SafeWeb: A Middleware for Securing Ruby-Based Web Applications

Web applications in many domains such as healthcare and finance must process sensitive data, while complying with legal policies regarding the release of different classes of data to different parties. Currently, software bugs may lead to irreversible disclosure of confidential data in multi-tier web applications. An open challenge is how developers can guarantee these web applications only ever release sensitive data to authorised users without costly, recurring security audits. Our solution is to provide a trusted middleware that acts as a “safety net” to event-based enterprise web applications by preventing harmful data disclosure before it happens. We describe the design and implementation of SafeWeb, a Ruby-based middleware that associates data with security labels and transparently tracks their propagation at different granularities across a multi-tier web architecture with storage and complex event processing. For efficiency, maintainability and ease-of-use, SafeWeb exploits the dynamic features of the Ruby programming language to achieve label propagation and data flow enforcement. We evaluate SafeWeb by reporting our experience of implementing a web-based cancer treatment application and deploying it as part of the UK National Health Service (NHS)

Synthesis, design and characterization of a distributed feedback grating based non-linear optical chemosensor

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.Includes bibliographical references.Current optical chemosensors that operate by a 3R sensing approach - recognize, relay and report -- generate a measurable luminescent signal in the presence of targeted analyte. However, the advancement of chemical sensing into the micro- and nanoscale regimes necessitates the development of new signaling transduction strategies. There are just too few sensing active sites on the micro- and nano-patterned structures to permit species detection, resulting in the compromise of device sensitivity and performance. This thesis work addresses these challenges by adopting a multidisciplinarv approach in combining chemistry, materials and optical sciences in the development of a chemical and biological sensor. The platform with which we have focused our efforts is the Distributed Feedback (DFB) laser cavity. The waveguide materials synthesized are Si and Ti inorganic matrices that were optimized for optical waveguiding by determining the appropriate film thickness, refractive index and film smoothness. Amplified stimulated emission was achieved for a Rhodamine 6G doped SiO₂/TiO₂ slab waveguide. Imprinting of the DFB architecture onto these thin films was successfully achieved using soft lithography techniques and lasing was observed for these devices (Q-factor [approx.] 245). We have explored analyte detection capabilities of these DFB structures by attempting to spoil the gain of the cavity, and by using them as simple diffraction gratings for chemical sensing. Optical sensors are not limited to chemical and biological sensing, and we have applied the 3R approach to understanding the flow and transport properties in microdomains.(cont.) In the final Chapter, new optical probes for measuring slow flows in microchannels are discussed. This thesis includes a detailed synthetic and photophysical study of reversible caged dye tracers with a [Cp*Ru]⁺ metal head group for the Molecular Tagging Velocimetry technique.by Aetna W. Wun.Ph.D

Co-targeting of DNA, RNA, and protein molecules provides optimal outcomes for treating osteosarcoma and pulmonary metastasis in spontaneous and experimental metastasis mouse models.

Metastasis is a major cause of mortality for cancer patients and remains as the greatest challenge in cancer therapy. Driven by multiple factors, metastasis may not be controlled by the inhibition of single target. This study was aimed at assessing the hypothesis that drugs could be rationally combined to co-target critical DNA, RNA and protein molecules to achieve "saturation attack" against metastasis. Independent actions of the model drugs DNA-intercalating doxorubicin, RNA-interfering miR-34a and protein-inhibiting sorafenib on DNA replication, RNA translation and protein kinase signaling in highly metastatic, human osteosarcoma 143B cells were demonstrated by the increase of γH2A.X foci formation, reduction of c-MET expression and inhibition of Erk1/2 phosphorylation, respectively, and optimal effects were found for triple-drug combination. Consequently, triple-drug treatment showed a strong synergism in suppressing 143B cell proliferation and the greatest effects in reducing cell invasion. Compared to single- and dual-drug treatment, triple-drug therapy suppressed pulmonary metastases and orthotopic osteosarcoma progression to significantly greater degrees in orthotopic osteosarcoma xenograft/spontaneous metastases mouse models, while none showed significant toxicity. In addition, triple-drug therapy improved the overall survival to the greatest extent in experimental metastases mouse models. These findings demonstrate co-targeting of DNA, RNA and protein molecules as a novel therapeutic strategy for the treatment of metastasis

Adrenal computed tomography and NP-59 usefulness for diagnosing aldosterone-producing adenomas and idiopathic hyperaldosteronism in primary hyperaldosteronism

AbstractObjectivesTwo major causes of primary aldosteronism are aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA). In this study, we attempted to determine the role of NP-59 in identifying APA prior to adrenalectomy, especially when diagnostic computer tomography (CT) is equivocal.MethodsWe performed a retrospective analysis in patients with a clinical diagnosis of primary aldosteronism. The medical records of 36 patients were reviewed, which included 25 patients who had received adrenalectomy. All patients underwent adrenal CT alone or a combination of adrenal CT and NP-59 prior to surgery for the subtyping of primary aldosteronism, based on the protocols established in our institution. The accuracy of the adrenal CT and NP-59 findings was determined by a comparison with the pathologic findings and postoperative outcomes.ResultsTwenty-three patients received unilateral adrenalectomy under the diagnosis of APA. The diagnoses were based on CT findings in 11 patients and on CT and NP-59 findings in 12 patients. The results of pathology were adrenal cortical adenoma in these 23 patients and the positive predictive value was 100%. Blood pressure and potassium levels significantly improved after surgery in these patients (p < 0.01). Serum biochemistry and adrenal size of the limbs and bodies of patients with IHA were not significantly different from those of patients with APA.ConclusionFor the subtyping of primary aldosteronism, the imaging modality of adrenal CT alone or the combination of adrenal CT and NP-59 adrenal scan has a high positive predictive value for APAs. We suggest that all patients undergo an adrenal CT as their initial study, after confirming the diagnosis of primary aldosteronism, and to use NP-59 when adrenal CT findings are atypical or inconclusive. Lateralization by this modality prior to adrenalectomy can reduce unnecessarily invasive examinations such as adrenal venous sampling and also provide excellent treatment outcomes

Preoperative treatment with 5α-reductase inhibitors and the risk of hemorrhagic events in patients undergoing transurethral resection of the prostate – A population-based cohort study

OBJECTIVES: To assess the associations between preoperative treatment with 5-alpha reductase inhibitors and the risks of blood transfusion during transurethral resection of the prostate and blood clot evacuation or emergency department visits for hematuria within 1 month after surgery. METHODS: We used data from the Taiwan National Health Insurance Research Database in this population-based cohort study. A total of 3,126 patients who underwent first-time transurethral resection of the prostate from 2004 to 2013 were identified. Adjusted odds ratios estimated by multiple logistic regression models were used to assess the independent effects of the preoperative use of 5-alpha reductase inhibitors on the risks of perioperative hemorrhagic events after adjustment for potential confounders. RESULTS: Two hundred and ninety-seven (9.4%) patients were treated with 5-alpha reductase inhibitors fo

Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner

BACKGROUND: Despite of the fact that mammalian genomes are far more spacious than prokaryotic genomes, recent nucleotide sequencing data have revealed that many mammalian genes are arranged in a head-to-head orientation and separated by a small intergenic sequence. Extensive studies on some of these neighboring genes, in particular homologous gene pairs, have shown that these genes are often co-expressed in a symmetric manner and regulated by a shared promoter region. Here we report the identification of two non-homologous brain disease-related genes, with one coding for a serine protease inhibitor (SERPINI1) and the other for a programmed cell death-related gene (PDCD10), being tightly linked together by an asymmetric bidirectional promoter in an evolutionarily conserved fashion. This asymmetric bidirectional promoter, in cooperation with some cis-acting elements, is responsible for the co-regulation of the gene expression pattern as well as the tissue specificity of SERPINI1 and PDCD10. RESULTS: While SERPINI1 is predominantly expressed in normal brain and down-regulated in brain tumors, PDCD10 is ubiquitously expressed in all normal tissues but its gene transcription becomes aberrant in different types of cancers. By measuring the luciferase activity in various cell lysates, their 851-bp intergenic sequence was shown to be capable of driving the reporter gene expression in either direction. A 175-bp fragment from nt 1 to 175 in the vicinity of PDCD10 was further determined to function as a minimal bidirectional promoter. A critical regulatory fragment, from nt 176-473 outside the minimal promoter in the intergenic region, was identified to contain a strong repressive element for SERPINI1 and an enhancer for PDCD10. These cis-acting elements may exist to help coordinate the expression and regulation of the two flanking genes. CONCLUSION: For all non-homologous genes that have been described to be closely adjacent in the mammalian genomes, the intergenic region of the head-to-head PDCD10-SERPINI1 gene pair provides an interesting and informative example of a complex regulatory system that governs the expression of both genes not only through an asymmetric bidirectional promoter, but also through fine-tuned regulations with some cis-acting elements

A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in Golden Syrian hamsters

The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.This research was supported in part by the Intramural Research Program of the NIH, NIAID; by NIH AID AI059136; and by the European Community (projects DISSECT SP22-CT-2004-511060 and Rivigene SSPE-CT-2005-022639)