The Right to Challenge the Accuracy of Breath Test Results Under Alaska Law

Section 28.90.020 of the Alaska Statutes provides that in prosecutions for drunk driving, if an offense described under this title requires that a chemical test of a person\u27s breath produce a particular result, and the chemical test is administered by a properly calibrated instrument approved by the Department of Public Safety, the result described by statute is not affected by the instrument\u27s working tolerance. This provision appears to prohibit the defense from calling into question the accuracy of a breath test by introducing evidence of uncertainty inherent in the testing procedure. The statute is problematic because due process requires that defendants be permitted to challenge the evidence presented against them. Moreover, there is a strong argument that basing conviction on a single breath sample that is within a known margin of error is a per se violation of due process, as it bases guilt or innocence on a purely fortuitous result. This Article examines the issues with Alaska\u27s statute and proposes using multiple breath tests as a simple, cost-effective solution to this potential abuse of due process

Cyber Threat Intelligence Model: An Evaluation of Taxonomies, Sharing Standards, and Ontologies within Cyber Threat Intelligence

Cyber threat intelligence is the provision of evidence-based knowledge about existing or emerging threats. Benefits of threat intelligence include increased situational awareness and efficiency in security operations and improved prevention, detection, and response capabilities. To process, analyze, and correlate vast amounts of threat information and derive highly contextual intelligence that can be shared and consumed in meaningful times requires utilizing machine-understandable knowledge representation formats that embed the industry-required expressivity and are unambiguous. To a large extend, this is achieved by technologies like ontologies, interoperability schemas, and taxonomies. This research evaluates existing cyber-threat-intelligence-relevant ontologies, sharing standards, and taxonomies for the purpose of measuring their high-level conceptual expressivity with regards to the who, what, why, where, when, and how elements of an adversarial attack in addition to courses of action and technical indicators. The results confirmed that little emphasis has been given to developing a comprehensive cyber threat intelligence ontology with existing efforts not being thoroughly designed, non-interoperable and ambiguous, and lacking semantic reasoning capability

No challenge-klausuler - dess rättsliga status och framtida utmaningar i samband med 2014-års gruppundantag för tekniköverföring

Licensiering av teknik anses utgöra ett viktigt verktyg för att kunna sprida teknisk utveckling och främja innovation. Genom licensavtalet ges licenstagaren tillgång till viktig teknik i utbyte mot en licensavgift. På så sätt kan uppfinningen exploateras av båda parterna. Således är licensiering av teknik normalt sett positivt för konkurrensen. Det finns dock fall då licensavtalet innehåller restriktiva klausuler som kan komma att aktualisera art 101.1 FEUF. En av dessa klausuler är icke-angreppsklausulen. Klausulen utgör ett förbud för licenstagaren att bestrida giltigheten av licensgivarens immaterialrätt och kan förekomma i både vanliga licensavtal och förlikningsavtal. Icke-angreppsklausuler i vanliga licensavtal har länge betraktats med skepsis av kommissionen, men är trots det inte förbjuden per se. I uppsatsen diskuteras dess möjliga användningsområde för att konstatera att det finns ett utrymme att använda dem, om än att det är mycket smalt. Situationen kompliceras ytterligare av det faktum att detta område till viss del utgörs av tillfällen då det får anses mindre troligt att licenstagaren kommer ifrågasätta immaterialrätten. I dessa situationer måste det ifrågasättas om licensgivaren, trots att klausulen anses giltig, anser det lönsamt att inkludera den i avtalet. Uppsatsen utreder även användningsområdet för de så kallade no-challenge termination-klausulerna. Det vill säga en klausul som möjliggör för licensgivaren att säga upp avtalet då licenstagaren bestrider licensgivarens immaterialrättighet. Dess rättsliga status är år 2014 synnerligen aktuell då ett nytt gruppundantag för teknologiöverföring har utfärdats. Gruppundantaget har medfört vissa förändringar för synen på dels dessa klausuler, dels på icke-angreppsklausulerna i förlikningsavtal. Avseende den sistnämnda klausulen har tidigare det gruppundantagets huvudregel, att dessa klausuler är tillåtna att använda, givits två undantag. Detta kommer givetvis förändra dess tillämpning, i synnerhet medför det ett nytt osäkerhetsmoment i jämförelse med tidigare reglering. De två undantagets tillämpningsområde ska dock inte tolkas som alltför omfattande. Icke-angreppsklausulerna i förlikningsavtal torde därför fortsatt kunna användas i relativt hög utsträckning. Däremot torde användningsområdet för no-challenge termination-klausuler blivit snävare. Klausulen kan fortfarande inkluderas i exklusiva licensavtal och licensavtal avseende know-how, men i fallet om icke-exklusiva licensavtal är klausulen som huvudregel inte giltig. Denna huvudregel aktualiseras dock främst i tre fall, varpå möjligheterna att inkludera klausulen även i icke-exklusiva avtal torde vara förhållandevis goda.Technology licensing is considered to be an important tool for the dissemination of technology development and the promotion of innovation. Through the licensing agreement the licensee is given access to important technology in exchange of a license fee, thereby making it possible for both parties to exploit the invention. Hence technology licensing is in most cases considered to be procompetitive. However, there are cases when licensing agreements contain restrictive clauses that may fall within the scope of article 101.1 FEUF. One of these clauses is the no-challenge clause. The clause constitutes a restriction where the licensee is forbidden to challenge the validity of the licensor’s intellectual property right and can be used in both normal licensing agreements and settlement agreements. For many years, the commission has viewed the clause with scepticism, but in spite of this fact, the clause is not forbidden per se. The essay discusses its possible use to conclude that there is an area in which the clause can be used, albeit very narrow. The situation is further complicated by the fact that this area is partly consists of occasions when it may be considered less likely that the licensee will question the validity of the intellectual property. In these situations, it must be questioned whether the licensor, even though the clause is valid, finds it profitable enough to include it in the contract. The essay also examines the possible use of the so-called no-challenge termination clause, i.e. a clause that provides a possibility for the licensor to terminate the contract in the event of the licensee challenging his intellectual property right. Their legal status is particularly relevant in 2014, when a new block exemption has been issued. This has led to some changes in the perception of these clauses, and of the no-challenge clauses in settlement agreements. Regarding the latter clause, the previous block exemption’s main rule, that these clauses are admissible, has been given two exemptions. This will naturally alter their scope; in particular this brings a new element of uncertainty in comparison to the previous regulation. However, the two exemptions should not be interpreted too excessively. The possibility to use a no-challenge clause in a settlement agreement should therefore continue to remain relatively good. In contrast, the scope in which the use of a no-challenge termination-clause is permitted has become narrower. The clause can still be included in exclusive licensing agreements and licensing agreements regarding know-how. However, in the case of non-exclusive licensing agreements, the new main rule is that the clause is not permitted. Even so, this main rule primarily regards three specific situations, whereupon the possibilities to include the clause in non-exclusive agreements still must be considered relatively good

Mucosal Adjuvanticity and Immunogenicity of LTR72, a Novel Mutant of Escherichia coli Heat-labile Enterotoxin with Partial Knockout of ADP-ribosyltransferase Activity

Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala → Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 μg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose–response experiments in mice, 20 μg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials

The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA+ plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37–deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37−/− mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37−/− mice. To demonstrate the importance of CD37—which can associate with the pattern-recognition receptor dectin-1—in immunity to infection, CD37−/− mice were exposed to Candida albicans. We report that CD37−/− mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans–specific IgA antibodies. Importantly, adoptive transfer of CD37−/− serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response

Intranasal Delivery of Cholera Toxin Induces Th17-Dominated T-Cell Response to Bystander Antigens

Cholera toxin (CT) is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2) response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses

The immune response of the human brain to abdominal surgery

ObjectiveSurgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.MethodsEight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.ResultsPatients showed a global downregulation of gray matter [11 C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11 C]PBR28 binding (p = 0.027).InterpretationThis study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582