CONFLLVM: A Compiler for Enforcing Data Confidentiality in Low-Level Code

We present an instrumenting compiler for enforcing data confidentiality in low-level applications (e.g. those written in C) in the presence of an active adversary. In our approach, the programmer marks secret data by writing lightweight annotations on top-level definitions in the source code. The compiler then uses a static flow analysis coupled with efficient runtime instrumentation, a custom memory layout, and custom control-flow integrity checks to prevent data leaks even in the presence of low-level attacks. We have implemented our scheme as part of the LLVM compiler. We evaluate it on the SPEC micro-benchmarks for performance, and on larger, real-world applications (including OpenLDAP, which is around 300KLoC) for programmer overhead required to restructure the application when protecting the sensitive data such as passwords. We find that performance overheads introduced by our instrumentation are moderate (average 12% on SPEC), and the programmer effort to port OpenLDAP is only about 160 LoC.Comment: Technical report for CONFLLVM: A Compiler for Enforcing Data Confidentiality in Low-Level Code, appearing at EuroSys 201

Role and Importance of NS1 Protein of Avian Influenza Virus to Grow in the Presence of Interferon and Evaluation of the NS1 Mutant Viruses as Potential DIVA Vaccines

A proper vaccination program can play a critical role in prevention and control of avian influenza (AI) in commercial poultry. Low pathogenic avian influenza viruses (LPAIV) of H5 and H7 AI subtypes cause serious economic losses to the poultry industry and have the potential to mutate to highly pathogenic AI (HPAI) strains. Due to trade implications, differentiation of infected from vaccinated animals (DIVA) is an important issue in the control of AI. Therefore, the development and characterization of vaccine candidates with DIVA properties is critical in improving vaccination programs. Keeping these aspects in mind, we investigated the role of an NS1 mutant virus as a potential live attenuated DIVA vaccine. The NS1 protein of influenza virus plays a major role in blocking the host's antiviral response. Using an eight-plasmid reverse genetics system, we recovered the low pathogenic parental (H5N3) and NS1 mutant (H5N3/NS1/144) viruses. H5N3/NS1/144 expresses only the first 144 amino acids of the NS1 protein compared to the 230 of the parental H5N3. The growth properties of H5N3 and H5N3/NS1/144 were compared in cell culture and in different age embryonated chicken eggs. Our results confirmed that NS1 is involved in down regulation of interferon as shown by IFN-beta mRNA expression analysis and by the inability of H5N3/NS1-144 to efficiently grow in older age, interferon competent, chicken embryos. However with regards to safety the virus reverted to virulence within five back passages in chickens and was therefore not a safe vaccine candidate. However the killed form of H5N3/NS1-144 was a safer alternative and it also induced antibody titers and protection not significantly different from the parental H5N3 as vaccine. To further understand the reversion of H5N3/NS1/144 to virulence, we carried out 3 independent serial passages of H5N3/NS1/144 in increasing age of embryonated chicken eggs and examined the NS1 gene for presence of mutations. RT-PCR and sequence analysis of the NS gene in all three lineages showed the presence of a 54 amino acid deletion resulting in the generation of a 87 amino acids long NS1 ORF with a point mutation (L80V) at the site of deletion. In addition, the NS1 ORF in lineages L2 and L3 presented two additional point mutations in the RNA binding domain (Q40R and T73M). To determine if these mutations played a role in increased virulence, recombinant viruses expressing these mutant NS1 proteins in the background of parental virus were generated by reverse genetics and their replication properties and pathogenicity was examined in vitro, in ovo and in vivo systems. Our results showed that the 87 amino acid long NS1 protein clearly increased virus replication and virulence specifically in interferon competent systems. In addition, the two point mutations in the RNA binding domain of NS1 ORF expressing 87 a protein slightly increased the virus virulence. Overall this study reinforces the role of NS1 in influenza virus pathogenicity and supports the use of killed inactivated NS1 mutant virus vaccines as potential DIVA vaccines

An Instrumenting Compiler for Enforcing Confidentiality in Low-Level Code

We present an instrumenting compiler for enforcing data confidentiality in low-level applications (e.g. those written in C) in the presence of an active adversary. In our approach, the programmer marks secret data by writing lightweight annotations on top-level definitions in the source code. The compiler then uses a static flow analysis coupled with efficient runtime instrumentation, a custom memory layout, and custom control-flow integrity checks to prevent data leaks even in the presence of low-level attacks. We have implemented our scheme as part of the LLVM compiler. We evaluate it on the SPEC micro-benchmarks for performance, and on larger, real-world applications (including OpenLDAP, which is around 300KLoC) for programmer overhead required to restructure the application when protecting the sensitive data such as passwords. We find that performance overheads introduced by our instrumentation are moderate (average 12% on SPEC), and the programmer effort to port OpenLDAP is only about 160 LoC

A STUDY OF OUTCOME OF ROSE K LENSES IN KERATOCONUS

Background: Cornea is affected by several distinct disorders that produce marked thinning without significant inflammation. They are keratoconus, posterior keratoconus, pellucid marginal degeneration, and keratoglobus. keratoconus and posterior keratoconus produces central and inferior thinning with ectasia. Materials and Methods: All patients of keratoconus in age group 15 to 60 years at various stages of progression were included this was a prospective study, 20 Eyes of 15 patients of keratoconus in age group of 15 to 60 years at various stages of progression were included in the study. Visual acuity, slit lamp Biomicroscopy was done, corneal topography and Fundus examination was done by both direct and indirect ophthalmoscopy with full dilatation when possible. Results: Subjective score of pre rose k eyes when compared to post rose k lens eye was highly significant, which signifies that the same patient was highly satisfied after wearing rose k lens. Conclusion: Present study observed that, Rose K lenses improved patient\u27s overall quality of life in moderate and advance cases of keratoconus. KEYWORDS: Keratoconus; Pellucid marginal degeneration; Keratoglobus; rose k lenses

A STUDY OF OUTCOME OF ROSE K LENSES IN KERATOCONUS

Background: Cornea is affected by several distinct disorders that produce marked thinning without significant inflammation. They are keratoconus, posterior keratoconus, pellucid marginal degeneration, and keratoglobus. keratoconus and posterior keratoconus produces central and inferior thinning with ectasia. Materials and Methods: All patients of keratoconus in age group 15 to 60 years at various stages of progression were included this was a prospective study, 20 Eyes of 15 patients of keratoconus in age group of 15 to 60 years at various stages of progression were included in the study. Visual acuity, slit lamp Biomicroscopy was done, corneal topography and Fundus examination was done by both direct and indirect ophthalmoscopy with full dilatation when possible. Results: Subjective score of pre rose k eyes when compared to post rose k lens eye was highly significant, which signifies that the same patient was highly satisfied after wearing rose k lens. Conclusion: Present study observed that, Rose K lenses improved patient's overall quality of life in moderate and advance cases of keratoconus. KEYWORDS: Keratoconus; Pellucid marginal degeneration; Keratoglobus; rose k lenses

IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans

An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults

Identification of differentially expressed miRNAs in chicken lung and trachea with avian influenza virus infection by a deep sequencing approach

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play critical roles in a wide spectrum of biological processes and have been shown to be important effectors in the intricate host-pathogen interaction networks. Avian influenza virus (AIV) not only causes significant economic losses in poultry production, but also is of great concern to human health. The objective of this study was to identify miRNAs associated with AIV infections in chickens.</p> <p>Results</p> <p>Total RNAs were isolated from lung and trachea of low pathogenic H5N3 infected and non-infected SPF chickens at 4 days post-infection. A total of 278,398 and 340,726 reads were obtained from lung and trachea, respectively. And 377 miRNAs were detected in lungs and 149 in tracheae from a total of 474 distinct chicken miRNAs available at the miRBase, respectively. Seventy-three and thirty-six miRNAs were differentially expressed between infected and non-infected chickens in lungs and tracheae, respectively. There were more miRNAs highly expressed in non-infected tissues than in infected tissues. Interestingly, some of these differentially expressed miRNAs, including miR-146, have been previously reported to be associated with immune-related signal pathways in mammals.</p> <p>Conclusion</p> <p>To our knowledge, this is the first study on miRNA gene expression in AIV infected chickens using a deep sequencing approach. During AIV infection, many host miRNAs were differentially regulated, supporting the hypothesis that certain miRNAs might be essential in the host-pathogen interactions. Elucidation of the mechanism of these miRNAs on the regulation of host-AIV interaction will lead to the development of new control strategies to prevent or treat AIV infections in poultry.</p

Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination.

Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals