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Current researches on NDP flooding behavior detection mainly focus on detecting RA flooding and NS flooding behaviors, and there is insufficient flooding detection for other messages of the NDP protocol. Moreover, traditional threshold rule detection methods suffer from poor dynamics and low accuracy, while most of the Al-based detection methods can only perform binary classification detection, and there are still challenges in performing multi-classification detection. In short, there is a lack of corresponding research in multi-classification flooding detection of all messages of NDP protocol. Therefore, this paper proposed a multi-classification detection framework for NDP protocol flooding behaviors, and proposed a flooding behavior detection method for NDP protocol based on time interval characteristics. The framework constructed the first multiclassification dataset for NDP flooding detection through the processes of traffic collection and data processing, it compared and used 5 machine learning and 5 deep learning algorithms to train the detection model. The experimental results show that the detection accuracy of the XGBOOST algorithm in machine learning can reach 99.18%, and the detection accuracy of the Transformer algorithm in deep learning can reach 98.45%. Compared with the existing detection methods, the accuracy is higher. Meanwhile, the detection framework can detect 9 types of flooding behaviors for all 5 types of messages of NDP protocol and classify the flooding behaviors into multiple types. [ABSTRACT FROM AUTHOR]

Internet Protocol version 6 (IPv6) is the most recent iteration of IP, designed to accommodate hundreds of thousands of devices with unique IP addresses. IPv6 introduces new features, such as the Neighbor Discovery Protocol (NDP) and Address Auto-configuration Scheme. For its effective operation, IPv6 relies on several protocols, including ICMPv6, which carries significant responsibilities. Similar to IPv4, IPv6 is susceptible to various attacks, including newer types like DDoS attacks executed via ICMPv6 messages, posing serious security and financial threats. Consequently, an Intrusion Detection System (IDS) is essential to safeguard against these attacks. IDS continuously evolve to incorporate features that can accurately detect such threats. However, feature selection strategies, particularly bio-inspired algorithms, often yield incorrect subsets of features. During machine learning processes, these inaccuracies impede the detection accuracy of DDoS attacks using ICMPv6. Many Optimization Search Algorithms become trapped in local minima and fail to consider multi-objective approaches, resulting in suboptimal feature selection. To address this, optimizing a bio-inspired algorithm within an IPv6 network has been proposed. Specifically, hybridizing the MFPA algorithm with the PSO algorithm is suggested to enhance detection accuracy. The selected features are used to train the dataset with a Support Vector Machine (SVM) classifier. The proposed approach is evaluated using the ICMPv6 dataset on various attacks, demonstrating superior classification accuracy of 97.99 %. It also reduced the number of features from 19 to 8, showcasing its efficiency. [ABSTRACT FROM AUTHOR]

The majority of local IPv6 networks continue to remain insecure and vulnerable to neighbor spoofing attacks. The Secure Neighbor Discovery (SEND) standard and its concomitant Cryptographically Generated Addressing (CGA) scheme were accepted by large standard bodies to codify practical mitigations. SEND and CGA have never seen widespread adoption due to their complexities, obscurity, costs, compatibility issues, and continued lack of mature implementations. In light of their poor adoption, research since their standardization has continued to find new perspectives and proffer new ideas. The orthodox solutions for securing Neighbor Discovery have historically struggled to successfully harmonize three core ideals: simplicity, flexibility, and privacy preservation. This research introduces Voucher-Based Addressing, a low-configuration, low-cost, and high-impact alternative to IPv6 address generation methods. It secures the Neighbor Discovery address resolution process while remaining simple, highly adaptable, indistinguishable, and privacy-focused. Applying a unique concoction of cryptographic key derivation functions, link-layer address binding, and neighbor consensus on the parameters of address generation, the resolved address bindings are verifiable without the need for complex techniques that have hindered the adoption of canonical specifications. [ABSTRACT FROM AUTHOR]

Internet Protocol version 6 (IPv6) is the most recent iteration of IP, designed to accommodate hundreds of thousands of devices with unique IP addresses. IPv6 introduces new features, such as the Neighbor Discovery Protocol (NDP) and Address Auto-configuration Scheme. For its effective operation, IPv6 relies on several protocols, including ICMPv6, which carries significant responsibilities. Similar to IPv4, IPv6 is susceptible to various attacks, including newer types like DDoS attacks executed via ICMPv6 messages, posing serious security and financial threats. Consequently, an Intrusion Detection System (IDS) is essential to safeguard against these attacks. IDS continuously evolve to incorporate features that can accurately detect such threats. However, feature selection strategies, particularly bio-inspired algorithms, often yield incorrect subsets of features. During machine learning processes, these inaccuracies impede the detection accuracy of DDoS attacks using ICMPv6. Many Optimization Search Algorithms become trapped in local minima and fail to consider multi-objective approaches, resulting in suboptimal feature selection. To address this, optimizing a bio-inspired algorithm within an IPv6 network has been proposed. Specifically, hybridizing the MFPA algorithm with the PSO algorithm is suggested to enhance detection accuracy. The selected features are used to train the dataset with a Support Vector Machine (SVM) classifier. The proposed approach is evaluated using the ICMPv6 dataset on various attacks, demonstrating superior classification accuracy of 97.99 %. It also reduced the number of features from 19 to 8, showcasing its efficiency.

The majority of local IPv6 networks continue to remain insecure and vulnerable to neighbor spoofing attacks. The Secure Neighbor Discovery (SEND) standard and its concomitant Cryptographically Generated Addressing (CGA) scheme were accepted by large standard bodies to codify practical mitigations. SEND and CGA have never seen widespread adoption due to their complexities, obscurity, costs, compatibility issues, and continued lack of mature implementations. In light of their poor adoption, research since their standardization has continued to find new perspectives and proffer new ideas. The orthodox solutions for securing Neighbor Discovery have historically struggled to successfully harmonize three core ideals: simplicity, flexibility, and privacy preservation. This research introduces Voucher-Based Addressing, a low-configuration, low-cost, and high-impact alternative to IPv6 address generation methods. It secures the Neighbor Discovery address resolution process while remaining simple, highly adaptable, indistinguishable, and privacy-focused. Applying a unique concoction of cryptographic key derivation functions, link-layer address binding, and neighbor consensus on the parameters of address generation, the resolved address bindings are verifiable without the need for complex techniques that have hindered the adoption of canonical specifications.

The exponential increase in Internet-facing devices in the last decade has resulted in IP address exhaustion due to the limitations of the existing IPv4 address space. Therefore, the Internet Engineering Task Force engineered a new version of the Internet protocol known as Internet Protocol Version 6 (IPv6) to resolve the issue. However, IPv6 is highly dependent on the neighbor discovery protocol (NDP), which, unfortunately, has well-known vulnerabilities in its underlying messaging protocol, the Internet Control Message Protocol version 6. So, the NDP flaws leave the IPv6 network open to many security threats and attacks, including man-in-the-middle, spoofing, and denial-of-service attacks, which are the most annoying attack at the network layer. Unfortunately, one of the critical issues plaguing the existing anomaly-based detection system is the effectiveness of detecting NDP-based DDoS attacks, which requires urgent attention. This paper suggests a system to find network traffic patterns that are not normal that are caused by NDP-based attacks. It does this by teaching neural networks how to recognize network attack patterns using the backpropagation algorithm. The proposed system is a big step forward from where the field is now because it uses a complex neural network algorithm to create an NDP anomaly-based detection system. Using a real dataset to test the proposed system's performance shows that it can find NDP anomalies with a 99.95% success rate, a 99.92% precision rate, a 99.98% recall rate, an F1-Score of 99.98%, and a 0.040% false positive rate. Also, the proposed approach shows better results compared to other existing approaches. [ABSTRACT FROM AUTHOR]

Familial exudative vitreoretinopathy (FEVR) is a severe inherited disease characterized by defective retinal vascular development. With genetic and clinical heterogeneity, FEVR can be inherited in different patterns and characterized by phenotypes ranging from moderate visual defects to complete vision loss. This study was conducted to unravel the genetic and functional etiology of a 4-month-old female FEVR patient. Targeted gene panel and Sanger sequencing were utilized for genetic evaluation. Luciferase assays, western blot, quantitive real-time PCR, and immunocytochemistry were performed to verify the functional defects in the identified candidate variant. Here, we report a 4-month-old girl with bilateral retinal folds and peripheral avascularization, and identified a novel frameshift heterozygous variant c.37dup (p.Leu13ProfsTer13) in NDP. In vitro experiments revealed that the Leu13ProfsTer13 variant led to a prominent decrease in protein levels instead of mRNA levels, resulting in compromised Norrin/β-catenin signaling activity. Human androgen receptor assay further revealed that a slight skewing of X chromosome inactivation could partially cause FEVR. Thus, the pathogenic mechanism by which heterozygous frameshift or nonsense variants in female carriers cause FEVR might largely result from a loss-of-function variant in one X chromosome allele and a slightly skewed X-inactivation. Further recruitment of more FEVR-affected females carrying NDP variants and genotype–phenotype correlation analysis can ultimately offer valuable information for the prognosis prediction of FEVR. [ABSTRACT FROM AUTHOR]

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases. [ABSTRACT FROM AUTHOR]

Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X‐linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno‐associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease. Synopsis: Norrie disease is a genetic condition causing blindness and progressive deafness. Successful AAV‐mediated gene augmentation therapy in a mouse model showed that the Norrie phenotype is responsive to treatment after the onset of degeneration, preventing further progression of hearing loss.Injection of AAV9 NDP gene therapy in neonatal Ndp‐KO mice prevented retinal dysfunction and hearing loss in adult mice and rescued retinal and cochlea vasculature abnormalities.Treatment of older Ndp‐KO mice also preserved hearing by preventing the loss of sensory hair cells in the cochlea.RNAseq analyses showed that dysregulated gene expression patterns in the Ndp‐KO cochlea were normalised by AAV9 NDP gene therapy. [ABSTRACT FROM AUTHOR]

Pediatric retinal vascular diseases are a spectrum with overlapping phenotypes and related genes. Retinal vascular development is biphasic. Vasculogenesis is responsible for the formation of primordial vessels leading to the four major arcades in the posterior retina. Angiogenesis, which is vascular endothelial growth factor dependent, is responsible for the formation of new vessels through budding from existing vessels, forming the peripheral vessels, increasing the capillary density of the central retina, and forming the superficial and deep capillary plexus. This process is controlled by WNT signaling, which is important for cell proliferation, division, and migration. Disorders of WNT signaling, such as familial exudative vitreoretinopathy (FEVR), have overlapping clinical findings. Conversely, pathogenic variants in some of the FEVR-related genes are reported in conditions such as retinopathy of prematurity (ROP), persistent fetal vasculature, and Coats disease. The various overlapping features and underlying genetic basis in the pathogenesis of pediatric retinal vascular developmental diseases suggest that genetic variants may provide a framework or a background for these conditions, upon which further insults can affect the development at any phase (such as prematurity and oxygenation in ROP), influencing and determining the final phenotype. [ABSTRACT FROM AUTHOR]

Abstract Deafness affects 5% of the world's population, yet there is a lack of treatments to prevent hearing loss due to genetic causes. Norrie disease is a recessive X‐linked disorder, caused by NDP gene mutation. It manifests as blindness at birth and progressive sensorineural hearing loss, leading to debilitating dual sensory deprivation. To develop a gene therapy, we used a Norrie disease mouse model (Ndptm1Wbrg), which recapitulates abnormal retinal vascularisation and progressive hearing loss. We delivered human NDP cDNA by intravenous injection of adeno‐associated viral vector (AAV)9 at neonatal, juvenile and young adult pathological stages and investigated its therapeutic effects on the retina and cochlea. Neonatal treatment prevented the death of the sensory cochlear hair cells and rescued cochlear disease biomarkers as demonstrated by RNAseq and physiological measurements of auditory function. Retinal vascularisation and electroretinograms were restored to normal by neonatal treatment. Delivery of NDP gene therapy after the onset of the degenerative inner ear disease also ameliorated the cochlear pathology, supporting the feasibility of a clinical treatment for progressive hearing loss in people with Norrie disease.

The distribution of wireless network systems challenges the communication security of Internet of Things (IoT), and the IPv6 protocol is gradually becoming the main communication protocol under the IoT. The Neighbor Discovery Protocol (NDP), as the base protocol of IPv6, includes address resolution, DAD, route redirection and other functions. The NDP protocol faces many attacks, such as DDoS attacks, MITM attacks, etc. In this paper, we focus on the communication-addressing problem between nodes in the Internet of Things (IoT). We propose a Petri-Net-based NS flooding attack model for the flooding attack problem of address resolution protocols under the NDP protocol. Through a fine-grained analysis of the Petri Net model and attacking techniques, we propose another Petri-Net-based defense model under the SDN architecture, achieving security for communications. We further simulate the normal communication between nodes in the EVE-NG simulation environment. We implement a DDoS attack on the communication protocol by an attacker who obtains the attack data through the THC-IPv6 tool. In this paper, the SVM algorithm, random forest algorithm (RF) and Bayesian algorithm (NBC) are used to process the attack data. The NBC algorithm is proven to exhibit high accuracy in classifying and identifying data through experiments. Further, the abnormal data are discarded through the abnormal data processing rules issued by the controller in the SDN architecture, to ensure the security of communications between nodes. [ABSTRACT FROM AUTHOR]

When drivers need to take over a vehicle during shared autonomy, the standard driving postures based on their body size are the basis of non-driving posture (NDP) motion reconstruction. This study focused on the prediction of standard driving postures using a deep learning neural network (DNN) method. Firstly, the main factors influencing the standard driving posture were extracted through qualitative analysis, and their weights were analyzed using an orthogonal test method. Based on this, the main parameters of the standard driving posture prediction model were determined. Secondly, the point cloud data of typical vehicles on the market were obtained through laser scanning. After extracting the key input and output parameters required for the prediction model through point cloud data processing and feature matching, a dataset of standard driving postures was established. Finally, a supervised learning model using a deep learning neural network (DNN) was established to predict the standard driving postures of different drivers under different vehicle package layouts. This method allows for the quick evaluation of corresponding standard driving postures during non-driving activities, laying the foundation for risk-level assessment of non-driving postures and motion reconstruction in vehicle takeover. The results show that the trained algorithm model can predict standard driving postures with high accuracy and robustness.

Objective To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics.Patients and methods Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants.Results Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density.Conclusions Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.

GDP, even net of obsolescence (NDP) has to be considered only as an expense (investment is an expense; consumption is an expense). As an entrepreneur you will never manage your investments by looking only the expenses; it is clear you will make decisions on gains. As a person, will you look at the expenses you make to acquire stocks or at the gains? Thus it must have been clear that you will never manage a country by costs, so why do governments use GDP (consumption plus investment spending) to drive their economy? Governments should manage gains: wealth created, which is the full result you get from all these expenses. [ABSTRACT FROM AUTHOR]

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder; however, the known FEVR‐associated variants account for approximately only 50% cases. Currently, the pathogenesis of most reported variants is not well studied, we aim to identify novel variants from FEVR‐associated genes and perform a comprehensive functional analysis to uncover the pathogenesis of variants that cause FEVR. Using targeted gene panel and Sanger sequencing, we identified six novel and three known variants in TSPAN12 and NDP. These variants were demonstrated to cause significant inhibition of Norrin/β‐catenin pathway by dual‐luciferase reporter assay and western blot analysis. Structural analysis and co‐immunoprecipitation revealed compromised interactions between missense variants and binding partners in the Norrin/β‐catenin pathway. Immunofluorescence and subcellular protein extraction were performed to reveal the abnormal subcellular trafficking. Additionally, over‐expression of TSPAN12 successfully enhanced the Norrin/β‐catenin signaling activity by strengthening the binding affinity of mutant Norrin with FZD4 or LRP5. Together, these observations expanded the spectrum of FEVR‐associated variants for the genetic counseling and prenatal diagnosis of FEVR, as well providing a potential therapeutic strategy for the treatment of FEVR. [ABSTRACT FROM AUTHOR]

Purpose: To describe a novel case of Norrie disease and X-linked Kabuki syndrome caused by a microdeletion encompassing multiple genes on the X chromosome. Observations: A 3-day-old boy born at full term had bilateral retrolental fibrovascular plaques. Surgery with lensectomy and vitrectomy revealed bilateral, closed funnel retinal detachments consistent with a clinical diagnosis of Norrie disease. In addition, the baby had congenital heart defects, hearing loss, and dysmorphic facies. His mother carried a clinical diagnosis of Kabuki syndrome. Genetic testing of the baby revealed an Xp11.3 microdeletion that included the NDP and KDM6A genes, confirming the baby had both Norrie disease and X-linked Kabuki syndrome. The mother was found via ultrawide-field fluorescein angiography to have asymptomatic peripheral retinal vascular anomalies, consistent with NDP-associated familial exudative vitreoretinopathy (FEVR). Conclusions and importance: This is the first reported case of Norrie disease together with X-linked Kabuki syndrome. Contiguous gene deletions may explain some of the variable systemic involvement in Norrie disease.

To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR). A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described. Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone. The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring. [ABSTRACT FROM AUTHOR]

To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics. Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants. Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease. We identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic). The proportion of variants was the highest for the LRP5 gene. FZD4 variants may be responsible for greater FEVR severity than LRP5 variants. [ABSTRACT FROM AUTHOR]

Abstract Background Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR. Methods All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant. Results Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families. Conclusions These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Internet Protocol version 6 (IPv6) is envisioned as the cornerstone for future internet connectivity and information technology (IT) expansion. Due to its enormous address pool, extendable headers, high level of security, and mobility, IPv6 is positioned as the next-generation Internet Protocol. NDP is an integral component of IPv6 since it resolves addresses, locates routers, and finds duplicated addresses in a local-link network. Because NDP is based on the premise that all nodes in the network are trustworthy, it is subject to a variety of attacks, including Denial of Service (DoS) on Duplicate Address Detection (DAD) attacks (aka. DoS-on-DAD), Address Resolution-based attacks, Router Advertisement (RA) based attacks, and Redirect attacks. This paper proposes an NDP security (NDPsec) mechanism based on the Ed25519 digital signature to authenticate IPv6 hosts to prevent unauthorized devices from joining the network. The proposed NDPsec mechanism is evaluated and compared to Secure NDP (SeND), Match-Prevention, and Trust-ND mechanisms. The performance is measured in terms of processing time, traffic overhead, and resilience against network-based attacks. The results obtained from the experiments showed that NDPsec successfully prevented cyberattacks, with approximately 144% less processing time and over 50% less traffic overhead compared to SeND (the default security mechanism for NDP protocol). The proposed NDPsec mechanism has remarkable superiority in terms of resilience against attacks compared to Match-Prevention and Trust-ND mechanisms.

Much attention has been paid to the changing class cleavage that structured political conflict in the twentieth century. In contrast to most advanced democracies, class voting has traditionally been weak in Canada. Using the entire series of the Canadian Election Study (1965–2019), we find the historic pattern of working-class voting for the New Democratic Party (NDP) held outside of Quebec in recent elections, before suddenly falling off in 2019. Starting in 2004, we find a clear and distinct trend where the working class has increased its support for the Conservatives. Although greater partisan sorting is occurring over the economy, cultural issues such as moral traditionalism and anti-immigration are now significant drivers of working-class Conservative support. The findings carry important implications for class-party relationships and reveal that Canada, despite its comparatively weak nativist cleavage, is not immune from the tensions social democratic parties have recently experienced in maintaining cross-class coalitions amid socio-economic structural changes. [ABSTRACT FROM AUTHOR]

A Norrie disease protein gene (NDP) variant, c.174 + 1G > A, was found in a Chinese family through next-generation sequencing and verified with Sanger sequencing. A case of Norrie disease was reported in the first child, and the symptoms were consistent with the results of gene sequencing. The child's mother, who was pregnant at the time, was found to be a carrier of the identified pathogenic variant. To determine if the fetus carried the same disease-causing variant, prenatal examination and prenatal diagnosis were conducted. The fetus had biocular vitreous abnormalities and complete retinal abnormalities. Genetic testing showed that the fetus had maternally inherited the NDP gene variant found in the proband. It was concurrently confirmed that the NDP gene variant led to the deletion of 246 bp at the 3' end of exon 2, resulting in the deletion of the initiation codon and the occurrence of disease. Our study suggests that the diagnosis of rare diseases through next-generation sequencing, combined with prenatal ultrasound and prenatal diagnosis, can help families with known familial genetic diseases. Furthermore, the findings of this study broaden the known genetic spectrum of Norrie disease. [ABSTRACT FROM AUTHOR]

The Canadian party system experienced a period of remarkable transition between 2006 and 2015, with the New Democratic Party (NDP) and Liberals trading places as the main competitor to the Conservatives. While national-level explanations are often used to explain this volatility, William Cross's research has shown that local association revitalization played a central role in the Liberals' 2015 resurgence. This article examines the relationship between NDP local spending and success between 2006 and 2015. It shows that the NDP was consistently outspent by its opponents overall but that it often had a spending advantage in marginal ridings. As a result, this article finds little evidence that the NDP's local spending disadvantage cost the NDP seats, even though it finds a positive correlation between NDP local spending and NDP vote share. [ABSTRACT FROM AUTHOR]

Abstract Objective Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein–protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.

The distribution of wireless network systems challenges the communication security of Internet of Things (IoT), and the IPv6 protocol is gradually becoming the main communication protocol under the IoT. The Neighbor Discovery Protocol (NDP), as the base protocol of IPv6, includes address resolution, DAD, route redirection and other functions. The NDP protocol faces many attacks, such as DDoS attacks, MITM attacks, etc. In this paper, we focus on the communication-addressing problem between nodes in the Internet of Things (IoT). We propose a Petri-Net-based NS flooding attack model for the flooding attack problem of address resolution protocols under the NDP protocol. Through a fine-grained analysis of the Petri Net model and attacking techniques, we propose another Petri-Net-based defense model under the SDN architecture, achieving security for communications. We further simulate the normal communication between nodes in the EVE-NG simulation environment. We implement a DDoS attack on the communication protocol by an attacker who obtains the attack data through the THC-IPv6 tool. In this paper, the SVM algorithm, random forest algorithm (RF) and Bayesian algorithm (NBC) are used to process the attack data. The NBC algorithm is proven to exhibit high accuracy in classifying and identifying data through experiments. Further, the abnormal data are discarded through the abnormal data processing rules issued by the controller in the SDN architecture, to ensure the security of communications between nodes.

Aims and Rationale: The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR). However, little is known about whether the nature or location of the NDP variant is predictive of severity. In this systematic review we summarise all reported NDP variants and draw conclusions about whether the nature of the NDP variant is predictive of the severity of the resulting ocular pathology and associated hearing loss and intellectual disability. Findings: 201 different variants in the NDP gene have been reported as disease-causing. The pathological phenotype that may result from a disease-causing NDP variant is quite diverse but generally comprises a consistent cluster of features (retinal hypovascularisation, exudation, persistent foetal vasculature, tractional/exudative retinal detachment, intellectual disability and hearing loss) that vary predictably with severity. Previous reviews have found no clear pattern in the nature of NDP mutations that cause either FEVR or Norrie disease, with the exception that mutations affecting cysteine residues have been associated with Norrie Disease and that visual loss amongst patients with Norrie disease tends to be more severe if the NDP mutation results in an early termination of translation as opposed to a missense related amino acid change. A key limitation of previous reviews has been variability in the case definition of Norrie disease and FEVR amongst authors. We thus reclassified patients into two groups based only on the severity of their retinal disease. Of the reported pathogenic variants that have been described in more than one patient, we found that any given variant caused an equivalent severity of retinopathy each time it was reported with very few exceptions. We therefore conclude that specific NDP mutations generally result in a consistent retinal phenotype each time they arise. Reports by different authors of the same variant causing either FEVR or Norrie disease conflict primarily due to variability in the authors' respective case definitions rather than true differences in disease severity. [ABSTRACT FROM AUTHOR]

Norrie disease (ND; OMIM 310600), a rare X-linked recessive genetic disorder, is characterized by congenital blindness and occasionally, sensorineural hearing loss, and developmental delay. The congenital blindness of ND patients is almost untreatable; thus, hearing is particularly important for them. However, the mechanism of hearing loss of ND patients is unclear, and no good treatment is available except wearing hearing-aid. Therefore, revealing the mechanism of hearing loss in ND patients and exploring effective treatment methods are greatly important. In addition, as a serious monogenic genetic disease, convenient gene identification method is important for ND patients and their family members, as well as prenatal diagnosis and preimplantation genetic diagnosis to block intergenerational transmission of pathogenic genes. In this study, a Norrie family with two male patients was reported. This pedigree was ND caused by large fragment deletion of NDP (norrin cystine knot growth factor NDP) gene. In addition to typical severe ophthalmologic and audiologic defects, the patients showed new pathological features of endolymphatic hydrops (EH), and they also showed acoustic nerves abnormal as described in a very recent report. PCR methods were developed to analyze and diagnose the variation of the family members. This study expands the understanding of the clinical manifestation and pathogenesis of ND and provides a new idea for the treatment of patients in this family and a convenient method for the genetic screen for this ND family. [ABSTRACT FROM AUTHOR]

Background: Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR. Methods: All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant. Results: Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families. Conclusions: These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR. [ABSTRACT FROM AUTHOR]

In IPv6, the DAD (Duplicate Address Detection) protocol detects duplicate addresses configured on the local link. Once the IPv6 address is auto configured on an IPv6 enabled host, the host verifies that its address is unique using the DAD procedure. This protocol works when hosts can communicate. If the DAD protocol fails to detect duplication, both the hosts assign the same link-local address. The neighbor discovery protocol verifies the generated address is unique or already exists on the local link. This process is known as Duplicate Address Detection (DAD). This process has critical security vulnerability and is susceptible to many attacks, especially allowing hackers to perform denial of service attacks (DOS). With that, the new devices will not be able to join the network. Researchers have developed various techniques to address DAD vulnerabilities, such as NDPMon, SEND, and Software-defined networking, SAVA, and extension headers. These techniques appear to be neither robust nor performance-oriented with DAD's DOS detection and mitigation techniques. We have proposed a novel approach that detects and mitigates DOS attacks consuming low bandwidth and overhead. [ABSTRACT FROM AUTHOR]

Aims and Rationale: The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR). However, little is known about whether the nature or location of the NDP variant is predictive of severity. In this systematic review we summarise all reported NDP variants and draw conclusions about whether the nature of the NDP variant is predictive of the severity of the resulting ocular pathology and associated hearing loss and intellectual disability.Findings: 201 different variants in the NDP gene have been reported as disease-causing. The pathological phenotype that may result from a disease-causing NDP variant is quite diverse but generally comprises a consistent cluster of features (retinal hypovascularisation, exudation, persistent foetal vasculature, tractional/exudative retinal detachment, intellectual disability and hearing loss) that vary predictably with severity. Previous reviews have found no clear pattern in the nature of NDP mutations that cause either FEVR or Norrie disease, with the exception that mutations affecting cysteine residues have been associated with Norrie Disease and that visual loss amongst patients with Norrie disease tends to be more severe if the NDP mutation results in an early termination of translation as opposed to a missense related amino acid change. A key limitation of previous reviews has been variability in the case definition of Norrie disease and FEVR amongst authors. We thus reclassified patients into two groups based only on the severity of their retinal disease. Of the reported pathogenic variants that have been described in more than one patient, we found that any given variant caused an equivalent severity of retinopathy each time it was reported with very few exceptions. We therefore conclude that specific NDP mutations generally result in a consistent retinal phenotype each time they arise. Reports by different authors of the same variant causing either FEVR or Norrie disease conflict primarily due to variability in the authors’ respective case definitions rather than true differences in disease severity.

Norrie disease (ND; OMIM 310600), a rare X-linked recessive genetic disorder, is characterized by congenital blindness and occasionally, sensorineural hearing loss, and developmental delay. The congenital blindness of ND patients is almost untreatable; thus, hearing is particularly important for them. However, the mechanism of hearing loss of ND patients is unclear, and no good treatment is available except wearing hearing-aid. Therefore, revealing the mechanism of hearing loss in ND patients and exploring effective treatment methods are greatly important. In addition, as a serious monogenic genetic disease, convenient gene identification method is important for ND patients and their family members, as well as prenatal diagnosis and preimplantation genetic diagnosis to block intergenerational transmission of pathogenic genes. In this study, a Norrie family with two male patients was reported. This pedigree was ND caused by large fragment deletion of NDP (norrin cystine knot growth factor NDP) gene. In addition to typical severe ophthalmologic and audiologic defects, the patients showed new pathological features of endolymphatic hydrops (EH), and they also showed acoustic nerves abnormal as described in a very recent report. PCR methods were developed to analyze and diagnose the variation of the family members. This study expands the understanding of the clinical manifestation and pathogenesis of ND and provides a new idea for the treatment of patients in this family and a convenient method for the genetic screen for this ND family.

In this work, thickness of AsF5 intercalation doped, Multilayer Graphene Nanoribbon (MLGNR) interconnects is optimized by minimizing various performance and power metrics (i.e. crosstalk-induced signal transmission delay, noise parameters, Noise-delay product (NDP), Energy-delay product (EDP), Power-delay product (PDP) and Noise bandwidth ratio (NBWR)). For perfectly and nearly specular MLGNRs (i.e. specularity index, P = 1 and P = 0.8 respectively), the optimal thicknesses for minimizing the crosstalk-induced delay are 25 nm and 100 nm for intermediate and global level MLGNR interconnects, respectively. However, it is observed that perfectly and nearly specular MLGNRs are immune to noise for thickness less than 40 nm at intermediate level and 200 nm at global level interconnects. They outperform Cu in terms of signal transmission delay, noise width and noise area at both levels of interconnect. But in terms of peak crosstalk noise, Cu is better than all types of MLGNR interconnects. When we talk about NDP, EDP and NBWR, MLGNR thickness optimizes at 25 nm for intermediate level and 100 nm for global level. As far as power dissipation is concerned, perfectly and nearly specular, intermediate and global level MLGNRs are many times better than copper in the whole range of its thickness which can be optimized by minimizing its PDP at 100 nm irrespective of the level of interconnects. It can be inferred from the simulated results that global level MLGNR interconnects are amenable to scaling, whereas intermediate level interconnects have adverse effects of scaling. [ABSTRACT FROM AUTHOR]

Abstract Background Hereditary ophthalmic pathology is a genetically heterogeneous group of diseases that occur either as an isolated eye disorder or as a symptom of hereditary syndromes (chromosomal or monogenic). Thus, a diagnostic search in some cases of ophthalmic pathology can be time- and cost-consuming. The most challenging situation can arise when prenatal diagnosis is needed during an ongoing pregnancy. Case presentation A family was referred to the Research Centre for Medical Genetics (RCMG) for childbirth risk prognosis at 7–8 week of gestation because a previous child, a six-year-old boy, has congenital aniridia, glaucoma, retinal detachment, severe psychomotor delay, and lack of speech and has had several ophthalmic surgeries. The affected child had been previously tested for PAX6 mutations and 11p13 copy number variations, which revealed no changes. Considering the lack of pathogenic changes and precise diagnosis for the affected boy, NGS sequencing of clinically relevant genes was performed for the ongoing pregnancy; it revealed a novel hemizygous substitution NM_000266.3(NDP):c.385G > T, p.(Glu129*), in the NDP gene, which is associated with Norrie disease (OMIM #310600). Subsequent Sanger validation of the affected boy and his mother confirmed the identified substitution inherited in X-linked recessive mode. Amniotic fluid testing revealed the fetus was hemizygous for the variant and lead to the decision of the family to interrupt the pregnancy. Complications which developed during the termination of pregnancy required hysterectomy due to medical necessity. Conclusions Clinical polymorphism of hereditary ophthalmic pathology can severely complicate establishment of an exact diagnosis and make it time- and cost-consuming. NGS appears to be the method-of-choice in complicated cases, and this could substantially hasten the establishment of a diagnosis and genetic risk estimation.

Purpose: Norrie disease is a rare X-linked recessive vitreoretinopathy. Variants of the NDP gene are associated with this condition. This case reports aims to demonstrate the variations of clinical presentations and exam findings of this disease. Observations: A retrospective chart review of the patient's ocular and systemic findings and imaging results was performed. The patient had received genetic testing, including mutational analysis of targeted genes associated with retrolental masses. The patient had a comprehensive eye exam for bilateral leukocoria, demonstrating large retrolental masses, anterior polar cataracts, stretched ciliary processes, and roving eye movements. B-scan ultrasonography and magnetic resonance imaging indicated total, funnel-shaped retinal detachments, which is a unique retinal configuration in Norrie disease. Genetic testing confirmed deletion of the coding region of all three exons in the NDP gene, which confirmed Norrie disease. He has not shown any extraocular involvement to date. Conclusions and Importance: This is a case demonstrating the association between deletion of the coding region NDP gene and Norrie disease. The phenotypical variation of this disease warrants further studies of genotype-phenotype correlations and mutations of the NDP gene.

Objective: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein–protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease. [ABSTRACT FROM AUTHOR]

Small Objects Networks is a wireless network that we used to define any type of network. These networks use the IPv6 protocol for communication. Indeed, it allows, via standardized and unified electronic identification systems, to identify directly, unambiguously physical objects and thus ability to retrieve, store, transfer, and process related data. In such a network, the IPv6 Neighbor Discovery protocol is used by an object to communicate with its neighbors in order to establish the relationship between the IPv6 (Internet Protocol Version 6) address and that MAC. Since the NDP (Neighbor Discovery Protocol) messages are relatively long and large, several operating parameters, such as power consumption, are affected accordingly which reduces the lifetime of the connected objects and adversely affects the proper functioning of the network. The goal of our paper is to reduce the use of these messages in 6lowpan networks to minimize energy consumption and maximize network lifetime... The results of our simulation show a big reduction of the signals used in the network compared to the standard NDP-RFC4861. Our algorithm also shows better performance in terms of energy consumption. [ABSTRACT FROM AUTHOR]

Purpose: To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/β-catenin genes., Design: This was a multicenter, cross-sectional, observational, and genetic study., Subjects: Two-hundred eighty-one probands with FEVR were studied., Methods: Whole-exome sequence and/or Sanger sequence was performed for the Norrin/β-catenin genes, the FZD4 , LRP5 , TSPAN12 , and NDP genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/β-catenin genes., Main Outcome Measures: The phenotype associated with or without pathogenic variants of the Norrin/β-catenin genes., Results: One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the FZD4 , 42 with the LRP5 , 10 with the TSPAN12 , and 12 with the NDP gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, P < 0.0001), progression during infancy (75.0% vs. 53.8%, P  = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, P  = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, P  = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, P  < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, P  = 0.0346). Nine probands with NDP variants had features different from probands with typical Norrin/β-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease., Conclusions: The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/β-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Objective: This research aimed to assess the efficacy and safety of pembrolizumab (PBL) combined with albumin-bound paclitaxel (ab-Pac) and nedaplatin (NDP) for advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 47 ESCC patients were administered PBL or NDP on day 1 and ab-Pac on days 1 and 8, every 21 days for one cycle. Tumor and toxicities were evaluated every two cycles and every cycle, respectively. Results: The objective response rate was 68.1% and the disease control rate was 100%. The median follow-up was 16.7 months; median progression-free and overall survival were 12.6 and 19.9 months, respectively. Conclusion: The combination of PBL with ab-Pac and NDP proved to be an effective and safe treatment regimen for advanced ESCC.

A three-step numerical procedure has been developed, which facilitates the conversion of NDP energy spectra into lithium concentration depth profiles for thin-film Li-ion batteries. The procedure is based on Monte Carlo modeling of the energy loss of charged particles (ions) in the solid media, using the publically available SRIM/TRIM software. For the energy-to-depth conversion, the battery stack has been split into finite volume elements. Each finite volume element becomes a source of ions according to the employed nuclear reaction. Ions loos energy when they move across the battery stack towards the detector. The as-obtained simulated spectra have been compared with the experimentally measured spectra. The thicknesses of the battery stack layers were estimated by minimizing the deviation between the simulated and measured spectra. Subsequently, a relation between the average energy of detected ions and the depth of the corresponding finite volume element, yielding a calibration function, was used to relate that particular part of the spectra with the depth of its source. At the final stage, a Bayesian estimator was used to find the distribution of lithium at a particular depth. The developed procedure was applied to a practically relevant case study of Si immobilization in the LPO electrolyte of all-solid-state thin-film batteries. It is shown that the lithium immobilization process in the LPO electrolyte is responsible for the battery degradation process. [ABSTRACT FROM AUTHOR]

Background: Familial exudative vitreoretinopathy (FEVR) is an inheritable retinal vascular disease, which often leads to severe vision loss and blindness in children. However, reported mutations can only account for 50–60% of patients with FEVR. The purpose of this study was to identify novel frizzled class receptor 4 (FZD4) and Norrin cystine knot growth factor NDP (NDP) mutations in a cohort of Indian patients with FEVR by whole-exome sequencing. Methods: We performed data filtering and bioinformatic analyses. Results: Two novel heterozygous mutations in FZD4 gene were identified, each in two different families: c.1499_1500del [p.500_500del] and c.G296C [p.C99S]. One novel mutation in NDP in another family was identified: c.A256G [p.K86E]. All FZD4 mutations affected conserved amino acid residues and were absent in 1000 control individuals. To assess the effect of these FZD4 mutations on the biological activity of the protein, we introduced each FZD4 mutation into FZD4 cDNA by the site-directed mutagenesis techniques. A Norrin/beta-catenin pathway-based luciferase reporter assay revealed that the c.1499_1500del failed to activate the luciferase reporter; in contrast, compared with the wild-type FZD4 protein, the, c.G296C [p.C99S] mutation exhibited increased luciferase reporter activity. Conclusion: Our study found two novel FZD4 mutations, with opposite effects regarding functional expression levels in Indian patients with FEVR and expands on the mutational spectrum of FZD4 in Indian FEVR patients. [ABSTRACT FROM AUTHOR]

Stateless Address Autoconfiguration (SLAAC) is one of the novel features introduced in IPv6 Neighbor Discovery Protocol (NDP) providing for self-configuration of nodes and supplementing the reduction of operational and deployment cost of networks. Although self-configuration elevates the idea of autonomy for network, it has also introduced vulnerabilities that require substantial solutions. The SLAAC is pivoted on the presumption that network consists of authentic and entrusted nodes, however with inception of public sector wireless networks; any node can affix to the link with trivial authentication and situation changes radically. Although some security extensions like IPsec or SeND have been proposed, but these security protocols have been reported to have serious limitations like complex cryptographic algorithms which negate their adoption. This paper revisits the stateless auto configuration process and discusses its inherent vulnerabilities. The paper surveys existing research and available defense mechanisms available to protect SLAAC. The paper also suggests some guidelines from existing literature which can further promote and supplement the research to secure the auto configuration process. Finally, a novel technique is proposed for securing IPv6 link layer communication against DoS and Man-in-the-Middle attack which can be used as an alternate approach for CGA and SeND protocol. [ABSTRACT FROM AUTHOR]