Utility of CD123 immunohistochemistry in differentiating lupus erythematosus from cutaneous T cell lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149293/1/his13817_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149293/2/his13817.pd

Gemini Deep Deep Survey VI: Massive Hdelta-strong galaxies at z=1

We show that there has been a dramatic decline in the abundance of massive galaxies with strong Hdelta stellar absorption lines from z=1.2 to the present. These ``Hdelta-strong'', or HDS, galaxies have undergone a recent and rapid break in their star-formation activity. Combining data from the Gemini Deep Deep and the Sloan Digital Sky Surveys to make mass-matched samples (M*>=10^10.2 Msun), with 25 and 50,255 galaxies, respectively), we find that the fraction of galaxies in an HDS phase has decreased from about 50% at z=1.2 to a few percent today. This decrease in fraction is due to an actual decrease in the number density of massive HDS systems by a factor of 2-4, coupled with an increase in the number density of massive galaxies by about 30 percent. We show that this result depends only weakly on the threshold chosen for the Hdelta equivalent width to define HDS systems (if greater than 4 A) and corresponds to a (1+z)^{2.5\pm 0.7} evolution. Spectral synthesis studies of the high-redshift population using the PEGASE code, treating Hdelta_A, EW[OII], Dn4000, and rest-frame colors, favor models in which the Balmer absorption features in massive Hdelta-strong systems are the echoes of intense episodes of star-formation that faded about 1 Gyr prior to the epoch of observation. The z=1.4-2 epoch appears to correspond to a time at which massive galaxies are in transition from a mode of sustained star formation to a relatively quiescent mode with weak and rare star-formation episodes. We argue that the most likely local descendants of the distant massive HDS galaxies are passively evolving massive galaxies in the field and small groups.Comment: 16 pages, 12 figures, 3 tables, uses emulateapj.sty; updated to match the version accepted by ApJ. One figure added, conclusions unchange

Expression of the p40 isoform of p63 has high specificity for cutaneous sarcomatoid squamous cell carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109645/1/cup12387.pd

Zwitterionic PEG-PC hydrogels modulate the foreign body response in a modulus-dependent manner

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and crosslinking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with co-monomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

Atypical functional connectivity during unfamiliar music listening in children with autism

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula.Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning.info:eu-repo/semantics/publishedVersio

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

The Sloan Digital Sky Survey-II Supernova Survey: Search Algorithm and Follow-up Observations

The Sloan Digital Sky Survey-II Supernova Survey has identified a large number of new transient sources in a 300 sq. deg. region along the celestial equator during its first two seasons of a three-season campaign. Multi-band (ugriz) light curves were measured for most of the sources, which include solar system objects, Galactic variable stars, active galactic nuclei, supernovae (SNe), and other astronomical transients. The imaging survey is augmented by an extensive spectroscopic follow-up program to identify SNe, measure their redshifts, and study the physical conditions of the explosions and their environment through spectroscopic diagnostics. During the survey, light curves are rapidly evaluated to provide an initial photometric type of the SNe, and a selected sample of sources are targeted for spectroscopic observations. In the first two seasons, 476 sources were selected for spectroscopic observations, of which 403 were identified as SNe. For the Type Ia SNe, the main driver for the Survey, our photometric typing and targeting efficiency is 90%. Only 6% of the photometric SN Ia candidates were spectroscopically classified as non-SN Ia instead, and the remaining 4% resulted in low signal-to-noise, unclassified spectra. This paper describes the search algorithm and the software, and the real-time processing of the SDSS imaging data. We also present the details of the supernova candidate selection procedures and strategies for follow-up spectroscopic and imaging observations of the discovered sources.Comment: Accepted for publication in The Astronomical Journal (66 pages, 13 figures); typos correcte

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion