27 research outputs found
A Task Analysis of Static Binary Reverse Engineering for Security
Software is ubiquitous in society, but understanding it, especially without access to source code, is both non-trivial and critical to security. A specialized group of cyber defenders conducts reverse engineering (RE) to analyze software. The expertise-driven process of software RE is not well understood, especially from the perspective of workflows and automated tools. We conducted a task analysis to explore the cognitive processes that analysts follow when using static techniques on binary code. Experienced analysts were asked to statically find a vulnerability in a small binary that could allow for unverified access to root privileges. Results show a highly iterative process with commonly used cognitive states across participants of varying expertise, but little standardization in process order and structure. A goal-centered analysis offers a different perspective about dominant RE states. We discuss implications about the nature of RE expertise and opportunities for new automation to assist analysts using static techniques
Characterization of the extent of a large outbreak of Legionnaires' disease by serological assays
The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice
The nonobese diabetic (NOD) Nss1 and Idd5 loci have been associated with sialadenitis development in mice. In this study the NOD Nss1 and Idd5 loci were backcrossed onto the healthy control strain B10.Q by using the speed congenic breeding strategy, resulting in three congenic strains: B10.Q.Nss1, B10.Q.Nss1/Idd5 heterozygous and B10.Q.Nss1/Idd5 homozygous. We investigated the effects of the Nss1 and Idd5 loci on sialadenitis and gene expression in NOD congenic mice. One submandibular salivary gland from each mouse was used for histological analysis of sialadenitis, whereas the contralateral salivary gland was used for gene expression profiling with the Applied Biosystems Mouse Genome Survey chip v.1.0. The results were validated using quantitative reverse transcriptase PCR. The NOD Nss1 and Idd5 loci had clear influence on the onset and progression of sialadenitis in congenic mice. Double congenic mice exhibited the most severe phenotype. We successfully identified several genes that are located in the NOD congenic regions to be differentially expressed between the congenic strains and the control strain. Several of these were found to be co-regulated, such as Stat1, complement component C1q genes and Tlr12. Also, a vast contingency of interferon-regulated genes (such as Ltb, Irf7 and Irf8) and cytokine and chemokine genes (such as Ccr7 and Ccl19) were differentially expressed between the congenic strains and the control strain. Over-representation of inflammatory signalling pathways was observed among the differentially expressed genes. We have found that the introgression of the NOD loci Nss1 and Idd5 on a healthy background caused sialadenitis in NOD congenic mouse strains, and we propose that genes within these loci are important factors in the pathogenesis. Furthermore, gene expression profiling has revealed several differentially expressed genes within and outside the NOD loci that are similar to genes found to be differentially expressed in patients with Sjögren's syndrome, and as such are interesting candidates for investigation to enhance our understanding of disease mechanisms and to develop future therapies
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells
Abstract
Background
Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.
Methods
We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles.
Results
Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an integrative computational approach we constructed a modular network of over 80 gene sets that were highly enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling. Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity, highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis.
Conclusions
BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may modulate disease progression
Characterization of the extent of a large outbreak of Legionnaires’ disease by serological assays
Reisen hjem
Bakgrunn: I 2012 ble 3512 (5,9 %) premature barn født før uke 37 i Norge (Folkehelseinstituttet, 2014, s. 23). Bakgrunnen for denne litteraturstudien er å finne ut hvordan sykepleier kan trygge foreldre i «Reisen hjem» fra sykehus til hjemmet, gjennom funksjonsområdet undervisning og veiledning. Temaet er valgt på bakgrunn av erfaringer fra praksisperiode på barneavdeling. I denne oppgaven ønsker jeg å besvare følgende spørsmål: «Hvordan kan sykepleier gjennom veiledning og undervisning trygge foreldre til prematurfødte barn i overgang fra sykehus til avansert hjemmesykehus?»
Fremgangsmåte: Metoden benyttet for å svare på problemstillingen er litteraturstudie. Søk er foretatt i databasene Academic Serach Premier, Cochrane Library, Chinal og Medline. Sammen med det teoretiske grunnlaget er åtte vitenskapelige artikler plukket ut til å svare på oppgavens spørsmål. Funn, diskusjon og konklusjon: Funn viste at overgangen fra langtidsopphold på sykehuset til hjemmet var overveldende for mange foreldre. Foreldrene rapporterte også at det var godt å komme hjem og endelig føle seg som foreldre. Samtidig var de redde for at de ikke var klare for å reise hjem, eller at noe uforutsett skulle skje. Teori og funn viser at undervisning og veiledning, samt støtte fra foreldre i samme situasjon er nyttig i overgangen fra sykehuset til hjemmet. Det ga trygghet og mestringsfølelse i foreldrerollen. Ved videre, å dekke foreldrenes behov for informasjon, opplevelse av mestring og emosjonell støtte kan sykepleier ut i fra mine funn, bidra til å redusere foreldrenes utrygghet og manglende mestringsfølelse i foreldrerollen
Protection by Natural Human Immunoglobulin M Antibody to Meningococcal Serogroup B Capsular Polysaccharide in the Infant Rat Protection Assay Is Independent of Complement-Mediated Bacterial Lysis
Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease develops with age, but the specificity and functional activity of natural antibodies associated with protection are poorly understood. We addressed this question by using a selected subset of prevaccination sera (n = 26) with convergent or discrepant serum bactericidal activity (SBA) and infant rat protective activity (IRPA) against the serogroup B meningococcal strain 44/76-SL (B:15:P1.7,16) from Icelandic teenagers (B. A. Perkins et al., J. Infect. Dis. 177:683-691, 1998). The sera were analyzed by opsonophagocytic activity (OPA) assay, immunoblotting, immunoglobulin G (IgG) quantitation against live meningococcal cells by flow cytometry, and enzyme immunosorbent assay (EIA). High levels of SBA and OPA were reflected in distinct IgG binding to major outer membrane proteins and/or lipopolysaccharide in immunoblots. However, we could not detect any specific antibody patterns on blots that could explain IRPA. Only IgM antibody to group B capsular polysaccharide (B-PS), measured by EIA, correlated positively (r = 0.76, P < 0.001) with IRPA. Normal human sera (NHS; n = 20) from healthy Finnish children of different ages (7, 14, and 24 months and 10 years) supported this finding and showed an age-related increase in IRPA that coincided with the acquisition of B-PS specific IgM antibody. The protection was independent of complement-mediated bacterial lysis, as detected by the inability of NHS to augment SBA in the presence of human or infant rat complement and the equal protective activity of NHS in rat strains with fully functional or C6-deficient complement
Antibody Specificities and Effect of Meningococcal Carriage in Icelandic Teenagers Receiving the Norwegian Serogroup B Outer Membrane Vesicle Vaccine
Antibody specificities of pre- and postvaccination serum samples from 40 (53%) teenagers who received three doses of the Norwegian Neisseria meningitidis serogroup B vaccine (B:15:P1.7,16) during a previous trial in Iceland (Perkins et al., J. Infect. Dis. 177:683-691, 1998) were analyzed with serum bactericidal activity (SBA) and immunoblotting assays with reference and isogenic meningococcal H44/76 vaccine strains. The H44/76 variants demonstrated significant vaccine-induced SBA to P1.7,16 PorA and Opc but not to PorB, Opa5.5, and a heterologous PorA protein. On blots, immunoglobulin G levels to all these proteins increased significantly after vaccination. Measurement of SBA to the two main variable regions (P1.7 and P1.16) on the P1.7,16 PorA with PorA deletion mutants revealed significantly higher activity to the P1.7,− and P1.−,16 mutants compared to the P1.7,16 strain, indicating exposure of new accessible epitopes. Only 12 (30%) serum samples showed distinct decreases with these or the P1.−,− mutant, with most samples containing SBA to the P1.7 and P1.16 combination. In contrast, P1.16-specific antibodies were mainly found on blots. Thirteen of the vaccinees (32.5%) were carriers of meningococci at the time of the third dose, of whom four (30.8%) harbored strains of the ET-5 complex. Carriage of P1.15 strains was generally reflected in ≥4-fold increases in SBA and distinct immunoglobulin G binding to the P1.19,15 PorA on blots. Although vaccination did not elicit bactericidal activity to the serotype 15 PorB, most carriers of serotype 15 strains showed ≥4-fold increases in SBA to this antigen