2,658 research outputs found
TAuth: Verifying timed security protocols
Quantitative timing is often explicitly used in systems for better security, e.g., the credentials for automatic website logon often has limited lifetime. Verifying timing relevant security protocols in these systems is very challenging as timing adds another dimension of complexity compared with the untimed protocol verification. In our previous work, we proposed an approach to check the correctness of the timed authentication in security protocols with fixed timing constraints. However, a more difficult question persists, i.e., given a particular protocol design, whether the protocol has security flaws in its design or it can be configured secure with proper parameter values? In this work, we answer this question by proposing a parameterized verification framework, where the quantitative parameters in the protocols can be intuitively specified as well as automatically analyzed. Given a security protocol, our verification algorithm either produces the secure constraints of the parameters, or constructs an attack that works for any parameter values. The correctness of our algorithm is formally proved. We implement our method into a tool called PTAuth and evaluate it with several security protocols. Using PTAuth, we have successfully found a timing attack in Kerberos V which is unreported before.No Full Tex
Characterization of the c.190T>C missense mutation in BRCA1 codon 64 (Cys64Arg).
In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional implications of the c.190T>C mutation at the molecular level, and to search whether additional polymorphisms might be linked to the peculiar phenotypic features observed in the Italian pedigree. Molecular modelling studies suggested that substitution of the cysteine 64 with an arginine likely disrupts the architecture of the BRCA1 RING finger domain, responsible for the interaction with BARD1, essential for the tumor-suppressor activity of the BRCA1-BARD1 complex. By splicing site information analysis, exonic splicing enhancer site characterization, and analysis of transcript fragment length and sequence, we showed that the c.190T>C mutation was able to modulate the splicing of exon 5 in a fashion opposite to the c.190T>G transversion, responsible for the functionally-related Cys64Gly amino acid substitution. Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations. Analysis of these SNPs in a genotypically-unrelated Polish family, characterized by prevalent breast neoplasms in carriers of the c.190T>C mutation, revealed a genetic profile consistent with the hypothetic role of both polymorphisms
ABT-199 (Venetoclax), a BH3-mimetic Bcl-2 inhibitor, does not cause Ca^{2+}-signalling dysregulation or toxicity in pancreatic acinar cells
Background and Purpose: Many cancer cells depend on anti‐apoptotic B‐cell lymphoma 2 (Bcl‐2) proteins for their survival. Bcl‐2 antagonism through Bcl‐2 homology 3 (BH3) mimetics has emerged as a novel anti‐cancer therapy. ABT‐199 (Venetoclax), a recently developed BH3 mimetic that selectively inhibits Bcl‐2, was introduced into the clinic for treatment of relapsed chronic lymphocytic leukaemia. Early generations of Bcl‐2 inhibitors evoked sustained Ca2+ responses in pancreatic acinar cells (PACs) inducing cell death. Therefore, BH3 mimetics could potentially be toxic for the pancreas when used to treat cancer. Although ABT‐199 was shown to kill Bcl‐2‐dependent cancer cells without affecting intracellular Ca2+ signalling, its effects on PACs have not yet been determined. Hence, it is essential and timely to assess whether this recently approved anti‐leukaemic drug might potentially have pancreatotoxic effects. Experimental Approach: Single‐cell Ca2+ measurements and cell death analysis were performed on isolated mouse PACs. Key Results: Inhibition of Bcl‐2 via ABT‐199 did not elicit intracellular Ca2+ signalling on its own or potentiate Ca2+ signalling induced by physiological/pathophysiological stimuli in PACs. Although ABT‐199 did not affect cell death in PACs, under conditions that killed ABT‐199‐sensitive cancer cells, cytosolic Ca2+ extrusion was slightly enhanced in the presence of ABT‐199. In contrast, inhibition of Bcl‐xL potentiated pathophysiological Ca2+ responses in PACs, without exacerbating cell death. Conclusion and Implications: Our results demonstrate that apart from having a modest effect on cytosolic Ca2+ extrusion, ABT‐199 does not substantially alter intracellular Ca2+ homeostasis in normal PACs and should be safe for the pancreas during cancer treatment
Physicochemical and Antibacterial Characterisation of a Novel Fluorapatite Coating
Peri-implantitis remains the major impediment to the long-term use of dental
implants. With increasing concern over growing antibiotic resistance there is
considerable interest in the preparation of antimicrobial dental implant coatings that
also induce osseointegration. One such potential coating material is fluorapatite
(FA). The aim of this study was to relate the antibacterial effectiveness of FA
coatings against pathogens implicated in peri-implantitis to the physicochemical
properties of the coating. Ordered and disordered FA coatings were produced on the
under and upper surface of stainless steel (SS) discs respectively, using a
hydrothermal method. Surface charge, surface roughness, wettability and fluoride
release were measured for each coating. Surface chemistry was assessed by X-ray
photoelectron spectroscopy and FA crystallinity by X-ray diffraction. Antibacterial
activity against periodontopathogens was assessed in vitro using viable counts,
confocal and scanning electron (SEM) microscopies. SEM showed that the
hydrothermal method produced FA coatings predominately aligned perpendicular to
the SS substrate or disordered FA coatings consisting of randomly aligned rod-like
crystals. Both FA coatings significantly reduced the growth of all the examined
bacterial strains in comparison to the control. The FA coatings, and especially the
disordered ones, presented significantly lower charge, higher roughness and area
when compared to the control, enhancing bacteria–material interactions and
therefore bacterial deactivation by fluoride ions. The ordered FA layer reduced not
only bacterial viability but adhesion too. Ordered FA crystals produced as a potential
novel implant coating showed significant antibacterial activity against bacteria
implicated in peri-implantitis which could be explained by a detailed understanding of
their physicochemical properties
Preliminary studies of sediments from the Dobczyce drinking water reservoir
The analysis of river and lake sediments indicates that the physical, chemical, biochemical and geochemical
processes that influence the fate of toxic compounds and elements in sediments are numerous and complex
(for example: sorption - desorption, oxidation - reduction, ion-exchange, biological activity). Due to the
above-mentioned general statement, only a long term and complex research programme can lead to satisfactory
answers to the questions relating to possible changes of water and environmental quality in the future.
The aim of our study consisted in physical and chemical characterisation of sediments in in-depth profiles
taken from the Dobczyce reservoir in southern Poland that is a main source of drinking water for the city
of Kraków. Due to morphological reasons, 7 layers of sediment samples were distinguished from the ground
level to about 90 cm below (total thickness of the sediments in the sampling site). Analysis of grain size distribution
and application of x-ray diffraction method, enabled mineralogical description of sediments.
The use of proton-induced x-ray emission (PIXE) and atomic absorption spectrometry (AAS) revealed
elemental composition of the samples (Al, P, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn). Concentrations
of natural 40K and artificial 137Cs radionuclides were determined by the use of gamma spectrometry.
The following facts were established: 1) the oldest (deepest) and newest, recently deposited layers of
sediments are similar in their physical and chemical properties. It means that the inflow of contaminants
and biogenic compounds to the reservoir has changed little since it was constructed and filled with water;
2) the severe flood in 1997 changed significantly sediment composition and, in fact, led to purification of
sediments in the Dobczyce reservoir
Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism
<p>Abstract</p> <p>Background</p> <p>The variable penetrance of ovarian cancer in <it>BRCA1 </it>mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (<it>PHB</it>) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring <it>BRCA1 </it>mutations.</p> <p>Methods</p> <p>To investigate whether the <it>PHB </it>3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and <it>BRCA1 </it>mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.</p> <p>Results</p> <p>A comparison of the genotype frequencies between cases and controls revealed no association of the <it>PHB </it>3'UTR _CT+TT genotypes with ovarian cancer risk (OR<sub>adj </sub>1.34; 95% CI, 0.59–3.11).</p> <p>Conclusion</p> <p>Our data suggest that the <it>PHB </it>3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish <it>BRCA1 </it>founder mutations.</p
A Multiset Rewriting Model for Specifying and Verifying Timing Aspects of Security Protocols
Catherine Meadows has played an important role in the advancement of formal methods for protocol security verification. Her insights on the use of, for example, narrowing and rewriting logic has made possible the automated discovery of new attacks and the shaping of new protocols. Meadows has also investigated other security aspects, such as, distance-bounding protocols and denial of service attacks. We have been greatly inspired by her work. This paper describes the use of Multiset Rewriting for the specification and verification of timing aspects of protocols, such as network delays, timeouts, timed intruder models and distance-bounding properties. We detail these timed features with a number of examples and describe decidable fragments of related verification problems
FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium
Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.
Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.
Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.
Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis
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