The Effect of Freeze-Thaw Cycles on Gene Expression Levels in Lymphoblastoid Cell Lines

Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene expression. We report a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene expression levels in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. We found that previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that while insight drawn from gene regulatory studies in mature LCLs may generally not be affected by the artificial nature of the LCL model system, many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures.</p

BRP-187: A potent inhibitor of leukotriene biosynthesis that acts through impeding the dynamic 5-lipoxygenase/5-lipoxygenase-activating protein (FLAP) complex assembly

The pro-inflammatory leukotrienes (LTs) are formed from arachidonic acid (AA) in activated leukocytes, where 5-lipoxygenase (5-LO) translocates to the nuclear envelope to assemble a functional complex with the integral nuclear membrane protein 5-LO-activating protein (FLAP). FLAP, a MAPEG family member, facilitates AA transfer to 5-LO for efficient conversion, and LT biosynthesis critically depends on FLAP. Here we show that the novel LT biosynthesis inhibitor BRP-187 prevents the 5-LO/FLAP interaction at the nuclear envelope of human leukocytes without blocking 5-LO nuclear redistribution. BRP-187 inhibited 5-LO product formation in human monocytes and polymorphonuclear leukocytes stimulated by lipopolysaccharide plus N-formyl-methionyl-leucyl-phenylalanine (IC50=7-10nM), and upon activation by ionophore A23187 (IC50=10-60nM). Excess of exogenous AA markedly impaired the potency of BRP-187. Direct 5-LO inhibition in cell-free assays was evident only at >35-fold higher concentrations, which was reversible and not improved under reducing conditions. BRP-187 prevented A23187-induced 5-LO/FLAP complex assembly in leukocytes but failed to block 5-LO nuclear translocation, features that were shared with the FLAP inhibitor MK886. Whereas AA release, cyclooxygenases and related LOs were unaffected, BRP-187 also potently inhibited microsomal prostaglandin E2 synthase-1 (IC50=0.2μM), another MAPEG member. In vivo, BRP-187 (10mg/kg) exhibited significant effectiveness in zymosan-induced murine peritonitis, suppressing LT levels in peritoneal exudates as well as vascular permeability and neutrophil infiltration. Together, BRP-187 potently inhibits LT biosynthesis in vitro and in vivo, which seemingly is caused by preventing the 5-LO/FLAP complex assembly and warrants further preclinical evaluation

Composing Urban Orders from Rubbish Electronics: Cityness and the Site Multiple

What do cities look like when rubbish electronics are the vehicle with which they are explored? This article is an experiment designed to offer a response to that question, and in doing so to productively intervene in the conversation about ‘cityness’, ‘metrocentricity’ and ‘subaltern urbanism’. We intervene by following flows of rubbish electronics and the action that enacts them as waste and value, drawing on fieldwork in Dhaka, Singapore, Accra and Canada’s Greater Golden Horseshoe. Our intervention is an experiment in writing an urban geography of rubbish electronics as a site multiple. We show how following the circulation of rubbish electronics offers a many-folded synopsis of cities: urban enclaves of high finance and the information economy are also industrial waste producers. Peri-urban industrial zones are also managers of brands, legal liability and corporate public relations. Cities off the map are also urban innovation systems, while waste is rekindled as value and accumulated as poison. Thereby we suggest how a sensitivity to the site multiple may be a helpful way of grappling with shifting ontology and the performativity of our research practices in urban studies

Performative Work: Bridging Performativity and Institutional Theory in the Responsible Investment Field

Callon’s performativity thesis has illuminated how economic theories and calculative devices shape markets, but has been challenged for its neglect of the organizational, institutional and political context. Our seven-year qualitative study of a large financial data company found that the company’s initial attempt to change the responsible investment field through a performative approach failed because of the constraints posed by field practices and organizational norms on the design of the calculative device. However, the company was subsequently able to put in place another form of performativity by attending to the normative and regulative associations of the device. We theorize this route to performativity by proposing the concept of performative work, which designates the necessary institutional work to enable translation and the subsequent adoption of the device. We conclude by considering the implications of performative work for the performativity and the institutional work literatures

Abundance analysis of the outer halo globular cluster Palomar 14

We determine the elemental abundances of nine red giant stars belonging to Palomar 14 (Pal 14). Pal 14 is an outer halo globular cluster (GC) at a distance of \sim 70 kpc. Our abundance analysis is based on high-resolution spectra and one-dimensional stellar model atmospheres.We derived the abundances for the iron peak elements Sc, V, Cr, Mn, Co, Ni, the {\alpha}-elements O, Mg, Si, Ca, Ti, the light odd element Na, and the neutron-capture elements Y, Zr, Ba, La, Ce, Nd, Eu, Dy, and Cu. Our data do not permit us to investigate light element (i.e., O to Mg) abundance variations. The neutron-capture elements show an r-process signature. We compare our measurements with the abundance ratios of inner and other outer halo GCs, halo field stars, GCs of recognized extragalactic origin, and stars in dwarf spheroidal galaxies (dSphs). The abundance pattern of Pal 14 is almost identical to those of Pal 3 and Pal 4, the next distant members of the outer halo GC population after Pal 14. The abundance pattern of Pal 14 is also similar to those of the inner halo GCs, halo field stars, and GCs of recognized extragalactic origin, but differs from what is customarily found in dSphs field stars. The abundance properties of Pal 14 as well as those of the other outer halo GCs are thus compatible with an accretion origin from dSphs. Whether or not GC accretion played a role, it seems that the formation conditions of outer halo GCs and GCs in dSphs were similar.Comment: 19 pages, 15 figures. Accepted by A&

Surveying the spirit of absolute summability on multilinear operators and homogeneous polynomials

[EN] We draw a fundamental compendium of the most valuable results of the theory of summing linear operators and detail those that are not shared by known multilinear and polynomial extensions of absolutely summing linear operators. The lack of such results in the theory of non-linear summing operators justifies the introduction of a class of polynomials and multilinear operators that satisfies at once all related non-linear results. Surprisingly enough, this class, defined by means of a summing inequality, happens to be the well known ideal of composition with a summing operator.D. Pellegrino acknowledges with thanks the support of CNPq Grant 401735/2013-3-PVE (Linha 2)-Brazil. P. Rueda acknowledges with thanks the support of the Ministerio de Economia y Competitividad (Spain) MTM2011-22417. E. A. Sanchez Perez acknowledges with thanks the support of the Ministerio de Economia y Competitividad (Spain) MTM2012-36740-C02-02.Pellegrino, D.; Rueda, P.; Sánchez Pérez, EA. (2016). 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Cosmology with the Laser Interferometer Space Antenna

The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational wave observations by LISA to probe the universe

Endoskopik üçüncü ventrikülostominin başarısını etkileyen faktörler.

Amaç: Obstrüktif hidrosefali tedavisinde E3V, kliniğimizde son 17 yıldır giderek daha fazla kullanılmaktadır. Bu çalışmanın amacı, düşük E3V başarı oranı ile demografik, etyolojik, radyolojik ve operasyon ile ilgili faktörler ile ilişkilendirmektir. Materyal ve Metod: Ege üniversitesi Tıp Fakültesi Beyin ve Sinir Cerrahisi kliniğinde, Ocak 2010 ile Şubat 2015 tarihleri arasında endoskopik üçüncü ventrikülostomi (E3V) uygulanan 88 olgu retrospektif olarak incelenmiştir. Bu çalışmada hasta seçimi konusunda titiz olundu, buna bağlı olarak daha önce eksternal ventriküler drenaj ya da ventriküloperitoneal şant takılan, daha önce E3V yapılan olgular dahil, kranial herhangi bir cerrahi uygulanan olgular ile intrakranial kitlesi olan olgular çalışma dışında bırakılmıştır. Olgular ile ilgili veriler, klinik veri tabanı, radyolojik veri tabanı [Manyetik Rezonans Görüntüleme (MRG)], operasyon notları ve operasyon video kayıtları kullanılarak toplanmıştır. E3V başarısını etkileyen aşağıdaki veriler analiz edilmiştir; yaş ( 5 gruba ayrılmıştır: 0-1 ay, 1-6 ay, 6-12 ay, 1-18 yaş, erişkin), semptom, hidrosefaliye neden olan obstrüksiyonun etyolojisi (saf mekanik ve inflamatuar nedenler), preoperatif beyin MRG ( tüber sinerum çöküklüğü, akım artefaktı, ideal burr-hole noktası ve ventriküle giriş açıları), postoperatif beyin MRG ( tüber sinerum çöküklüğü, akım artefaktı, cerrah tarafından kullanılan burr-hole noktası ve ventriküle giriş açıları), operasyon video kaydı ( köşelerini korpus mamillareler ve infundibulumun oluşturduğu üçgen ile ostiumun alan oranı, hemoraji, venöz açı hasarı, forniks hasarı), peroperatif komplikasyon (minör ve majör kanamalar), postoperatif komplikasyon ( BOS fistülü, enfeksiyon, hematom). Başarılı E3V, olgunun şikayetlerinin düzelmesi, BOS akım MRG, 3 boyutlu T2 ağırlıklı beyin MRG (CISS)'da ostium seviyesinde akım artefaktının görülmesi ve izlemde uzun süre ventriküloperitoneal şant gereksiniminin olmaması olarak tanımlanmıştır. Veri analizleri, Ki-kare testi, Eşli gruplar T testi (Paired samples T test) ve Bağımsız gruplar T testi (Independent samples T test) kullanılmıştır. Sonuçlar: Bu seride en az 3 ay takip edilen 88 olgu bulunmaktadır. Ortalama takip süresi 20.9 aydır (3 ay - 4.5 yıl). Çalışmada 48 (% 54.5) kadın, 40 (% 45.5) erkek olgu bulunmaktadır. Operasyon sırasında olguların ortalama yaşı, 17,8'dir. 28 olgu (% 31.8), 18 yaş üzerinde iken; en fazla olgunun olduğu 1-18 yaş grubunda ise 60 olgu (% 68.2) bulunmaktadır. Bu grupta ortalama yaş 66 ay olarak bulunmuştur. en sık semptom baş ağrısı (% 48.9), en sık etyoloji ise saf mekanik nedenler (% 93.2), en sık komplikasyon ise hemoraji (% 33)'dir. İdeal burr-hole noktasının koroner süture uzaklığı, ortalama 10.9 mm.; orta hatta uzaklığı, 24.3 mm. olarak; operasyonda kullanılan burr-hole noktasının koroner süture uzaklığı, ortalama 11.5 mm.; orta hatta uzaklığı, 29 mm. olarak bulunmuştur. İdeal ventriküle giriş açısı anterior-posterior doğrultuda, 87.8°; lateral doğrultuda 88.0; operasyonda kullanılan ventriküle giriş açısı anterior-posterior doğrultuda, 90°; lateral doğrultuda 88.1° şeklinde hesaplanmıştır. Ortalama ostium alan oranı, % 13.8 (% 2 - % 49) olarak bulunmuştur. E3V başarı oranı, 0-1 ay grubunda % 0; 1-6 ay grubunda % 28.6, 6-12 ay grubunda % 28.6, 1-18 yaş grubunda % 73.9, erişkin yaş grubunda % 85.8, tüm çalışma grubunda ise % 70.5 bulunmuştur. E3V başarısızlığı ortalama 85 günde (1 gün - 396 gün) gerçekleşmiştir. İstatistiksel olarak ideal burr-hole noktası ile operasyonda kullanılan burr-hole noktası arasında ve ideal ventriküle giriş açıları ile operasyonda kullanılan ventriküle giriş açıları arasında anlamlı bir fark bulunmamıştır (p: 0.69, p: 0.59). BOS fistülü, 0-1 ay ile 0-1 yaş grubu istatistiksel olarak yüksek derecede anlamlı bulunmuş ve E3V başarısızlığı için yüksek risk oluşturmuşlardır (p: 0.001, p: 0.002, p: 0.003). İlginç olarak, ortalama ostium alanı, peroperatif gelişen hemoraji ve tüber sinerum çöküklüğünün düzelmemesi ile E3V başarısızlığı arasında anlamlı bir ilişki bulunamamıştır.(p: 0.83, p: 0.32, p: 0.24) Tartışma: E3V, son 20 yılda ventriküloperitoneal şantın alternatifi olmuştur. Bunun nedeni ventrikloperitoneal şantın getirdiği disfonksiyon ve komplikasyon oranlarıdır (59, 60). Küçük çocuklarda, E3V'nin yüksek başarısızlık oranları göstermesinden ve yaşın E3V başarısını etkilediğinden sıkça bahsedilmiştir (61, 62, 63, 64, 64, 65). Bu çalışmada çocuk yaş grubunda inflamatuar nedenlerden dolayı E3V başarı oranları düşük bulunmuştur. Bu sonuç literatür verileri ile benzerlik gösterse de istatistiksel olarak anlamlı bulunmamıştır (65). Çalışmamızda tüber sinerum çöküklüğünde düzelme ile E3V başarısı arasında anlamlı bir ilişki bulunamamıştır ve bu bilgi, literatür ile benzerlik göstermemektedir (72, 73, 74). Postoperatif MRG'nin erken dönemde çekilmesinin bu duruma neden olabileceği düşünülmüştür. İstatistiksel olarak ideal burr-hole noktası ile operasyonda kullanılan burrhole noktası arasında ( koronal süture olan ortalama uzaklık hariç; fark: 4.7 mm.) ve ideal ventriküle giriş açıları ile operasyonda kullanılan ventriküle giriş açıları arasında anlamlı bir fark bulunmamıştır ancak bu sonuçlar, cerrahi deneyimin önemli olduğunu göstermektedir. BOS fistülünün, ostiumun kapanması sonucunda oluşan basınç farkı nedeni ile geliştiği düşünülmekte olup BOS fistülü gelişimi ile E3V başarısızlığı arasında yüksek derecede anlamlı bir ilişki bulunmaktadır ve bu veri literatür ile benzerdir (84, 85, 86). Tüm bunlardan farklı olarak, ostium alan oranı ile E3V başarısı arasında anlamlı bir ilişki bulunamamıştır. Bu ilginç sonuç, literatürdeki bu konu ile ilgili yapılmış tek çalışma ile paralellik göstermektedir (81). Bu çalışmaya göre, E3V hidrosefali tedavisinde güvenli ve efektif bir yöntemdir. Buna karşın gelişen E3V başarısızlığı; her tedavi protokolünde beklenebilecek, doğal bir sonuçtur. Tüm bunların ışığında, doğru hasta seçimi ve cerrahi deneyim ile E3V başarı oranlarının arttırılabileceğini düşünüyoruz