Aloha-HE: A Low-Area Hardware Accelerator for Client-Side Operations in Homomorphic Encryption

Homomorphic encryption (HE) has gained broad attention in recent years as it allows computations on encrypted data enabling secure cloud computing. Deploying HE presents a notable challenge since it introduces a performance overhead by orders of magnitude. Hence, most works target accelerating server-side operations on hardware platforms, while little attention has been given to client-side operations. In this paper, we present a novel design methodology to implement and accelerate the client-side HE operations on area-constrained hardware. We show how to design an optimized floating-point unit tailored for the encoding of complex values. In addition, we introduce a novel hardware-friendly algorithm for modulo-reduction of floating-point numbers and propose various concepts for achieving efficient resource sharing between modular ring and floating-point arithmetic. Finally, we use this methodology to implement an end-to-end hardware accelerator, Aloha-HE, for the client-side operations of the CKKS scheme. In contrast to existing work, Aloha-HE supports both encoding and encryption and their counterparts within a unified architecture. Aloha-HE achieves a speedup of up to 59x compared to prior hardware solutions

PROTEUS: A Tool to generate pipelined Number Theoretic Transform Architectures for FHE and ZKP applications

Emerging cryptographic algorithms such as fully homomorphic encryption (FHE) and zero-knowledge proof (ZKP) perform arithmetic involving very large polynomials. One fundamental and time-consuming polynomial operation is the Number theoretic transform (NTT) which is a generalization of the fast Fourier transform. Hardware platforms such as FPGAs could be used to accelerate the NTTs in FHE and ZKP protocols. One major problem is that the FHE and ZKP protocols require different parameter sets, e.g., polynomial degree and coefficient size, depending on their applications. Therefore, a basic research question is: How to design scalable hardware architectures for accelerating NTTs in the FHE and ZKP protocols? In this paper, we present ‘PROTEUS’, an open-source and parametric tool that generates synthesizable bandwidth-efficient NTT architectures for user-specified parameter sets. The architectures can be tuned to utilize different memory bandwidths and parameters which is a very important design requirement in both FHE and ZKP protocols. The generated NTT architectures show a significant performance speedup compared to similar NTT architectures on FPGA. Further comparisons with state-of-the-art show a reduction of up to 23% and 35% in terms of DSP and BRAM utilization

A Hardware Implementation of MAYO Signature Scheme

We present a hardware implementation for the MAYO post-quantum digital signature scheme, which is submitted to the American National Institute of Standards and Technology’s call for diversification of quantum-resistant public key cryptographic standards. The scheme is based on the Unbalanced Oil and Vinegar signature scheme, which operates on the fact that solving systems of multivariate polynomial equations is NP-complete. MAYO utilizes a unique whipping technique in combination with emulsifier maps to offer a significant reduction in key size compared to other Unbalanced Oil and Vinegar signature schemes. In this paper, we demonstrate how to design a hardware architecture for the MAYO post-quantum signature scheme. We also provide a comprehensive analysis and propose multiple optimization techniques to reduce resource utilization and accelerate computation on hardware platforms

Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1δ impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo

"Anna, Paul! Ich will eure Potenziale sehen!" - "Potenzialfokussierter Unterricht" unter dem Aspekt der Motivation

Die vorliegende Masterarbeit führt in einem analytischen Stil in den neuen Ansatz der „Potenzialfokussierten Pädagogik“ (Lueger 2014b) ein. Es werden dabei die sieben Prinzipien der „Potenzialfokussierten Schule“, der theoretische Ursprung und die Genese des „Potenzialfokus“ (De Shazer & Berg 1997) sowie die praktische Ableitung des Konzeptes, der „Potenzialfokussierte Unterricht“, beleuchtet. Anschließend wird unter dem Aspekt der Motivation die Selbstbestimmungstheorie von Deci und Ryan (1993, 2000) vorgestellt. Anhand einer empirischen Inhaltsanalyse wird zwischen den beiden Ansätzen eine hohe inhaltliche Übereinstimmung identifiziert, die eine konkrete empirische Forschungsperspektive im Kontext von Unterrichtsqualität (Helmke 2015) öffnet, auf jener die weitere Forschung aufbaut. In einer quasi-experimentellen Studie im Methoden Mix werden erste empirische Daten einer diesbezüglichen Querschnittserhebung (n=119), die in Klassen der 5. Schulstufe an Wiener Schulen durchgeführt wurde, präsentiert. Abschließend werden die bildungstheoretischen und empirischen Haupterkenntnisse der Arbeit resümiert, die methodischen Reflexionen diskutiert und zudem wird ein Ausblick in weiterführende Forschungsmöglichkeiten im Kontext dieser entwickelten Forschungsperspektive gegeben.This master's thesis introduces the new approach of "Potential-focused pedagogy" (Lueger 2014b) in an analytical style. It highlights the seven principles of the "Potential Focused School" as well as the theoretical foundation and genesis of the "Potential focus" (De Shazer & Berg 1997) and the practical part of the concept – the "Potential Focused Teaching". Subsequently the self-determination theory of Deci and Ryan (1993, 2000) is presented as the main part along the aspect of motivation. Based on an empirical content analysis a high level of substantive agreement is identified between the two approaches, which opens a concrete empirical research perspective in the context of teaching quality (Helmke 2015) on which further research of this master’s thesis is based. In a quasi-experimental study in mix methods design first empirical data of a cross-sectional survey (n = 119), which was carried out in classes of the 5th grade at Viennese schools, are presented. Finally the main findings of the thesis will be summed up, the methodological reflections gained from the study are discussed and an outlook is given on further research opportunities

Immunomodulatory effects of Eps®7630 (Umckaloabo) on PBMC of healthy donors in vitro

Das Medikament Umckaloabo (Eps®7630) stellt einen ethanolischen Auszug aus den Wurzeln von Pelargonium sidoides und P. reniforme dar, einer südafrikanischen Geranienart, die in der dortigen traditionellen Medizin zur Behandlung von Infektionskrankheiten eingesetzt wird. Es ist in Deutschland zur Behandlung von Bronchitiden zugelassen. Chemische Analysen des Pflanzenauszuges ergaben ein großes Spektrum an Polyphenolen. In bisherigen experimentellen Studien wurde bei Zugabe von Umckaloabo u.a eine erhöhte IFN-gamma-Synthese in virusinfizierten Zellen nachgewiesen sowie eine Aktivierung von Zellen des angeborenen Immunsystems einhergehend mit einer Freisetzung von TNF-alpha, IL-1, IL-12, Il-18 und IFN-alpha/gamma und Stickoxiden. Ziel der vorliegenden Arbeit war daher, die Wirkung von Umckaloabo auf Zellen des erworbenen Immunsystems in vitro zu analysieren mittels PBMC (peripheral blood mononuclear cells) von insgesamt 20 gesunden Probanden. Durch kostimulierende Antigene (BCG, purified protein derivative [PPD] und Tetanus-Toxoid [TT]) wurden TH1- bzw. TH2-Immunreaktionen provoziert und der Einfluss von Umckaloabo in unterschiedlichen Konzentrationen innerhalb dieses in-vitro-Testsystems untersucht. Zum Einsatz kamen Proliferationsassays, Methoden zur quantitativen Zytokinbestimmung mittels Sandwich-ELISA, sowie durchflusszytometri¬sche Detektionsmethoden zum Nachweis verschiedener Zelloberflächenmoleküle (CD3, CD4, CD8, CD19, CD45, CD56) sowie des frühen Aktivierungsmarkers CD69 und der Expression des für regulatorische T-Zellen (Treg) charakteristischen intrazellulären Proteins Foxp3. Umckaloabo führte in Konzentrationen von 1 bis 1000 µg/ml zu einer signifikanten Steigerung der Proliferation von Lymphozyten: Ohne Kostimulation und bei Kostimulation mit PPD um den Faktor 10, bei Kostimulation mit TT um den Faktor 2. Durchflusszytometrisch konnte gezeigt werden, dass insbesondere die CD4-positiven T-Helferzellen zunahmen, etwas weniger auch die CD8-positiven zytotoxischen T- bzw. CD56-positiven natürlichen Killer (NK)-Zellen. CD19-positive B-Zellen wurden dagegen kaum beeinflusst. In einer Konzentration von 10 µg/ml führte Umckaloabo zu einem signifikanten Anstieg der Expression von CD69, d.h. einer Aktivierung dieser Zellsubpopulationen. Die Analyse der Zytokinproduktion ergab, dass die für Makrophagen typischen Zytokine wie IL-1, IL-6 und TNF-alpha bei 10 µg/ml signifikant anstiegen, ebenso bei Kostimulation durch PPD oder TT. Die Ausschüttung von TNF-alpha bei Kostimulation mit TT wurde bei 10 µg/ml signifikant gehemmt, die von IFN-gamma signifikant gesteigert. Die durch TT induzierte Produktion der TH2-typischen Zytokine IL-5 und IL-13 wurde durch Umckaloabo bei 1 µg/ml signifikant gehemmt. Die Ausschüttung von IL-10 durch Umckaloabo wurde bei 1 µg/ml signifikant gesteigert, ebenso bei Kostimulation mit PPD, während die IL-10-Spiegel bei den starken Kostimuli TT bzw, BCG durch Zugabe von Umckaloabo nicht verändert wurden. Die durchflusszytometrische Analyse der regulatorischen T-Zellen ergab eine deutliche Zunahme des Anteils an Treg innerhalb der Population der CD4-positiven Zellen bei Zugabe von Umckaloabo, die in schwächerer Ausprägung auch bei Kostimulation mit TT bzw. PPD zu sehen war. Zusammenfassend konnten die angeführten experimentellen Untersuchungen zeigen, dass Umckaloabo in einem in-vitro-System komplexe Wirkungen auf PBMC hat. Es führt in erster Linie zu einer Aktivierung von Makrophagen, TH1-Zellen und NK-Zellen, während TH2-Reaktionen inhibiert werden. Darauf könnte durchaus der in vivo beschriebene positive Effekt bei Infektionskrankheiten zurückzuführen sein. Ferner scheint die Substanz Treg zu aktivieren, was möglicherweise erklärt, dass das Medikament nur in seltenen Fällen zu Überreaktionen führt. Die vorliegende Arbeit ist somit ein Beitrag, den bisher nur empirisch belegten immunstimulierenden Einsatz von Umckaloabo wissenschaftlich zu untermauern, macht aber auch weiteren Forschungsbedarf deutlich. Anzustreben sind insbesondere eine Zuordnung der immunologischen Effekte zu bestimmten Komponenten des Extraktes sowie prospektive Studien unter Einnahme von Umckaloabo.Ectracts of the Geraniacea Pelargonium sidoides have been traditionally used for the treatment of respiratory tract infections in southern Africa. Nowadays, the modern equivalent termed Eps®7630 (trademark: Umckaloabo), an ethanolic extract of the roots of the plant is succesfully used in phytotherapy. Numerous clinical studies have provided evidence of the beneficial effects of Eps®7630 therapy in patients afflicted with bronchitis, sinusitis and rhinopharyngitis but the molecular mechanisms that provide these effects are not yet known. Therefore it is promising that Eps®7630 alone as well as several of its major constituents could be recently shown to have effects on innate immunity in vitro, e.g. they enhanced the release of TNF-alpha and iNO in Leishmania-infected macrophages. Therefore, aim of this project was to study the influence of Eps®7630 in adaptive immune responses in vitro by means of FACS, proliferation and cytokine assays. PBMC of 20 healthy donors were isolated and cultivated with different concentrations of Umckaloabo. Addition of different antigen stimuli (BCG, PPD and tetanus toxoid) provocated different immunologic reactions (TH1 respectively TH2). In these in-vitro studies we could show that addition of Umckaloabo in concentrations from 1µg/ml up to 1000 µg/ml significantly enhanced proliferation of different kinds of lymphocytes, especially of CD-4 positive cells and Treg -cells. Analysis of cytokines showed a significantly enhanced secretion of IL-1, IL-6, TNF-alpha and IL-10. We could prove that Umckaloabo does not only influence the innate immune system but also influences lymphocytes by different mechanisms. Enhancing of TH1 reactions could be a possible mechanism of antiviral effects of Umckaloabo

Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents

BACKGROUND: Abdominal surgery results in a molecular and cellular inflammatory response in the intestine, leading to postoperative ileus. It was hypothesised that resident macrophages within the intestinal muscularis have an important role in this local inflammation. AIMS: To investigate whether chemical or genetic depletion of resident muscularis macrophages would lead to a reduction in the local inflammation and smooth‐muscle dysfunction. METHODS: Two rodent models were used to deplete and inactivate macrophages: (1) a rat model in which resident macrophages were depleted by chlodronate liposomes; (2) a model of mice with osteopetrosis mice, completely lacking the resident muscularis macrophages, used as an additional genetic approach. Animals with normal or altered intestinal macrophages underwent surgical intestinal manipulation. The inflammatory response was investigated by quantitative reverse transcriptase‐polymerase chain reaction for mRNA of MIP‐1α, interleukin (IL)1β, IL6, intracellular adhesion molecule 1 (ICAM‐1) and monocyte chemotractant protein 1 (MCP)‐1 in the isolated small bowel muscularis. In addition, muscularis whole mounts were used for histochemical and immunohistochemical analysis to quantify leucocyte infiltration and detect cytokine expression. Subsequently, in vitro muscle contractility and in vivo gastrointestinal transit were measured. RESULTS: Both models resulted in markedly decreased expression of MIP‐1α, IL1β, IL6, ICAM‐1 and MCP‐1 after manipulation compared with controls. In addition to this decrease in inflammatory mediators, recruitment of leucocytes into the muscularis was also diminished. Macrophage‐altered animals had near normal in vitro jejunal circular muscle function and gastrointestinal transit despite surgical manipulation. CONCLUSIONS: Resident intestinal muscularis macrophages are initially involved in inflammatory responses resulting in postoperative ileus. Depletion and inactivation of the muscularis macrophage network prevents postoperative ileus

Characterization of the CK1 activity present in SV-52 and Rev2 cells.

<p><b>(A) Phosphorylation of T-Ag by CK1δKD.. </b><i>In vitro</i> kinase assays were performed using baculovirus-expressed T-Ag as a substrate and a C-terminally truncated CK1δ (CK1δKD) as enzyme. The phosphorylated proteins were separated by SDS-PAGE (12.5%) and visualized by Coomassie staining. The degree of phosphorylation was documented by autoradiography. Addition of C-terminally truncated CK1δ is indicated by + or −. kDa: kilo dalton. <b>(B) Detection of CK1 activity in fractions derived from anion exchange chromatography.</b> Soluble extracts of SV-52 and Rev2 cells were prepared and equal amounts of protein were loaded onto a 1 ml Resource Q column. The proteins were eluted with a linear gradient of increasing NaCl concentration. 0.25 ml fractions were collected, and kinase activity was determined as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029709#s2" target="_blank">Materials and Methods</a>. The kinase activities in the peak fractions of SV-52 and Rev2 cells were determined using either T-Ag or GST-p53^1–64 as a substrate. SV-52 cells: purple, closed circles; Rev2 cells: blue, closed triangles; — mM NaCl. <b>(C) Detection of CK1 in kinase peak fractions.</b> Western blot analyses were performed using proteins from the peak fractions of fractionated SV-52 and Rev2 cell lysates as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029709#s2" target="_blank">Materials and Methods</a>. CK1δ was detected using the CK1δ specific mouse monoclonal antibody 128A. <b>(D) Inhibition of CK1 kinase activity in SV-52 and Rev2 cellular extracts using the CK1 specific inhibitor IC261.. </b><i>In vitro</i> kinase assays were performed in the presence of 1 µM, 3 µM and 10 µM of IC261 using cellular fractions from fractionated SV-52 and Rev2 protein lysates as source of kinase. Phosphate incorporation into T-Ag and GST-p53^1–64, respectively, was normalized towards DMSO control reactions.</p

Analysis of changes in the expression of genes involved in <i>wnt</i>-signaling.

<p>Total RNA isolated from tumors of WAP-T transgenic and WAP-mutCK1δ/WAP-T bi-transgenic animals was transcribed into complementary DNA. Gene profiling was done using RT² profiler PCR array “mouse <i>wnt</i>-signaling pathway” (84 genes) (Superarray SABioscience, Karlsruhe, Germany). The values represent the mean of the observed changes in gene expression in tumors of WAP-T and WAP-mutCK1δ/WAP-T mice compared to the according non-tumor control tissue. Data are presented as ± standard error of the mean (SEM). Increased expression: ↑; decreased expression: ↓.</p