bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of unique venous thromboembolism-susceptibility variants in African-Americans
Authors: Armasu Sebastian , McCauley Bryan , Kullo Iftikhar , Sicotte Hugues , Pathak Jyotishman , Chute Christopher , Gottesman Omri , Bottinger Erwin , Denny Joshua , Roden Dan , Li Rongling , Ritchie Marylyn D. , de Andrade Mariza , Heit John A.
Published: February 2017

To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Six theses on forced labor in the Portuguese empire of continental Africa
Authors: Cahen Michel
Published: February 2017

Forced labor in Portugal’s African colonies during the twentieth century is often generalized in the literature as a “simple continuation” of slavery because the historiography related to the continental territories of Portugal’s third African empire has been overly influenced by the situation of São Tomé e Príncipe, where this “continuation” was the case. This article defends six theses: 1. In Portugal’s continental colonies, the end of the slave trade and the beginning of forced labor did not succeed each other through a regime of transition, but rather of rupture. 2. The introduction of forced labor was not a Portuguese “archaism” but a modern capitalist rupture. 3. Forced labor was able to function only in the framework of an articulation of the modes of production by maintaining a subalternized domestic production, which subsisted thanks to an acute gender oppression. 4. It was not the case of the law promulgated in Portugal being “erroneously applied in the colonies”. 5. This legislation was racist not only in terms of phenotype, but also in its function as a discrimination founded on the sphere of production, defining the exclusion of an entire people. 6. It is this situation that paradoxically nourished the ideology of assimilation
The historiography of “conversions” in Portugal’s African colonies and the trajectory of Jesse Chiula Chipenda
Authors: Dulley Iracema
Published: February 2017

The text below relates the trajectory of Jesse Chiula Chipenda (1903-1969) to the colonial context in the Central Highlands of Angola. Born in Bailundo in the last year of the region’s ‘pacification’ war (1902-1903) and the chief of Lomanda’s son, Jesse Chipenda was introduced to the missions of the Congregationalist American Board of Commissioners for Foreign Missions (ABCFM) and converted into Protestantism. He became a catechist and a prominent pastor. In analyzing Jesse Chipenda’s trajectory, one seeks to understand the constitution of a Christian habitus in the Central Highlands based on the indexing of elements from the local social structure. It is also shown how, due to his schooling and insertion into the missionary context, Jesse acquired dispositions that allowed him to leave the status of ‘indígena’ (native) for that of a ‘citizen’ upon his ‘assimilation,’ that is, his display of the behavior standards and skills expected from a ‘civilized’ person
Unexpected Functional Consequences of the Loss of the Autophagy-Related Conjugation System
Authors: Saito Toshiro , Sadoshima Junichi
Published: February 2017

We discuss the recent finding by Mizishima’s group regarding the role of the autophagy-related conjugation system in mediating the closure of autophagosomes and its implication in the study of autophagy in mammalian cells. The study not only shows a novel function of the autophagy-related conjugation system but also indicates that mammalian cells are capable of generating autophagosomes even without it.
GAMBIT: A Parameterless Model-Based Evolutionary Algorithm for Mixed-Integer Problems
Authors: Sadowski Krzysztof L. , Thierens Dirk , Bosman Peter A.N.
Published: February 2017

Learning and exploiting problem structure is one of the key challenges in optimization. This is especially important for black-box optimization (BBO) where prior structural knowledge of a problem is not available. Existing model-based Evolutionary Algorithms (EAs) are very efficient at learning structure in both the discrete, and in the continuous domain. In this article, discrete and continuous model-building mechanisms are integrated for the Mixed-Integer (MI) domain, comprising discrete and continuous variables. We revisit a recently introduced model-based evolutionary algorithm for the MI domain, the Genetic Algorithm for Model-Based mixed-Integer opTimization (GAMBIT). We extend GAMBIT with a parameterless scheme that allows for practical use of the algorithm without the need to explicitly specify any parameters. We furthermore contrast GAMBIT with other model-based alternatives. The ultimate goal of processing mixed dependences explicitly in GAMBIT is also addressed by introducing a new mechanism for the explicit exploitation of mixed dependences. We find that processing mixed dependences with this novel mechanism allows for more efficient optimization. We further contrast the parameterless GAMBIT with Mixed-Integer Evolution Strategies (MIES) and other state-of-the-art MI optimization algorithms from the General Algebraic Modeling System (GAMS) commercial algorithm suite on problems with and without constraints, and show that GAMBIT is capable of solving problems where variable dependences prevent many algorithms from successfully optimizing them.
20/X: Visuality, Representation and Epistemology in the Age of Intelligent Seeing Machines
Authors: McMullen Shannon C. , Winkler Fabian
Published: February 2017

To understand, critique and shape the impact of machines that can see in ways exceeding human capabilities, humans may need to learn to see like machines, to understand their abstractions and categorizations. The installation 20/X explores visuality, representation and epistemology in the age of intelligent seeing machines. This project is a collaboration between artists and biomedical researchers in an attempt to bring science, technology and the arts together to create an opportunity for public dialogue around an invention that will soon permeate the designed world.
Interdependent Group Contingencies Decrease Adolescents’ Disruptive Behaviors During Group Therapy: A Practitioner’s Demonstration
Authors: Brogan Kristen M. , Falligant John Michael , Rapp John T.
Published: February 2017

Adolescents who have been adjudicated for illegal sexual behavior may receive treatment that requires attending group therapy sessions and classes. For some adolescents, nonsexual problem behavior (e.g., verbal outbursts, noncompliance) interferes with their ability to participate in group treatment. Researchers used a multiple-baseline across groups design with an embedded changing criterion design to evaluate the effects of an interdependent group contingency for decreasing disruptive behavior in adolescents across two therapy groups. Results indicated that the procedure was effective in reducing disruptive behavior emitted by adolescents in group therapy. Measures of social validity indicated that both the therapists and students viewed the overall procedures and outcomes as acceptable. Implications for interdependent group contingencies across diverse populations are discussed.
Exploring the potential operation of a local tourism production system: The case of Messinia, Greece
Authors: Drakakis Panayiotis , Papadaskalopoulos Athanasios , Christofakis Manolis
Published: February 2017

The local tourism production system has been used in the literature as a territorial model to analyse a tourism destination and examine the interrelationships among its stakeholders. In this paper, we elaborate on this model by additionally analysing the economic linkages of the local tourism production system activities with local sectors, and seek to examine whether Messinia, a region in south-western Greece, fulfils the conditions for the operation of a local tourism production system. For this purpose, in conjunction with secondary data, 276 questionnaires were used from a business survey conducted via personal interviews at enterprises that are directly or indirectly affected by tourism. The results of the analysis show that our study area fulfils all four criteria set for the operation of such a system, though it does display strengths (high concentration of small- and medium-sized enterprises, strong economic linkages) and weaknesses (marginal specialisation, unsteady social ties). Meanwhile, the operation of a large tourism enterprise in the region does not act competitively but rather as a propulsive activity to the local tourism production system, thus supporting the notion that a large enterprise can boost a local production system and extending it within the tourism context. The paper concludes that investigating the economic linkages of the local tourism production system activities allows for a more accurate assessment of its operation, which in our case could be further enhanced by establishing a focal actor in a tourism network or cluster.
Supporting hospital renewal through strategic environmental sustainability programs
Authors: Pisters Peter , Bien Belinda , Dankner Stewart , Rubinstein Ed , Sheriff Fatima
Published: February 2017

Although the impact the environment can have on human health is well understood, the healthcare system’s impact on the environment is a topic that’s only been explored since the mid-1990s. More recent has been a realization of the risks that climate change poses to health and healthcare. Although there are numerous direct benefits for hospitals adapting environmental sustainability programs, this article examines how the systemic approach taken by the University Health Network’s (UHN) Energy & Environment program not only improves the hospital’s environmental performance and provides significant cost savings but also supports several areas of focus that are part of UHN’s current journey of renewal.
The Roots of Polish Culture-Centered Politics: Toward a Non–Purely Cultural Model of Cultural Domination in Central and Eastern Europe
Authors: Zarycki Tomasz , Smoczyński Rafał , Warczok Tomasz
Published: February 2017

This article’s main aim is to propose a novel model explaining the continuous domination of identity issues in modern Polish political discourse. The model proposed here may also appear useful as an explanation of similar tendencies in some other Central European countries. It is based on a specific reading of the modern history of the region—one relying on a structural perspective and specifically using Pierre Bourdieu’s notion of a “field of power.” In conclusion, the article suggests that the perspective it proposes may challenge what it calls simplistic accounts of processes of long duration.
Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report
Authors: Kido Kazuhiko , Evans Rickey A. , Gopinath Anil , Flynn Jeremy D.
Published: February 2017

Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis.

Conclusion:

Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.
Temporal and spatial variation of catastrophic river floodings in the Lower Yellow River from AD 960 to 1938
Authors: Zhang Xiangping , Fang Xiuqi
Published: February 2017

This study is intended to investigate the patterns for the temporal and spatial changes of catastrophic river floodings which took place in the Lower Yellow River, based on the available records collected from historical documents, and rearranged in a GIS database. A series of catastrophic river floodings from AD 960 to 1938 was reconstructed, and their temporal and spatial variations were analyzed, which leads to the conclusions, among others. (1) The increasing trend of frequency of catastrophic river floodings in the Lower Yellow River is not so significant in the past 1000 years. (2) Most dike breachings and overtoppings occurred near the apex of the Yellow River Alluvial Fan, and the number of dike breaching and overtopping was gradually reduced as the elevation decreased. (3) Under different spatio-temporal backgrounds, dike breaching and overtopping developed either downstream or upstream, which is evidenced by both the downstream movement for large temporal and spatial scales in dike breaching and overtopping places in AD 1128–1344 and 1391–1447 and the upstream movement for small temporal and spatial scales in AD 960–969, 1730–1761, and 1807–1819.
Validity of the timed 25-foot walk as an ambulatory performance outcome measure for multiple sclerosis
Authors: Motl Robert W , Cohen Jeffrey A , Benedict Ralph , Phillips Glenn , LaRocca Nicholas , Hudson Lynn D , Rudick Richard ,   Multiple Sclerosis Outcome Assessments Consortium
Published: February 2017

The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with multiple sclerosis (MS). One of the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful in MS. This article addresses the history, application, and psychometric properties of one such MSOAC metric of ambulation or walking namely, the timed 25-foot walk (T25FW). The T25FW has strong reliability over both brief and long periods of time in MS across a large range of disability levels. The outcome of walking speed from the T25FW has obvious real-world relevance and has correlated strongly with other measures of walking and lower extremity function. The T25FW is responsive for capturing intervention effects in pharmacological and rehabilitation trials and has an established value for capturing clinically meaningful change in ambulation. Directions for future research involve validating clinically meaningful improvements on the T25FW as well as determining whether 20% change is clinically meaningful across the disability spectrum. Researchers might further consider synchronizing accelerometers and motion sensors with the T25FW for capturing walking speed in everyday life and the patient’s real environment.
Control and flight test of a tilt-rotor unmanned aerial vehicle
Authors: Chen Chao , Zhang Jiyang , Zhang Daibing , Shen Lincheng
Published: February 2017

Tilt-rotor unmanned aerial vehicles have attracted increasing attention due to their ability to perform vertical take-off and landing and their high-speed cruising abilities, thereby presenting broad application prospects. Considering portability and applications in tasks characterized by constrained or small scope areas, this article presents a compact tricopter configuration tilt-rotor unmanned aerial vehicle with full modes of flight from the rotor mode to the fixed-wing mode and vice versa. The unique multiple modes make the tilt-rotor unmanned aerial vehicle a multi-input multi-output, non-affine, multi-channel cross coupling, and nonlinear system. Considering these characteristics, a control allocation method is designed to make the controller adaptive to the full modes of flight. To reduce the cost, the accurate dynamic model of the tilt-rotor unmanned aerial vehicle is not obtained, so a full-mode flight strategy is designed in view of this situation. An autonomous flight test was conducted, and the results indicate the satisfactory performance of the control allocation method and flight strategy.
Passive impedance-based second-order sliding mode control for non-linear teleoperators
Authors: García-Valdovinos Luis G , Santacruz-Reyes Hugo , López-Segovia Alan G , Bandala-Sánchez Manuel , García-Zarco Luis A
Published: February 2017

Bilateral teleoperation systems have attracted significant attention in the last decade mainly because of technological advancements in both the communication channel and computers performance. In addition, non-linear multi-degree-of-freedom bilateral teleoperators along with state observers have become an open research area. In this article, a model-free exact differentiator is used to estimate the full state along with a chattering-free second-order sliding mode controller to guarantee a robust impedance tracking under both constant and an unknown time delay of non-linear multi-degree-of-freedom robots. The robustness of the proposed controller is improved by introducing a change of coordinates in terms of a new nominal reference similar to that used in adaptive control theory. Experimental results that validate the predicted behaviour are presented and discussed using a Phantom Premium 1.0 as the master robot and a Catalyst-5 virtual model as the slave robot. The dynamics of the Catalyst-5 system is solved online.
A Qualitative Investigation of Cross-domain Influences on Medical Decision Making and the Importance of Social Context for Understanding Barriers to Hospice Use
Authors: Spencer Karen Lutfey , Hammad Mrig Emily , Matlock Daniel D. , Kessler Elizabeth R.
Published: February 2017

Hospice utilization has the potential to improve quality of life for patients while also decreasing healthcare costs at end of life. Barriers to hospice utilization have been identified, but less is known about how patient, provider, and system domains influence one another. We use in-depth interviews with physicians to examine the social, cultural, and economic contexts of decision making and how physician and organizational domains influence patient decision making around hospice. We identify sources of delay in physicians advocating for hospice referrals for their late-life patients that show how patient, physician, and system factors interact. Our results reveal incentives to postpone discussion of hospice that are not fully captured in policy perspectives, clinical guidelines, or current research paradigms focused on individual domains of influence. Opportunities to address previously identified barriers to hospice will benefit from consideration of how seemingly separate domains function in an integrated social context.
Relation between cathodoluminescence and trace-element distribution of magmatic topaz from the Ary-Bulak massif, Russia
Authors: Agangi Andrea , Gucsik Arnold , Nishido Hirotsugu , Ninagawa Kiyotaka , Kamenetsky Vadim S.
Published: February 2017

In order to define the cathodoluminescence (CL) properties of magmatic topaz and its relation with trace-element composition, we studied topaz phenocrysts from the Ary-Bulak ongonite massif, Russia using a wide array of analytical techniques. Scanning electron microscopy CL panchromatic images reveal strong variations, which define micrometre-scale euhedral growth textures. Several truncations of these growth textures occur in single grains implying multiple growth and resorption events. The CL-spectra of both CLbright and -dark domains have a major peak in the near-ultraviolet centred at 393 nm. Cathodoluminescence images taken after several minutes of electron bombardment show decreasing emission intensity. Electron microprobe analyses indicate high F concentrations (average OH/(OH + F) = 0.04 calculated by difference, 100 wt.% – total from electron probe microanalyses), consistent with what has been found previously in topaz-bearing granites, and the OH stretching vibration (∼3653 cm–1) was detected in Raman spectra. Laser ablation inductively-coupled plasma mass spectrometry traverses performed across the CL textures detected trace elements at ppm to thousands of ppm levels, including: Fe, Mn, Li, Be, B, P, Nb, Ta, W, Ti, Ga, light rare-earth elements, Th and U. Lithium, W, Nb and Ta appear to be correlated with CL intensity, suggesting a role for some of these elements in the activation of CL in topaz. In contrast, no clear correlation was found between CL intensity and F contents, despite the fact that the replacement of OH for F is known to affect the cell parameters of topaz.
From structure topology to chemical composition. XX. Titanium silicates: the crystal structure of hejtmanite, Ba2Mn4Ti2(Si2O7)2O2(OH)2F2, a Group-II TS-block mineral
Authors: Sokolova E. , Cámara F. , Hawthorne F. C. , Pautov L. A.
Published: February 2017

The crystal structure of hejtmanite, Ba2Mn4Ti2(Si2O7)2O2(OH)2F2, from Mbolve Hill, Mkushi River area, Central Province, Zambia (holotype material) has been refined on a twinned crystal to R1 = 1.88% on the basis of 4539 [|F| > 4|F|] reflections. Hejtmanite is triclinic, C1̅, a = 10.716(2), b = 13.795(3), c = 11.778 (2) , = 90.07(3), = 112.24(3), = 90.03(3), V = 1612(2) 3. Chemical analysis (electron microprobe) gives: Ta2O5 0.09, Nb2O5 1.27, ZrO2 0.65, TiO2 14.35, SiO2 23.13, BaO 26.68, SrO 0.19, FeO 11.28, MnO 15.12, Cs2O 0.05, K2O 0.33, F 3.82, H2Ocalc. 1.63, O = F 1.61, total 97.10 wt.%, where the H2O content was calculated from the crystal-structure refinement, with (OH F) = 4 apfu. The empirical formula, calculated on the basis of 20 (O F) anions, is of the form (Si2O7)2(XO)4(XP)2, Z=4: (Ba1.82K0.07 Sr0.02)Σ1.91(Mn2.33Zr0.04Mg0.03)Σ3.95(Ti1.88Nb0.10Zr0.02)Σ2(Si2.02O7)2O2[(OH)1.89 F0.11]Σ2F2. The crystal structure is a combination of a TS (Titanium Silicate) block and an I (intermediate) block. The TS block consists of HOH sheets (H heteropolyhedral, O octahedral). The topology of the TS block is as in Group-II TS-block minerals: Ti ( Nb) = 2 apfu per (Si2O7)2 [as defined by Sokolova (2006)]. In the O sheet, five [6]MO sites are occupied mainly by Mn, less Fe2 and minor Zr and Mg, with  = 2.198 (φ = O,OH), ideally giving Mn4 apfu. In the H sheet, two [6]MH sites are occupied mainly by Ti, with  = 1.962 (φ = O,F), ideally giving Ti2 apfu; four [4]Si sites are occupied by Si, with < SiO> = 1.625 . The MH octahedra and Si2O7 groups constitute the H sheet. The two [12]Ba-dominant AP(1,2) sites, with  = 2.984 (φ = O, F), ideally give Ba2 apfu. Two (1,2) and two (1,2) sites are occupied by O atoms and OH groups with minor F, respectively, ideally giving (XO)4 = ()2 ()2=O2(OH)2 pfu. Two (1,2) sites are occupied by F, giving F2 apfu. TS blocks link via a layer of Ba atoms which constitute the I block. Simplified and end-member formulae of hejtmanite are Ba2(Mn,Fe2)4Ti2 (Si2O7)2O2(OH,F)2 F2 and Ba2Mn4Ti2(Si2O7)2O2(OH)2F2, Z = 4. Hejtmanite is a Mn-analogue of bafertisite, Ba2 4 Ti2(Si2O7)2O2(OH)2F2.
The crystal structure of gianellaite, [(NHg2)2](SO4)(H2O)x, a framework of (NHg4) tetrahedra with ordered (SO4) groups in the interstices
Authors: Cooper M. A. , Abdu Y. A. , Hawthorne F. C. , Kampf Anthony R.
Published: February 2017

The crystal structure of gianellaite, [(NHg2)2](SO4)(H2O)x, cubic,F4̄3m, a = 9.521(6) ÅV= 863.1(1.6) Å3,Z= 4, was solved by direct methods and refined to anR1index of 2.1% based on 167 unique observed reflections collected on a three-circle rotating-anode (MoKα X-radiation) diffractometer equipped with multilayer optics and an APEX-II detector. In the structure of gianellaite, nitrogen-centred (NHg4)5+tetrahedra share all corners to form a framework of tetrahedra with an ordered arrangement of interstitial (SO4)2–tetrahedra that show strong orientational disorder. Infrared spectroscopy in the principal O–H stretching region shows peaks at ∼3300 and 1600 cm–1, indicating the presence of (H2O), the position(s) of which could not be discerned in difference-Fourier maps.
Crystal structure of adamite at high temperature
Authors: Zema M. , Tarantino S. C. , Boiocchi M. , Callegari A. M.
Published: February 2017

Structural modifications with temperature of adamite, Zn2(AsO4)(OH), were determined by single-crystal X-ray diffraction up to dehydration and collapse of the crystal structure. In the temperature range 25–400°C, adamite shows positive and linear expansion. Axial thermal expansion coefficients, determined over this temperature range, are αa= 1.06(2) × 10–5K–1, αb= 1.99(2) × 10–5K–1, αc= 3.7(1) × 10–6K–1and αV= 3.43(3) × 10–5K–1. Axial expansion is then strongly anisotropic withαa:αb:αc= 2.86: 5.38 : 1. Structure refinements of X-ray diffraction data collected at different temperatures allowed us to characterize the mechanisms by which the adamite structure accommodates variations in temperature. Expansion is limited mainly by edge sharing Zn(2) dimers along a and by edge sharing Zn(1) octahedra chains along c; on the other hand, connections of polyhedra along b, the direction of maximum expansion, is governed by corner sharing. Increasing temperature induces mainly an axial expansion of Zn(1) octahedron, which becomes more elongated, and no significant variations of the Zn(2) trigonal bipyramids and As tetrahedra. Starting from 400°C, deviation from a linear evolution of unit-cell parameters is observed, associated with some deterioration of the crystal, a sign of incipient dehydration. The process leads to the formation of Zn4(AsO4)2O.
Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL
Authors: Erdmann Tabea , Klener Pavel , Lynch James T. , Grau Michael , Vočková Petra , Molinsky Jan , Tuskova Diana , Hudson Kevin , Polanska Urszula M. , Grondine Michael , Mayo Michele , Dai Beiying , Pfeifer Matthias , Erdmann Kristian , Schwammbach Daniela , Zapukhlyak Myroslav , Staiger Annette M. , Ott German , Berdel Wolfgang E. , Davies Barry R. , Cruzalegui Francisco , Trneny Marek , Lenz Peter , Barry Simon T. , Lenz Georg
Published: February 2017

Key Points

PI3Kα/δ inhibition induces cytotoxicity in ABC DLBCLs through downregulation of NF-κB signaling. Inhibition of AKT induces cytotoxicity by downregulation of MYC in PTEN-deficient DLBCL models in vivo and in vitro.
A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human Term Nonlaboring Myometrium
Authors: Fanning Rebecca A. , Sheehan Florike , Leyden Claire , Duffy Niamh , Iglesias-Martinez Luis F. , Carey Michael F. , Campion Deirdre P. , O’Connor John J.
Published: February 2017

BACKGROUND:

Ergometrine is a uterotonic agent that is recommended in the prevention and management of postpartum hemorrhage. Despite its long-standing use, the mechanism by which it acts in humans has never been elucidated fully. The objective of this study was to investigate the role of adrenoreceptors in ergometrine’s mechanism of action in human myometrium. The study examined the hypothesis that α-adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine.

METHODS:

Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. After the generation of an ergometrine concentration–response curve (10–15 to 10–5 M), strips were treated with increasing concentrations of ergometrine (10–15 to 10–7 M) alone and ergometrine (10–7 to 10–5 M) in the presence of phentolamine (10–7 M), prazosin (10–7 M), propranolol (10–6 M), or yohimbine (10–6 M). The effects of adding ergometrine and the effect of drug combinations were analyzed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10 min), and motility index (g×contractions/10 min).

RESULTS:

A total of 157 experiments were completed on samples obtained from 33 women. There was a significant increase in the motility index (adding 0.342 g × counts/10 min/μM; 95% confidence interval [CI], 0.253–0.431, P < .001), amplitude (0.078 g/μM; 95% CI, 0.0344–0.121, P = 5e-04), and frequency (0.051 counts/10 min/μM; 95% CI, 0.038–0.063, P < .001) in the presence of ergometrine. The α-adrenergic antagonist phentolamine and the more selective α1-adrenergic antagonist prazosin inhibited the ergometrine mediated increase in motility index, amplitude, and frequency (−1.63 g × counts/10 min/μM and −16.70 g × counts/10 min/μM for motility index, respectively).

CONCLUSIONS:

These results provide novel evidence for a role for α-adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting. Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.
Cinetopia: Leftist Street Theatre and the Musical Production of the Metropolis in 1950s Bombay Cinema
Authors: Dass Manishita
Published: February 2017

The city of Bombay emerged as an emblematic space of India's postcolonial modernity in Hindi cinema during the 1950s, India's first decade of independence. This article focuses on the mise-en-scène of musical sequences—from popular Hindi films such as C.I.D. (dir. Raj Khosla, 1956), Awara (The Vagabond, dir. Raj Kapoor, 1951), Shree 420 (The Gentleman Cheat, dir. Raj Kapoor, 1955), Aar paar (This Way or That, dir. Guru Dutt, 1954), and Pocket maar (Pickpocket, dir. H. S. Rawail, 1956), as well as less commercially successful films such as Phir subah hogi (Dawn Will Come Again, dir. Ramesh Saigal, 1958)—that featured Bombay in a prominent role and delivered it to the Indian public as an iconic space oscillating between exuberance and disenchantment. The author analyzes how these musical sequences use performance, music, and set design to reimagine the metropolis as a site of social critique and utopian fantasy. The urban landscape created through these musical performances and the often highly stylized studio sets is not meant to be read as an authentic representation of real-life locales. Instead, the set as artifice insistently draws attention to its constructed nature and, in fact, relies, for its legibility and evocative power, on this “unreality effect.” The author's aim is to show how this unreal city emerges, in part, out of popular cinema's encounter with the Indian left cultural movement and leftist street theater of the 1940s, and how it functions as a “cinetopia,” a heterogeneous space of utopian longings and dystopian disenchantment.
A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells
Authors: Goicoechea Silvia M. , Zinn Ashtyn , Awadia Sahezeel S. , Snyder Kyle , Garcia-Mata Rafael
Published: February 2017

One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. In summary, we have identified a novel signaling pathway involving SGEF, RhoG and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.
Oxidized phagosomal NOX2 complex is replenished from lysosomes
Authors: Dingjan Ilse , Linders Peter T. A. , van den Bekerom Luuk , Baranov Maksim V. , Halder Partho , ter Beest Martin , van den Bogaart Geert
Published: February 2017

In dendritic cells, the NADPH oxidase 2 complex (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome that kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b558 (which comprises CYBB and CYBA), traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b558 is initially recruited to the phagosome from the plasma membrane during phagosome formation. Cytochrome b558 also traffics from a lysosomal pool to phagosomes and this is required to replenish oxidatively damaged NOX2. We identified syntaxin-7, SNAP23 and VAMP8 as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediating this process. Our data describe a key mechanism of how dendritic cells sustain ROS production after antigen uptake that is required to initiate T cell responses.
Competências Gerenciais (esperadas versus percebidas) de Professores-gestores de Instituições Federais de Ensino Superior: percepções dos professores de uma Universidade Federal
Authors: Barbosa Milka Alves Correia , Mendonça José Ricardo Costa de , Cassundé Fernanda Roda de Souza Araújo
Published: February 2017

Este trabalho analisou as competências gerenciais (competências esperadas e competências percebidas) associadas ao papel de professor-gestor em universidades federais à luz do modelo proposto por Mendonça et al. (2012). Argumenta-se que o papel social de professor-gestor é composto pelas competências gerenciais, que, em alguns asectos, são diferentes daquelas exigidas em outras facetas do papel de professor do Ensino Superior. O estudo foi de abordagem qualitativa e os dados foram coletados por meio de entrevistas semiestruturadas com professores-gestores da Universidade Federal do Vale do São Francisco (Univasf). A análise de conteúdo, com o suporte do software Atlas.ti, foi adotada para análise dos dados. As competências gerenciais esperadas indicaram aproximação com os componentes cognitivo, comportamental, ético e político assinalados por Mendonça et al. (2012) para os saberes de gestão. Sobre as competências gerenciais percebidas, os entrevistados acreditam possuir aquelas caracterizadas por componentes políticos, interpessoais e éticos. Acredita-se que os resultados desta pesquisa possam contribuir com o entendimento sobre as competências dos professores-gestores de instituições federais de ensino superior.
Chenodeoxycholic acid stimulates glucagon‐like peptide‐1 secretion in patients after Roux‐en‐Y gastric bypass
Authors: Nielsen Signe , Svane Maria S. , Kuhre Rune E. , Clausen Trine R. , Kristiansen Viggo B. , Rehfeld Jens F. , Holst Jens J. , Madsbad Sten , Bojsen‐Moller Kirstine N.
Published: February 2017

Postprandial secretion of glucagon‐like peptide‐1 (GLP‐1) is enhanced after Roux‐en‐Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP‐1 secretion through activation of TGR5‐receptors. We aimed to evaluate GLP‐1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB‐operated participants. Eleven participants (BMI 29.1 ± 1.2, age 37.0 ± 3.2 years, time from RYGB 32.3 ± 1.1 months, weight loss after RYGB 37.0 ± 3.1 kg) were studied in a placebo‐controlled, crossover‐study. On three different days, participants ingested (1) placebo (water), (2) UDCA 750 mg, (3) CDCA 1250 mg (highest recommended doses). Oral intake of CDCA increased plasma concentrations of GLP‐1, C‐peptide, glucagon, peptide YY, neurotensin, total bile acids, and fibroblast growth factor 19 significantly compared with placebo (all P < 0.05 for peak and positive incremental area‐under‐the‐curve (piAUC)). All plasma hormone concentrations were unaffected by UDCA. Neither UDCA nor CDCA changed glucose, cholecystokinin or glucose‐dependent insulinotropic polypeptide (GIP) concentrations. In conclusion, our findings demonstrate that the primary bile acid chenodeoxycholic acid is able to enhance secretion of gut hormones when administered orally in RYGB‐operated patients—even in the absence of nutrients.
To report or not to report: a proposal on how to deal with altered test results in hemolytic samples
Authors: Cadamuro Janne , Mrazek Cornelia , Haschke-Becher Elisabeth , Sandberg Sverre
Published: February 2017

Preanalytically altered test results are a challenge every laboratory has to face. The release of such results may be to the harm of the patient by triggering wrong clinical decision making in monitoring or treatment. On the other hand, their deletion also might be to the harm of the patient by delaying the time to decision making as the exact value sometimes is not even necessary but rather an answer to the question “Is it raised or lowered”. Based on this dilemma and forced to produce laboratory values without any clinical information on the respective patient, laboratories have developed their own preferred way on how to deal with preanalytically altered test results. Some release the value with a comment, some reject the value with or without a comment and others again provide only general information about the hemolytic sample. To date there is no guideline or standardization to this postanalytical topic. Therefore, with this opinion paper, we want to start the scientific discussion on this important issue by providing one possible method to overcome the lack of clinical information which the laboratory would need to correctly decide whether or not to release an altered test result. We suggest providing the clinician with all the information on the hemolytic sample and its impact on the respective parameter needed to make his/her own decision on the usage of the respective test result. We believe that reporting a preanalytically altered laboratory value including a respective comment is preferable to not reporting it.
Electrochemical reduction of CO2 on a Cu2O/polyaniline /stainless steel based electrode
Authors: Zhang Qin , Liang Yanping
Published: February 2017

Reduction of CO
Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe?
Authors: Ferris Jessica A. , Geffner Mitchell E.
Published: February 2017

Background:

The aim of this study was to assess aromatase inhibitor (AI) efficacy in increasing predicted adult height (PAH) and to describe clinical and biochemical safety profiles of AI-treated boys.

Methods:

A retrospective chart review was conducted at an academic children’s hospital endocrinology clinic. Twenty-one boys with predicted short stature and/or rapidly advancing bone age, divided as Tanner stage (TS) I–III Group 1 (G1, n=9) and TS IV–V Group 2 (G2, n=12), were treated with AIs, either letrozole or anastrozole (mean duration, G1: 2.4 years and G2: 0.9 years). Primary outcomes included PAH, hormonal/biochemical analytes, and clinical data.

Results:

PAH did not significantly change in either group. Mean peak testosterone significantly increased from baseline to 650±458 ng/dL (p=0.008) in G1 and to 1156±302 ng/dL (p=0.002) in G2. Estradiol did not significantly change in either group. Compared to baseline, G2 showed increased mean FSH (p=0.002), LH (p=0.002), hematocrit (p=0.0001), body mass index (BMI) z-score (p=0.0005), and acne (p=0.01).

Conclusions:

AIs did not increase PAH, regardless of TS. Boys in late puberty had significant increases in testosterone, gonadotropins, hematocrit, acne, and BMI, but no reduction in estradiol. The potential consequences of these findings are concerning and require long-term study, especially if AIs are started in late puberty.
Justifying Climate Engineering?
Authors: Stelzer Harald
Published: February 2017

This paper analyses four justifications for the deployment of climate engineering that have evolved in the debate (cost-effectiveness, buying time, indispensability, and last resort / lesser evil). The analysis includes basic assumptions, arguments and problems of these justifications with special attention given to aspects of intergenerational justice.
Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep
Authors: Chen Audrey , Singh Chanpreet , Oikonomou Grigorios , Prober David A.
Published: February 2017

Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation ofhcrt-expressing neurons is not blocked inhdcorhrh1mutants. We also found that the number ofhcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.
Quedar: cambio de estado y locación en el español de México
Authors: González Martínez Ana Gabriela , Maldonado Soto Ricardo
Published: February 2017

Uno de los problemas principales en la caracterización del verbo quedar es su multiplicidad de significados y funciones. Algunos trabajos distinguen valores de permanencia y significados locativos que suelen equipararse con estar. Esta equivalencia no resuelve los casos en los que la locación no solo designa ubicación, sino que integra también la noción de trayectoria. A partir de un análisis de habla oral, basado en datos del español de México, este trabajo propone que en quedar la noción de resultado es imperante y que puede designar tanto situaciones resultativas (cambio de estado) como situaciones locativas con cambio de locación y de movimiento abstracto. Pese a que quedar puede configurar dominios distintos, los significados estudiados presentan la misma configuración resultativa, de manera que las diferencias semánticas responden a relaciones espaciales y temporales en las que la determinación del cambio semántico involucra un proceso de integración subjetiva del conceptualizador.
Fortalecimiento de la expresión oral y escrita en inglés a través de un andamiaje de escritura creativa colaborativa: un estudio de diseño desde la cognición distribuida
Authors: Vergara Novoa Alonso , Perdomo Cerquera María Elena
Published: February 2017

Este artículo presenta los hallazgos de un estudio que buscó determinar la incidencia de un andamiaje de escritura creativa colaborativa en el desarrollo de la expresión oral y escrita en inglés de un grupo de estudiantes de Filología e Idiomas en la Universidad Nacional de Colombia. En el andamiaje confluyeron los fundamentos conceptuales de la adquisición de lenguas, la escritura creativa y la cognición distribuida. La investigación fue un estudio de diseño de corte cualitativo, a través del cual se pudo determinar que el andamiaje favoreció las habilidades expresivas, al generar un alto nivel de interacción en la lengua extranjera, mayor conciencia metalingüística y autorregulación del aprendizaje. Se considera que este estudio puede contribuir a la generación de estrategias que coadyuven a mejorar la cualificación de los licenciados en inglés en Colombia, ya que, según las estadísticas, un alto porcentaje se gradúa con niveles más bajos de los requeridos.
PROSPEK PENGEMBANGAN PLASMA NUTFAH IKAN BAUNG (Mystus nemurus C.V.l
Authors: Muflikhah N iam , Nurdawati Syarifah , Aida Siti Nurul
Published: February 2017

lkan baung (Mysfus nemurus C V.) termasuk ikan asli perairan umum yang mempunyai nrlai ekonomi yang cukup tlnggi dan layak untuk dibudidayakan, seperti halnya ikan-ikan perairan umum lainnya (jelawat, patin, lampam,tembakang, dan lain-lain). lkan ini berpotensi untuk diekspor baik di tingkat konsumsi mautun di tingkat benih. Masalah yang dihadapi dalam budi daya adalah pertumbuhannya retatif lambat dibandingkan ikan patin, terutama pada saat air surut pada musim kemarau pertumbuhan sangat lambat bahkan minusdibandingkan pada saA air besar atau penghujan. lkan baung bersifat karnivora tetapi sudah dapat tumbuh baik dengan pakan berbentuk pelet, baik komersil maupun racikan Induk betina memiliki fekunditas yang tinggi dengan Jumlah telur dari 2.500 sampai dengan 128.000 dari bobot 300 sampai dengan 1 250 g, induk jantan juga memiliki sperma yang cukup banyak terutama di daerah Jambi dan Riau. Selain itu, memiliki ukuran yang relatif besar-besar dibanding ikan baung dari Sumatera Selalan (Palembang). perbaikan mutu genetik ikan baung akan sangat berguna bagj pengembangan budi daya di masa yang akan datang.