23 research outputs found
Information Disclosure and Security Vulnerability Awareness: A Large-Scale Randomized Field Experiment in Pan-Asia
This paper investigates how the disclosure of a security vulnerability index based on outgoing spams and phishing website hosting which may serve as an indicator of a firm’s inadequate security controls affects companies’ security protection strategy. Our core objective is to study whether firms improve their security when they become aware of their vulnerabilities and such information is publicized. To achieve this goal, we conduct a randomized field experiment on 1,262 firms in six Pan-Asian countries and regions. Among 631 treatment firms, we alert them of their security vulnerability index and ranking over time, and their relative performance compared to their peers via emails and a public advisory website. Compared with control firms without being informed of their security vulnerability index, treatment firms improve their security over time, with a significant reduction of outgoing spam volume. A marginally significant improvement in reducing phishing hosting websites is also observed among non-web hosting treatment firms. The security improvement may be attributed to firms’ proactive reaction to the public security vulnerability information. Our study provides cybersecurity policy makers with useful insights to motivate firms to adopt better security measures
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Formulation of Metal-Organic Framework-Based Drug Carriers by Controlled Coordination of Methoxy PEG Phosphate: Boosting Colloidal Stability and Redispersibility.
Metal-organic framework nanoparticles (nanoMOFs) have been widely studied in biomedical applications. Although substantial efforts have been devoted to the development of biocompatible approaches, the requirement of tedious synthetic steps, toxic reagents, and limitations on the shelf life of nanoparticles in solution are still significant barriers to their translation to clinical use. In this work, we propose a new postsynthetic modification of nanoMOFs with phosphate-functionalized methoxy polyethylene glycol (mPEG-PO3) groups which, when combined with lyophilization, leads to the formation of redispersible solid materials. This approach can serve as a facile and general formulation method for the storage of bare or drug-loaded nanoMOFs. The obtained PEGylated nanoMOFs show stable hydrodynamic diameters, improved colloidal stability, and delayed drug-release kinetics compared to their parent nanoMOFs. Ex situ characterization and computational studies reveal that PEGylation of PCN-222 proceeds in a two-step fashion. Most importantly, the lyophilized, PEGylated nanoMOFs can be completely redispersed in water, avoiding common aggregation issues that have limited the use of MOFs in the biomedical field to the wet form-a critical limitation for their translation to clinical use as these materials can now be stored as dried samples. The in vitro performance of the addition of mPEG-PO3 was confirmed by the improved intracellular stability and delayed drug-release capability, including lower cytotoxicity compared with that of the bare nanoMOFs. Furthermore, z-stack confocal microscopy images reveal the colocalization of bare and PEGylated nanoMOFs. This research highlights a facile PEGylation method with mPEG-PO3, providing new insights into the design of promising nanocarriers for drug delivery
pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread.
The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.Wellcome Trust Senior Research Fellowship (219447/Z/19/Z),
Wellcome Trust Senior Research Fellowship (106207/Z/14/Z), Biotechnology and Biological Sciences Research Council Research Grant (BB/M021424/1),
Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (098406/Z/12/B)
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Zirconium-based metal-organic frameworks as drug delivery systems
Metal-organic frameworks (MOFs) are highly ordered porous materials made up of metal ions or clusters connected by organic linkers. The ease of surface modification for zirconium-based MOFs allows for a variety of designs for targeted therapeutic delivery. This thesis aims to understand and develop the Zr-based MOFs as a drug delivery system.
Firstly, a Zr-based MOF, NU-1000, was examined for its ability to encapsulate and deliver a large hydrophobic drug, fulvestrant, in breast cancer cells. NU-1000 was shown to be internalised by the human breast cancer cell line, MCF-7 cells, within 24 hours of incubation. Fulvestrant loaded NU-1000 reduced cancer cell proliferation and inhibited the expression of oestrogen receptors in MCF-7 cells. Although NU-1000 was able to load fulvestrant without defects in its crystalline structure, potential aggregations were observed, which could interfere MOFs’ colloidal stability for drug delivery applications.
In order to improve MOFs' colloidal stability, a panel of Zr-based MOFs were surface functionalised with methoxy polyethylene glycol (mPEG-PO3) followed by lyophilisation. These PEGylated nanoMOFs were able to maintain their hydrodynamic diameter in water and PBS compared to their non-PEGylated counterparts. PEGylated nanoMOFs also reduced cytotoxicity in vitro and were taken up by HeLa cells within 24 hours of incubation. Their ability to load, store and delivery drugs were tested using an anti-cancer drug, doxorubicin, where delayed drug-release capability was observed.
Since nanoparticles will almost inevitably be in contact with immune cells in the blood circulation system upon administration, human peripheral blood mononuclear cells were used to gain insights into PEGylated MOFs' interactions with the human immune system. PEGylated NU-901 has shown some toxicity towards monocytes but not in T cells, but no toxicity was observed for PEGylated UiO-66, ZIF-8 and PCN-222. The expression of inflammatory cytokines was also examined, where elevated IL-6 was observed for cells treated with PEGylated ZIF-8, a zinc-based MOFs.
In summary, Zr-based MOFs have shown many promises to deliver drugs in vitro. Their colloidal stability and biocompatibility can be significantly improved by controlled coordination of mPEG-PO3. This thesis also presented a comprehensive study on MOFs’ immunotoxicity with human primary immune cells, which offers new insights for their potential clinical applications
PFYOLOv4: An Improved Small Object Pedestrian Detection Algorithm
With the development of deep convolutional neural networks, the effect of pedestrian detection has been rapidly improved. However, there are still many problems in small target pedestrian detection, for example noise (such as light) interference, target occlusion, and low detection accuracy. In order to solve the above problems, based on YOLOv4 algorithm, this paper proposes an improved small target pedestrian detection algorithm named PF_YOLOv4. The algorithm is improved in three aspects on the basis of the YOLOv4 algorithm: firstly, a soft thresholding module is added to the residual structure of the backbone network to perform noise reduction process on interference factors, such as light to enhance the robustness of the algorithm; secondly, the depthwise separable convolution replaces the traditional convolution in the YOLOv4 residual structure, to reduce the number of network model parameters; finally, the Convolutional Block Attention Module (CBAM) is added after the output feature map of the backbone network to enhance of the network feature expression. Experimental results show that the PF_YOLOv4 algorithm outperforms most of the state-of-the-art algorithms in detecting small target pedestrians. The mean Average Precision (mAP) of the PF_YOLOv4 algorithm is 2.35% higher than that of the YOLOv4 algorithm and 9.67% higher than that of the YOLOv3 algorithm, while the detection speed is slightly higher than that of YOLOv4 algorithm
A new unpredictability-based RFID privacy model
Ind-privacy and unp-privacy, later refined to unp privacy, are two different classes of privacy models for RFID authentication protocols. These models have captured the major anonymity and untraceability related attacks regarding RFID authentication protocols with privacy, and existing work indicates that unp privacy seems to be a stronger notion when compared with ind-privacy. In this paper, we continue studying the RFID privacy models, and there are two folds regarding our results. First of all, we describe a new traceability attack and show that schemes proven secure in unp privacy may not be secure against this new and practical type of traceability attacks. We then propose a new unpredictability-based privacy model to capture this new type of attacks. Secondly, we show that this new model, where we called it the unp privacy, is stronger than both unp privacy and ind-privacy
A new unpredictability-based radio frequency identification forward privacy model and a provably secure construction
The privacy model of radio frequency identification (RFID) systems is for formalizing the adversarial capabilities and the security requirements of RFID anonymity and untraceability. Existing unpredictability-based privacy models such as unp-privacy, eunp-privacy, unp*-privacy, and unpτ-privacy have captured different kinds of practical attacks, and some of them also have mutual authentication included. However, forward privacy, which allows a tag to remain untraceable even after its corruption, is yet to be well captured in any unpredictability-based privacy models. In this paper, we describe some forward privacy-related attacks that can be launched against RFID tags in practice. We then propose a new unpredictability-based forward privacy model called unpfτ-privacy. It extends an existing one called unpτ-privacy, which has been shown to be stronger than ind-privacy, unp-privacy, and unp*-privacy. We also propose an RFID protocol that supports forward privacy and mutual authentication. We show that it can be proven secure in the unpfτ-privacy mode