Stoics against stoics in Cudworth's "A Treatise of Freewill"

In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS

Stretch controlled shading capabilities of special elastomeric silicone films

A hitherto unexploited effect: the reversible stretch-induced change of translucency and transparency of certain silicone materials is experimentally investigated with regard to an application in a new type of shading system for biaxial bent, free-form building envelopes. In a first step the silicone raw materials showing the effect are processed into membrane shape and the stretch-dependent optical characteristics of the silicone film samples are examined. Shading effects are measured during cyclic and long term uniaxial tension tests. For multiaxial loading conditions, as appearing in planar biaxial tension tests with cross shaped specimens and bulge tests with inflated circular specimens, optical inhomogeneity effects due to locally varying elongations are documented. Further results concerning a variable transparency depending on the distance of the observer and an object behind the membrane are discussed. A conceptual application of the materials into translucent facades for shading purposes is presented. The closed cavity concept of planar stretched films located between window screens and the implementation of silicone films as inflatable shading structures are discussed. Furthermore, the advantages of silicone films in these kinds of cladding types are pointed out, as typical problems i.e. fogging and high-temperature stability pose no major issue

The Virtual Insect Brain protocol: creating and comparing standardized neuroanatomy

BACKGROUND: In the fly Drosophila melanogaster, new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain are rapidly accumulating. These diverse investigations on the function of the insect brain use gene expression patterns that can be visualized and provide the means for manipulating groups of neurons as a common ground. To take advantage of these patterns one needs to know their typical anatomy. RESULTS: This paper describes the Virtual Insect Brain (VIB) protocol, a script suite for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira, version 3.x (Mercury Inc.) [1]. Besides its backbone, a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel) the VIB protocol provides an elaborate data management system for data administration. The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at an intuitively usable graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well. CONCLUSION: Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila. The script suite is freely available at [2

Global trends in pediatric burn injuries and care capacity from the World Health Organization Global Burn Registry

BackgroundBurn injuries are a major cause of death and disability globally. The World Health Organization (WHO) launched the Global Burn Registry (GBR) to improve understanding of burn injuries worldwide, identify prevention targets, and benchmark acute care. We aimed to describe the epidemiology, risk factors, and outcomes of children with burns to demonstrate the GBR's utility and inform needs for pediatric burn prevention and treatment.MethodsWe performed descriptive analyses of children age ≤ 18 years in the WHO GBR. We also described facility-level capacity. Data were extracted in September of 2021.ResultsThere were 8,640 pediatric and adult entries from 20 countries. Of these, 3,649 (42%) were children (0–18 years old) from predominantly middle-income countries. The mean age was 5.3 years and 60% were boys. Children aged 1–5 years comprised 62% (n = 2,279) of the cohort and mainly presented with scald burns (80%), followed by flame burns (14%). Children >5 years (n = 1,219) more frequently sustained flame burns (52%) followed by scald burns (29%). More than half of pediatric patients (52%) sustained a major burn (≥15% total body surface area) and 48% received surgery for wound closure during the index hospitalization. Older children had more severe injuries and required more surgery. Despite the frequency of severe injuries, critical care capacity was reported as “limited” for 23% of pediatric patients.ConclusionsChildren represent a large proportion of people with burn injuries globally and often sustain major injuries that require critical and surgical intervention. However, critical care capacity is limited at contributing centers and should be a priority for healthcare system development to avert preventable death and disability. This analysis demonstrates that the GBR has the potential to highlight key epidemiological characteristics and hospital capacity for pediatric burn patients. To improve global burn care, addressing barriers to GBR participation in low- and low-middle-income countries would allow for greater representation from a diversity of countries, regions, and burn care facilities

Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress

Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson’s disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H(2)O(2) or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed “mitospheres”. Mitosphere formation mechanistically depended on the fission factor Drp1, and was paralleled by reduced mitochondrial fusion. Furthermore, mitospheres were linked to a decrease in mitochondrial activity, and preceded Caspase3 activation. Even though fragmentation of dysfunctional mitochondria is considered to be a prerequisite for mitochondrial degradation, mitospheres were not degraded via Parkin-mediated mitophagy. Importantly, we provide compelling evidence that aSyn prevents mitosphere formation and reduces apoptosis under OS. In contrast, aSyn did not protect against Rotenone, which led to a different, previously described donut-shaped mitochondrial morphology. Our findings reveal a dichotomic role of aSyn in mitochondrial biology, which is linked to distinct types of stress-induced mitochondrial fragmentation. Specifically, aSyn may be part of a cellular defense mechanism preserving neural mitochondrial homeostasis in the presence of increased OS levels, while not protecting against stressors directly affecting mitochondrial function

New flexible protective coating for printed smart textiles

In the field of food packaging, the addition of exfoliated layered silicates in polymers has been established to improve the polymers’ gas barrier properties. Using these polymers as coatings to protect smart textiles from oxidation and corrosion while maintaining their textile properties should significantly extend their lifetime and promote their market penetration. The aim of this study was to print new polymer dispersions containing layered silicates to protect screen-printed conductive structures, and to test the resulting samples. For this, appropriate printing parameters were determined by statistical design of experiments. According to these results, conductive structures were printed and protected with the selected coating. The abrasion resistance and the continuity of the protective layer of the printed samples were then measured. A continuous protective coating of approximately 70–80 µm thickness was applied on a conductive structure. The printed samples showed a very high resistance to abrasion (unchanged by 85,000 abrasion cycles) while remaining flexible and presenting a lower water vapor permeability (<2.5 g/m² d) than the coatings commonly used in the textile field.Arbeitsgemeinschaft industrieller Forschungsvereinigunge

Identifying Determinants of Cullin Binding Specificity Among the Three Functionally Different Drosophila melanogaster Roc Proteins via Domain Swapping

BACKGROUND: Cullin-dependent E3 ubiquitin ligases (CDL) are key regulators of protein destruction that participate in a wide range of cell biological processes. The Roc subunit of CDL contains an evolutionarily conserved RING domain that binds ubiquitin charged E2 and is essential for ubiquitylation. Drosophila melanogaster contains three highly related Roc proteins: Roc1a and Roc2, which are conserved in vertebrates, and Roc1b, which is specific to Drosophila. Our previous genetic data analyzing Roc1a and Roc1b mutants suggested that Roc proteins are functionally distinct, but the molecular basis for this distinction is not known. METHODOLOGY/PRINCIPAL FINDINGS: Using co-immunoprecipitation studies we show that Drosophila Roc proteins bind specific Cullins: Roc1a binds Cul1-4, Roc1b binds Cul3, and Roc2 binds Cul5. Through domain swapping experiments, we demonstrate that Cullin binding specificity is strongly influenced by the Roc NH(2)-terminal domain, which forms an inter-molecular beta sheet with the Cullin. Substitution of the Roc1a RING domain with that of Roc1b results in a protein with similar Cullin binding properties to Roc1a that is active as an E3 ligase but cannot complement Roc1a mutant lethality, indicating that the identity of the RING domain can be an important determinant of CDL function. In contrast, the converse chimeric protein with a substitution of the Roc1b RING domain with that of Roc1a can rescue the male sterility of Roc1b mutants, but only when expressed from the endogenous Roc1b promoter. We also identified mutations of Roc2 and Cul5 and show that they cause no overt developmental phenotype, consistent with our finding that Roc2 and Cul5 proteins are exclusive binding partners, which others have observed in human cells as well. CONCLUSIONS: The Drosophila Roc proteins are highly similar, but have diverged during evolution to bind a distinct set of Cullins and to utilize RING domains that have overlapping, but not identical, function in vivo