Predictable arguments of knowledge

We initiate a formal investigation on the power of predictability for argument of knowledge systems for NP. Specifically, we consider private-coin argument systems where the answer of the prover can be predicted, given the private randomness of the verifier; we call such protocols Predictable Arguments of Knowledge (PAoK). Our study encompasses a full characterization of PAoK, showing that such arguments can be made extremely laconic, with the prover sending a single bit, and assumed to have only one round (i.e., two messages) of communication without loss of generality. We additionally explore PAoK satisfying additional properties (including zero-knowledge and the possibility of re-using the same challenge across multiple executions with the prover), present several constructions of PAoK relying on different cryptographic tools, and discuss applications to cryptography

Primary immunodeficiency

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders

Commentary: Neural correlates of expected risks and returns in risky choice across development

“Wisdom comes with age” is an oft-heard expression. It suggests that across development we improve in our ability to make decisions—but evidence for its validity is equivocal. In real-world decision-making, there is an adolescent-specific increased propensity to engage in behaviors associated with morbidity and mortality (e.g., road traffic accidents, unprotected sex, violence, drug, and alcohol abuse; Blum and Nelson-Mmari, 2004). However, this inverted u-shape developmental trajectory for risk-taking is typically not observed in laboratory-based studies (Defoe et al., 2015). As such, there exists a need to: (a) bridge the gap between laboratory and real world behavior; and (b) clarify the processes underlying developmental differences in decision-making to inform interventions that target a reduction in health-risking adolescent activities

Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations

Radiation-induced G1 arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/–) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon–intron boundaries, 3′ and 5′ untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G1 arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/–) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent. © 1999 Cancer Research Campaig

Improved Primitives for MPC over Mixed Arithmetic-Binary Circuits

This work introduces novel techniques to improve the translation between arithmetic and binary data types in secure multi-party computation. We introduce a new approach to performing these conversions using what we call extended doubly-authenticated bits (edaBits), which correspond to shared integers in the arithmetic domain whose bit decomposition is shared in the binary domain. These can be used to considerably increase the efficiency of non-linear operations such as truncation, secure comparison and bit-decomposition. Our edaBits are similar to the daBits technique introduced by Rotaru et al. (Indocrypt 2019). However, we show that edaBits can be directly produced much more efficiently than daBits, with active security, while enabling the same benefits in higher-level applications. Our method for generating edaBits involves a novel cut-and-choose technique that may be of independent interest, and improves efficiency by exploiting natural, tamper-resilient properties of binary circuits that occur in our construction. We also show how edaBits can be applied to efficiently implement various non-linear protocols of interest, and we thoroughly analyze their correctness for both signed and unsigned integers. The results of this work can be applied to any corruption threshold, although they seem best suited to dishonest majority protocols such as SPDZ. We implement and benchmark our constructions, and experimentally verify that our technique yield a substantial increase in efficiency. EdaBits save in communication by a factor that lies between $2$ and $60$ for secure comparisons with respect to a purely arithmetic approach, and between 2 and 25 with respect to using daBits. Improvements in throughput per second are slightly lower but still as high as a factor of 47. We also apply our novel machinery to the tasks of biometric matching and convolutional neural networks, obtaining a noticeable improvement as well

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

The regulation of television sports broadcasting: a comparative analysis

Based on seven different sports broadcasting markets (Australia, Brazil, Italy, India, South Africa, United Kingdom and the United States), this article provides a comparative analysis of the regulation of television sports broadcasting. The article examines how contrasting perspectives on television and sport – economic and sociocultural – have been reflected in two main approaches to the regulation of sports broadcasting, namely competition law and major events legislation. The results of this analysis suggest that in many cases, the balance between commerce and culture in sports broadcasting has shifted too far in favour of the commercial interests of dominant pay-TV operators and sports organisations. Here, the case is made for the pursuit of an approach to sports broadcasting regulation that seeks to balance the commercial priorities of broadcasters and sports organisations with the wider sociocultural benefits citizens gain from freeto- air sports broadcasting