaA, EnaB and EnaC in the response to these stress conditions in the filamentous fungusAspergillus nidulans. While EnaC has a minor role, EnaB is a key element for tolerance to Na+and Li+toxicity. Adaptation to alkaline pH requires the concerted action of EnaB with EnaA. Accordingly, expression ofenaAandenaBwas induced by Na+, Li+and pH 8. These expression patterns are altered in asltAΔ background and completely inhibited in a mutant expressing non-functional PacC protein (palH72). However, a constitutively active PacC form was not sufficient to restore maximumenaAexpression. In agreement with their predicted role as membrane ATPases, EnaA localized to the plasma membrane while EnaB accumulated at structures resembling the endoplasmic reticulum. Overall, results suggest different PacC- and SltA-dependent roles for EnaB in pH and salt homeostasis, acting in coordination with EnaA at pH 8 but independently under salt stress.
HPV-EM: an accurate HPV detection and genotyping EM algorithm
Authors: Inkman Matthew J. , Jayachandran Kay , Ellis Thomas M. , Ruiz Fiona , McLellan Michael D. , Miller Christopher A. , Wu Yufeng , Ojesina Akinyemi I. , Schwarz Julie K. , Zhang Jin
Published: August 2020

Accurate HPV genotyping is crucial in facilitating epidemiology studies, vaccine trials, and HPV-related cancer research. Contemporary HPV genotyping assays only detect < 25% of all known HPV genotypes and are not accurate for low-risk or mixed HPV genotypes. Current genomic HPV genotyping algorithms use a simple read-alignment and filtering strategy that has difficulty handling repeats and homology sequences. Therefore, we have developed an optimized expectation–maximization algorithm, designated HPV-EM, to address the ambiguities caused by repetitive sequencing reads. HPV-EM achieved 97–100% accuracy when benchmarked using cell line data and TCGA cervical cancer data. We also validated HPV-EM using DNA tiling data on an institutional cervical cancer cohort (96.5% accuracy). Using HPV-EM, we demonstrated HPV genotypic differences in recurrence and patient outcomes in cervical and head and neck cancers.
Prevention of acute kidney injury by low intensity pulsed ultrasound via anti-inflammation and anti-apoptosis
Authors: Chiang Chih-Kang , Loh Jui-Zhi , Yang Ting-Hua , Huang Kuo-Tong , Wu Cheng-Tien , Guan Siao-Syun , Liu Shing-Hwa , Hung Kuan-Yu
Published: August 2020

The therapeutic effects of low intensity pulsed ultrasound (LIPUS) on renal ischemia/reperfusion injury (IRI) with acute kidney injury (AKI) are still unclear. A renal tubule cell model under H2O2 or hypoxia/reoxygenation (H/R) conditions with or without LIPUS pre-treatment (1 MHz, 30 and 100 mW/cm2, 15 min) was used to test the in vitro effects of LIPUS. An AKI mouse model of unilateral IRI with nephrectomy of the contralateral kidney for 48 h with or without LIPUS treatment (3 MHz, 100 mW/cm2, 20 min/day) 5 day before IRI were used to investigate the in vivo effects of LIPUS. LIPUS significantly protected the renal tubule cell viability and prevented inflammatory signals against H2O2 challenge. LIPUS could inhibit the apoptosis-related molecular signals and increase the protein levels of endogenous antioxidant enzymes, α-Klotho, and Sirt1 in renal tubule cells after H/R challenge. LIPUS alleviated the increases in the serum levels of blood urea nitrogen, creatinine, and cystatin C, renal pathological changes and apoptosis-related molecular signals, and impaired antioxidant enzymes in AKI mice. The IRI-induced inflammatory responses in the kidneys and spleens could be reversed by LIPUS. These findings suggest that LIPUS treatment displays the benefits for renal protection in IRI-induced AKI mice.
Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients
Authors: Son Seung-Myoung , Woo Chang Gok , Kim Dae Hoon , Yun Hyo Yung , Kim Hongsik , Kim Hee Kyung , Yang Yaewon , Kwon Jihyun , Kwon Minsuk , Kim Tae-Yong , Kim Hyung-Don , Koh June-Young , Park Su-Hyung , Shin Eui-Cheol , Han Hye Sook
Published: August 2020

This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4+ and CD8+ T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8+ T-cell, PD-L1+ cell, and PD-L1+CK+ cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (≥ 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8+ T-cell density was an independent prognostic marker in both PGC and MGC (univariate P = 0.002, multivariate P = 0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.
Colorimetric sensing of imidacloprid in cucumber fruits using a graphene quantum dot/Au (III) chemosensor
Authors: Babazadeh Saeedeh , Moghaddam Parviz Ahmadi , Keshipour Sajjad , Mollazade Kaveh
Published: August 2020

The current research presents a very simple method for the colorimetric detection of imidacloprid using a graphene quantum dot/Au (III) chemosensor. The results demonstrated that there is an interaction between Au3+ ions and the imidazole group of the pesticide toward reduction of Au3+ to Au0 in the presence of graphene quantum dots. This phenomenon changes the color of gold nanoparticles from yellow to grey or red, and causes a shift in the peak of localized surface plasmon resonance (LSPR) as gold nanoparticles are formed or aggregated based on the concentration of imidacloprid. Imidacloprid was determined by the developed sensor in a linear area of 0.01–1 ppm with a detection limit of 0.007 ppm. Therefore, a simple, quick, and sustainable sensor has been developed for the determination of the investigated analyte. Moreover, the sensor was applied to determine imidacloprid in the real cucumber samples fairly successful.
Prevalence and clinical implications of germline predisposition gene mutations in patients with acute myeloid leukemia
Authors: Kim Borahm , Yun Woobin , Lee Seung-Tae , Choi Jong Rok , Yoo Keon Hee , Koo Hong Hoe , Jung Chul Won , Kim Sun Hee
Published: August 2020

Acute myeloid leukemia (AML) is one of the most common types of leukemia. With the recent advances in sequencing technology and the growing body of knowledge on the genetics of AML, there is increasing concern about cancer predisposing germline mutations as well as somatic mutations. As familial cases sharing germline mutations are constantly reported, germline predisposition gene mutations in patients with AML are gaining attention. We performed genomic sequencing of Korean patients diagnosed with AML to identify the prevalence and characteristics of germline predisposition mutations. Among 180 patients, germline predisposition mutations were identified in 13 patients (13/180, 7.2%, eight adults and five children). Germline mutations of BLM, BRCA1, BRCA2, CTC1, DDX41, ERCC4, ERCC6, FANCI, FANCM, PALB2, and SBDS were identified. Most of the mutations are in genes involved in DNA repair and genomic stability maintenance. Patients harboring germline mutations tended to have earlier onset of AML (p = 0.005), however, the presence of germline mutations did not showed significant association with other clinical characteristics or treatment outcome. Since each mutation was rare, further study with a larger number of cases would be needed to establish the effect of the mutations.
Heritability estimates of the novel trait ‘suppressed in ovo virus infection’ in honey bees (Apis mellifera)
Authors: de Graaf Dirk C. , Laget Dries , De Smet Lina , Claeys Boúúaert David , Brunain Marleen , Veerkamp Roel F. , Brascamp Evert W.
Published: August 2020

Honey bees are under pressure due to abnormal high colony death rates, especially during the winter. The infestation by the Varroa destructor mite and the viruses that this ectoparasite transmits are generally considered as the bees’ most important biological threats. Almost all efforts to remedy this dual infection have so far focused on the control of the Varroa mite alone and not on the viruses it transmits. In the present study, the sanitary control of breeding queens was conducted on eggs taken from drone brood for 4 consecutive years (2015–2018). The screening was performed on the sideline of an ongoing breeding program, which allowed us to estimate the heritabilities of the virus status of the eggs. We used the term ‘suppressed in ovo virus infection’ (SOV) for this novel trait and found moderate heritabilities for the presence of several viruses simultaneously and for the presence of single viral species. Colonies that expressed the SOV trait seemed to be more resilient to virus infections as a whole with fewer and less severe Deformed wing virus infections in most developmental stages, especially in the male caste. The implementation of this novel trait into breeding programs is recommended.
Habitat preference and diverse migration in threespine sticklebacks, Gasterosteus aculeatus and G. nipponicus
Authors: Arai Takaomi , Ueno Daisuke , Kitamura Takefumi , Goto Akira
Published: August 2020

Threespine sticklebacks of the genusGasterosteus, are small teleost fish that are widely distributed across the northern hemisphere. The fish is believed to have two major types of life history, freshwater resident and anadromous; however little is known about their migration ecology. Comprehensive research on the migratory history, habitat use and relative composition of migratory types was conducted by analysing the otolith strontium and calcium concentrations collected in various environments of northern Japan. The present study first demonstrated that approximately 90% of morphologically anadromous sticklebacks had estuarine resident migration pattern, consistently living in brackish water and/or marine environments through their life cycle without any time spent in freshwater. The dominant occurrence of the estuarine resident was temporally and spatially consistent with their general migration ecology. The estuarine resident is thought to be the ancestral migrations ofG. aculeatusandG. nipponicus, which thereafter gradually immigrated into freshwater habitats and settled in the anadromous form in both species and finally became the freshwater residentG. aculeatus. Thus, this study provides novel insights into the evolutionary migration of these fish, as well as a new discovery regarding the dominant migratory history and habitat use in threespine sticklebacks.
Edge effects on optically detected magnetic resonance of vacancy defects in hexagonal boron nitride
Authors: Sajid A. , Thygesen Kristian S. , Reimers Jeffrey R. , Ford Michael J.
Published: August 2020

The chemical and structural nature of defects responsible for quantum emission in hexagonal boron nitride (h-BN) remain unknown. Optically detected magnetic resonance (ODMR) measured from these defects was reported in two recent papers. In one case, the ODMR was tentatively attributed to the negatively charged boron vacancy,$$V_{\mathrm{B}}^ -$$VB−. Here we show how the key optical and magnetic properties vary with location within the bulk and along edges of h-BN sheets for this and the negatively charged nitrogen vacancy,$$V_{\mathrm{N}}^ -$$VN−. Sign changes of the axial zero-field interaction parameterDare predicted, as well interchange of singlet and triplet ground states. Based on the latest experimental information, we assign the observed ODMR signal to bulk$$V_{\mathrm{B}}^ -$$VB−. The other observed ODMR has some features reminiscent of our calculations for$$V_{\mathrm{N}}^ -$$VN−edge defects.
Complete spatiotemporal and polarization characterization of ultrafast vector beams
Authors: Alonso Benjamín , Lopez-Quintas Ignacio , Holgado Warein , Drevinskas Rokas , Kazansky Peter G. , Hernández-García Carlos , Sola Íñigo J.
Published: August 2020

The use of structured ultrashort pulses with coupled spatiotemporal properties is emerging as a key tool for ultrafast manipulation. Ultrafast vector beams are opening exciting opportunities in different fields such as microscopy, time-resolved imaging, nonlinear optics, particle acceleration or attosecond science. Here, we implement a technique for the full characterization of structured time-dependent polarization light waveforms with spatiotemporal resolution, using a compact twofold spectral interferometer, based on in-line bulk interferometry and fibre-optic coupler assisted interferometry. We measure structured infrared femtosecond vector beams, including radially polarized beams and complex-shaped beams exhibiting both temporal and spatial evolving polarization. Our measurements confirm that light waveforms with polarization evolving at the micrometer and femtosecond scales can be achieved through the use of structured waveplates and polarization gates. This new scale of measurement achieved will open the way to predict, check and optimize applications of structured vector beams at the femtosecond and micrometer scales.