On wireless channel parameters for key generation in industrial environments

The advent of industry 4.0 with its idea of individualized mass production will significantly increase the demand for more flexibility on the production floor. Wireless communication provides this type of flexibility but puts the automation system at risk as potential attackers now can eavesdrop or even manipulate the messages exchanged even without getting access to the premises of the victim. Cryptographic means can prevent such attacks if applied properly. One of their core components is the distribution of keys. The generation of keys from channel parameters seems to be a promising approach in comparison to classical approaches based on public key cryptography as it avoids computing intense operations for exchanging keys. In this paper we investigated key generation approaches using channel parameters recorded in a real industrial environment. Our key results are that the key generation may take unpredictable long and that the resulting keys are of low quality with respect to the test for randomness we applied

How Different Electrical Circuits of ECC Designs Influence the Shape of Power Traces measured on FPGA

Side channel and fault attacks take advantage from the fact that the behavior of crypto implementations can be observed and provide hints that simplify revealing keys. These attacks use identical devices either for preparation of attacks or for measurements. By the preparation of attacks the structure and the electrical circuit of devices, that are identical to the target, is analyzed. By side channel attacks usually the same device is used many times for measurements, i.e. measurements on the identical device are made serially in time. Another way is to exploit the difference of side channel leakages; here two identical devices are used parallel, i.e. at the same time. In this paper we investigate the influence of the electrical circuit of a cryptographic implementation on the shape of the resulting power trace, because individualizing of circuits of cryptographic devices can be a new means to prevent attacks that use identical devices. We implemented three different designs that provide exactly the same cryptographic function, i.e. an ECC kP multiplication. For our evaluation we use two different FPGAs. The visualization of the routed design and measurement results show clear differences in the resources consumed as well as in the power traces

Proposing Individualization of the design of cryptographic hardware accelerators as countermeasure against structure and side channel analysis

Side channel and fault attacks take advantage from the fact that the behavior of crypto implementations can be observed and provide hints that simplify revealing keys. These attacks are normally prepared by analyzing devices that are identical to the real target. Here we propose to individualize the design of cryptographic devices in order to prevent attacks that use identical devices. We implemented three different designs that provide exactly the same cryptographic function, i.e. an ECC kP multiplication. The synthesis and power simulation results show clear differences in the area consumed as well as in the power traces. We envision that this type of protection mechanism is relevant e.g. for wireless sensor networks from which devices can easily be stolen for further analysis in the lab

Horizontal DEMA Attack as the Criterion to Select the Best Suitable EM Probe

Implementing cryptographic algorithms in a tamper resistant way is an extremely complex task as the algorithm used and the target platform have a significant impact on the potential leakage of the implementation. In addition the quality of the tools used for the attacks is of importance. In order to evaluate the resistance of a certain design against electromagnetic emanation attacks – as a highly relevant type of attacks – we discuss the quality of different electromagnetic (EM) probes as attack tools. In this paper we propose to use the results of horizontal attacks for comparison of measurement setup and for determining the best suitable instruments for measurements. We performed horizontal differential electromagnetic analysis (DEMA) attacks against our ECC design that is an im-plementation of the Montgomery kP algorithm for the NIST elliptic curve B-233. We experimented with 7 different EM probes under same conditions: attacked FPGA, design, inputs, measurement point and measurement equipment were the same, excepting EM probes. The used EM probe influences the success rate of performed attack significantly. We used this fact for the comparison of probes and for determining the best suitable one

Quantification of silver nanoparticle uptake and distribution within individual human macrophages by FIB/SEM slice and view

Background: Quantification of nanoparticle (NP) uptake in cells or tissues is very important for safety assessment. Often, electron microscopy based approaches are used for this purpose, which allow imaging at very high resolution. However, precise quantification of NP numbers in cells and tissues remains challenging. The aim of this study was to present a novel approach, that combines precise quantification of NPs in individual cells together with high resolution imaging of their intracellular distribution based on focused ion beam/ scanning electron microscopy (FIB/SEM) slice and view approaches. Results: We quantified cellular uptake of 75 nm diameter citrate stabilized silver NPs (Ag 75 Cit) into an individual human macrophage derived from monocytic THP-1 cells using a FIB/SEM slice and view approach. Cells were treated with 10 μg/ml for 24 h. We investigated a single cell and found in total 3138 ± 722 silver NPs inside this cell. Most of the silver NPs were located in large agglomerates, only a few were found in clusters of fewer than five NPs. Furthermore, we cross-checked our results by using inductively coupled plasma mass spectrometry and could confirm the FIB/SEM results. Conclusions: Our approach based on FIB/SEM slice and view is currently the only one that allows the quantification of the absolute dose of silver NPs in individual cells and at the same time to assess their intracellular distribution at high resolution. We therefore propose to use FIB/SEM slice and view to systematically analyse the cellular uptake of various NPs as a function of size, concentration and incubation time

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naive healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4(+) T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients

Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 >= 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 >= 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 >= 1:320)

Urinary Proteomics to Support Diagnosis of Stroke

Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (−0.30 to 1.25) in cases compared to −1.04 (IQR −1.86 to −0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment