The prime spectrum of algebras of quadratic growth

We study prime algebras of quadratic growth. Our first result is that if $A$ is a prime monomial algebra of quadratic growth then $A$ has finitely many prime ideals $P$ such that $A/P$ has GK dimension one. This shows that prime monomial algebras of quadratic growth have bounded matrix images. We next show that a prime graded algebra of quadratic growth has the property that the intersection of the nonzero prime ideals $P$ such that $A/P$ has GK dimension 2 is non-empty, provided there is at least one such ideal. From this we conclude that a prime monomial algebra of quadratic growth is either primitive or has nonzero locally nilpotent Jacobson radical. Finally, we show that there exists a prime monomial algebra $A$ of GK dimension two with unbounded matrix images and thus the quadratic growth hypothesis is necessary to conclude that there are only finitely many prime ideals such that $A/P$ has GK dimension 1.Comment: 23 page

eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications

CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.

Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy

Chapter Plant Name Resources

Plant names are the key to communicating and managing information about plants. This paper considers how providers of high quality technical plant name information can better meet the requirements non-botanical audiences who also rely on plant names for elements of their work. The International Plant Name Index, World Checklist of Selected Plant Families and The Plant List are used as examples to illustrate the strengths and weaknesses of plant name resources from a non-expert user’s perspective. The above resources can be thought of as botanists pushing data at audiences. Without closer engagement with users, however, there is a limit to their relevance and impact. The need to cover common names is a frequent criticism of existing resources. The Medicinal Plant Names Services (MPNS, www.kew.org/mpns) is an example of how plant name resources can be adapted to better address the needs of a non-botanical audience. Some of the major challenges are outlined and solutions suggested

Sustained low-dose treatment with the histone deacetylase inhibitor LBH589 induces terminal differentation of osteosarcoma cells

Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity

Information Display System for Atypical Flight Phase

Method and system for displaying information on one or more aircraft flights, where at least one flight is determined to have at least one atypical flight phase according to specified criteria. A flight parameter trace for an atypical phase is displayed and compared graphically with a group of traces, for the corresponding flight phase and corresponding flight parameter, for flights that do not manifest atypicality in that phase

The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Concept Design Update

In preparation for the 2020 Astrophysics Decadal Survey, NASA has commissioned the study of four large mission concepts, including the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor. The LUVOIR Science and Technology Definition Team (STDT) has identified a broad range of science objectives including the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the epoch of reionization, star and planet formation, and the remote sensing of Solar System bodies. NASAs Goddard Space Flight Center (GSFC) is providing the design and engineering support to develop executable and feasible mission concepts that are capable of the identified science objectives. We present an update on the first of two architectures being studied: a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100 nm to 2.5 microns. Four instruments are being developed for this architecture: an optical / near-infrared coronagraph capable of 10(exp -10) contrast at inner working angles as small as 2 lambda/D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100 400 nm) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-IR imager; and a UV spectro-polarimeter being contributed by Centre National dEtudes Spatiales (CNES). A fifth instrument, a multi-resolution optical-NIR spectrograph, is planned as part of a second architecture to be studied in late 2017

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis

Background & AimsEtrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did.MethodsWe performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1.ResultsColon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell−associated genes than patients who did not respond (P < .05). Colonic CD4+ integrin αE+ cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4+ αE− cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMAhigh vs 19% GZMAlow and 44% ITGAEhigh vs 19% ITGAElow). Compared with ITGAElow and GZMAlow patients, patients with ITGAEhigh and GZMAhigh had higher baseline numbers of epithelial crypt-associated integrin αE+ cells (P < .01 for both), but a smaller number of crypt-associated integrin αE+ cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%−80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline.ConclusionsLevels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarkerhigh patients. Larger, prospective studies of markers are needed to assess their clinical value

A strong Dixmier-Moeglin equivalence for quantum Schubert cells

Dixmier and Moeglin gave an algebraic condition and a topological condition for recognising the primitive ideals among the prime ideals of the universal enveloping algebra of a finite-dimensional complex Lie algebra; they showed that the primitive, rational, and locally closed ideals coincide. In modern terminology, they showed that the universal enveloping algebra of a finite-dimensional complex Lie algebra satisfies the Dixmier–Moeglin equivalence. We define quantities which measure how “close” an arbitrary prime ideal of a noetherian algebra is to being primitive, rational, and locally closed; if every prime ideal is equally “close” to satisfying each of these three properties, then we say that the algebra satisfies the strong Dixmier–Moeglin equivalence . Using the example of the universal enveloping algebra of sl2(C), we show that the strong Dixmier–Moeglin equivalence is strictly stronger than the Dixmier–Moeglin equivalence. For a simple complex Lie algebra g, a non-root of unity q?0 in an infinite field K, and an element w of the Weyl group of g, De Concini, Kac, and Procesi have constructed a subalgebra Uq[w] of the quantised enveloping K-algebra Uq(g). These quantum Schubert cells are known to satisfy the Dixmier–Moeglin equivalence and we show that they in fact satisfy the strong Dixmier–Moeglin equivalence. Along the way, we show that commutative affine domains, uniparameter quantum tori, and uniparameter quantum affine spaces satisfy the strong Dixmier–Moeglin equivalence