Surface and sub-surface multi-proxy reconstruction of middle to late Holocene palaeoceanographic changes in Disko Bugt, West Greenland

We present new surface water proxy records of meltwater production (alkenone derived), relative sea surface temperature (diatom, alkenones) and sea ice (diatoms) changes from the Disko Bugt area off central West Greenland. We combine these new surface water reconstructions with published proxy records (benthic foraminifera - bottom water proxy; dinocyst assemblages – surface water proxy), along with atmospheric temperature from Greenland ice core and Greenland lake records. This multi-proxy approach allows us to reconstruct centennial scale middle to late Holocene palaeoenvironmental evolution of Disko Bugt and the Western Greenland coastal region with more detail than previously available. Combining surface and bottom water proxies identifies the coupling between ocean circulation (West Greenland Current conditions), the atmosphere and the Greenland Ice Sheet. Centennial to millennial scale changes in the wider North Atlantic region were accompanied by variations in the West Greenland Current (WGC). During periods of relatively warm WGC, increased surface air temperature over western Greenland led to ice sheet retreat and significant meltwater flux. In contrast, during periods of cold WGC, atmospheric cooling resulted in glacier advances. We also identify potential linkages between the palaeoceanography of the Disko Bugt region and key changes in the history of human occupation. Cooler oceanographic conditions at 3.5 ka BP support the view that the Saqqaq culture left Disko Bugt due to deteriorating climatic conditions. The cause of the disappearance of the Dorset culture is unclear, but the new data presented here indicate that it may be linked to a significant increase in meltwater flux, which caused cold and unstable coastal conditions at ca. 2 ka BP. The subsequent settlement of the Norse occurred at the same time as climatic amelioration during the Medieval Climate Anomaly and their disappearance may be related to harsher conditions at the beginning of the Little Ice Age

Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent dementia in the world. Its cause(s) are presently largely unknown. The most common explanation for AD, now, is the amyloid cascade hypothesis, which states that the cause of AD is senile plaque forma- tion by the amyloid β peptide, and the formation of neurofibrillary tangles by hyperphosphorylated tau. A second, burgeoning theory by which to explain AD is based on the infection hypothesis. Much experimental and epidemiological data support the involvement of infections in the development of dementia. According to this mechanism, the infection either directly or via microbial virulence factors precedes the formation of amyloid β plaques. The amyloid β peptide, possessing antimicrobial properties, may be beneficial at an early stage of AD, but becomes detrimental with the progression of the disease, concomi- tantly with alterations to the innate immune system at both the peripheral and central levels. Infection results in neuroinflam- mation, leading to, and sustained by, systemic inflammation, causing eventual neurodegeneration, and the senescence of the immune cells. The sources of AD-involved microbes are various body microbiome communities from the gut, mouth, nose, and skin. The infection hypothesis of AD opens a vista to new therapeutic approaches, either by treating the infection itself or modulating the immune system, its senescence, or the body’s metabolism, either separately, in parallel, or in a multi-step way.Basque Government under the grant “Artificial Intelligence in BCAM number EXP. 2019/00432

Search for Exotic Mesons in pi- P Interactions at 18 GeV/c

The recent search for non $q \bar{q}$ mesons in $\pi^{-}p$ interactions at Brookhaven National Laboratory is summarized. Many final states such as $\eta \pi$, $\eta' \pi^{-}$, $a_{0} \pi$, $f_{1} \pi$, $a_{2} \pi$, $b_{1} \pi$, which are favored decay modes of exotics, are under investigation.Comment: 9 pages, PostScript, Presented at the International School of Nuclear Physics, Erice, Sicily, Italy, September 199

Confirmation of a pi_1^0 Exotic Meson in the \eta \pi^0 System

The exclusive reaction $\pi^- p \to \eta \pi^0 n$, $\eta \to \pi^+ \pi^- \pi^0$ at 18 GeV$/c$ has been studied with a partial wave analysis on a sample of 23~492 $\eta \pi^0 n$ events from BNL experiment E852. A mass-dependent fit is consistent with a resonant hypothesis for the $P_+$ wave, thus providing evidence for a neutral exotic meson with $J^{PC} = 1^{-+}$, a mass of $1257 \pm 20 \pm 25$ MeV$/c^2$, and a width of $354 \pm 64 \pm 60$ MeV$/c^2$. New interpretations of the meson exotics in neutral $\eta \pi^0$ system observed in E852 and Crystal Barrel experiments are discussed.Comment: p3, rewording the paragraph (at the bottom) about the phase variations. p4, rewording paragrath "The second method ..." . p4, at the bottom of paragrath "The third method ..." added consistent with the results of methods 1 and 2

Exotic Meson Production in the f1(1285)π−f_{1}(1285)\pi^{-} System observed in the Reaction π−p→ηπ+π−π−p\pi^{-} p \to \eta\pi^{+}\pi^{-}\pi^{-} p at 18 GeV/c

This letter reports results from the partial wave analysis of the $\pi^{-}\pi^{-}\pi^{+}\eta$ final state in $\pi^{-}p$ collisions at 18GeV/c. Strong evidence is observed for production of two mesons with exotic quantum numbers of spin, parity and charge conjugation, $J^{PC} = 1^{-+}$ in the decay channel $f_{1}(1285)\pi^{-}$. The mass $M = 1709 \pm 24 \pm 41$ MeV/c^2 and width $\Gamma = 403 \pm 80 \pm 115$ MeV/c^2 of the first state are consistent with the parameters of the previously observed $\pi_{1}(1600)$. The second resonance with mass $M = 2001 \pm 30 \pm 92$ MeV/c^2 and width $\Gamma = 333 \pm 52 \pm 49$ MeV/c^2 agrees very well with predictions from theoretical models. In addition, the presence of $\pi_{2}(1900)$ is confirmed with mass $M = 2003 \pm 88 \pm 148$ MeV/c^2 and width $\Gamma = 306 \pm 132 \pm 121$ MeV/c^2 and a new state, $a_{1}(2096)$, is observed with mass $M = 2096 \pm 17 \pm 121$ MeV/c^2 and width $\Gamma = 451 \pm 41 \pm 81$ MeV/c^2. The decay properties of these last two states are consistent with flux tube model predictions for hybrid mesons with non-exotic quantum numbers

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives: AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results: We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion: Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention

Observation of a New J(PC)=1(+-) Isoscalar State in the Reaction Pi- Proton -> Omega Eta Neutron at 18 GeV/c

Results are presented on a partial wave analysis of the Omega Eta final state produced in Pi- Proton interactions at 18 GeVc where Omega -> Pi+ Pi- Pi0, Pi0 -> 2 Gammas, and Eta -> 2 Gammas. We observe the previously unreported decay mode Omega(1650) -> Omega Eta and a new 1(+-) meson state h1(1595) with a mass M=1594(15)(+10)(-60) MeV/c^2 and a width Gamma=384(60)(+70)(-100) MeV/c^2. The h1(1595) state exhibits resonant-like phase motion relative to the Omega(1650).Comment: Submitted to Physics Letters B Eight total pages including 11 figures and 1 tabl

Spiral anchoring in anisotropic media with multiple inhomogeneities: a dynamical system approach

Various PDE models have been suggested in order to explain and predict the dynamics of spiral waves in excitable media. In two landmark papers, Barkley noticed that some of the behaviour could be explained by the inherent Euclidean symmetry of these models. LeBlanc and Wulff then introduced forced Euclidean symmetry-breaking (FESB) to the analysis, in the form of individual translational symmetry-breaking (TSB) perturbations and rotational symmetry-breaking (RSB) perturbations; in either case, it is shown that spiral anchoring is a direct consequence of the FESB. In this article, we provide a characterization of spiral anchoring when two perturbations, a TSB term and a RSB term, are combined, where the TSB term is centered at the origin and the RSB term preserves rotations by multiples of $\frac{2\pi}{\jmath^*}$, where $\jmath^*\geq 1$ is an integer. When $\jmath^*>1$ (such as in a modified bidomain model), it is shown that spirals anchor at the origin, but when $\jmath^* =1$ (such as in a planar reaction-diffusion-advection system), spirals generically anchor away from the origin.Comment: Revised versio

A study of the reaction pim p --> omega pim p at 18 GeV/c: The D and S decay amplitudes for b1(1235) --> omega pi

The reaction pim p --> omega pim p, omega --> pip pim pi0 has been studied at 18 GeV/c. The omega pim mass spectrum is found to be dominated by the b1(1235). Partial Wave Analysis shows that b1 production is dominated by natural parity exchange. The S-wave and D-wave amplitudes for b1(1235) --> omega pi have been determined, and it is found that the amplitude ratio, |D/S| = 0.269 +/- (0.009)stat +/- (0.01)sys and the phase difference, phi(D-S) = 10.54 deg +/- (2.4)stat +/- (3.9)sys.Comment: 7 pages, 9 figures, revtex4 format, to be published in Physics Letters

Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome

Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1+ (Ph+) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event-free survival in both patient cohorts. Among them are EMP1, which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1, encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease