Vulnerable Point Research Articles

Integrating data-driven risk mitigation into supply chain planning and management

The supply chain disruptions that occurred during the COVID-19 pandemic, and continue to a lesser degree today, exposed vulnerabilities in many supply chains and increased C-level focus on supply chain resiliency. At the same time, the supply chain risk landscape is becoming more challenging to navigate with more points of vulnerability and an increase in the frequency of disruptive events. The semiconductor shortage that crippled automotive and electronics manufacturers was the most widely publicised example, but across industries material and component shortages, port congestion, severe weather events and other disruptions have taken their toll on business continuity and profitability. Supply chain organisations are taking a multifaceted approach to these challenges, including increasing inventory levels, diversifying supplier networks and re-engineering their supply chains. This paper focuses on using analytics-based risk mitigation tools to support decision making around these strategies and enable a more comprehensive and data-driven approach to supply chain risk. These tools integrate advanced technologies such as predictive analytics, artificial intelligence (AI) and virtualisation to improve risk identification, model complex supply chains during planning and enable proactive management during disruptive events. The paper reviews the current risk landscape, outlines how risk mitigation tools have evolved to meet current needs and the capabilities available in the current generation. It describes how the tools are used in procurement to improve supplier identification and management, in planning to design risk out of the network where possible, and in transportation management to adapt in real time to minimise the impact of disruptive events on delivery and production schedules. Finally, it outlines how these tools work with existing systems and processes to embed an analytics-based approach to risk mitigation into supply chain management.

DIGITAL ENTITIES COMMUNICATION WITHIN A BLOCKCHAIN-ENABLED INTELLIGENT TRANSPORT SYSTEM

Nowadays the blockchain is considered to be an integral part of intelligent transport systems. Intelligence of a transport systems allows to increase road safety, wisely utilize systems’ resources and provide additional services to participants. However, blockchain implementations for intelligent transport systems must be adopted to the peculiarities of such systems. This work analyzes existing blockchain solutions, their features, advantages, drawbacks, and presents a consortium type blockchain implementation for an intelligent transport system. This implementation includes a two-layered architecture of digital entities interaction, consideration for digital entities distribution over the layers, consensus mechanism selection and its implementation, trust model considerations, and a block structure for the proposed blockchain implementation. The article also brings the solution to the single point of failure vulnerability of the proposed blockchain system. Thus, the paper covers key aspects of a blockchain design for an intelligent transport system.

Systemic risk assessment using complex networks approach: Evidence from the Brazilian (re)insurance market

In this paper, we assess the systemic risk of the Brazilian (re)insurance market using static and dynamic complex network approach, where the companies are connected to each other through co-insurance, reinsurance and retrocession transactions. We found that some local reinsurers and non-life insurers act as bridges connecting the local and international markets. Furthermore, the Brazilian (re)insurance market is robust to extreme scenarios of insolvency, although there are points of vulnerability: a few local reinsurers and non-life insurers. Finally, this study contributes to the creation of a stress testing framework that relies solely on publicly available data.

Whole Watershed-based Estimation of FEWS Installation Site Using UAV Photogrammetry

For small rivers and reservoirs, a flood early warning system (FEWS) is generally used to prepare for sudden flood events whose impact is augmented from homonized environment and climate change. Currently, a FEWS requires the installation of a water gauge, typically on a bridge. This is a limitation of the FEWS owing to the possibility of existence of areas that are more vulnerable than the bridge. Therefore, to analyze the flood risk over the entire target basin, a procedure to install a FEWS was proposed. First, unmanned aerial vehicle (UAV)-based photogrammetry information is analyzed to preselect flood-prone areas. Second, further investigation including the ground surveying is followed for the preselected areas. Finally, the flood amount is estimated and the UAV photogrammetry information for issuing the alarm levels of the FEWS. For this purpose, Malgol Reservoir, a reservoir with high-risk level from floods, containing residential areas was selected as the current study area. Eleven flood-prone points were identified by analyzing the UAV photogrammetry information. Then, the flooding point with the lowest flood volume among the 11 points was selected as the most vulnerable point; this section was located at 464 m from the Malgol Reservoir spillway in the downstream direction. The warning alarm for the basin-wide FEWS could be issued according to the embankment of the most vulnerable section. This ensured the safety over the entire basin including the reservoir and its downstream area. The proposed procedure can overcome the limitations of the current bridge water level-based analysis by employing UAV-photogrammetry information of the entire basin and considering the entire flood-prone cross-sections.

Exploring interdependencies, vulnerabilities, gaps and bridges in care transitions of patients with complex care needs using the Functional Resonance Analysis Method

BackgroundHospital discharge is a complex process encompassing multiple interactions and requiring coordination. To identify potential improvement measures in care transitions for people with complex care needs, intra- and inter-organisational everyday work needs to be properly understood, including its interdependencies, vulnerabilities and gaps. The aims of this study were to 1) map coordination and team collaboration across healthcare and social care organisations, 2) describe interdependencies and system variability in the discharge process for older people with complex care needs, and 3) evaluate the alignment between discharge planning and the needs in the home.MethodsData were collected through participant observations, interviews, and document review in a region of southern Sweden. The Functional Resonance Analysis Method (FRAM) was used to model the discharge process and visualise and analyse coordination of care across healthcare and social care organisations.ResultsHospital discharge is a time-sensitive process with numerous couplings and interdependencies where healthcare professionals’ performance is constrained by system design and organisational boundaries. The greatest vulnerability can be found when the patient arrives at home, as maladaptation earlier in the care chain can lead to an accumulation of issues for the municipal personnel in health and social care working closest to the patient. The possibilities for the personnel to adapt are limited, especially at certain times of day, pushing them to make trade-offs to ensure patient safety. Flexibility and appropriate resources enable for handling variability and responding to uncertainties in care after discharge.ConclusionsMapping hospital discharge using the FRAM reveals couplings and interdependencies between various individuals, teams, and organisations and the most vulnerable point, when the patient arrives at home. Resilient performance in responding to unexpected events and variations during the first days after the return home requires a system allowing flexibility and facilitating successful adaptation of discharge planning.

Home-specific performance and the digital staging of the domestic in Flanker Origami

ABSTRACT This paper discusses home as a stage and its intersection with new technologies through an autoethnographic recollection and analysis of practice research, whose processes and methods are entangled with both digital and domestic environments on the virtual stage of Flanker Origami, a live online performance on Zoom devised by Organic Theatre. Premiered as part of the digital programme of the Edinburgh Festival Fringe 2021, the performance is discussed as a case study of shifts in practice driven by the COVID19 pandemic in the real home of the two devisers/performers. This enquiry introduces and discusses home-specific performance as a practice research methodology, which exploits the deep nexus between home, identity and gender in the digital staging of the domestic in Flanker Origami. Analysing online training, hybrid scenography and digital performativity specific to the performers’ home, this practice-based investigation evaluates the benefits and challenges of developing online theatre in a situation of social confinement. The conclusion evidences that home as a digital stage was instrumental in reconfiguring notions of self and authenticity in performance processes driven by the pandemic, while creatively reframing the familiar and the domestic to expand and innovate artistic practice at a critical point of social and personal vulnerability.

Analisis Keamanan Infrastruktur Jaringan Berdasarkan Cyber Kill Chain Framework

This study concentrates on examining the security of network infrastructure using the cyber kill chain framework approach. The research is conducted within a company operating in network security services. In its operations, it offers a Virtual Private Cloud (VPC) containing various crucial information such as applications, internal data, client data, and product demos. Despite the attractive features of cloud computing, there are significant threats as well. Handling attacks cannot be swiftly and efficiently executed, resulting in temporary operational unavailability until the attacks are resolved. This research delves into the security of the company's infrastructure by testing several points of vulnerability exploited by malicious parties. The cyber kill chain framework approach is employed to systematically assess the company's infrastructure. The study reveals that certain issues have been adequately detected; however, security gaps persist, as evidenced by the testing conducted and the inadequate response from the company's security systems.

Vulnerable point detection and repair against adversarial attacks for convolutional neural networks

Vulnerable point detection and repair against adversarial attacks for convolutional neural networks

The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.

DNA replication is a tightly controlled process that ensures the faithful duplication of the genome. However, DNA damage arising from both endogenous and exogenous assaults gives rise to DNA replication stress associated with replication fork slowing or stalling. Therefore, protecting the stressed fork while prompting its recovery to complete DNA replication is critical for safeguarding genomic integrity and cell survival. Specifically, the plasticity of the replication fork in engaging distinct DNA damage tolerance mechanisms, including fork reversal, repriming, and translesion DNA synthesis, enables cells to overcome a variety of replication obstacles. Furthermore, stretches of single-stranded DNA generated upon fork stalling trigger the activation of the ATR kinase, which coordinates the cellular responses to replication stress by stabilizing the replication fork, promoting DNA repair, and controlling cell cycle and replication origin firing. Deregulation of the ATR checkpoint and aberrant levels of chronic replication stress is a common characteristic of cancer and a point of vulnerability being exploited in cancer therapy. Here, we discuss the various adaptive responses of a replication fork to replication stress and the roles of ATR signaling that bring fork stabilization mechanisms together. We also review how this knowledge is being harnessed for the development of checkpoint inhibitors to trigger the replication catastrophe of cancer cells.

Transferring critical pediatric patients from emergency department to intensive care: A quality improvement initiative

BackgroundTransfer of care, moving hospitalized patients between care areas, is a critical point of vulnerability for healthcare organizations. Patient information handoff is an essential activity occurring frequently in hospital environments. Poor communication has been linked with adverse events and poor patient outcomes. This evidence-based quality project aimed to enhance the handoff process between the Emergency Department (ED) and Pediatric Intensive Care Unit (PICU) by standardizing transfer of care steps. This was accomplished through customizing a reporting tool to contain all the information the receiving department deemed necessary for safe patient care. MethodsA customized situation, background, assessment, recommendation (SBAR) form handoff tool was developed for ED to PICU transfers. This SBAR tool included information that PICU nurses identified as critical to transfer of care. Nurse perceptions were surveyed pre- and post-implementation. Patient safety event reports were tracked to evaluate events related to transfer of care before and after the practice change. FindingsAn increased number of PICU nurses agreed the customized handoff tool was complete and organized. Additionally, more nurses agreed that handoff gave all information needed to safely care for critically ill patients transferred from the ED. Lastly, bedside patient checks increased, and patient safety events related to transfer of care decreased. DiscussionThis project demonstrated that implementation of a standardized transfer of care process coupled with a customized handoff tool increased PICU nurse perceptions that handoff was organized, and all information needed to safely care for critically ill patients was conveyed. Application to practiceTransfer of care processes between the ED and PICU should be standardized. The use of customized tools may improve information exchange between nurses and ensure that all vital patient information is communicated.

Abstract A013: Minor intron splicing is critical for survival of lethal prostate cancer

Abstract The role of major intron splicing in PCa is well established and highly investigated. However, the equally important and impactful minor spliceosome (MiS) and minor intron splicing have remained underexplored in PCa. Here for the first time, we show that minor intron containing genes (MIGs) are enriched as direct interactors of PCa-causing genes and that their expression levels correspond to different stages of PCa progression. Accordingly, we show that U6atac expression and MiS activity reinforces cell growth and correlates with PCa progression. Consequently, highly proliferative PCa cells are strongly susceptible to siU6atac-mediated MiS inhibition. In this sense, siU6atac is significantly more efficient in lowering the tumor burden of castration resistant prostate cancer (CRPC) cells and organoids than the current state-of-the-art combination therapy. Mechanistically, we show that inhibition of the MiS through siU6atac causes minor and major intron mis-splicing and aberrant expression of MIG and non-MIG transcripts and encoded proteins, which enriches for MAPK activity, DNA repair, and cell cycle. Single cell-RNAseq confirms cell cycle defects and lineage dependency on the MiS from primary to CRPC and neuroendocrine PCa. Finally, our data provides strong evidence that Androgen receptor signaling functions as a regulator of MiS activity throughout PCa disease progression to CRPC while p38MAPK influences MiS activity in neuroendocrine PCa. Furthermore, we discovered that MiS inhibition in neuroendocrine PCa shifts alternative splicing in favor of canonical REST1 isoform thereby blocking lineage plasticity and progression to lethal therapy resistant PCa. This finding positions the MiS as yet another disruptor of a crucial molecular pathway underpinning the emergence of CRPC and neuroendocrine PCa. Based on these findings we posit that the MiS may be a common denominator of prominent PCa driver genes and a driving factor of advanced lethal PCa. We hypothesize that the MiS represents a point of vulnerability in therapy-resistant PCa. Citation Format: Anke Augspach, Mark Andrew Rubin, Rahul Kanadia. Minor intron splicing is critical for survival of lethal prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A013.

Constructing a "Border" with China: The Russian Approach

Abstract: The Russian and Soviet governments believed the border to be a social and political construct. They often described and considered it as a foreign policy issue and a point of military vulnerability. In the course of 70 years of Sino-Russian relations since 1949, the border turned from a porous imperial fringe to a line of defense, a zone of economic growth, and a zone of economic anxiety. Throughout this evolution process, the Russian central government failed to grant agency to the local authorities and indigenous communities. The article argues that the current Russian federal government entrusts the local government with two conflicting goals in the borderlands: building strong cross-border ties and maintaining a "strong vertical of power" with top-down management and absolute supremacy of national security matters.

Vulnerabilities and weaknesses points in the Iranian-(Israeli) conflict: a strategic readability include the changing of regional environment

The Iran-(Israel) conflict has had a great impact on the regional environment in the Middle East. This conflict has been going on for decades and has been characterized by mistrust and permanent hostility. The Iran-(Israel) conflict has led to a growing sense of insecurity in the region, as the two sides have engaged in proxy wars and cyberattacks. And other forms of aggression, which constituted in this conflict hypotheses or points of vulnerability and weakness in the regional environment, as other countries in the region drifted into the conflict and got involved in crises as a result of this conflict. In the end, it became highly influential and highly reflective of what the strategic reading of the conflict’s dialectics aspires to.

Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.

The structure of DNA replication forks is preserved by TIMELESS (TIM) in the fork protection complex (FPC) to support seamless fork progression. While the scaffolding role of the FPC to couple the replisome activity is much appreciated, the detailed mechanism whereby inherent replication fork damage is sensed and counteracted during DNA replication remains largely elusive. Here, we implemented an auxin-based degron system that rapidly triggers inducible proteolysis of TIM as a source of endogenous DNA replication stress and replisome dysfunction to dissect the signaling events that unfold at stalled forks. We demonstrate that acute TIM degradation activates the ATR-CHK1 checkpoint, whose inhibition culminates in replication catastrophe by single-stranded DNA accumulation and RPA exhaustion. Mechanistically, unrestrained replisome uncoupling, excessive origin firing, and aberrant reversed fork processing account for the synergistic fork instability. Simultaneous TIM loss and ATR inactivation triggers DNA-PK-dependent CHK1 activation, which is unexpectedly necessary for promoting fork breakage by MRE11 and catastrophic cell death. We propose that acute replisome dysfunction results in a hyper-dependency on ATR to activate local and global fork stabilization mechanisms to counteract irreversible fork collapse. Our study identifies TIM as a point of replication vulnerability in cancer that can be exploited with ATR inhibitors.

Orbitocranial Penetration of Ball Bearing Gun Trauma: A Prospective Human Cadaveric Study.

Objective We completed a prospective human cadaveric study to determine the ability of a ball bearing (BB) pellet to penetrate the orbit and/or surrounding structures. Methods A single trained sergeant officer discharged an alloy steel air rifle to eight cadaver orbits from four adult human cadaver heads. Five BB pellets each were aimed at three locations (caruncle, upper eyelid, or lower eyelid) at 10 cm and 1 m, and then less specifically, at the orbital region for 3- and 5-m distances. Computed tomography (CT) of the cadaver heads was performed. Final locations of BB pellets are divided into three categories: intracranial, surrounding orbital structures including the pterygopalatine fossa and infratemporal fossa, and orbit. Results Of 40 BB pellets, 37 penetrated soft tissue and were visualized on CT: 19 (51%) rested in the intracranial space, 17 (46%) in surrounding orbital structures, and 1 (3%) within the orbit. The deepest position of a pellet was in the parietal lobe, and most superficial location anterior to the frontal bone. Pellets discharged from 1 m were more likely to rest in the intracranial space compared with those from 10 cm ( p < 0.001), 3 m ( p = 0.011), and 5 m ( p = 0.004). The distance of discharge was associated with final pellet location ( p = 0.001). Conclusion BB guns should be considered dangerous and potentially deadly when aimed at the orbit. Although the thick calvarium can protect the intracranial space from BB penetration, the orbit may be a vulnerable entry point with relatively low resistance, allowing penetration of the intracranial and periorbital spaces.

Progress and challenges in RET-targeted cancer therapy.

The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Vulnerability and economic loss evaluation model of a typical group structure considering empirical field inspection data

Evaluating the earthquake economic loss of building clusters is an essential index to measure regional seismic risk and resilience. This study developed a rapid financial loss evaluation model based on the empirical vulnerability parameters of the group structure. The quantitative failure parameters used to evaluate the seismic vulnerability of regional group structures are optimized comprehensively, and a loss evaluation model considering the economic vulnerability index is innovatively proposed. The empirical vulnerability database (field survey data of 212 destructive earthquakes in China from 1975 to 2013 (98,916.841 × 104 m2 buildings)) of typical structures is established. An updated model for structural economic loss assessment is proposed. Using the proposed innovation model and probability statistical method, the economic loss evaluation model and database of typical group structures based on the economic vulnerability index are developed. Using the nonlinear Gaussian distribution and the actual cumulative damage quantification method, the economic loss evaluation comparison model and mean value calculation model of five typical buildings considering the empirical group structural vulnerability database are performed. Ultimately, combined with the proposed innovative quantitative model, the economic vulnerability index matrix (database) and point cloud of typical group structures of 212 destructive earthquakes in China are calculated. The proposed model can cooperate with the macroseismic intensity standard to realize the rapid economic loss assessment of typical buildings. The results of this study can contribute to the evaluation of the economic losses of building clusters in multiple macroseismic intensity regions.

Strategies to Aid Successful Transition of Adolescents with Congenital Heart Disease: A Systematic Review

The majority of patients born with congenital heart disease (CHD) need lifelong surveillance with serial clinical attendance and examinations. However, loss of follow-up (namely no documented follow-up for 3 years or more) is a recognised common problem since it is often related to remarkable worsening in the health of CHD patients with increased morbidity and mortality. Transitioning from paediatric to adult care has proven to be the most vulnerable point in the care of these subjects. As such, a systematic review was carried out to ask the following questions: What is the percentage of loss of follow-up worldwide? Are there regional fluctuations in the percentage? Is there a link between loss of follow-up and the complexity of CHD? What strategies should be employed to lower the risk of discontinuity in care? The most recent worldwide averaged loss of follow-up is 26.1%, with significant fluctuations across continents and countries. This percentage is even higher (31.9%) when one includes all untraceable patients, presuming that they are not having any cardiac follow-up. The highest discontinuity of care was reported in the USA and in patients with simple CHD. Planning the rules of transition seems to be one of the most reliable tools to minimise the number of CHD patients who are lost in transition. Recalling patients, with general practitioners who are crucial in readdressing half of the lost to follow-up CHD patients to adult CHD specialists, and a good relationship between paediatric cardiologists and the adult CHD team are two other valuable strategies in aiding successful transition.

Enhancing IoT Device Security through Blockchain Technology: A Decentralized Approach

The rapidly growing Internet of Things (IoT) devices pose significant security challenges due to their decentralized nature, limited computing power and reliance on centralized security models Traditional IoT security systems often face issues such as single point of failure, limited scalability and vulnerability to distributed denial of service (DDoS) attacks They also require la-doable security solutions. Blockchain technology has emerged as a potential solution due to its decentralized, immutable and transparent nature, providing advanced security for IoT environments. This study proposes a blockchain-based security strategy aimed at mitigating security risks in IoT networks. The system uses smart contracts to perform basic functions such as device authentication, data integrity verification, and access control. The main goal of the research is to develop IoT security solutions that increase device reliability speeds, reduce power consumption, reduce connection latency, and maximize network availability. The results of the survey show significant improvements over existing IoT security measures. The blockchain-based system achieves device authentication time of 0.1 to 2 seconds, 95% detection rate for unauthorized access, and supports 1000 devices, double the capacity of traditional models Also, the system reduces energy consumption 0.5–2 joules per transaction and transaction latency to 1–5 seconds , making it suitable for real-time IoT applications.