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"Webster, Scott"
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Educating for meaningful lives : through existential spirituality
\"Why are students becoming disengaged from schooling? Many teachers, administrators and designers of policy and curriculum are expressing concern over this issue. Current approaches to schooling are dominated by a perceived need to enable learners to particulate in the knowledge economy. Both knowledge and learning how to learn knowledge have become the primary discourses in schooling - rather than education. School curricula rarely offer any sense of personal significance and for many learners such an approach to the curriculum is meaningless. Educating for meaningful lives must be a central aim for educative curricula. This book offers curriculum designers and teachers a greater understanding of this relation that education has with living significantly meaningful lives and it does so through the notion of existential spirituality. Spirituality is not to be reduced to something religious but rather pertains to how a life is lived. An existential perspective enables the meaningfulness of life to provide the necessary significance which is required of a curriculum if it is to be understood as offering personal meaning for learners. Approaching the design and teaching of curricula through this perspective of existential spirituality enables learners to live a meaningful life in an uncertain world.\"--Back cover.
Book
Hybrid guided space-time optical modes in unpatterned films
Light is confined transversely and delivered axially in a waveguide. However, waveguides are lossy static structures whose modal characteristics are fundamentally determined by their boundary conditions. Here we show that unpatterned planar waveguides can provide low-loss two-dimensional waveguiding by using space-time wave packets, which are unique one-dimensional propagation-invariant pulsed optical beams. We observe hybrid guided space-time modes that are index-guided in one transverse dimension and localized along the unbounded dimension. We confirm that these fields enable overriding the boundary conditions by varying post-fabrication the group index of the fundamental mode in a 2-μm-thick, 25-mm-long silica film, achieved by modifying the field’s spatio-temporal structure. Tunability of the group index over an unprecedented range from 1.26 to 1.77 is verified while maintaining a spectrally flat zero-dispersion profile. Our work paves the way to utilizing space-time wave packets in on-chip platforms, and enable phase-matching strategies that circumvent restrictions due to intrinsic material properties.
Waveguides typically function by using boundary conditions to contain light. Here, the authors show that by using space-time wavepackets, light can be guided in an unpatterned planar waveguide as the field remains localized along the unbounded dimension.
Journal Article
The white devil
\"Adultery, intrigue, murder, revenge: the densely-packed plot of The White Devil touches on topics that are representative of the atmosphere of Jacobean tragedy. Part tragedy, part satire of a corrupt political world, the play explores the relations of the powerful to the disempowered; the opportunities and constraints of women trying to survive in a male-dominated society; the complex distribution of social hierarchy by birth, wealth, gender, race; and the way the skills licensed by the theatre itself - including disguise and both the performance and interpretation of character - become crucial survival skills, in a world of hidden motives and concealed intentions. Now comprehensively re-edited, with an introduction that addresses issues of performance, cultural and historical context, and interpretation, exploring the dark energy that has impelled audiences and scholars to return to this play again and again across four centuries. Arden Early Modern Drama editions offer the best in contemporary scholarship, providing a wealth of helpful and incisive commentary and guiding the reader to a deeper understanding and appreciation of the play\"-- Provided by publisher.
Book
11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis
Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P<0.01) final volume (0.158 ± 0.037 cm 3 ) than in control mice (0.051 ± 0.007 cm 3 ). However, PDAC tumour growth was unaffected. Immunofluorescent analysis of SCC tumours did not show differences in vessel density (CD31/alpha-smooth muscle actin) or cell proliferation (Ki67) after 11β-HSD1 inhibition, and immunohistochemistry of SCC tumours did not show changes in inflammatory cell (CD3- or F4/80-positive) infiltration. In culture, the growth/viability (assessed by live cell imaging) of SCC cells was not affected by UE2316 or corticosterone. Second Harmonic Generation microscopy showed that UE2316 reduced Type I collagen (P<0.001), whilst RNA-sequencing revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated SCC tumours. 11β-HSD1 inhibition increases SCC tumour growth, likely via suppression of inflammatory/immune cell signalling and extracellular matrix deposition, but does not promote tumour angiogenesis or growth of all solid tumours.
Journal Article
The haunted cave
When Rod and Brody go on a camping trip to earn their camping badges, they explore a spooky cave that may be haunted.
Book
Analyzing coordination structures for effective humanitarian relief operations
Despite significant efforts by humanitarian actors, initiatives, and donors to improve coordination among humanitarian organizations during disaster response, the challenge of insufficient coordination persists. Drawing on practical considerations, we develop a stylized non-cooperative game-theoretical model to examine the coordination dynamics between large international and small local humanitarian organizations in the aftermath of a disaster, comparing both
pooled
and
partitioned
coordination models. Our findings reveal that bureaucratic delays commonly associated with coordination efforts not only deter collaboration but can also result in coordination levels that are detrimental to overall relief system performance. This analysis underscores the importance of rethinking coordination structures to better reflect the specific context of relief efforts. In alignment with calls for increased localization, we demonstrate that an efficiently designed partitioned coordination model outperforms a pooled model, which often marginalizes smaller local actors. This partitioned approach proves particularly effective in emergency settings, bringing actors’ decisions closer to the optimal outcome for the entire system.
Journal Article
Kynurenine 3-monooxygenase is a critical regulator of renal ischemia–reperfusion injury
Acute kidney injury (AKI) following ischemia–reperfusion injury (IRI) has a high mortality and lacks specific therapies. Here, we report that mice lacking kynurenine 3-monooxygenase (KMO) activity (
Kmo
null
mice) are protected against AKI after renal IRI. We show that KMO is highly expressed in the kidney and exerts major metabolic control over the biologically active kynurenine metabolites 3-hydroxykynurenine, kynurenic acid, and downstream metabolites. In experimental AKI induced by kidney IRI,
Kmo
null
mice had preserved renal function, reduced renal tubular cell injury, and fewer infiltrating neutrophils compared with wild-type (
Kmo
wt
) control mice. Together, these data confirm that flux through KMO contributes to AKI after IRI, and supports the rationale for KMO inhibition as a therapeutic strategy to protect against AKI during critical illness.
Kidney disease: drug target for acute injury following reperfusion
Inhibition of a metabolic enzyme linked to inflammation could be a novel treatment approach for sudden kidney failure following a “reperfusion” injury caused by blood flow returning to the organ after a period of insufficient blood supply. Damian Mole and colleagues from the University of Edinburgh, UK, temporarily blocked blood vessels leading to the kidneys of mice to induce organ damage. Mice that lacked a working copy of kynurenine 3-monooxygenase (
KMO
), a gene that encodes an enzyme involved in metabolizing an essential amino acid linked to immune activation, were protected from injury. These
KMO
-mutant mice experienced less damage to the kidney’s tubular cells and had fewer pro-inflammatory cells than genetically normal animals. The findings support the idea that blocking KMO and its associated metabolic pathway could help mitigate kidney damage following reperfusion injury in humans.
Journal Article
Generation and Behavior Characterization of CaMKIIβ Knockout Mice
The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIβ knockout (KO) mouse. The CaMKIIβ KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIβ KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIβ KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIβ KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the β isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIβ in brain structure, function and development.
Journal Article
Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice
The parasitic protist
Trypanosoma brucei
is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of
Trypanosoma brucei
phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.
Journal Article
Post-domicide artefacts: Mapping resistance and loss onto Palestinian house-keys
This article is concerned with the experiences of domicide-that is, the suffering caused by the deliberate destruction of home by human agency in pursuit of certain objectives-faced by Palestinians as a legacy (as well the present) of the ongoing conflict with Israel. Existing scholarly and activist research provides some essential data about these experiences, but intellectual contributions remain primarily focused on the act of demolition or displacement. This act alone does not constitute 'domicide'. What must follow is an attempt by the displaced to grapple with the whole affective dimension of being forcibly separated from home and the symbolic and creative responses that this begets. The significance house-keys have acquired within Palestinian inter-familial and communal customs, as well as within cultural (re)production, provides insight into this suffering. Attachment to the house-key is viewed as emblematic of feelings towards the lost home-a continuation of that connection by other means. This article explores the range of ways the key's symbolic value has been reconfigured as it permeates different arenas of cultural production and activity, and how the keys have come to embody both loss of home and resistance of the goals of Israeli domicide.
Journal Article