Miracle-dz/UniFAR-FTUs huggingface dataset:
A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity

The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit vaccines.
Plant Community Diversity Influences Allocation to Direct Chemical Defence in Plantago lanceolata

Background Forecasting the consequences of accelerating rates of changes in biodiversity for ecosystem functioning requires a mechanistic understanding of the relationships between the structure of biological communities and variation in plant functional characteristics. So far, experimental data of how plant species diversity influences the investment of individual plants in direct chemical defences against herbivores and pathogens is lacking. Methodology/Principal Findings We used Plantago lanceolata as a model species in experimental grasslands differing in species richness and composition (Jena Experiment) to investigate foliar concentrations of the iridoid glycosides (IG), catalpol and its biosynthetic precursor aucubin. Total IG and aucubin concentrations decreased, while catalpol concentrations increased with increasing plant diversity in terms of species or functional group richness. Negative plant diversity effects on total IG and aucubin concentrations correlated with increasing specific leaf area of P. lanceolata, suggesting that greater allocation to light acquisition reduced the investment into these carbon-based defence components. In contrast, increasing leaf nitrogen concentrations best explained increasing concentrations of the biosynthetically more advanced IG, catalpol. Observed levels of leaf damage explained a significant proportion of variation in total IG and aucubin concentrations, but did not account for variance in catalpol concentrations. Conclusions/Significance Our results clearly show that plants growing in communities of varying species richness and composition differ in their defensive chemistry, which may modulate plant susceptibility to enemy attack and consequently their interactions with higher trophic level organisms.
Testing Strength of Biotic Resistance against an Introduced Fish: Inter-Specific Competition or Predation through Facultative Piscivory?

Biotic resistance is the process where aspects of the receiving environment inhibit the establishment and invasion of an introduced species. Resistance against an introduced fish can be through strong competition and/or predation from resident fishes. Here, the biotic resistance against introduced topmouth gudgeon Pseudorasbora parva (a highly invasive fish in Europe) by resident carp Cyprinus carpio was tested in experimental mesocosms. The introduction scenario was six adult P. parva (three male, three female) on a single occasion. Resistance to their establishment was provided by three and six resident C. carpio whose effects on P. parva growth and reproduction were compared to a Control (no resident fish at the time of introduction) and treatments containing three and six P. parva. After 120 days, the growth rates of the introduced P. parva were significantly depressed in C. carpio presence and in mesocosms with three C. carpio present, significantly decreased numbers of 0+P. parva were recorded. Where six C. carpio were present, no 0+P. parva were recorded, indicating resistance strength increased with carp abundance. In contrast, there were no differences in P. parva reproduction and growth rates between the Control and treatments containing conspecifics. Stable isotope analysis (δ15N, δ13C) revealed C. carpio were feeding at one trophic level above 0+P. parva, suggesting the process of resistance was predation (facultative piscivory) rather than competition. Thus, if P. parva are to establish and invade following an introduction, they must overcome this biotic resistance from cyprinid fishes such as C. carpio.
Beyond green niches? Growth strategies of environmentally-motivated social enterprises

The article examines the strategies by which environmentally-motivated social enterprises seek to scale up their positive impacts, drawing on a theoretical understanding of the role of entrepreneurial agency in transitions to a more sustainable economy and society. Case study evidence is used to explore different forms of enterprise growth, contributions to economic, environmental and social value, and the capabilities involved in their realisation. A typology of three distinct approaches or modes is introduced to help explain orientations and strategies that reflect both conventional conceptions of growth and alternative ways of growing social and environmental value. The role of values, capabilities and relational learning in shaping strategies and addressing the tensions and challenges encountered within each category is highlighted.
Oxygen, carbon, and nutrients in the oligotrophic eastern subtropical North Atlantic

The Beta Triangle, a region of the oligotrophic subtropical eastern North Atlantic Ocean, is notorious for its enigmatic oxygen, carbon, and nitrogen balances, in which nutrient supply is said to explain only a fraction of production necessary for estimated carbon export. Rates of dissolved organic carbon accumulation and dissolved organic nitrogen utilization in surface water and an assessment of oxygen utilized, organic matter consumed, and nitrate and phosphate regenerated in subsurface water, show that conventional production estimates miss substantial shares of biotic production. The shallow export of total organic carbon, predominantly dissolved (DOC), by subduction is responsible for about 50–70% of apparent oxygen utilization in subsurface water between the base of the surface layer at ca. 140 m and ca. 195 m depth, but it is insignificant below. Additionally, there is an estimated accumulation of 1.0 to 1.75 mol DOC m−2 a−1 in surface water. Including DOC dynamics in its carbon balance reveals the surface of this ultra-oligotrophic part of the ocean to be net autotrophic. Increasing subsurface values of excess nitrogen (DINxs) imply the export of nitrogen from surface water stemming from production not exclusively fuelled by new nitrate supplied from below. Total organic nitrogen (almost exclusively dissolved, DON) is consumed in the surface layer at a rate estimated at 0.13 to 0.23 mol m−2 a−1. There is no variation in dissolved organic phosphorus (DOP) in the same direction. DON utilization thus contributes to the pronounced subsurface DINxs signature. DOC export and accumulation are important in the carbon balance in surface and near-surface water. DON utilization and, probably, N2 fixation contribute significant amounts to the nitrogen supply of surface water. These processes can close part of the enigmatic carbon and nitrogen balances in the Beta Triangle. There are, however, no comparable processes which can explain the equally enigmatic situation concerning phosphorus supply in this area.
NUMERICAL COMPUTATION OF DIRECT EXCHANGE AREAS IN THERMAL RADIATION ANALYSIS Abbreviated title : EFFICIENT COMPUTATION OF DIRECT EXCHANGE AREAS

The analysis of thermal radiation in multi-surface enclosures typically involves multiple integrals with four, five, or six variables. Major difficulties for the numerical evaluation of these integrals are non-convex geometries and singular integral kernels. This paper presents hierarchical visibility concepts and coordinate transformations which eliminate these difficulties. In the transformed form, standard quadrature techniques are applied and accurate results are achieved with moderate numerical effort. In benchmark example problems, the effectiveness and accuracy of the method are validated. A simulation model of an industrial furnace demonstrates the applicability of the method for large-scale problems. NOMENCLATURE Bα bounding box b radiosity, W/m2 C(α) function for computing the visibility D integration domain d side length, distance, m f continuous function or part of the kernel k, m4 g part of the integral kernel k, 1/m2 H heat flux density absorbed by a volume zone, W/m2 ∗Corresponding author. Email: andreas.steinboeck@tuwien.ac. at
Noise2Noise: Learning Image Restoration without Clean Data

We apply basic statistical reasoning to signal reconstruction by machine learning -- learning to map corrupted observations to clean signals -- with a simple and powerful conclusion: under certain common circumstances, it is possible to learn to restore signals without ever observing clean ones, at performance close or equal to training using clean exemplars. We show applications in photographic noise removal, denoising of synthetic Monte Carlo images, and reconstruction of MRI scans from undersampled inputs, all based on only observing corrupted data.
The key role of differential diagnosis in diagnosis

Abstract Differential diagnosis, that is, the creation of a list of suspected diseases, is important as it guides us in looking for these diseases in a patient during diagnosis. If a disease is not included in differential diagnosis, it is not likely to be diagnosed. It is important to include uncommon as well as common diseases in differential diagnosis.
Endosomal-Lysosomal Cholesterol Sequestration by U18666A Differentially Regulates Amyloid Precursor Protein (APP) Metabolism in Normal and APP-Overexpressing Cells

ABSTRACT Amyloid β (Aβ) peptide, derived from amyloid precursor protein (APP), plays a critical role in the development of Alzheimer's disease. Current evidence indicates that altered levels or subcellular distribution of cholesterol can regulate Aβ production and clearance, but it remains unclear how cholesterol sequestration within the endosomal-lysosomal (EL) system can influence APP metabolism. Thus, we evaluated the effects of U18666A, which triggers cholesterol redistribution within the EL system, on mouse N2a cells expressing different levels of APP in the presence or absence of extracellular cholesterol and lipids provided by fetal bovine serum (FBS). Our results reveal that U18666A and FBS differentially increase the levels of APP and its cleaved products, the α-, β-, and η-C-terminal fragments, in N2a cells expressing normal levels of mouse APP (N2awt), higher levels of human wild-type APP (APPwt), or “Swedish” mutant APP (APPsw). The cellular levels of Aβ1–40/Aβ1–42 were markedly increased in U18666A-treated APPwt and APPsw cells. Our studies further demonstrate that APP and its cleaved products are partly accumulated in the lysosomes, possibly due to decreased clearance. Finally, we show that autophagy inhibition plays a role in mediating U18666A effects. Collectively, these results suggest that altered levels and distribution of cholesterol and lipids can differentially regulate APP metabolism depending on the nature of APP expression.
An Updated Meta-Analysis of Risk of Multiple Sclerosis following Infectious Mononucleosis

Background Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published. Methods/Principal Findings We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97–2.39; p<10−54). Discussion Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors.
Radiation situation dynamics at the Andreeva Bay site for temporary storage of spent nuclear fuel and radioactive waste over the period 2002–2016

The Coastal Technical Base (CTB) №569 at Andreeva Bay was established in the early 1960s and intended for the refueling of nuclear submarine reactors and temporary storage of spent nuclear fuel (SNF) and radioactive waste (RW). In 2001, the base was transferred to the Russian Ministry for Atomic Energy and the site remediation began. The paper describes in detail the radiation situation change at the technical site in Andreeva Bay from 2002–2016, the period of preparation for the most critical phase of remedial work: removal of spent fuel assemblies. The analysis of aggregated indicators and data mining were used. The article suggests the best number and location of checkpoints needed to ensure sufficient accuracy of the radiation situation description. The fractal properties of the radiation field are studied using the Hurst index. The relationship between checkpoints was assessed using the method of searching for checkpoint communities. The decrease in the integral of the ambient dose equivalent rate (ADER) at the technical site was evaluated by the method of time series decomposition. Three components of time series were identified: trend, seasonal and residual. The trend of the ADER integral over the technical site is a monotonic decreasing function, where the initial and final values differ tenfold. Taking into account that 137Cs dominates the radiation situation on-site, it is clear that the ADER due to the radionuclide decay will have decreased by 1.4 times. It is estimated that only a small proportion of 137Cs has migrated off-site. Therefore, approximately a sevenfold decrease in dose rate is mainly due to remediation activities of personnel. During the year, the seasonal component varies the ADER integral by a factor of two, due to snowfall. The residual component reflects the uncertainty of the ADER integral calculation and phases of active SNF and RW management. The methods developed are used to support the optimization of remediation work as well as regulatory supervision of occupational radiation protection.
Measuring Human-Chosen PINs : Characteristics , Distribution and Security

Personal Identification Numbers (PINs) are ubiquitously used in computer systems where user input interfaces are constrained, such as ATMs, POS terminals, electronic doors and mobile devices. Yet, so far little attention has been paid to this important kind of authentication credentials, especially for 6-digit PINs which dominate in Asian countries and are gaining popularity worldwide. Unsurprisingly, many fundamental questions (e.g., what’s the distribution that human-chosen PINs follow? ) remain as intact as about fifty years ago when they first arose. In this work, we conduct a systematic investigation into the characteristics, distribution and security of both 4-digit PINs and 6-digit PINs by using a corpus of 9.74 million 4-digit and 8.64 million 6-digit secret sequences extracted from real-life passwords of two groups of users (i.e., Chinese users and English users), and perform a comprehensive comparison of the PIN characteristics and security among users with distinctive language and cultural backgrounds. Our results show that there are great differences in PIN choices between these two groups of users, a small number of popular patterns prevail in both groups, and surprisingly, over 50% of every PIN datasets can be accounted for by just the top 5%∼8% most popular PINs. What’s most staggering is the observation that, when online guessing is the primary concern, longer PINs essentially mean less security: human-chosen 4-digit PINs can offer about 5.3 bits of security against online guessing and 8.4 bits of security against offline guessing, and this figure for 6-digit PINs is 5.2 bits and 13.2 bits, respectively. Most interestingly, by conducting linear regressions on the collected corpus, we unveil that Zipf’s law perfectly exists in humanchosen PINs. Despite distant space and distinct language and cultural backgrounds, both groups of users, unbelievably, follow nearly the same distribution function. We also investigate some foundational implications of our observations for PIN creation policies, strength measurements, migration strategies, etc. keywords– Authentication, Personal Identification Number, Zipf’s law, Statistics, Markov-Chain-based Cracking.
Optimizing field and analytical procedures for estimating densities of arboreal and threatened primates in tropical rainforest

The application of distance sampling to primate density estimation is challenging and susceptible to estimation biases, mainly due to the difficulties of properly accounting for variation in species’ detectability and of accurately sampling the spread of the social groups. We apply a hierarchical distance sampling approach to primate data, to account for a comprehensive set of environmental covariates of both detectability and abundance, and we propose a novel field routine to measure the spread of groups during transect sampling. We confirm the good potential of this approach, given we obtained refined estimates of primate density (as measured by the Akaike Information Criterion) in comparison to estimates from models without covariates.
Romidepsin in relapsed/refractory T-cell lymphomas: Italian experience and results of a named patient program

Abstract Clinical trial results indicate that romidepsin, a histone deacetylase inhibitor, is a promising treatment in relapsed/refractory T-cell lymphomas (TCLs). This retrospective multicenter study was conducted in patients with relapsed/refractory TCL treated with romidepsin monotherapy through a Named Patient Program (NPP) in Italy. Principal endpoints were overall response rate (ORR), safety, and overall survival (OS). The ORR in 33 evaluable patients was 24.2% with an ORR in the cutaneous TCL of 35.7%. Global OS was 39.3% at 30 months. There were not any specific differences on hematological and extrahematological adverse events. Data from patients treated with romidepsin outside a controlled clinical trial give additional information about the clinical use, efficacy, and toxicity of the drug given to relapsed or refractory TCL patients in a real life context as TCLs are rare diseases and more information is needed. These findings suggest that romidepsin is effective and safe for heavily pretreated TCL patients.
Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

Paclitaxel (Taxol®) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS), the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6), the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN) and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days −1 to 13) completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg) systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day −1 to 12) did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals alone.