The need of data harmonization to derive robust empirical relationships between soil conditions and vegetation.

Question: Is it possible to improve the general applicability and significance of empirical relationships between abiotic conditions and vegetation by harmonization of temporal data? Location: The Netherlands. Methods: Three datasets of vegetation, recorded after periods with different meteorological conditions, were used to analyze relationships between soil moisture regime (expressed by the mean spring groundwater level - MSLt calculated for different periods) and vegetation (expressed by the mean indicator value for moisture regime Fm). For each releve, measured groundwater levels were interpolated and extrapolated to daily values for the period 1970-2000 by means of an impulse-response model. Sigmoid regression lines between MSLt and Fm were determined for each of the three datasets and for the combined dataset. Results: A measurement period of three years resulted in significantly different relationships between Fm and MSLt for the three datasets (F-test,/? <0.05>. The three regression lines only coincided for the mean spring groundwater level computed over the period 1970-2000 (AfSLclimate) and thus provided a general applicable relationship. Precipitation surplus prior to vegetation recordings strongly affected the relationships. Conclusions: Harmonization of time series data (1) eliminates biased measurements, (2) results in generally applicable relationships between abiotic and vegetation characteristics and (3) increases the goodness of fit of these relationships. The presented harmonization procedure can be used to optimize many relationships between soil and vegetation characteristics. © IAVS; Opulus Press Uppsala

Naturally Rehearsing Passwords

We introduce quantitative usability and security models to guide the design of password management schemes --- systematic strategies to help users create and remember multiple passwords. In the same way that security proofs in cryptography are based on complexity-theoretic assumptions (e.g., hardness of factoring and discrete logarithm), we quantify usability by introducing usability assumptions. In particular, password management relies on assumptions about human memory, e.g., that a user who follows a particular rehearsal schedule will successfully maintain the corresponding memory. These assumptions are informed by research in cognitive science and validated through empirical studies. Given rehearsal requirements and a user's visitation schedule for each account, we use the total number of extra rehearsals that the user would have to do to remember all of his passwords as a measure of the usability of the password scheme. Our usability model leads us to a key observation: password reuse benefits users not only by reducing the number of passwords that the user has to memorize, but more importantly by increasing the natural rehearsal rate for each password. We also present a security model which accounts for the complexity of password management with multiple accounts and associated threats, including online, offline, and plaintext password leak attacks. Observing that current password management schemes are either insecure or unusable, we present Shared Cues--- a new scheme in which the underlying secret is strategically shared across accounts to ensure that most rehearsal requirements are satisfied naturally while simultaneously providing strong security. The construction uses the Chinese Remainder Theorem to achieve these competing goals

Exogenous IFN-alpha Administration Reduces Influenza A Virus Replication in the Lower Respiratory Tract of Rhesus Macaques

To determine the role of innate immune responses in controlling influenza A virus replication, rhesus macaques (RM) were administered pegylated IFN-alpha prior to virus challenge. Systemic and mucosal pegylated IFN-alpha administration induced expression of the interferon-stimulated genes (ISG) MxA and OAS in the airways. RM treated with IFN-alpha 24 hours prior to influenza virus challenge had significantly lower peak vRNA levels in the trachea compared to untreated animals. In addition to blunting viral replication, IFN-alpha treatment minimized the weight loss and spike in body temperature after influenza infection of RM. These results confirm the importance of IFN-alpha induced innate immune responses in the rapid control of influenza A virus replication in primates

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1)

Host cells respond to exogenous infectious agents such as viruses, including HIV-1. Studies have evaluated the changes associated with virus infection at the transcriptional and translational levels of the cellular genes involved in specific pathways. While this approach is useful, in our view it provides only a partial view of genome-wide changes. Recently, technological advances in the expression profiling at the microRNA (miRNA) and mRNA levels have made it possible to evaluate the changes in the components of multiple pathways. To understand the role of miRNA and its interplay with host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative global miRNA and mRNA microarray using human PBMCs infected with HIV-1. The PBMCs were derived from multiple donors and were infected with virus generated from the molecular clone pNL4-3. The results showed that HIV-1 infection led to altered regulation of 21 miRNAs and 444 mRNA more than 2-fold, with a statistical significance of p<0.05. Furthermore, the differentially regulated miRNA and mRNA were shown to be associated with host cellular pathways involved in cell cycle/proliferation, apoptosis, T-cell signaling, and immune activation. We also observed a number of inverse correlations of miRNA and mRNA expression in infected PBMCs, further confirming the interrelationship between miRNA and mRNA regulation during HIV-1 infection. These results for the first time provide evidence that the miRNA profile could be an early indicator of host cellular dysfunction induced by HIV-1

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

Severe pediatric COVID-19 and multisystem inflammatory syndrome in children from wild-type to population immunity: a prospective multicenter cohort study with real-time reporting

Background:SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data.Methods:This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity.Results:We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curacao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies.Conclusions:Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.Transplantation and immunomodulatio

On the Complexity of Compressing Obfuscation

Indistinguishability obfuscation has become one of the most exciting cryptographic primitives due to its far reaching applications in cryptography and other fields. However, to date, obtaining a plausibly secure construction has been an illusive task, thus motivating the study of seemingly weaker primitives that imply it, with the possibility that they will be easier to construct. In this work, we provide a systematic study of compressing obfuscation, one of the most natural and simple to describe primitives that is known to imply indistinguishability obfuscation when combined with other standard assumptions. A compressing obfuscator is roughly an indistinguishability obfuscator that outputs just a slightly compressed encoding of the truth table. This generalizes notions introduced by Lin et al.~(PKC 2016) and Bitansky et al.~(TCC 2016) by allowing for a broader regime of parameters. We view compressing obfuscation as an independent cryptographic primitive and show various positive and negative results concerning its power and plausibility of existence, demonstrating significant differences from full-fledged indistinguishability obfuscation. First, we show that as a cryptographic building block, compressing obfuscation is weak. In particular, when combined with one-way functions, it cannot be used (in a black-box way) to achieve public-key encryption, even under (sub-)exponential security assumptions. This is in sharp contrast to indistinguishability obfuscation, which together with one-way functions implies almost all cryptographic primitives. Second, we show that to construct compressing obfuscation with perfect correctness, one only needs to assume its existence with a very weak correctness guarantee and polynomial hardness. Namely, we show a correctness amplification transformation with optimal parameters that relies only on polynomial hardness assumptions. This implies a universal construction assuming only polynomially secure compressing obfuscation with approximate correctness. In the context of indistinguishability obfuscation, we know how to achieve such a result only under sub-exponential security assumptions together with derandomization assumptions. Lastly, we characterize the existence of compressing obfuscation with \emph{statistical} security. We show that in some range of parameters and for some classes of circuits such an obfuscator exists, whereas it is unlikely to exist with better parameters or for larger classes of circuits. These positive and negative results reveal a deep connection between compressing obfuscation and various concepts in complexity theory and learning theory