Equilibrium Studies of Binary and Ternary Complexes of Cycloserine

The complex-formation equilibria between copper(II), nickel(II), cobalt(II) and zinc(II) and cycloserine (n-s-amino-Svtsoxazolidone, C3H602N2)were investigated potentimetrically. It was found that cycloserine forms 1: 1 and 1: 2 (metal ion: ligand)complexes. The ternary complex of Cu" with nitrilotriacetic acid and cycloserine was investigated potentiometrically and spectrophotometrically. The probable bonding in the chelated compounds formed in aqueous solution was deduced. The formation constants follow the Irving- Williams series

A Framework for Evaluating Security in the Presence of Signal Injection Attacks

Sensors are embedded in security-critical applications from medical devices to nuclear power plants, but their outputs can be spoofed through electromagnetic and other types of signals transmitted by attackers at a distance. To address the lack of a unifying framework for evaluating the effects of such transmissions, we introduce a system and threat model for signal injection attacks. We further define the concepts of existential, selective, and universal security, which address attacker goals from mere disruptions of the sensor readings to precise waveform injections. Moreover, we introduce an algorithm which allows circuit designers to concretely calculate the security level of real systems. Finally, we apply our definitions and algorithm in practice using measurements of injections against a smartphone microphone, and analyze the demodulation characteristics of commercial Analog-to-Digital Converters (ADCs). Overall, our work highlights the importance of evaluating the susceptibility of systems against signal injection attacks, and introduces both the terminology and the methodology to do so.Comment: This article is the extended technical report version of the paper presented at ESORICS 2019, 24th European Symposium on Research in Computer Security (ESORICS), Luxembourg, Luxembourg, September 201

Cloud-Based Quadratic Optimization with Partially Homomorphic Encryption

This article develops a cloud-based protocol for a constrained quadratic optimization problem involving multiple parties, each holding private data. The protocol is based on the projected gradient ascent on the Lagrange dual problem and exploits partially homomorphic encryption and secure communication techniques. Using formal cryptographic definitions of indistinguishability, the protocol is shown to achieve computational privacy. We show the implementation results of the protocol and discuss its computational and communication complexity. We conclude this article with a discussion on privacy notions

Limited T Cell Receptor Diversity of HCV-specific T Cell Responses Is Associated with CTL Escape

Escape mutations are believed to be important contributors to immune evasion by rapidly evolving viruses such as hepatitis C virus (HCV). We show that the majority of HCV-specific cytotoxic T lymphocyte (CTL) responses directed against viral epitopes that escaped immune recognition in HCV-infected chimpanzees displayed a reduced CDR3 amino acid diversity when compared with responses in which no CTL epitope variation was detected during chronic infection or with those associated with protective immunity. Decreased T cell receptor (TCR) CDR3 amino acid diversity in chronic infection could be detected long before the appearance of viral escape mutations in the plasma. In both chronic and resolved infection, identical T cell receptor clonotypes were present in liver and peripheral blood. These findings provide a deeper understanding of the evolution of CTL epitope variations in chronic viral infections and highlight the importance of the generation and maintenance of a diverse TCR repertoire directed against individual epitopes

Murine B Cell Development and Antibody Responses to Model Antigens Are Not Impaired in the Absence of the TNF Receptor GITR

The Glucocorticoid-Induced Tumor necrosis factor Receptor GITR, a member of the tumor necrosis factor receptor superfamily, has been shown to be important in modulating immune responses in the context of T cell immunity. B lymphocytes also express GITR, but a role of GITR in humoral immunity has not been fully explored. To address this question, we performed studies to determine the kinetics of GITR expression on naïve and stimulated B cells and the capacity of B cells to develop and mount antibody responses in GITR−/− mice. Results of our studies indicate that all mature B cells express GITR on the cell surface, albeit at different levels. Expression of GITR on naïve mature B cells is upregulated by BCR signaling, but is counteracted by helper T cell-related factors and other inflammatory signals in vitro. In line with these findings, expression of GITR on germinal center and memory B cells is lower than that on naïve B cells. However, the expression of GITR is strongly upregulated in plasma cells. Despite these differences in GITR expression, the absence of GITR has no effect on T cell-dependent and T cell-independent antibody responses to model antigens in GITR−/− mice, or on B cell activation and proliferation in vitro. GITR deficiency manifests only with a slight reduction of mature B cell numbers and increased turnover of naïve B cells, suggesting that GITR slightly contributes to mature B cell homeostasis. Overall, our data indicate that GITR does not play a significant role in B cell development and antibody responses to T-dependent and independent model antigens within the context of a GITR-deficient genetic background

Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein

The humoral response to hepatitis C virus (HCV) may contribute to controlling infection. We previously isolated human monoclonal antibodies to conformational epitopes on the HCV E2 glycoprotein. Here, we report on their ability to inhibit infection by retroviral pseudoparticles incorporating a panel of full-length E1E2 clones representing the full spectrum of genotypes 1–6. We identified one antibody, CBH-5, that was capable of neutralizing every genotype tested. It also potently inhibited chimeric cell culture-infectious HCV, which had genotype 2b envelope proteins in a genotype 2a (JFH-1) background. Analysis using a panel of alanine-substitution mutants of HCV E2 revealed that the epitope of CBH-5 includes amino acid residues that are required for binding of E2 to CD81, a cellular receptor essential for virus entry. This suggests that CBH-5 inhibits HCV infection by competing directly with CD81 for a binding site on E2

Impaired Hepatitis C Virus-Specific T Cell Responses and Recurrent Hepatitis C Virus in HIV Coinfection

BACKGROUND: Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. METHODS AND FINDINGS: We measured T cell responsiveness by lymphoproliferation and interferon-γ ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r (2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-γ response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = −0.94, p = 0.017). CONCLUSIONS: These results indicate that HIV infection impairs the immune response to HCV—including in persons who have cleared HCV infection—and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population

CD4+ T Cell Effects on CD8+ T Cell Location Defined Using Bioluminescence

T lymphocytes of the CD8+ class are critical in delivering cytotoxic function and in controlling viral and intracellular infections. These cells are “helped” by T lymphocytes of the CD4+ class, which facilitate their activation, clonal expansion, full differentiation and the persistence of memory. In this study we investigated the impact of CD4+ T cells on the location of CD8+ T cells, using antibody-mediated CD4+ T cell depletion and imaging the antigen-driven redistribution of bioluminescent CD8+ T cells in living mice. We documented that CD4+ T cells influence the biodistribution of CD8+ T cells, favoring their localization to abdominal lymph nodes. Flow cytometric analysis revealed that this was associated with an increase in the expression of specific integrins. The presence of CD4+ T cells at the time of initial CD8+ T cell activation also influences their biodistribution in the memory phase. Based on these results, we propose the model that one of the functions of CD4+ T cell “help” is to program the homing potential of CD8+ T cells

Coaching as a social process

In this conceptual paper, we argue the importance to the coaching profession of a critical understanding of coaching as a social process, in order to promote coaching as an enabler for change, and facilitate its use in other cultures and challenging contexts. We start with a critical analysis of the origin of coaching, arguing that neoliberal values have been embedded in the discourse of coaching. We also discuss the impact of coaching as an instrumental and ideological device, sometimes used in organisations as a process of control, and suggest that understanding coaching as a social process has the potential to transform it into an enabler for change. We propose a framework for understanding how different philosophical positions affect the way coaches may respond to the challenges of intercultural or oppressive social contexts. We conclude with a discussion of the implications for coaching research and development