Role of p52 (NF-κB2) in LPS tolerance in a human B cell line

Cells of the weakly CD14 positive human B cell line RPMI 8226, clone 1, will mobilize NF-κB (p50/p65 and p50/p50) proteins and produce TNF mRNA when stimulated with lipopolysaccharide (LPS), When such cells are precultured with a low amount of LPS (50 - 250 ng/ml) for 3 - 4 days followed by a secondary stimulation with a high dose of LPS (1 mu g/ml) then the cytokine expression is strongly reduced, i.e, the cells have become tolerant. Western blot analysis of proteins of the NF-kappa B/rel family demonstrates cytoplasmic p50 and p65 for naive B cells plus a low level of p52. While with tolerance induction the pattern of p50 and p65 proteins remains essentially unchanged, the LPS tolerant 8226 cells show a dramatic increase of both p52 protein and its p100 precursor in the cytosol. This p52 is found strongly upregulated in Western blots of extracts from purified nuclei of tolerant cells, Also, gelshift analysis with the -605 kappa B motif Of the human TNF 5'-region shows an additional high mobility complex in LPS tolerant cells - a complex that is supershifted with an anti-p52 antibody, Functional analysis with the -1064 TNF 5'-region in front of the luciferase reporter gene demonstrates that transactivation of the TNF promoter is strongly reduced in tolerant cells, Also, overexpression of p52 will suppress activity of TNF promoter reporter gene constructs. Taken together these data show that tolerance to LPS in the human RPM1 8226 a cell line involves upregulation of the p52 (NF-kappa B2) gene, which appears to be instrumental in the blockade of TNF gene expression

Physical Characterization of Arbiter PUFs

As intended by its name, Physically Unclonable Functions (PUFs) are considered as an ultimate solution to deal with insecure stor- age, hardware counterfeiting, and many other security problems. How- ever, many different successful attacks have already revealed vulnera- bilities of certain digital intrinsic PUFs. Although settling-state-based PUFs, such as SRAM PUFs, can be physically cloned by semi-invasive and fully-invasive attacks, successful attacks on timing-based PUFs were so far limited to modeling attacks. Such modeling requires a large sub- set of challenge-response-pairs (CRP) to successfully model the targeted PUF. In order to provide a final security answer, this paper proves that all arbiter-based (i.e. controlled and XOR-enhanced) PUFs can be com- pletely and linearly characterized by means of photonic emission analy- sis. Our experimental setup is capable of measuring every PUF-internal delay with a resolution of 6 picoseconds. Due to this resolution we in- deed require only the theoretical minimum number of linear independent equations (i.e. physical measurements) to directly solve the underlying inhomogeneous linear system. Moreover, we neither require to know the actual PUF challenges nor the corresponding PUF responses for our physical delay extraction. On top of that devastating result, we are also able to further simplify our setup for easier physical measurement han- dling. We present our practical results for a real arbiter PUF implemen- tation on a Complex Programmable Logic Device (CPLD) from Altera manufactured in a 180 nanometer process

Sicherheit der IC Rückseite

Das Vertrauen eines vermeintlich sicheren Systems ist oftmals in Hardware verankert. Die wichtigste Komponente solcher Hardware basiert auf speziellen integrierten Schaltungen (Integrated Circuits, ICs). Sicherheits-ICs müssen jegliche Art von Angriffen standhalten, um eine Kompromittierung der Sicherheitsanwendung zu vermeiden. Aus diesem Grund wird bei Sicherheits-ICs ein wesentlicher Anteil der Designressourcen für eine Erhöhung des Sicherheitsniveaus verwendet. Dennoch gibt es Analysetechniken, die Angriffe auf ICs ermöglichen. Im Bereich der IC-Analyse haben invasive Analysetechnicken die höchste Erfolgsrate. Zu invasiven Angriffen zählen sowohl Techniken, die in der Lage sind temporäre Fehler zur Laufzeit zu erzeugen, als auch Techniken, die zugrundeliegende Schaltungen dauerhaft modifizieren können. Um darauf basierende Angriffe zu verhindern, implementieren moderne Sicherheits-ICs spezielle Angriffssensoren und Schutzschichten. Allerdings schützen solche Schutzmaßnahmen lediglich die aktive, das heißt die Forderseite des ICs. Diese Arbeit untersucht wie anfällig moderne ICs gegen Analysetechniken sind die durch das Silizium durch die Rückseite hindurchgehen. Solche Techniken umgehen bekannte Gegemaßnahmen dadurch, dass sie die Rückseite des ICs angreifen. Diese Arbeit stellt neue semi- sowie voll-invasive Analysetechniken vor. Die Vor- und Nachteile der verschiedenen Techniken werden erörtert. Des Weiteren diskutiert diese Arbeit weitere Gegenmaßnahmen, die zukünftig von IC-Herstellern berücksichtigt werden können, um ICs sicherer zu gestalten.Secure systems are generally built around secure hardware. The key component of many secure implementations are security Integrated Circuits (ICs) at the core of the root of trust. For this reason, security ICs must withstand all potential classes of attacks to prevent the overall system from being compromised. As a result, security ICs dedicate a substantial amount of design resources for implementing additional layers of security. Although security ICs raise the security threshold by making analysis more difficult to the attacker, they are not provably secure. In the field of IC analysis, invasive analysis techniques have the highest rates of success. These attacks range from temporary faults at runtime to permanent modifications of the underlying circuit. To thwart such attacks, modern security ICs implement countermeasures including attack sensors and integrity meshes. However, these countermeasures currently only prevent attacks targeting the active side of the device, i.e., the IC frontside. This work investigates the susceptibility of modern ICs to through-silicon analysis. The analysis techniques introduced in this work circumvent most known countermeasures on modern security ICs by targeting the IC backside. This work introduces several semi- and fully-invasive analysis techniques. The advantages and disadvantages of each are also explained in detail. Moreover, this work proposes several mitigation techniques that can be implemented by vendors to secure their devices in the future

Hypoacylated LPS from Foodborne Pathogen Campylobacter jejuni Induces Moderate TLR4-Mediated Inflammatory Response in Murine Macrophages

Toll-like receptor 4 (TLR4) initiates immune response against Gram-negative bacteria upon specific recognition of lipid A moiety of lipopolysaccharide (LPS), the major component of their cell wall. Some natural differences between LPS variants in their ability to interact with TLR4 may lead to either insufficient activation that may not prevent bacterial growth, or excessive activation which may lead to septic shock. In this study we evaluated the biological activity of LPS isolated from pathogenic strain of Campylobacter jejuni, the most widespread bacterial cause of foodborne diarrhea in humans. With the help of hydrophobic chromatography and MALDI-TOF mass spectrometry we showed that LPS from a C. jejuni strain O2A consists of both hexaacyl and tetraacyl forms. Since such hypoacylation can result in a reduced immune response in humans, we assessed the activity of LPS from C. jejuni in mouse macrophages by measuring its capacity to activate TLR4-mediated proinflammatory cytokine and chemokine production, as well as NFκB-dependent reporter gene transcription. Our data support the hypothesis that LPS acylation correlates with its bioactivity

LTα, TNF, and ILC3 in Peyer’s Patch Organogenesis

TNF and LTα are structurally related cytokines of the TNF superfamily. Their genes are located in close proximity to each other and to the Ltb gene within the TNF/LT locus inside MHC. Unlike Ltb, transcription of Tnf and of Lta is tightly controlled, with the Tnf gene being an immediate early gene that is rapidly induced in response to various inflammatory stimuli. Genes of the TNF/LT locus play a crucial role in lymphoid tissue organogenesis, although some aspects of their specific contribution remain controversial. Here, we present new findings and discuss the distinct contribution of TNF produced by ILC3 cells to Peyer’s patch organogenesis

Photonic Side-Channel Analysis of Arbiter PUFs

As intended by its name, Physically Unclonable Functions (PUFs) are considered as an ultimate solution to deal with insecure storage, hardware counterfeiting, and many other security problems. However, many different successful attacks have already revealed vulnerabilities of certain digital intrinsic PUFs. This paper demonstrates that legacy arbiter PUF and its popular extended versions (i.e., Feed-forward and XOR-enhanced) can be completely and linearly characterized by means of photonic emission analysis. Our experimental setup is capable of measuring every PUF-internal delay with a resolution of 6 picoseconds. Due to this resolution we indeed require only the theoretical minimum number of linear independent equations (i.e., physical measurements) to directly solve the underlying inhomogeneous linear system. Moreover, it is not required to know the actual PUF responses for our physical delay extraction. We present our practical results for an arbiter PUF implementation on a Complex Programmable Logic Device (CPLD) manufactured with a 180 nanometer process. Finally, we give an insight into photonic emission analysis of arbiter PUF on smaller chip architectures by performing experiments on a Field Programmable Gate Array (FPGA) manufactured with a 60 nanometer process

Structural relationship of the lipid A acyl groups to activation of murine Toll-like receptor 4 by lipopolysaccharides from pathogenic strains of Burkholderia mallei, Acinetobacter baumannii and Pseudomonas aeruginosa

Toll-like receptor 4 (TLR4) is required for activation of innate immunity upon recognition of lipopolysaccharide (LPS) of Gram-negative bacteria. The ability of TLR4 to respond to a particular LPS species is important since insufficient activation may not prevent bacterial growth while excessive immune reaction may lead to immunopathology associated with sepsis. Here we investigated the biological activity of LPS from Burkholderia mallei that causes glanders, and from the two well-known opportunistic pathogens Acinetobacter baumannii and Pseudomonas aeruginosa (causative agents of nosocomial infections). For each bacterial strain, R-form LPS preparations were purified by hydrophobic chromatography and the chemical structure of lipid A, an LPS structural component, was elucidated by HR-MALDI-TOF mass spectrometry. The biological activity of LPS samples was evaluated by their ability to induce production of proinflammatory cytokines, such as IL-6 and TNF, by bone marrow-derived macrophages (BMDM). Our results demonstrate direct correlation between the biological activity of LPS from these pathogenic bacteria and the extent of their lipid A acylation