julilili42/papers huggingface dataset:
Detailed seismic bathymetry beneath Ekström Ice Shelf, Antarctica: Implications for glacial history and ice-ocean interaction
2020-04-21

The shape of ice-shelf cavities are a major source of uncertainty in understanding ice-ocean interactions. This limits assessments of the response of the Antarctic ice sheets to climate change. Here we use vibroseis seismic reflection surveys to map the bathymetry beneath the Ekström Ice Shelf, Dronning Maud Land. The new bathymetry reveals an inland-sloping trough, reaching depths of 1100 m below sea level, near the current grounding line, which we attribute to erosion by palaeo-ice streams. The trough does not cross-cut the outer parts of the continental shelf. Conductivity-temperature-depth profiles within the ice-shelf cavity reveal the presence of cold water at shallower depths and tidal mixing at the ice-shelf margins. It is unknown if warm water can access the trough. The new bathymetry is thought to be representative of many ice shelves in Dronning Maud Land, which together regulate the ice loss from a substantial area of East Antarctica.
Faculty Opinions recommendation of Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins.
2020-04-21

Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variantspecific surface proteins (VSPs) on trophozoites that protects the parasite inside the host's intestine.Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner.We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration.Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro.Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors.This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
Faculty Opinions recommendation of The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis.
2020-04-21

Background: Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine.Methods: We systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for the following four vaccination groups: current season only, prior season only, both seasons, and neither season.We pooled differences in VE (ΔVE) between vaccination groups by influenza season and type/subtype using a random-effects model.The study protocol is registered with PROSPERO (registration number: CRD42016037241).Results: We identified 3435 unique articles, reviewed the full text of 634, and included 20 for meta-analysis.Compared to prior season vaccination only, vaccination in both seasons was associated with greater protection against influenza H1N1 (ΔVE = 25%; 95% CI 14%, 35%) and B (ΔVE = 18%; 95% CI 3%, 33%), but not H3N2 (ΔVE = 7%; 95% CI -7%, 21%).Compared to no vaccination for either season, individuals who received the current season's vaccine had greater protection against H1N1 (ΔVE = 62%; 95% CI 51%, 70%), H3N2 (ΔVE = 45%; 95% CI 35%, 53%), and B (ΔVE = 64%; 95% CI 57%, 71%).We observed no differences in VE between vaccination in both seasons and the current season only for H1N1 (ΔVE = 3%; 95% CI -8%, 13%), but less protection against influenza H3N2 (ΔVE = -20%; 95% CI -36%, -4%), and B (ΔVE = -11%; 95% CI -20%, -2%).Conclusions: Our results support current season vaccination regardless of prior season vaccination because VE for vaccination in the current season only is higher compared to no vaccination in either season for all types/subtypes, and for H1N1 and influenza B, vaccination in both seasons provides better VE than vaccination in the prior season only.Although VE was lower against H3N2 and B for individuals vaccinated in both seasons compared to those vaccinated in the current season only, it should be noted that past vaccination history cannot be altered and this comparison disregards susceptibility to influenza during the prior season among those vaccinated in the current season only.In addition, our results for H3N2 were particularly influenced by the 2014-2015 influenza season and the impact of repeated vaccination for all types/subtypes may vary from season to season.It is important that future VE studies include vaccination history over multiple seasons to evaluate repeated vaccination in more detail.
Faculty Opinions recommendation of Lipid Nanoparticles Potentiate CpG-Oligodeoxynucleotide-Based Vaccine for Influenza Virus.
2020-04-21

Current influenza vaccines are generally effective against highly similar (homologous) strains, but their effectiveness decreases markedly against antigenically mismatched (heterologous) strains.One way of developing a universal influenza vaccine with a broader spectrum of protection is to use appropriate vaccine adjuvants to improve a vaccine's effectiveness and change its immune properties.Oligodeoxynucleotides (ODNs) with unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG ODNs), which are Toll-like-receptor 9 (TLR9) agonists, are among the most promising adjuvants and are already being used in humans.However, the development of novel delivery vehicles to improve adjuvant effects in vivo is highly desirable.Here, we assessed the potential of lipid nanoparticles (LNPs) as CpG ODN delivery vehicles in mice to augment the vaccine adjuvant effects of CpG ODN and enhance the protective spectrum of conventional influenza split vaccine (SV).In vitro, compared with CpG ODN, LNPs containing CpG ODNs (LNP-CpGs) induced significantly greater production of cytokines such as IL-12 p40 and IFN-α by mouse dendritic cells (DCs) and significantly greater expression of the co-stimulatory molecules CD80 and CD86 on DCs.In addition, after subcutaneous administration in mice, compared with CpG ODN, LNP-CpGs enhanced the expression of CD80 and CD86 on plasmacytoid DCs in draining lymph nodes.LNP-CpGs given with SV from H1N1 influenza A virus improved T-cell responses and gave a stronger not only SV-specific but also heterologous-virus-strain-specific IgG2c response than CpG ODN.Furthermore, immunization with SV plus LNP-CpGs protected against not only homologous strain challenge but also heterologous and heterosubtypic strain challenge, whereas immunization with SV plus CpG ODNs protected against homologous strain challenge only.We therefore demonstrated that LNP-CpGs improved the adjuvant effects of CpG ODN and broadened the protective spectrum of SV against influenza virus.We expect that this strategy will be useful in developing adjuvant delivery vehicles and universal influenza vaccines.
Faculty Opinions recommendation of Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.
2020-04-21

Emerging evidence indicates a central role for the microbiome in immunity.However, causal evidence in humans is sparse.Here we administered broad spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination.Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected.However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses.In addition, in both studies antibiotics treatment resulted in: (i) Enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (ii) Divergent metabolic trajectories, with a 1000-fold reduction in serum secondary bile acids which was highly correlated with AP-1/NR4A signaling and inflammasome activation.Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.
Faculty Opinions recommendation of Why are CD8 T cell epitopes of human influenza A virus conserved?
2020-04-21

The high degree of conservation of CD8 T cell epitopes of influenza A virus (IAV) may allow for the development of T cell-inducing vaccines that provide protection across different strains and subtypes.This conservation is not fully explained by functional constraint, since an additional mutation(s) can compensate for the replicative fitness loss of IAV escape variants.Here, we propose three additional mechanisms that contribute to the conservation of CD8 T cell epitopes of IAV.First, influenza-specific CD8 T cells may protect predominantly against severe pathology rather than infection and may have only a modest effect on transmission.Second, polymorphism of the human major histocompatibility complex class I (MHC-I) gene restricts the advantage of an escape variant to only a small fraction of the human population who carry the relevant MHC-I alleles.Finally, infection with CD8 T cell escape variants may result in a compensatory increase in the responses to other epitopes of IAV.We use a combination of population genetics and epidemiological models to examine how the interplay between these mechanisms affects the rate of invasion of IAV escape variants.We conclude that for a wide range of biologically reasonable parameters, the invasion of an escape variant virus will be slow, with a timescale of a decade or more.The results suggest T cell-inducing vaccines do not engender the rapid evolution of IAV.Finally, we identify key parameters whose measurement will allow for more accurate quantification of the long-term effectiveness and impact of universal T cell-inducing influenza vaccines.IMPORTANCE Universal influenza vaccines against the conserved epitopes of influenza A virus have been proposed to minimize the burden of seasonal outbreaks and prepare for the pandemics.However, it is not clear how rapidly T cell-inducing vaccines will select for viruses that escape these T cell responses.Our mathematical models explore the factors that contribute to the conservation of CD8 T cell epitopes and how rapidly the virus will evolve in response to T cell-inducing vaccines.We identify the key biological parameters to be measured and questions that need to be addressed in future studies.
Faculty Opinions recommendation of Impact of aging and HIV infection on serologic response to seasonal influenza vaccination.
2020-04-21

Objective: To determine influence of age and HIV infection on influenza vaccine responses.Design: Evaluate serologic response to seasonal trivalent influenza vaccine (TIV) as the immunologic outcome in HIV-infected (HIV + ) and age-matched HIV negative (HIV -) adults.Methods: During 2013-2016, 151 virologically controlled HIV + individuals on antiretroviral therapy and 164 HIV -volunteers grouped by age as young (<40 years), middle aged (40-59 years) and old (≥60 years) were administered TIV and investigated for serum antibody response to vaccine antigens.Results: At prevaccination (T0) titers were in seroprotective range in more than 90% of participants.Antibody titers increased in all participants postvaccination but frequency of classified vaccine responders to individual or all three vaccine antigens at 3-4 weeks was higher in HIV -than HIV + adults with the greatest differences manifesting in the young age group.Of the three vaccine strains in TIV, antibody responses at T2 were weakest against H3N2 with those to H1N1 and B antigens dominating.Among the age groups, the titers for H1N1 and B were lowest in old age, with evidence of an age-associated interaction in HIV + persons with antibody to B antigen.
Changes in the building stock of DaNang between 2015 and 2017
2020-04-21

<strong>Description</strong> This dataset consist of two vector files which show the change in the building stock of the City of DaNang retrieved from satellite image analysis. Buildings were first identified from a Pléiades satellite image from 24.10.2015 and classified into 9 categories in a semi-automatic workflow desribed by Warth et al. (2019) and Vetter-Gindele et al. (2019). In a second step, these buildings were inspected for changes based on a second Pléiades satellite image acquired on 13.08.2017 based on visual interpretation. Changes were also classified into 5 categories and aggregated by administrative wards (first dataset: <em>adm</em>) and a hexagon grid of 250 meter length (second dataset: <em>hex</em>). The full workflow of the generation of this dataset, including a detailled description of its contents and a discussion on its potential use is published by Braun et al. 2020: Changes in the building stock of DaNang between 2015 and 2017 <strong>Contents</strong> Both datasets (<em>adm </em>and <em>hex</em>) are stored as ESRI shapefiles which can be used in common Geographic Information Systems (GIS) and consist of the following parts: shp: <strong>polygon geometries</strong> (geometries of the administrative boundaries and hexagons) dbf: <strong>attribute table</strong> (containing the number of buildings per class for 2015 and 2017 and the underlying changes (e.g. number of new buildings, number of demolished buildings, ect.) shx: index file combining the geometries with the attributes cpg: encoding of the attributes (UTF-8) prj: spatial reference of the datasets (UTM zone 49 North, EPSG:32649) for ArcGIS qpj: spatial reference of the datasets (UTM zone 49 North, EPSG:32649) for QGIS lyr: symbology suggestion for the polygons(predefined is the number of <em>local type shophouses</em> in 2017) for ArcGIS qml: symbology suggestion for the polygons (predefined is the number of new buildings between 2015 and 2017) for QGIS <strong>Citation and documentation</strong> To cite this dataset, please refer to the publication Braun, A.; Warth, G.; Bachofer, F.; Quynh Bui, T.T.; Tran, H.; Hochschild, V. (2020): <strong>Changes in the Building Stock of Da Nang between 2015 and 2017</strong>. <em>Data</em>, 5, 42. doi:10.3390/data5020042 This article contains a detailed description of the dataset, the defined building type classes and the types of changes which were analyzed. Furthermore, the article makes recommendations on the use of the datasets and discusses potential error sources.
On the Role and Production of Polyhydroxybutyrate (PHB) in the Cyanobacterium Synechocystis sp. PCC 6803
2020-04-22

The cyanobacterium Synechocystis sp. PCC 6803 is known for producing polyhydroxybutyrate (PHB) under unbalanced nutrient conditions. Although many cyanobacteria produce PHB, its physiological relevance remains unknown, since previous studies concluded that PHB is redundant. In this work, we try to better understand the physiological conditions that are important for PHB synthesis. The accumulation of intracellular PHB was higher when the cyanobacterial cells were grown under an alternating day–night rhythm as compared to continuous light. In contrast to previous reports, a reduction of PHB was observed when the cells were grown under conditions of limited gas exchange. Since previous data showed that PHB is not required for the resuscitation from nitrogen starvation, a series of different abiotic stresses were applied to test if PHB is beneficial for its fitness. However, under none of the tested conditions did cells containing PHB show a fitness advantage compared to a PHB-free-mutant (ΔphaEC). Additionally, the distribution of PHB in single cells of a population Synechocystis cells was analyzed via fluorescence-activated cell sorting (FACS). The results showed a considerable degree of phenotypic heterogeneity at the single cell level concerning the content of PHB, which was consistent over several generations. These results improve our understanding about how and why Synechocystis synthesizes PHB and gives suggestions how to further increase its production for a biotechnological process.
Plant's‐eye view of temperature governs elevational distributions
2020-04-22

Abstract Explaining species geographic distributions by macroclimate variables is the most common approach for getting mechanistic insights into large‐scale diversity patterns and range shifts. However, species' traits influencing biophysical processes can produce a large decoupling from ambient air temperature, which can seriously undermine biogeographical inference. We combined stable oxygen isotope theory with a trait‐based approach to assess leaf temperature during carbon assimilation ( T L ) and its departure (Δ T ) from daytime free air temperature during the growing season ( T gs ) for 158 plant species occurring from 3,400 to 6,150 m a.s.l. in Western Himalayas. We uncovered a general extent of temperature decoupling in the region. The interspecific variation in Δ T was best explained by the combination of plant height and δ 13 C, and leaf dry matter content partly captured the variation in T L . The combination of T L and Δ T , with Δ T contributing most, explained the interspecific difference in elevational distributions. Stable oxygen isotope theory appears promising for investigating how plants perceive temperatures, a pivotal information to species biogeographic distributions.
Nodal and planar cell polarity signaling cooperate to regulate zebrafish convergence and extension gastrulation movements
2020-04-22

During vertebrate gastrulation, convergence and extension (C and E) of the primary anteroposterior (AP) embryonic axis is driven by polarized mediolateral (ML) cell intercalations and is influenced by AP axial patterning. Nodal signaling is essential for patterning of the AP axis while planar cell polarity (PCP) signaling polarizes cells with respect to this axis, but how these two signaling systems interact during C and E is unclear. We find that the neuroectoderm of Nodal-deficient zebrafish gastrulae exhibits reduced C and E cell behaviors, which require Nodal signaling in both cell- and non-autonomous fashions. PCP signaling is partially active in Nodal-deficient embryos and its inhibition exacerbates their C and E defects. Within otherwise naïve zebrafish blastoderm explants, however, Nodal induces C and E in a largely PCP-dependent manner, arguing that Nodal acts both upstream of and in parallel with PCP during gastrulation to regulate embryonic axis extension cooperatively.
Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma
2020-04-22

Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p &lt; 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.
Clinical and Kinematic Correlates of Favorable Gait Outcomes From Subthalamic Stimulation
2020-04-22

<b>Objective:</b> Gait and freezing of gait (FoG) are highly relevant to the outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Previous studies pointed to variable response to combined dopaminergic and STN-DBS treatment. Here, we performed a prospective exploratory study on associations of preoperative clinical and kinematic gait measures with quantitative gait and FoG outcomes after STN-DBS implantation. <b>Methods:</b> We characterized 18 consecutive PD patients (13 freezers) before and after STN-DBS implantation. The patients received preoperative levodopa challenges (MedOff vs. MedOn) and a postoperative reassessment at 6 months from surgery in MedOn/StimOn condition. We correlated the FoG outcome, calculated as improvement of Freezing of Gait Assessment Course (FoG-AC) from baseline MedOff to 6-month follow-up MedOn/StimOn, with the levodopa response of preoperative clinical and kinematic gait measures. We considered measures with significant correlations for a multiple regression model. <b>Results:</b> We found that the postoperative gait and FoG outcomes were associated with the preoperative levodopa response of clinical and kinematic gait measures. In particular, preoperative levodopa sensitivity of FoG showed high correlation with a favorable quantitative FoG outcome. Among kinematic measures, preoperative levodopa response of stride length and range of motion showed high correlation with favorable FoG outcome. In addition, the preoperative levodopa sensitivity of FoG predicted postoperative FoG outcome with high accuracy (<i>R</i> <sup>2</sup> = 0.952; 95% CI: 0.95-1.29; <i>P</i> < 0.001). <b>Conclusions:</b> Preoperative clinical and kinematic measures correlated with favorable postoperative gait and FoG outcomes. The findings should be reproduced in larger and independent cohorts to verify their predictive value.