The Use of Software Design Patterns to Teach Secure Software Design: An Integrated Approach

Part 2: Software Security EducationInternational audienceDuring software development, security is often dealt with as an add-on. This means that security considerations are not necessarily seen as an integral part of the overall solution and might even be left out of a design. For many security problems, the approach towards secure development has recurring elements. Software design patterns are often used to address a commonly occurring problem through a “generic” approach towards this problem. The design pattern provides a conceptual model of a best-practices solution, which in turn is used by developers to create a concrete implementation for their specific problem. Most software design patterns do not include security best-practices as part of the generic solution towards the commonly occurring problem. This paper proposes an extension to the widely used MVC pattern that includes current security principles in order to teach secure software design in an integrated fashion

The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes.

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine [measured as furosine]) and AGE levels (glyoxal and methylglyoxal hydroimidazolones [G-(1)H, MG-(1)H], carboxymethyllysine [CML], carboxyethyllysine [CEL], pentosidine) were measured in patient serum samples. RESULTS Forty-eight weeks of salsalate treatment lowered levels of HbA1c and serum furosine (P \u3c 0.001) and CML compared with placebo. The AGEs CEL and G-(1)H and MG-(1)H levels were unchanged, whereas pentosidine levels increased more than twofold (P \u3c 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA1c levels during follow-up (P \u3c 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines. CONCLUSIONS Salsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of pentosidine precursor

The Effect of Imagery Rescripting on Prospective Mental Imagery of a Feared Social Situation

Negative mental images in social anxiety disorder (SAD) are often rooted in autobiographical memories of formative, distressing life events. In the present study, 25 participants with SAD retrieved an idiosyncratic negative mental image and associated autobiographical memory. Participants were then randomly assigned either to a single-session of imagery rescripting (IR) targeting the retrieved autobiographical memory or to a non-intervention control condition (no-IR). Outcomes were assessed one week later. Compared to control participants, those who received IR experienced substantial reduction in SAD symptoms accompanied by more positive and less negative appraisals of their autobiographical memories. Moreover, IR relative to no-IR participants reported marked shifts in the content, validity, and accuracy of their memory-derived negative core beliefs about self and others, but not about the world. Results support the promise of IR as a stand-alone intervention for SAD and suggest important directions for future research to enhance our understanding of the cognitive mechanisms that underlie its effects

Neutron-Rich Freeze-Out in Viscously Spreading Accretion Disks Formed from Compact Object Mergers

Accretion disks with masses ~0.001-0.1 Msun form during the merger of neutron star (NS)-NS and black hole-NS binaries. Initially, such hyper-accreting disks cool efficiently by neutrino emission and their composition is driven neutron-rich by pair captures under degenerate conditions. However, as the disk viscously spreads and its temperature drops, cooling becomes inefficient and the disk becomes advective. Analytic arguments and numerical simulations suggest that once this occurs, powerful winds likely drive away most of the disk's remaining mass. We calculate the thermal evolution and nuclear composition of viscously spreading accretion disks formed from compact object mergers using one-dimensional height-integrated simulations. We show that freeze-out from weak equilibrium necessarily accompanies the disk's late-time transition to an advective state. As a result, hyper-accreting disks generically freeze out neutron-rich (with electron fraction Ye ~ 0.2-0.4), and their late-time outflows robustly synthesize rare neutron-rich isotopes. Using the measured abundances of these isotopes in our solar system, we constrain the compact object merger rate in the Milky Way to be < 1e-5 (M_d,0/0.1 Msun)^(-1) per year, where M_d,0 is the average initial mass of the accretion disk. Thus, either the NS-NS merger rate is at the low end of current estimates or the average disk mass produced during a typical merger is << 0.1 Msun. We also show that if most short duration gamma-ray bursts (GRBs) are produced by compact object mergers, their beaming fraction must exceed f_b ~ 0.13(M_d,0/0.1 Msun), corresponding to a jet half-opening angle > 30(M_d,0/0.1 Msun)^(1/2) degrees. This is consistent with other evidence that short duration GRB outflows are less collimated than those produced in long duration GRBs.Comment: 12 pages, 9 figures, 1 table; accepted to MNRAS; minor changes to text and figure

Exploiting the Bipartite Structure of Entity Grids for Document Coherence and Retrieval

International audienceDocument coherence describes how much sense text makes in terms of its logical organisation and discourse flow. Even though coherence is a relatively difficult notion to quantify precisely, it can be approximated automatically. This type of coherence modelling is not only interesting in itself, but also useful for a number of other text processing tasks, including Information Retrieval (IR), where adjusting the ranking of documents according to both their relevance and their coherence has been shown to increase retrieval effectiveness.The state of the art in unsupervised coherence modelling represents documents as bipartite graphs of sentences and discourse entities, and then projects these bipartite graphs into one–mode undirected graphs. However, one–mode projections may incur significant loss of the information present in the original bipartite structure. To address this we present three novel graph metrics that compute document coherence on the original bipartite graph of sentences and entities. Evaluation on standard settings shows that: (i) one of our coherence metrics beats the state of the art in terms of coherence accuracy; and (ii) all three of our coherence metrics improve retrieval effectiveness because, as closer analysis reveals, they capture aspects of document quality that go undetected by both keyword-based standard ranking and by spam filtering. This work contributes document coherence metrics that are theoretically principled, parameter-free, and useful to IR

Inflammation, insulin resistance, and diabetes-mendelian randomization using CRP haplotypes points upstream

Background Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. Methods and Findings We genotyped three tagging SNPs (CRP + 2302G &gt; A; CRP + 1444T &gt; C; CRP + 4899T &gt; G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p=0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p=0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p=0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. Conclusions Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP

Isolation of a small molecule inhibitor of DNA base excision repair

The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3′-phosphodiesterase and 3′-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy

Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA

Endonucleolytic cleavage of the coding region determinant (CRD) of c-myc mRNA appears to play a critical role in regulating c-myc mRNA turnover. Using 32P-labeled c-myc CRD RNA as substrate, we have purified and identified two endoribonucleases from rat liver polysomes that are capable of cleaving the transcript in vitro. A 17-kDa enzyme was identified as RNase1. Apurinic/apyrimidinic (AP) DNA endonuclease 1 (APE1) was identified as the 35-kDa endoribonuclease that preferentially cleaves in between UA and CA dinucleotides of c-myc CRD RNA. APE1 was further confirmed to be the 35-kDa endoribonuclease because: (i) the endoribonuclease activity of the purified 35-kDa native enzyme was specifically immuno-depleted with APE1 monoclonal antibody, and (ii) recombinant human APE1 generated identical RNA cleavage patterns as the native liver enzyme. Studies using E96A and H309N mutants of APE1 suggest that the endoribonuclease activity for c-myc CRD RNA shares the same active center with the AP-DNA endonuclease activity. Transient knockdown of APE1 in HeLa cells led to increased steady-state level of c-myc mRNA and its half-life. We conclude that the ability to cleave RNA dinucleotides is a previously unidentified function of APE1 and it can regulate c-myc mRNA level possibly via its endoribonuclease activity

Electromagnetic Counterparts of Compact Object Mergers Powered by the Radioactive Decay of R-process Nuclei

The most promising astrophysical sources of kHz gravitational waves (GWs) are the inspiral and merger of binary neutron star(NS)/black hole systems. Maximizing the scientific return of a GW detection will require identifying a coincident electro-magnetic (EM) counterpart. One of the most likely sources of isotropic EM emission from compact object mergers is a supernova-like transient powered by the radioactive decay of heavy elements synthesized in ejecta from the merger. We present the first calculations of the optical transients from compact object mergers that self-consistently determine the radioactive heating by means of a nuclear reaction network; using this heating rate, we model the light curve with a one dimensional Monte Carlo radiation transfer calculation. For an ejecta mass ~1e-2 M_sun[1e-3 M_sun] the resulting light curve peaks on a timescale ~ 1 day at a V-band luminosity nu L_nu ~ 3e41[1e41] ergs/s (M_V = -15[-14]); this corresponds to an effective "f" parameter ~3e-6 in the Li-Paczynski toy model. We argue that these results are relatively insensitive to uncertainties in the relevant nuclear physics and to the precise early-time dynamics and ejecta composition. Due to the rapid evolution and low luminosity of NS merger transients, EM counterpart searches triggered by GW detections will require close collaboration between the GW and astronomical communities. NS merger transients may also be detectable following a short-duration Gamma-Ray Burst or "blindly" with present or upcoming optical transient surveys. Because the emission produced by NS merger ejecta is powered by the formation of rare r-process elements, current optical transient surveys can directly constrain the unknown origin of the heaviest elements in the Universe.Comment: 14 pages, 7 figures; accepted to MNRAS; title changed to highlight r-process connection and new figure added