Isolation of malicious external inputs in a security focused adaptive execution environment

pre-printReliable isolation of malicious application inputs is necessary for preventing the future success of an observed novel attack after the initial incident. In this paper we describe, measure and analyze, Input-Reduction, a technique that can quickly isolate malicious external inputs that embody unforeseen and potentially novel attacks, from other benign application inputs. The Input-Reduction technique is integrated into an advanced, security-focused, and adaptive execution environment that automates diagnosis and repair. In experiments we show that Input-Reduction is highly accurate and efficient in isolating attack inputs and determining casual relations between inputs. We also measure and show that the cost incurred by key services that support reliable reproduction and fast attack isolation is reasonable in the adaptive execution environment

Photo-responsive oil core based polymer nanocapsules

The following PhD project regards the field of the drug delivery systems. In particular, the aim of this project is the study of chemical modifications useful to activate photo-stimuli-responsive oil core polymer nanocapsules as theranostic delivery system. Mainly, we will focus the attention on layer by layer (LbL) polymer based nanocapsules loaded with natural drugs and safe contrast agents. In the tumor treatment context, our main purpose is the use of safe nanocarriers to reduce the side effects for the patient, improving the therapy efficacy and the bioavailability of the drugs. So in this PhD project we study systems which can enhance the clinical performance and the cancer detection exploring chemical modifications in the polymeric compositions and/or in the oil core formulations. To this aim we focused the attention on highly versatile nanocapsules built around an oil core and made of completely biocompatible natural polymers employable for therapeutic and diagnostic purposes. Chemical functionalization of nanoemulsions’ shells is studied to engineer a photo-responsive nanocarrier with spatio-temporal control in the release of the drug. In Chapter 2 a LbL O/W cross-linked photo-responsive nanoemulsion, loaded with a natural drug, curcumin, is explained. As just demonstrated in our group, it is possible to functionalize the polymers deposited on the oil core, such as glycol chitosan and heparin, with a thiol moiety and an allylic moiety respectively, and then create a covalent bond between the polymeric shells via a biocompatible photoinitatior free thiol-ene ‘click’ reaction, to improve the nanosystem’s stability. Starting from this strategy to obtain a stable cross-linked LbL systems, we introduced a photolabile chemical linker, based on a modified N-acetyl cysteine-o-nitrobenzyl moiety, between the polymeric materials of LbL. Functionalized the glycol chitosan with this thiol-photo-responsive moiety and the heparin with an allyl one, we were able to perform the cross-linkage and to stabilize our LbL O/W nanoemulsion multilayer shell by the photoinitiator free thiol-ene ‘click’ reaction. Interestingly, the photo-responsive linker gave us the possibility to trigger a controlled destabilization of the nanocarriers to release the drug by single or multi-photon UV light (365 nm or 740 nm). After the chemical modifications of the nanocarriers and its characterizations in terms of stability and conditions of release, we performed biological studies of uptake and cell viability on melanoma cells. In Chapter 3 it is reported a recent published article which is part of this PhD project. It regards an oral delivery application of our nanoemulsions encapsulating nutraceutical drugs, such as curcumin and lycopene and the study of their cardioprotection and anti-inflammatory effects. These properties have been assessed by in vitro tests performed on cardiomyoblasts (H9C2 cells) in presence of doxorubicin. In Chapter 4 we report another possibility concerning the modification of the oil core formulation of the nanoemulsions, using an inorganic compound, in particular cubic iron oxide nanoparticles as contrast agents. We prepared oil-core-PEG shell nanocarriers encapsulating nanocubic iron oxide nanoparticles to study how these systems respond to in vitro photoacoustic and in vitro and in vivo magnetic resonance imaging. Final conclusion and future perspectives are presented and discussed in Chapter 5. Each part of this work can be seen distinctly or in a more general point of view. In this case, we can think to engineer a photo-responsive LbL O/W nanoemulsion co-loaded with natural drugs and safe contrast agents to employ as theranostic nanocapsules

Development of Universal Biosensing Platforms Based on CRISPR/Cas12a systems

CRISPR/Cas technologies possess the promising potential to affect biosensing field by providing a sensitive, precise, rapid, versatile and cost-effective method for diverse target detections. This thesis focusses on the development of CRISP/Cas12a based biosensing platforms for nucleic acid and protein detection. Two distinct CRISPR/Cas based diagnostic methods were developed. The first developed method is a plasmonic CRISPR Cas12a assay for colorimetric detection of viral nucleic acid. This assay generates colorimetric signals for nucleic acid amplicons by combining the unique target-induced collateral cleavage activity of Cas12a with plasmon coupling of DNA functionalized gold nanoparticles. The practical applications of this assay were successfully demonstrated through the nucleic acid detection of hepatitis B virus (HBV) and Grapevine Red-Blotch Virus (GRBV). The second developed method is a universal proximity CRISPR Cas12a assay for ultrasensitive detection of nucleic acids and proteins. The target recognition is achieved through proximity binding rather than direct CRISPR/Cas 12a recognition, allows the flexible assay design and expansion to target diverse targets. This assay was successfully adapted to detect nucleic acids and antibodies in both buffer and diluted human serum

RAS enhancements for RDMA communications

textEthernet as the communication medium in the enterprise data center has outlived all competing mediums and resisted the test of time with regards to speed and costs. The future is also poised for growth with 40 and 100Gps speeds just over horizon. The current state of the technology is being enhanced and extended with lossless features to allow for fabric convergence of Storage and Inter Process Communication (IPC) Networks. It is under this medium that an increase in the adoption of Remote Direct Memory Access (RDMA) over Ethernet using offloaded TCP/IP (iWARP) and Infiniband over Ethernet (RoCE) communication stacks to RDMA capable NIC adapter s (RNIC) is observed. RDMA enables direct application to application communication over the network resulting in numerous and significant benefits such as reduced CPU utilization, lower latency communications, increased energy efficiency, and reduced overall system requirements. However, with said benefits also comes increased software complexity in how RDMA interface users communicate. The RDMA communication semantics, which originate from the HPC domain, are heavily biased towards Low-Latency and High-Bandwidth communications rather than Reliability, Availability, and Serviceability (RAS). As adoption increases, and enterprise data centers begins to leverage RDMA over Ethernet, enhancements to the OS stack software architecture and design of the components involved is required to address these deficiencies. Operating system interfaces, device drivers, adapter hardware design, and embedded firmware features must be viewed from a high-availability and maintainability point of view. RAS enhancements for RDMA communications proposes the software architectural tradeoffs for enhancing the iWARP and RoCE RDMA implementations for communications in the enterprise data center, with new and traditional RAS features for existing communications stacks and devices. The architecture leverages software enhancements in traceability, availability, maintainability, serviceability, fault-isolation and resource management; such that in the advent of errors, the probability that the forensics data points to identify root cause are immediately and automatically available is increased.Electrical and Computer Engineerin

Electrospun nanofiber meshes: applications in oil absorption, cell patterning, and biosensing

Nanofabrication techniques produce materials with enhanced physicochemical properties through a combination of nanoscale roughness and the use of chemically diverse polymers which enable advanced applications in separation science (air/water purification), tissue engineering, and biosensing. Since the late 1990’s, electrospinning has been extensively studied and utilized to produce nano- to microfiber meshes with 3D porosity on the gram scale. By combining a high surface area to volume ratio and tunable surface chemistry, electrospinning is a facile platform for generating non-woven polymeric fibers for many biomedical and industrial applications. This thesis describes three applications of electrospun nano- and microfiber meshes spun from both commercially available and novel polymer systems for: 1) oil and water separation after an accidental oil spill; 2) ultraviolet light controlled protein and cell patterning throughout 3-dimensional nanofiber meshes; and 3) novel diagnostic platform by combining electrospun nanofiber meshes with solid state nanopores for enhanced single molecule nucleic acid and protein detection. Each application embodies the philosophy that electrospun materials have the potential to solve a wide variety of problems by simply tuning the physicochemical properties and mesh morphologies towards the design requirements for a specific problem. For example, to solve the problem of recovering crude oil after an oil spill while generating a minimal waste burden, a hydrophobic and biodegradable microfiber mesh was designed to repeatedly separate oil and water and naturally biodegrade after use. In order to solve the problem of spatiotemporal placement of cells within a 3-dimensional tissue engineering construct, an ultraviolet light activated mesh was designed to transition from hydrophobic (water impermeable) to hydrophilic (water permeable) upon exposure to ultraviolet light facilitating protein and cell patterning. Finally to address two problems with single molecule solid state nanopore biosensors, namely rapid nucleic acid translocation rates and limited protein identification capabilities, a new biosensor platform was developed based on two novel polymeric systems which were synthesized and electrospun into high surface area nanofiber mesh coatings.2018-02-17T00:00:00

The Synthesis and Characterization of Multifunctional Nanoparticles of Elastin-Like Polypeptides for Theranostic Applications

Theranostics is a promising field that aims to combine therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanotechnology and specifically in the creation of multifunctional nanoparticles capable of providing the necessary functionalities. Elastin-like polypeptides (ELPs) are a class of environmentally responsive biopolymers that are known to undergo a transition in response to various stimuli. The organic nature of ELPs along with the ability to control their design at the gene level and the aforementioned responsive behavior make them a promising candidate for use in theranostic systems. The system presented here is one of the first examples of using ELPs as the base for multifunctional theranostic nanoparticles. Presented in this study is a fully protein based self-assembling nanoparticle system based on micelles of ELPs for use in theranostic applications. Micelle forming ELP constructs have been modified through the fusion of the protein based MRI contrast agent CA1.CD2 to the C terminal of existing protein constructs. Micelles were then crosslinked into stable nanoparticles that relied only on changes in temperature to drive the transition. In addition to that, a targeting peptide has been added to the system as well to provide active targeting to cancer cells. As a contrast agent the system has been shown to bind and retain gadolinium while effectively providing contrast in T1 weighted imaging and having higher relaxivity values than clinical contrast agents. Modification of the architecture of the construct through changes of the tail length, and through creation of mixtures did not drastically affect the behavior of the system demonstrating its flexibility. Here I detail, the design, synthesis of the expression, purification and characterization of all the required properties of the constructs

The Synthesis and Characterization of Multifunctional Nanoparticles of Elastin-Like Polypeptides for Theranostic Applications

Theranostics is a promising field that aims to combine therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanotechnology and specifically in the creation of multifunctional nanoparticles capable of providing the necessary functionalities. Elastin-like polypeptides (ELPs) are a class of environmentally responsive biopolymers that are known to undergo a transition in response to various stimuli. The organic nature of ELPs along with the ability to control their design at the gene level and the aforementioned responsive behavior make them a promising candidate for use in theranostic systems. The system presented here is one of the first examples of using ELPs as the base for multifunctional theranostic nanoparticles. Presented in this study is a fully protein based self-assembling nanoparticle system based on micelles of ELPs for use in theranostic applications. Micelle forming ELP constructs have been modified through the fusion of the protein based MRI contrast agent CA1.CD2 to the C terminal of existing protein constructs. Micelles were then crosslinked into stable nanoparticles that relied only on changes in temperature to drive the transition. In addition to that, a targeting peptide has been added to the system as well to provide active targeting to cancer cells. As a contrast agent the system has been shown to bind and retain gadolinium while effectively providing contrast in T1 weighted imaging and having higher relaxivity values than clinical contrast agents. Modification of the architecture of the construct through changes of the tail length, and through creation of mixtures did not drastically affect the behavior of the system demonstrating its flexibility. Here I detail, the design, synthesis of the expression, purification and characterization of all the required properties of the constructs