An exactly solvable quantum-lattice model with a tunable degree of nonlocality

An array of N subsequent Laguerre polynomials is interpreted as an eigenvector of a non-Hermitian tridiagonal Hamiltonian $H$ with real spectrum or, better said, of an exactly solvable N-site-lattice cryptohermitian Hamiltonian whose spectrum is known as equal to the set of zeros of the N-th Laguerre polynomial. The two key problems (viz., the one of the ambiguity and the one of the closed-form construction of all of the eligible inner products which make $H$ Hermitian in the respective {\em ad hoc} Hilbert spaces) are discussed. Then, for illustration, the first four simplest, $k-$parametric definitions of inner products with $k=0,k=1,k=2$ and $k=3$ are explicitly displayed. In mathematical terms these alternative inner products may be perceived as alternative Hermitian conjugations of the initial N-plet of Laguerre polynomials. In physical terms the parameter $k$ may be interpreted as a measure of the "smearing of the lattice coordinates" in the model.Comment: 35 p

Pennsylvania Folklife Vol. 43, No. 2

• The America\u27s Industrial Heritage Project: A Model for Cultural Tourism • The Harmonists are Waiting for You • The Quest for Authenticity in Tourism and Folklife Studies • Tourism and the Old Order Amish • The Log Cabin: Notes on its Structure and Dissemination • On the Making of Die Union Choral Harmonie (1833): Evidence from Henry C. Eyer\u27s Working Papers • In Memoriam: Paul R. Wieand, a True Artisthttps://digitalcommons.ursinus.edu/pafolklifemag/1139/thumbnail.jp

ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas

Glioma regression requires the recruitment of potent anti-tumor immune cells into the tumor microenvironment. Dendritic cells (DCs) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified especially to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the present study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence

Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis

International audienceWithin the last decade, it became clear that oxygen contributes to the pathogenesis of neonatal brain damage, leading to neurocognitive impairment of prematurely born infants in later life. Recently, we have identified a critical role for receptor-mediated neuronal apoptosis in the immature rodent brain. However, the contribution of the intrinsic apoptotic pathway accompanied by activation of caspase-2 under hyperoxic conditions in the neonatal brain still remains elusive. Inhibition of caspases appears a promising strategy for neuroprotection. In order to assess the influence of specific caspases on the developing brain, we applied a recently developed pentapeptide-based group II caspase inhibitor (5-(2,6-difluorophenoxy)-3(R,S)-(2(S)-(2(S)-(3-methoxycarbonyl-2(S)-(3-m ethyl-2(S)-((quinoline-2-carbonyl)-amino)-butyrylamino)propionylamino) 3-methylbutyrylamino) propionylamino)-4-oxo-pentanoic acid methyl ester; TRP601). Here, we report that elevated oxygen (hyperoxia) triggers a marked increase in active caspase-2 expression, resulting in an initiation of the intrinsic apoptotic pathway with upregulation of key proteins, namely, cytochrome c, apoptosis protease-activating factor-1, and the caspase-independent protein apoptosis-inducing factor, whereas BH3-interacting domain death agonist and the anti-apoptotic protein B-cell lymphoma-2 are downregulated. These results coincide with an upregulation of caspase-3 activity and marked neurodegeneration. However, single treatment with TRP601 at the beginning of hyperoxia reversed the detrimental effects in this model. Hyperoxia-mediated neurodegeneration is supported by intrinsic apoptosis, suggesting that the development of highly selective caspase inhibitors will represent a potential useful therapeutic strategy in prematurely born infants. Cell Death and Disease (2012) 3, e250; doi:10.1038/cddis.2011.133; published online 12 January 201

Ferromagnetism in Co7(TeO3)4Br6: A byproduct of complex antiferromagnetic order and single-ion anisotropy

Pronounced anisotropy of magnetic properties and complex magnetic order of a new oxi-halide compound Co7(TeO3)4Br6 has been investigated by powder and single crystal neutron diffraction, magnetization and ac susceptibility techniques. Anisotropy of susceptibility extends far into the paramagnetic temperature range. A principal source of anisotropy are anisotropic properties of the involved octahedrally coordinated single Co(2+) ions, as confirmed by angular-overlap-model calculations presented in this work. Incommensurate antiferromagnetic order sets in at TN=34 K. Propagation vector is strongly temperature dependent reaching k1=(0.9458(6), 0, 0.6026(5)) at 30 K. A transition to a ferrimagnetic structure with k2=0 takes place at TC=27 K. Magnetically ordered phase is characterized by very unusual anisotropy as well: while M-H scans along b-axis reveals spectacularly rectangular but otherwise standard ferromagnetic hysteresis loops, M-H studies along other two principal axes are perfectly reversible, revealing very sharp spin flop (or spin flip) transitions, like in a standard antiferromagnet (or metamagnet). Altogether, the observed magnetic phenomenology is interpreted as an evidence of competing magnetic interactions permeating the system, first of all of the single ion anisotropy energy and the exchange interactions. Different coordinations of the Co(2+)-ions involved in the low-symmetry C2/c structure of Co7(TeO3)4Br6 render the exchange-interaction network very complex by itself. Temperature dependent changes in the magnetic structure, together with an abrupt emergence of a ferromagnetic component, are ascribed to continual spin reorientations described by a multi-component, but yet unknown, spin Hamiltonian.Comment: 12 pages, 13 figures; submitted to PR

Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat model for preeclampsia

Preeclampsia is a multisystemic syndrome during pregnancy that is often associated with intrauterine growth retardation. Immunologic dysregulation, involving T cells, is implicated in the pathogenesis. The aim of this study was to evaluate the effect of upregulating regulatory T cells in an established transgenic rat model for preeclampsia. Application of superagonistic monoclonal antibody for CD28 has been shown to effectively upregulate regulatory T cells. In the first protocol (treatment protocol), we applied 1 mg of CD28 superagonist or control antibody on days 11 and 15 of pregnancy. In the second protocol (prevention protocol), the superagonist or control antibody was applied on days 1, 5, and 9. Superagonist increased regulatory T cells in circulation and placenta from 8.49+/-2.09% of CD4-positive T cells to 23.50+/-3.05% and from 3.85+/-1.45% to 23.27+/-7.64%, respectively. Blood pressure and albuminuria (30.6+/-15.1 versus 14.6+/-5.5 mg/d) were similar in the superagonist or control antibody-treated preeclamptic group for both protocols. Rats treated with CD28 superagonist showed increased pup weights in the prevention protocol (2.66+/-0.03 versus 2.37+/-0.05 g) and in the treatment protocol (3.04+/-0.04 versus 2.54+/-0.1 g). Intrauterine growth retardation, calculated by brain:liver weight ratio, was also decreased by the superagonist in both protocols. Further analysis of brain development revealed a 20% increase in brain volume by the superagonist. Induction of regulatory T cells in the circulation and the uteroplacental unit in an established preeclamptic rat model had no influence on maternal hypertension and proteinuria. However, it substantially improved fetal outcome by ameliorating intrauterine growth retardation

Spatially anisotropic S=1 square-lattice antiferromagnet with single-ion anisotropy realized in a Ni(II) pyrazine- n,n′ -dioxide coordination polymer

The Ni(NCS)2(pyzdo)2 coordination polymer is found to be an S=1 spatially anisotropic square lattice with easy-axis single-ion anisotropy. This conclusion is based upon considering in concert the experimental probes x-ray diffraction, magnetic susceptibility, magnetic-field-dependent heat capacity, muon-spin relaxation, neutron diffraction, neutron spectroscopy, and pulsed-field magnetization. Long-range antiferromagnetic (AFM) order develops at TN=18.5K. Although the samples are polycrystalline, there is an observable spin-flop transition and saturation of the magnetization at ≈80T. Linear spin-wave theory yields spatially anisotropic exchanges within an AFM square lattice, Jx=0.235meV, Jy=2.014meV, and an easy-axis single-ion anisotropy D=-1.622meV (after renormalization). The anisotropy of the exchanges is supported by density functional theory

Mortality trends in type 1 diabetes:a multicountry analysis of six population-based cohorts

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000–2016 in people with type 1 diabetes aged 0–79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from −2.1% (95% CI −2.8%, −1.3%) to −5.8% (95% CI −6.5%, −5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40–70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-022-05659-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users

RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models

Preeclampsia, with the hallmark features of new-onset hypertension and proteinuria after 20 weeks of gestation, is a major cause of fetal and maternal morbidity and mortality. Studies have demonstrated a role for the renin-angiotensin system (RAS) in its pathogenesis; however, small-molecule RAS blockers are contraindicated because of fetal toxicity. We evaluated whether siRNA targeting maternal hepatic angiotensinogen (Agt) could ameliorate symptoms of preeclampsia without adverse placental or fetal effects in 2 rodent models. The first model used a cross of females expressing human Agt with males expressing human renin, resulting in upregulation of the circulating and uteroplacental RAS. The second model induced ischemia/reperfusion injury and subsequent local and systemic inflammation by surgically reducing placental blood flow midgestation (reduced uterine perfusion pressure [RUPP]). These models featured hypertension, proteinuria, and fetal growth restriction, with altered biomarkers. siRNA treatment ameliorated the preeclamptic phenotype in both models, reduced blood pressure, and improved intrauterine growth restriction, with no observed deleterious effects on the fetus. Treatment also improved the angiogenic balance and proteinuria in the transgenic model, and it reduced angiotensin receptor activating antibodies in both. Thus, an RNAi therapeutic targeting Agt ameliorated the clinical sequelae and improved fetal outcomes in 2 rodent models of preeclampsia