Formal Analysis of V2X Revocation Protocols

Research on vehicular networking (V2X) security has produced a range of security mechanisms and protocols tailored for this domain, addressing both security and privacy. Typically, the security analysis of these proposals has largely been informal. However, formal analysis can be used to expose flaws and ultimately provide a higher level of assurance in the protocols. This paper focusses on the formal analysis of a particular element of security mechanisms for V2X found in many proposals: the revocation of malicious or misbehaving vehicles from the V2X system by invalidating their credentials. This revocation needs to be performed in an unlinkable way for vehicle privacy even in the context of vehicles regularly changing their pseudonyms. The REWIRE scheme by Forster et al. and its subschemes BASIC and RTOKEN aim to solve this challenge by means of cryptographic solutions and trusted hardware. Formal analysis using the TAMARIN prover identifies two flaws with some of the functional correctness and authentication properties in these schemes. We then propose Obscure Token (OTOKEN), an extension of REWIRE to enable revocation in a privacy preserving manner. Our approach addresses the functional and authentication properties by introducing an additional key-pair, which offers a stronger and verifiable guarantee of successful revocation of vehicles without resolving the long-term identity. Moreover OTOKEN is the first V2X revocation protocol to be co-designed with a formal model.Comment: 16 pages, 4 figure

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Reduction of T-Helper Cell Responses to Recall Antigen Medicated by Codelivery with Peptidoglycan via the Intestinal Nanomineral-Antigen Pathway

Naturally occurring intestinal nanomineral particles constituently form in the mammalian gut and trap luminal protein and microbial components. These cargo loaded nanominerals are actively scavenged by M cells of intestinal immune follicles, such as Peyer’s patches and are passed to antigen-presenting cells. Using peripheral blood mononuclear cell populations as an in vitro model of nanomineral uptake and antigen presentation, we show that monocytes avidly phagocytose nanomineral particles bearing antigen and peptidoglycan (PGN), and that the presence of PGN within particles downregulates their cell surface MHC class II and upregulates programmed death receptor ligand 1. Nanomineral delivery of antigen suppresses antigen-specific CD4+ T cell responses, an effect that is enhanced in the presence of PGN. Blocking the interleukin-10 receptor restores CD4+ T cell responses to antigen codelivered with PGN in nanomineral form. Using human intestinal specimens, we have shown that the in vivo nanomineral pathway operates in an interleukin-10 rich environment. Consequently, the delivery of a dual antigen–PGN cargo by endogenous nanomineral in vivo is likely to be important in the establishment of intestinal tolerance, while their synthetic mimetics present a potential delivery system for therapeutic applications targeting the modulation of Peyer’s patch T cell responses

Disentangling manual muscle testing and Applied Kinesiology: critique and reinterpretation of a literature review

Cuthbert and Goodheart recently published a narrative review on the reliability and validity of manual muscle testing (MMT) in the Journal. The authors should be recognized for their effort to synthesize this vast body of literature. However, the review contains critical errors in the search methods, inclusion criteria, quality assessment, validity definitions, study interpretation, literature synthesis, generalizability of study findings, and conclusion formulation that merit a reconsideration of the authors' findings. Most importantly, a misunderstanding of the review could easily arise because the authors did not distinguish the general use of muscle strength testing from the specific applications that distinguish the Applied Kinesiology (AK) chiropractic technique. The article makes the fundamental error of implying that the reliability and validity of manual muscle testing lends some degree of credibility to the unique diagnostic procedures of AK. The purpose of this commentary is to provide a critical appraisal of the review, suggest conclusions consistent with the literature both reviewed and omitted, and extricate conclusions that can be made about AK in particular from those that can be made about MMT. When AK is disentangled from standard orthopedic muscle testing, the few studies evaluating unique AK procedures either refute or cannot support the validity of AK procedures as diagnostic tests. The evidence to date does not support the use of MMT for the diagnosis of organic disease or pre/subclinical conditions

CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations

RATIONALE: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV-induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophil-related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV-induced exacerbations of asthma. METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LL-37) and neutrophil chemokines (CXCL1/GRO-α, CXCL2/GRO-β, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2, and CXCL8/IL-8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post-experimental infection. RESULTS: BAL HNP 1–3 and Elafin were higher, CXCL7/NAP-2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1–3 and CXCL8/IL-8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1–3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1–3 or IL-8 levels. CONCLUSIONS: We propose that RV infection in asthma leads to increased release of CXCL8/IL-8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL-8 may be useful in treatment of virus-induced asthma exacerbations

Damagnetization cooling of a gas

We demonstrate demagnetization cooling of a gas of ultracold $^{52}$Cr atoms. Demagnetization is driven by inelastic dipolar collisions which couple the motional degrees of freedom to the spin degree. By that kinetic energy is converted into magnetic work with a consequent temperature reduction of the gas. Optical pumping is used to magnetize the system and drive continuous demagnetization cooling. Applying this technique, we can increase the phase space density of our sample by one order of magnitude, with nearly no atom loss. This method can be in principle extended to every dipolar system and could be used to achieve quantum degeneracy via optical means.Comment: 10 pages, 5 figure

High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis

Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change