Some Spinor-Curvature Identities

We describe a class of spinor-curvature identities which exist for Riemannian or Riemann-Cartan geometries. Each identity relates an expression quadratic in the covariant derivative of a spinor field with an expression linear in the curvature plus an exact differential. Certain special cases in 3 and 4 dimensions which have been or could be used in applications to General Relativity are noted.Comment: 5 pages Plain TeX, NCU-GR-93-SSC

Investment Opportunities Forecasting: Extending the Grammar of a GP-based Tool

In this paper we present a new version of a GP financial forecasting tool, called EDDIE 8. The novelty of this version is that it allows the GP to search in the space of indicators, instead of using pre-specified ones. We compare EDDIE 8 with its predecessor, EDDIE 7, and find that new and improved solutions can be found. Analysis also shows that, on average, EDDIE 8's best tree performs better than the one of EDDIE 7. The above allows us to characterize EDDIE 8 as a valuable forecasting tool

A Quadratic Spinor Lagrangian for General Relativity

We present a new finite action for Einstein gravity in which the Lagrangian is quadratic in the covariant derivative of a spinor field. Via a new spinor-curvature identity, it is related to the standard Einstein-Hilbert Lagrangian by a total differential term. The corresponding Hamiltonian, like the one associated with the Witten positive energy proof is fully four-covariant. It defines quasi-local energy-momentum and can be reduced to the one in our recent positive energy proof. (Fourth Prize, 1994 Gravity Research Foundation Essay.)Comment: 5 pages (Plain TeX), NCU-GR-94-QSL

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

Ashtekar's New Variables and Positive Energy

We discuss earlier unsuccessful attempts to formulate a positive gravitational energy proof in terms of the New Variables of Ashtekar. We also point out the difficulties of a Witten spinor type proof. We then use the special orthonormal frame gauge conditions to obtain a locally positive expression for the New Variables Hamiltonian and thereby a ``localization'' of gravitational energy as well as a positive energy proof.Comment: 12 pages Plain Te

Proteolytic processing of TGFα redirects its mitogenic activity: the membrane-anchored form is autocrine, the secreted form is paracrine

AbstractWild-type transforming growth factor α (TGFα) expression in lactotrope cells in the pituitary gland led to lactotrope-specific pituitary hyperplasia and adenomata. To indicate whether the EGF receptor is involved in this TGFα-mediated phenotype, we bred TGFα mice with mice expressing the cytoplasmic truncated-EGF receptor (EGFR-tr), which is dominant-negative in other models. These bitransgenic mice developed pituitary pathology despite expression of the dominant-negative receptor. To further characterize this observation, we generated two lineages of transgenic mice that overexpress mutant forms of TGFα: a processed soluble form (s TGFα) and a cytoplasmic-deleted form (TGFαΔC). While sTGFα expression in lactotrope cells failed to induce autocrine lactotrope hyperplasia, the pituitary became very enlarged due to proliferation of neighboring interstitial cells. In contrast, the TGFαΔC mice did not develop a phenotype, although the mRNA and protein were present in the pituitary and this form of TGFα was confirmed to be biologically active and targeted properly to the plasma membrane of cultured CHO cells. The results suggest that the cytoplasmic domain of TGFα is required for autocrine parenchymal tumor formation in the pituitary gland. This signal cannot be inhibited by the EGFR-tr. Conversely, the released form of TGFα appears to have primarily paracrine activity

Deficiency of plasminogen activator inhibitor‐2 results in accelerated tumor growth

BackgroundUpregulation of the plasminogen activation system, including urokinase plasminogen activator (uPA), has been observed in many malignancies, suggesting that co‐opting the PA system is a common method by which tumor cells accomplish extracellular matrix proteolysis. PAI‐2, a serine protease inhibitor, produced from the SERPINB2 gene, inhibits circulating and extracellular matrix‐tethered uPA. Decreased SERPINB2 expression has been associated with increased tumor invasiveness and metastasis for several types of cancer. PAI‐2 deficiency has not been reported in humans and PAI‐2‐deficient (SerpinB2−/−) mice exhibit no apparent abnormalities.ObjectivesWe investigated the role of PAI‐2 deficiency on tumor growth and metastasis.MethodsTo explore the long‐term impact of PAI‐2 deficiency, a cohort of SerpinB2−/− mice were aged to >18 months, with spontaneous malignancies observed in 4/9 animals, all of apparently vascular origin. To further investigate the role of PAI‐2 deficiency in malignancy, SerpinB2−/− and wild‐type control mice were injected with either B16 melanoma or Lewis lung carcinoma tumor cells, with markedly accelerated tumor growth observed in SerpinB2−/− mice for both cell lines. To determine the relative contributions of PAI‐2 from hematopoietic or nonhematopoietically derived sources, bone marrow transplants between wild‐type C57BL/6J and SerpinB2−/− mice were performed.Results and ConclusionsOur results suggest that PAI‐2 deficiency increases susceptibility to spontaneous tumorigenesis in the mouse, and demonstrate that SerpinB2 expression derived from a nonhematopoietic compartment is a key host factor in the regulation of tumor growth in both the B16 melanoma and Lewis lung carcinoma models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163438/2/jth15054_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163438/1/jth15054.pd

miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.113324Ysciescopu

2021 occultations and transits of Linus orbiting (22) Kalliope: I. Polygonal and `cliptracing' algorithm

The satellite Linus orbiting the main-belt asteroid (22) Kalliope exhibited occultation and transit events in late 2021. A photometric campaign was organized and observations were taken by the TRAPPIST-South, SPECULOOS-Artemis, OWL-Net, and BOAO telescopes, with the goal to constrain models of this system. Our dynamical model is complex, with multipoles (up to the order $\ell = 2$), internal tides, and external tides. The model was constrained by astrometry (spanning 2001--2021), occultations, adaptive-optics imaging, calibrated photometry, as well as relative photometry. Our photometric model was substantially improved. A new precise (${<}\,0.1\,{\rm mmag}$) light curve algorithm was implemented, based on polygon intersections, which are computed exactly -- by including partial eclipses and partial visibility of polygons. Moreover, we implemented a `cliptracing' algorithm, based again on polygon intersections, in which partial contributions to individual pixels are computed exactly. Both synthetic light curves and synthetic images are then very smooth. Based on our combined solution, we confirmed the size of Linus, $(28\pm 1)\,{\rm km}$. However, this solution exhibits some tension between the light curves and the PISCO speckle-interferometry dataset. In most solutions, Linus is darker than Kalliope, with the albedos $A_{\rm w} = 0.40$ vs. $0.44$. This is confirmed on deconvolved images. A~detailed revision of astrometric data allowed us to revise also the $J_2 \equiv -C_{20}$ value of Kalliope. Most importantly, a~homogeneous body is excluded. For a differentiated body, two solutions exist: low-oblateness ($C_{20} \simeq -0.12$), with a~spherical iron core, and alternatively, high-oblateness ($C_{20} \simeq -0.22$) with an elongated iron core. These correspond to the low- and high-energy collisions, respectively, studied by means of SPH simulations in our previous work.Comment: Astronomy and Astrophysics, accepte