Spectrum of the Y=2 Pentaquarks

By assuming a mass formula for the spectrum of the Y=2 pentaquarks, where the chromo-magnetic interaction plays a main role, and identifying the lightest state with the Theta^+(1540), we predict a spectrum in good agreement with the few I=0 and I=1 candidates proposed in the past.Comment: 12 pages, 4 figures, LaTe

Pentaquark as Kaon-Nucleon Resonance

Several recent experiments have reported evidence for a narrow feature in the K(+)-neutron system, an apparent resonant state ~ 100 MeV above threshold and with a width < 25 MeV. This state has been labelled as Theta(+) (previously as Z(*)), and because of the implied inclusion of a anti-strange quark, is referred to as a pentaquark, that is, five quarks within a single bag. We present an alternative explanation for such a structure, as a higher angular momentum resonance in the isospin zero K(+) -N system. One might call this an exit channel or a molecular resonance. In a non-relativistic potential model we find a possible candidate for the kaon-nucleon system with relative angular momentum L=3, while L=1 and 2 states possess centrifugal barriers too low to confine the kaon and nucleon in a narrow state at an energy so high above threshold. A rather strong state-dependence in the potential is essential, however, for eliminating an observable L=2 resonance at lower energies.Comment: 4 page

Integrated analysis of RNA and DNA from the phase III trial CALGB 40601 identifies predictors of response to trastuzumab-based neoadjuvant chemotherapy in HER2-positive breast cancer

Purpose: Response to a complex trastuzumab-based regimen is affected by multiple features of the tumor and its microenvironment. Developing a predictive algorithm is key to optimizing HER2-targeting therapy. Experimental Design: We analyzed 137 pretreatment tumors with mRNA-seq and DNA exome sequencing from CALGB 40601, a neoadjuvant phase III trial of paclitaxel plus trastuzumab with or without lapatinib in stage II to III HER2-positive breast cancer. We adopted an Elastic Net regularized regression approach that controls for covarying features within high-dimensional data. First, we applied 517 known gene expression signatures to develop an Elastic Net model to predict pCR, which we validated on 143 samples from four independent trials. Next, we performed integrative analyses incorporating clinicopathologic information with somatic mutation status, DNA copy number alterations (CNA), and gene signatures. Results: The Elastic Net model using only gene signatures predicted pCR in the validation sets (AUC ¼ 0.76). Integrative analyses showed that models containing gene signatures, clinical features, and DNA information were better pCR predictors than models containing a single data type. Frequently selected variables from the multiplatform models included amplifications of chromosome 6p, TP53 mutation, HER2-enriched subtype, and immune signatures. Variables predicting resistance included Luminal/ERþ features. Conclusions: Models using RNA only, as well as integrated RNA and DNA models, can predict pCR with improved accuracy over clinical variables. Somatic DNA alterations (mutation, CNAs), tumor molecular subtype (HER2E, Luminal), and the microenvironment (immune cells) were independent predictors of response to trastuzumab and paclitaxel-based regimens. This highlights the complexity of predicting response in HER2-positive breast cancer

Kaon-Nucleon Scattering Amplitudes and Z∗^*-Enhancements from Quark Born Diagrams

We derive closed form kaon-nucleon scattering amplitudes using the ``quark Born diagram" formalism, which describes the scattering as a single interaction (here the OGE spin-spin term) followed by quark line rearrangement. The low energy I=0 and I=1 S-wave KN phase shifts are in reasonably good agreement with experiment given conventional quark model parameters. For $k_{lab}> 0.7$ Gev however the I=1 elastic phase shift is larger than predicted by Gaussian wavefunctions, and we suggest possible reasons for this discrepancy. Equivalent low energy KN potentials for S-wave scattering are also derived. Finally we consider OGE forces in the related channels K$\Delta$, K$^*$N and K$^*\Delta$, and determine which have attractive interactions and might therefore exhibit strong threshold enhancements or ``Z$^*$-molecule" meson-baryon bound states. We find that the minimum-spin, minimum-isospin channels and two additional K$^*\Delta$ channels are most conducive to the formation of bound states. Related interesting topics for future experimental and theoretical studies of KN interactions are also discussed.Comment: 34 pages, figures available from the authors, revte

Z^* Resonances: Phenomenology and Models

We explore the phenomenology of, and models for, the Z^* resonances, the lowest of which is now well established, and called the Theta. We provide an overview of three models which have been proposed to explain its existence and/or its small width, and point out other relevant predictions, and potential problems, for each. The relation to what is known about KN scattering, including possible resonance signals in other channels, is also discussed.Comment: 29 pages, uses RevTeX4; expanded version (published form

The Theta+ (1540) as a heptaquark with the overlap of a pion, a kaon and a nucleon

We study the very recently discovered Theta+ (1540) at SPring-8, at ITEP and at CLAS-Thomas Jefferson Lab. We apply the same RGM techniques that already explained with success the repulsive hard core of nucleon-nucleon, kaon-nucleon exotic scattering, and the attractive hard core present in pion-nucleon and pion-pion non-exotic scattering. We find that the K-N repulsion excludes the Theta+ as a K-N s-wave pentaquark. We explore the Theta+ as a heptaquark, equivalent to a N+pi+K borromean bound-state, with positive parity and total isospin I=0. We find that the kaon-nucleon repulsion is cancelled by the attraction existing both in the pion-nucleon and pion-kaon channels. Although we are not yet able to bind the total three body system, we find that the Theta^+ may still be a heptaquark state. We conclude with predictions that can be tested experimentally.Comment: 5 pages, 5 figures, 2 tables, submitted to Phys. Rev. D, rapid communicatio

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer&apos;s disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele