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The evolution of Connected Vehicles (CVs) has introduced significant advancements in both in-vehicle and vehicle-edge platforms, creating a highly connected ecosystem. These advancements, however, have heightened exposure to cybersecurity risks. This work reviews emerging security challenges in the CV ecosystem from a new perspective, focusing on the integration of in-vehicle platforms such as the infotainment system and vehicle-edge platforms. By analyzing case studies such as Android Automotive, Message Queuing Telemetry Transport (MQTT), and the Robot Operating System (ROS), we identify the primary security threats, including malware attacks, data manipulation, and Denial of Service (DoS) attacks. The discussion extends to privacy concerns and the lack of trust-building mechanisms in CVs, highlighting how these gaps can be exploited. To mitigate these risks, we retrieve solutions drawn from the broader field of Internet of Things (IoT) security research, including Multi-Factor Authentication (MFA) and trust-based systems. The proposed framework aims to increase the trustworthiness of devices within the CV ecosystem. Finally, we identify future research directions in adaptive mechanisms and cross-domain security.

Abstract Background Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. The extent to which a plant-based diet lowers the serum levels of amino acids in patients with cancer is unclear. Methods Patients with metastatic breast cancer (n = 17) were enrolled in a clinical trial with an ad libitum whole food, plant-based diet for 8 weeks without calorie or portion restriction. Dietary changes by participants were monitored using a three-day food record. Serum was collected from participants at baseline and 8 weeks. Food records and serum were analyzed for metabolic changes. Results We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF were reduced in participants. The diet contained lower levels of essential and non-essential amino acids, except for arginine (glutamine and asparagine were not measured). Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids). Conclusions These findings provide a tractable approach to limiting amino acid levels in persons with cancer. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities. Trial registration The clinical trial was registered with ClinicalTrials.gov identifier NCT03045289 on 2017–02-07.

(1) Background: In this qualitative study, we investigated the implementation of an art-based observation workshop as a tool to improve visualization and interpretation skills in a cohort of first-year dental students (N = 109) in a dental anatomy course. (2) Methods: The art workshop was held once for a total of 60 min in the pre-clinical simulation laboratory, which is the regular teaching setting for the dental anatomy course. Visualization and interpretation skills were assessed before (pre-test) and after the art-based observation workshop (post-test). The pre- and post-tests contained five images that guided students to describe dental anatomy images. The pre- and post-test had different but similar images. Dental students accessed the pre- and post-tests on CANVAS and recorded their answers. After that, the audio recording files were analyzed and compared to determine the frequency of use of dental anatomy-specific nomenclature while answering the pre- and post-test. (3) Results: Our results demonstrate that students used dental anatomy-specific nomenclature more frequently after the intervention. (4) Conclusions: we have concluded that students’ use of dental anatomy nomenclature in the first-year dental anatomy curriculum is enhanced following an art-based intervention in a regular dental simulation laboratory.

Abstract Multiple neurotoxic proteinopathies co-exist within vulnerable neuronal populations in all major neurodegenerative diseases. Interactions between these pathologies may modulate disease progression, suggesting they may constitute targets for disease-modifying treatments aiming to slow or halt neurodegeneration. Pairwise interactions between superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43) and ubiquitin-binding protein 62/sequestosome 1 (p62) proteinopathies have been reported in multiple transgenic cellular and animal models of amyotrophic lateral sclerosis (ALS), however corresponding examination of these relationships in patient tissues is lacking. Further, the coalescence of all three proteinopathies has not been studied in vitro or in vivo to date. These data are essential to guide therapeutic development and enhance the translation of relevant therapies into the clinic. Our group recently profiled SOD1 proteinopathy in post-mortem spinal cord tissues from familial and sporadic ALS cases, demonstrating an abundance of structurally-disordered (dis)SOD1 conformers which become mislocalized within these vulnerable neurons compared with those of aged controls. To explore any relationships between this, and other, ALS-linked proteinopathies, we profiled TDP-43 and p62 within spinal cord motor neurons of the same post-mortem tissue cohort using multiplexed immunofluorescence and immunohistochemistry. We identified distinct patterns of SOD1, TDP43 and p62 co-deposition and subcellular mislocalization between motor neurons of familial and sporadic ALS cases, which we primarily attribute to SOD1 gene status. Our data demonstrate co-deposition of p62 with mutant and wild-type disSOD1 and phosphorylated TDP-43 in familial and sporadic ALS spinal cord motor neurons, consistent with attempts by p62 to mitigate SOD1 and TDP-43 deposition. Wild-type SOD1 and TDP-43 co-deposition was also frequently observed in ALS cases lacking SOD1 mutations. Finally, alterations to the subcellular localization of the three proteins were tightly correlated, suggesting close relationships between the regulatory mechanisms governing the subcellular compartmentalization of these proteins. Our study is the first to profile spatial relationships between SOD1, TDP-43 and p62 pathologies in post-mortem spinal cord motor neurons of ALS patients, previously only studied in vitro. Our findings suggest interactions between these three key ALS-linked proteins are likely to modulate the formation of their respective proteinopathies, and perhaps the rate of motor neuron degeneration, in ALS patients.

Abstract There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.MethodsSamples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.ResultsThere were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10−12), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0×10−7). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0×10−4).DiscussionAlthough telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.

Abstract Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlations between altered retrotransposon expression and the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a subset of patients. The risk of an individual developing ALS is dependent on an interaction of genetic variants and subsequent modifiers during life. These modifiers could include environmental factors, which can lead to epigenetic and genomic changes, such as somatic mutations, occurring in the neuronal cells that degenerate as the disease develops. There are more than 1 million L1 copies in the human genome today, but only 80–100 L1 loci in the reference genome are considered to be retrotransposition-competent (RC) and an even smaller number of these RC-L1s loci are highly active. We hypothesise that RC-L1s could affect normal cellular function through their mutagenic potential conferred by their ability to retrotranspose in neuronal cells and through DNA damage caused by the endonuclease activity of the L1-encoded ORF2 protein. To investigate whether either an increase in the genomic burden of RC-L1s or epigenetic changes to RC-L1s altering their expression, could play a role in disease development, we chose a set of seven well characterised genomic RC-L1 loci that were reported earlier to be highly active in a cellular L1 retrotransposition reporter assay or serve as major source elements for germline and/or somatic retrotransposition events. Analysis of the insertion allele frequency of five polymorphic RC-L1s, out of the set of seven, for their presence or absence, did not identify an increased number individually or when combined in individuals with the disease. However, we did identify reduced levels of methylation of RC-L1s in the motor cortex of those individuals with both familial and sporadic ALS compared to control brains. The changes to the regulation of the loci encompassing these RC-L1s demonstrated tissue specificity and could be related to the disease process.

Adoption by livestock producers of preventive non-lethal innovations forms a critical pathway towards human and large carnivore coexistence. However, it is impeded by factors such as socio-cultural contexts, governing institutions, and ‘perverse’ economic incentives that result in a ‘lock-in’ of lethal control of carnivores in grazing systems. In Australian rangelands, the dingo is the dominant predator in conflict with ‘graziers’ and is subjected to lethal control measures despite evidence indicating that its presence in agricultural landscapes can provide multiple benefits. Here we explore the barriers to the uptake of preventive innovations in livestock grazing through 21 in-depth interviews conducted with Australian graziers, researchers, and conservation and government representatives. Drawing on Donella Meadow’s leverage points for system change framework, we focus, primarily, on barriers in the ‘political sphere’ because they appear to form the greatest impediment to the adoption of non-lethal tools and practices. These barriers are then discussed in relation to characteristics of lock-in traps (self-reinforcement, persistence, path dependencies, and undesirability) to assess how they constrain the promotion of human–dingo coexistence.

Mono-N-alkylated primary oxalamide derivatives with different sized branched alkyl tail-groups were excellent low molecular weight gelators for a variety of different organic solvents with different polarities and hydrogen-bonding abilities. Solvent-gelator interactions were analyzed using Hansen solubility parameters, while 1H NMR and FTIR spectroscopy were used to probe the driving forces for the supramolecular gelation. The molecular structures of the twin tail-groups did not significantly affect the supramolecular gelation behavior in different solvents. However, for select solvents, the molecular structures of the tail-groups did have a significant effect on gel properties such as the critical gelator concentration, thermal stability, gel stiffness, gel strength, network morphology, and molecular packing. Finally, metabolic activity studies showed that the primary alkyl oxalamide gelators had no effect on the metabolic activity of mouse immune cells, which suggests that the compounds are not cytotoxic and are suitable for use in biomedical applications.

This reflective essay follows a faculty working group as they attempt to understand barriers to access to course materials through the scholarship of teaching and learning (SoTL). Through the workgroup’s research and collaboration with students in a problem-based learning course, the workgroup uncovered elements of the hidden curriculum in assumptions regarding course material procurement. The collaboration has served as the foundation for efforts to begin to transform the way that faculty on campus make use of textbooks and course materials in their courses. This transformation should make explicit to faculty that the utilization of course materials for all aspects of the course are often hidden pedagogy and must be made explicit by each instructor.

A new series of 5-alkylamido isophthalic acid (ISA) derivatives with varying single and twin alkyl chain lengths were designed and synthesized as potential supramolecular organogelators. 5-alkylamido ISAs with linear or branched alkyl tail-groups of different lengths were effective gelators for low polarity solvents. In particular, among the presented series, a derivative with a branched, 24 carbon atom tail-group behaves as a “supergelator” with up to twenty organic solvents forming gels that are highly stable over time. The gelation behavior was analyzed using Hansen solubility parameters, and the thermal stability and viscoelastic properties of select gels were characterized. Microscopy, spectroscopy, powder X-ray diffraction, and computer modeling studies were consistent with a hierarchical self-assembly process involving the formation of cyclic H-bonded hexamers via the ISA carboxylic acid groups, which stack into elementary fibers stabilized by H-bonding of the amide linker groups and π–π stacking of the aromatic groups. These new nanomaterials exhibited potential for the phase-selective gelation of oil from oil–water mixtures and dye uptake from contaminated water. The work expands upon the design and synthesis of supramolecular self-assembled nanomaterials and their application in water purification/remediation.

Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2). Notably, GPT2 engages activated glycolysis to drive the utilization of glutamine as a carbon source for TCA cycle anaplerosis in colon cancer cells. Our data indicate that the Warburg effect supports oncogenesis via GPT2-mediated coupling of pyruvate production to glutamine catabolism. Although critical to the cancer phenotype, GPT2 activity is dispensable in cells that are not fully transformed, thus pinpointing a metabolic vulnerability specifically associated with cancer cell progression to malignancy.

Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

Many historical narratives take for granted that a conservative “Reagan Revolution” took place in the 1980s. Though the gap between the reality and the rhetoric of the Reagan era has been subject to historiographical debate, the expression is still used today by Reagan critics and supporters alike. This article suggests that the use of revolutionary rhetoric by American conservatives is an ideological tool that tends to undermine the very meaning of revolution, thus reducing the number of politically viable alternatives that would prompt significant change. This hypothesis is explored in two ways: first, by analyzing how Ronald Reagan presented both his policy objectives and his role in American history in terms of “revolution”; and second, by measuring the extent of a selection of actual changes that took place during and after the 1980s, so as to determine how revolutionary Reagan’s legacy is.

Increased vulnerability to natural disasters has been associated with particular groups in the community. This includes those who are considered de facto vulnerable (children, older people, those with disabilities etc.) and those who own pets (not to mention pets themselves). The potential for reconfiguring pet ownership from a risk factor to a protective factor for natural disaster survival has been recently proposed. But how might this resilience-building proposition apply to vulnerable members of the community who own pets or other animals? This article addresses this important question by synthesizing information about what makes particular groups vulnerable, the challenges to increasing their resilience and how animals figure in their lives. Despite different vulnerabilities, animals were found to be important to the disaster resilience of seven vulnerable groups in Australia. Animal attachment and animal-related activities and networks are identified as underexplored devices for disseminating or ‘piggybacking’ disaster-related information and engaging vulnerable people in resilience building behaviors (in addition to including animals in disaster planning initiatives in general). Animals may provide the kind of innovative approach required to overcome the challenges in accessing and engaging vulnerable groups. As the survival of humans and animals are so often intertwined, the benefits of increasing the resilience of vulnerable communities through animal attachment is twofold: human and animal lives can be saved together.

In the United States, there is a nationwide shortage of bilingual teachers, but limited research on factors that contribute to their burnout and attrition. This exploratory multiple case study aimed to identify stressors unique to Spanish-English bilingual teachers and how they cope with these stressors. Interviews with two dual language immersion teachers over the course of four months revealed multiple, significant stressors including instructional demands unique to the students they serve, workplace bullying, and lack of administrative support. Although teachers adopted palliative coping strategies, their high sense of teaching efficacy and advocacy for their students were major mitigating factors to burnout. In addition to teaching efficacy, competence in pedagogy and workplace engagement were mitigating factors to well-being. Teachers avoided burnout because of their high eudaimonic well-being (the subjective experiences associated with living a life of virtue in pursuit of human excellence) coupled with direct cognitive and behavioral coping strategies leading to an increase in job-related well-being and retention. That is, their coping strategies moderated the impact of a district culture that was perceived as negative.

The ABCA1 protein mediates the transfer of cellular cholesterol across the plasma membrane to apolipoprotein A-I. Loss-of-function mutations in the ABCA1 gene induce Tangier disease and familial hypoalphalipoproteinemia, both cardiovascular conditions characterized by abnormally low levels of serum cholesterol, increased cholesterol in macrophages, and subsequent formation of vascular plaque. Increased intracellular cholesterol levels are also frequently found in cancer cells. Here, we demonstrate anticancer activity of ABCA1 efflux function, which is compromised following inhibition of ABCA1 gene expression by oncogenic mutations or cancer-specific ABCA1 loss-of-function mutations. In concert with elevated cholesterol synthesis found in cancer cells, ABCA1 deficiency allows for increased mitochondrial cholesterol, inhibits release of mitochondrial cell death-promoting molecules, and thus facilitates cancer cell survival, suggesting that elevated mitochondrial cholesterol is essential to the cancer phenotype.

The talking book is a type of assistive technology where original print text is audio recorded and marked-up in order to make it accessible for people with print-disabilities, such as visual impairments or dyslexia. In this pilot study, we explore the implications of remediating a written text, the script of Shakespeare’s King Lear, into spoken text. We compare two readings of the play: a talking book version; and a commercial audiobook recording. We examine intonation choices in an excerpt from the play in the two readings. The analysis shows significant variation in choices of intonation, and thus the meanings that are produced in the two versions, resulting in not one but two King Lear plays. One implication of such variation might be that different styles of narration demand different ways of reading. The results point to the need to explore how intonation makes meaning for actual talking book readers in situ, where meaning-potentials are realised through the interaction and encounter between the text, the reader(s), the social settings in which they are reading, and the material properties of talking books.

Humans and animals share their lives with one another in many ways. Pets, for example, are often considered valuable members of the family. They are invited into human hearts and homes, where they share routines, food and space. Animals are not only important to human waking lives. Some of them also share human beds – be it by invitation or invasion! Yet, little is known about human-animal co-sleeping practices and their impact on humans, animals and human-animal relations. This is the first paper to critically collate the scant and disparate research on human-animal co-sleeping. Given that the research is risk-centric, the paper turns to established theories on animal attachment to propose explanations for the continued practice of human-animal co-sleeping and its benefits. To redress an anthropocentric bias in the limited existing research, an agenda for further research is outlined on human-animal co-sleeping that considers humans, animals and the human-animal relation.

Genetic mutations of FUS have been linked to many diseases including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration. A primate specific and polymorphic retrotransposon of the SINE-VNTR-Alu (SVA) family is present upstream of the FUS gene. Here we have demonstrated that this retrotransposon can act as a classical transcriptional regulatory domain in the context of a reporter gene construct both in vitro in the human SK-N-AS neuroblastoma cell line and in vivo in a chick embryo model. We have also demonstrated that the SVA is composed of multiple distinct regulatory domains, one of which is a variable number tandem repeat (VNTR). The ability of the SVA and its component parts to direct reporter gene expression supported a hypothesis that this region could direct differential FUS expression in vivo. The SVA may therefore contribute to the modulation of FUS expression exhibited in and associated with neurological disorders including ALS where FUS regulation may be an important parameter in progression of the disease. As VNTRs are often clinical associates for disease progression we determined the extent of polymorphism within the SVA. In total 2 variants of the SVA were identified based within a central VNTR. Preliminary analysis addressed the association of these SVA variants within a small sporadic ALS cohort but did not reach statistical significance, although we did not include other parameters such as SNPs within the SVA or an environmental factor in this analysis. The latter may be particularly important as the transcriptional and epigenetic properties of the SVA are likely to be directed by the environment of the cell.

Every year, thousands of purebred domestic dogs are bred by registered dog breeders. Yet, little is known about the rearing environment of these dogs, or the attitudes and priorities surrounding breeding practices of these dog breeders. The objective of this study was to explore some of the factors that dog breeders consider important for stock selection, with a particular emphasis on issues relating to the dam. Two-hundred and seventy-four Australian purebred dog breeders, covering 91 breeds across all Australian National Kennel Club breed groups, completed an online survey relating to breeding practices. Most breeders surveyed (76%) reported specialising in one breed of dog, the median number of dogs and bitches per breeder was two and three respectively, and most breeders bred two litters or less a year. We identified four components, relating to the dam, that were considered important to breeders. These were defined as Maternal Care, Offspring Potential, Dam Temperament, and Dam Genetics and Health. Overall, differences were observed in attitudes and beliefs across these components, showing that there is variation according to breed/breed groups. In particular, the importance of Maternal Care varied according to dog breed group. Breeders of brachycephalic breeds tended to differ the most in relation to Offspring Potential and Dam Genetics and Health. The number of breeding dogs/bitches influenced breeding priority, especially in relation to Dam Temperament, however no effect was found relating to the number of puppies bred each year. Only 24% of breeders used their own sire for breeding. The finding that some breeders did not test for diseases relevant to their breed, such as hip dysplasia in Labrador Retrievers and German Shepherds, provides important information on the need to educate some breeders, and also buyers of purebred puppies, that screening for significant diseases should occur. Further research into the selection of breeding dams and sires will inform future strategies to improve the health and behaviour of our best friend.

This paper presents a brief history of the use of happiness and wellbeing rhetoric to bolster political support for the expansion of homeownership in the United States. Recent research has studied the impact of homeownership on various dimensions of wellbeing, such as crime, education, health, and civic participation. However, less attention has been given to the way in which policymakers have historically defined the pursuit of happiness as a gateway to a virtuous way of life thanks to homeownership. After exploring the relations between the right to pursue happiness and the right to own property in the American founding documents, the paper studies the happiness discourse that accompanied the rise of the suburban model of homeownership in the 20th century, followed by that which accompanied the policy shifts implemented in the late 20th century to conserve this model.