Mitigating real-time relay phishing attacks against mobile push notification based two-factor authentication systems

This paper explores how existing push notification based two-factor authentication systems are susceptible to real-time man-in-the-middle relay attacks and proposes a system for mitigating such attacks. A fully functional reference system of the proposed mitigation was built and compared to an existing push notification two-factor authentication system while undergoing a real-time man-in-the-middle relay attack. The reference systems used cloud infrastructure for hosting, an Apple iPhone as the notification receiver, and Apple’s push notification service to send notifications. A publicly available tool for conducting real-time man-in-the-middle relay attacks was used to conduct the attacks. The results of the tests were recorded and contrasted to show how existing implementations fail to identify such attacks and how the proposed system could. It is recommended that the existing push notification two-factor authentication providers implement additional measures to protect users against real-time man-in-the-middle relay attacks while appropriately weighing key usability issues. While the proposed mitigation system is shown to prevent such attacks, it has usability drawbacks that should be considered

The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors

Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors - telaprevir, danoprevir, vaniprevir and MK-5172 - in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus

Effect of Resistance Training on Microvascular Density and eNOS Content in Skeletal Muscle of Sedentary Men

The effects of resistance training (RT) on muscle mass, strength and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study is to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity. Eight previously sedentary males (age 20±0.4y, BMI 24.5±0.9 kg.m-2) completed 6wk of RT 3x/week. Muscle biopsies were taken from the m. vastus lateralis and microvascular density and endothelial specific eNOS content, eNOS Ser1177 phosphorylation and NOX2 content were assessed pre- and post-RT using quantitative immunofluorescence microscopy. Whole body insulin sensitivity (measured as Matsuda Index), microvascular filtration capacity (functional measure of the total available endothelial surface area) and arterial stiffness (augmentation index, central and peripheral pulse wave velocity) were also measured. Measures of microvascular density, microvascular filtration capacity, microvascular eNOS content, basal eNOS phosphorylation and endothelial NOX2 content did not change from pre-RT to post-RT. RT increased insulin sensitivity (P <0.05) and reduced resting blood pressure and augmentation index (P <0.05), but did not change central or peripheral pulse wave velocity. In conclusion RT did not change any measure of muscle microvascular structure or function

Bisphenol-A and Sleep Adequacy Among Adults in the National Health and Nutrition Examination Surveys

Study Objectives: To evaluate bisphenol-A (BPA) level and its relationship to sleep adequacy in a nationally representative sample of U.S. adults. Methods: A population-based cross-sectional study was conducted using 2005-2010 National Health and Nutrition Examination Survey whereby data were collected using in-person interviews, physical examination and laboratory testing. BPA level was measured in urine samples and analyzed as loge-transformed variable and in quartiles (\u3c 0.9 ng/mL; 0.9 to \u3c 1.9 ng/mL; 1.9 to \u3c 3.7 ng/mL; 3.7+ ng/mL). Sleep adequacy was operationalized with three questions: How much sleep do you usually get at night on weekdays or workdays? , Have you ever told a doctor or other health professionals that you have trouble sleeping? and Have you ever been told by a doctor or other health professional that you have a sleep disorder? Sleep duration was further categorized as (\u3c 6 h, ≥ 6 h); (\u3c 7 h, 7-8 h, \u3e 8 h); (\u3c 5 h, 5-6 h, 7-8 h, ≥ 9 h). Linear, binary, and ordinal logistic regression models were constructed. Results: Loge-transformed BPA level was inversely related to sleep duration defined, in hours, as a continuous variable, a dichotomous variable (≥ 6, \u3c 6), or an ordinal variable (≥ 9, 7-8, 5-6, \u3c 5), after adjustment for confounders. Help-seeking behavior for sleep problems and diagnosis with sleep disorders were not significantly associated with loge-transformed BPA level in fully adjusted models. Conclusions: Loge-transformed BPA level may be associated with fewer hours of sleep among U.S. adults, with implications for prevention. Further research involving diverse populations are needed to confirm these study findings

Activation and Deactivation of a Robust Immobilized Cp*Ir-Transfer Hydrogenation Catalyst: A Multielement in Situ X-ray Absorption Spectroscopy Study

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and “hot filtration” experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide–iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure

Minimising fear and anxiety in working dogs:a review

The causes of fear and anxiety in working dogs are multifactorial and may include inherited characteristics that differ between individuals (e.g. Goddard and Beilharz, 1982; 1984a,b ), influences of the environment ( Lefebvre et al., 2007 ), and learned experiences during particular sensitive periods ( Appleby et al., 2002 ) and throughout life. Fear-related behavior compromises performance, leads to significant numbers of dogs failing to complete training (e.g., Murphy, 1995; Batt et al., 2008 ), early withdrawals from working roles ( Caron-Lormier et al., 2016 ), and can jeopardize dog and handler safety. Hence, amelioration of fear and anxiety is critical to maintain dogs in working roles and to ensure their well-being. Although current methods of selection and training are seemingly effective at producing many dogs which work in a remarkable array of environments, some dogs do not make the grade, and longevity of service is not always maximized. Programs should strive for optimal efficiency and they need to continually analyze the value of each component of their program, seek evidence for its value and explore potential evidence-based improvements. Here we discuss scientific evidence for methods and strategies which may be of value in reducing the risk of fear behaviors developing in the working dog population and suggest potentially valuable techniques and future research to explore the benefit of these approaches. The importance of environmental influences, learning opportunities, and effects of underlying temperament on the outward expression of fear and anxiety should not be underestimated. Identification of characteristics which predict resilience to stress are valuable, both to enable careful breeding for these traits and to develop predictive tests for puppies and procured animals. It is vitally important to rear animals in optimal environments and introduce them to a range of stimuli in a positive, controlled, and gradual way, as these can all help minimize the number of dogs which develop work-inhibiting fears. Future research should explore innovative methods to best measure the relative resilience of dogs to stressful events. This could include developing optimal exposure protocols to minimize the development of fear and anxiety, and exploring the influence of social learning and the most effective elements of stimulus presentation

Dysregulation of neuronal iron homeostasis as an alternative unifying effect of mutations causing familial Alzheimer's disease

The overwhelming majority of dominant mutations causing early onset familial Alzheimer's disease (EOfAD) occur in only three genes, PSEN1, PSEN2, and APP. An effect-in-common of these mutations is alteration of production of the APP-derived peptide, amyloid ß (Aß). It is this key fact that underlies the authority of the Amyloid Hypothesis that has informed Alzheimer's disease research for over two decades. Any challenge to this authority must offer an alternative explanation for the relationship between the PSEN genes and APP. In this paper, we explore one possible alternative relationship - the dysregulation of cellular iron homeostasis as a common effect of EOfAD mutations in these genes. This idea is attractive since it provides clear connections between EOfAD mutations and major characteristics of Alzheimer's disease such as dysfunctional mitochondria, vascular risk factors/hypoxia, energy metabolism, and inflammation. We combine our ideas with observations by others to describe a "Stress Threshold Change of State" model of Alzheimer's disease that may begin to explain the existence of both EOfAD and late onset sporadic (LOsAD) forms of the disease. Directing research to investigate the role of dysregulation of iron homeostasis in EOfAD may be a profitable way forward in our struggle to understand this form of dementia

2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines: Developed in collaboration with the International Society for Heart and Lung Transplantation

Heart failure (HF) is a major and growing public health problem in the United States. Approximately 5 million patients in this country have HF, and over 550,000 patients are diagnosed with HF for the first time each year. The disorder is the primary reason for 12 to 15 million office visits and 6.5 million hospital days each year. From 1990 to 1999, the annual number of hospitalizations has increased from approximately 810,000 to over 1 million for HF as a primary diagnosis and from 2.4 to 3.6 million for HF as a primary or secondary diagnosis. In 2001, nearly 53 000 patients died of HF as a primary cause. The number of HF deaths has increased steadily despite advances in treatment, in part because of increasing numbers of patients with HF due to better treatment and “salvage” of patients with acute myocardial infarctions (MIs) earlier in life. Heart failure is primarily a condition of the elderly, and thus the widely recognized “aging of the population” also contributes to the increasing incidence of HF. The incidence of HF approaches 10 per 1000 population after age 65, and approximately 80% of patients hospitalized with HF are more than 65 years old. Heart failure is the most common Medicare diagnosis-related group (i.e., hospital discharge diagnosis), and more Medicare dollars are spent for the diagnosis and treatment of HF than for any other diagnosis. The total estimated direct and indirect costs for HF in 2005 were approximately $27.9 billion. In the United States, approximately$2.9 billion annually is spent on drugs for the treatment of HF