bluuebunny/crossref_metadata_2025 huggingface dataset:
A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis
Authors: Olive Virginie , Sabio Erich , Bennett Margaux J , De Jong Caitlin S , Biton Anne , McGann James C , Greaney Samantha K , Sodir Nicole M , Zhou Alicia Y , Balakrishnan Asha , Foth Mona , Luftig Micah A , Goga Andrei , Speed Terence P , Xuan Zhenyu , Evan Gerard I , Wan Ying , Minella Alex C , He Lin
Published: October 2013

mir-17-92, a potent polycistronic oncomir, encodes six mature miRNAs with complex modes of interactions. In the Eμ-myc Burkitt’s lymphoma model, mir-17-92 exhibits potent oncogenic activity by repressing c-Myc-induced apoptosis, primarily through its miR-19 components. Surprisingly, mir-17-92 also encodes the miR-92 component that negatively regulates its oncogenic cooperation with c-Myc. This miR-92 effect is, at least in part, mediated by its direct repression of Fbw7, which promotes the proteosomal degradation of c-Myc. Thus, overexpressing miR-92 leads to aberrant c-Myc increase, imposing a strong coupling between excessive proliferation and p53-dependent apoptosis. Interestingly, miR-92 antagonizes the oncogenic miR-19 miRNAs; and such functional interaction coordinates proliferation and apoptosis during c-Myc-induced oncogenesis. This miR-19:miR-92 antagonism is disrupted in B-lymphoma cells that favor a greater increase of miR-19 over miR-92. Altogether, we suggest a new paradigm whereby the unique gene structure of a polycistronic oncomir confers an intricate balance between oncogene and tumor suppressor crosstalk.
Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling
Authors: Jin Yunyun , Xu Jinjin , Yin Meng-Xin , Lu Yi , Hu Lianxin , Li Peixue , Zhang Peng , Yuan Zengqiang , Ho Margaret S , Ji Hongbin , Zhao Yun , Zhang Lei
Published: October 2013

Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration. Drosophila intestinal stem cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and serve as an excellent model for studying cell growth and regeneration. In this study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm complex participates in ISC proliferation induced by the Scalloped–Yorkie transcriptional complex and that the Hippo (Hpo) signaling pathway directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted ISC proliferation. Our findings highlighted the importance of Hpo signaling in regulating epigenetic components such as Brm to control downstream transcription and hence ISC proliferation.
Sense of achievement
Authors: Knaden Markus , Hansson Bill S
Published: October 2013

Computational techniques developed to predict if odorants will interact with receptors in the olfactory system have achieved a success rate of 70%.
Survey Provides Insights About Recent Geoscience Graduates
Authors: Showstack Randy
Published: October 2013

Most new postsecondary geoscience graduates in the United States took an Earth science course in high school, 20% of those who graduated with master's and doctoral degrees did not have any postsecondary education chemistry courses, and nearly three quarters of master's graduates found positions within the oil and gas industry.
Reconstructing Past Sea Ice
Authors: Wolff E. W. , Gersonde R. , de Vernal Anne
Published: October 2013

One obvious manifestation of changing climate has been the recent rapid reduction in the extent and volume of Arctic sea ice. However, a dense observational data set spans only a few decades. To better understand sea ice dynamics and especially the context of the recent decline, scientists need to construct longer records. This relies on proxy data from marine sediments, ice cores, and coastal material, each providing evidence of past sea ice presence or absence.
Funding of Science Research and Education Stressed During Congressional Visits Day
Authors: Gilley Meg
Published: October 2013

Scientists across the country will look to Capitol Hill in the coming weeks as legislators decide the future of research funding in the next fiscal year (FY 2014). Battles over the FY 2014 budget, talks on raising the debt ceiling, and continued threats of further sequestration influence funding levels for federal scientific programs such as those in NASA, the Department of Energy, the Environmental Protection Agency, the National Oceanic and Atmospheric Administration, the National Science Foundation, and the U.S. Geological Survey (USGS).
Emplacement of the early Miocene Pinto Peak intrusion, Southwest Utah, USA
Authors: Petronis Michael S. , O'Driscoll Brian
Published: October 2013

In this contribution, we report rock magnetic, petrographic, and anisotropy of magnetic susceptibility (AMS) data from the Pinto Peak intrusion, all of which bear on volcanic construction. Rock magnetic data indicate that the dominant magnetic mineral phase is low‐Ti titanomagnetite of multidomain grain size, the composition of which varies spatially across the intrusion. The intrusion is a porphyritic andesite dominated by Ca‐rich plagioclase (>60%) as well as biotite, amphibole, olivine, and opaque minerals. Reflected light petrography reveals mostly euhedral‐subhedral (titano)magnetite crystals that often form clustered glomerocrysts and stringers of equant crystals, without exhibiting a consistent mineral alignment fabric. Moderate‐to‐shallow plunging prolate magnetic susceptibility ellipsoids dominate the northern part of the intrusion while steeply dipping/plunging magnetic susceptibility ellipsoids are generally restricted to the southern part of the intrusion. The vent facies rocks yield moderate‐to‐steep oblate susceptibility ellipsoids. We interpret the flow pattern in the north to reflect subhorizontal flow of magma, filling a tabular sheet‐like body associated with propagation of the intrusion to the north. We argue that the southern part of the intrusion represents the ascent site of the magma rising to shallow crustal levels along a steep feeder system. The oblate magnetic fabrics in the vent area plausibly represent flattening against the conduit walls as evidenced by a weak planar flow foliation observed in the vent conduit rocks. On reaching shallow crustal levels, the magma deformed and uplifted the roof rocks leading to gravitational instability. As the slide mass released from the roof, an explosive eruption ensued resulting in the emplacement of the Rocks of Paradise tuff and associated effusive lava flows. Following eruption, magma pressure decreased and the magma drained northward forming the northern intrusive phase.
Disentangling Mie and attenuation effects in rain using a Ka‐W dual‐wavelength Doppler spectral ratio technique
Authors: Tridon Frédéric , Battaglia Alessandro , Kollias Pavlos
Published: October 2013

A novel technique that enables to disentangle Mie and attenuation effects in coincident, beam‐matched Ka‐ and W‐band radar observations is presented here. The ratio of the measured radar Doppler spectra at the two frequencies is estimated, and the Doppler velocity regime that corresponds to Rayleigh scatterers is determined. The range variation of the Rayleigh regime “plateau” is directly linked to the differential attenuation between the two wavelengths and does represent the attenuation component of the dual‐wavelength ratio. The retrieval technique is applied to a light stratiform rain event and provides plausible results. The proposed Doppler spectral ratio methodology has potential for applications in precipitating snow, liquid and ice clouds and can be extended to other wavelength pairs.
A new semiempirical model of the peak electron density of the Martian ionosphere
Authors: Mendillo Michael , Marusiak Angela G. , Withers Paul , Morgan David , Gurnett Donald
Published: October 2013

Observations of the ionosphere of Mars have now reached a sufficient number to begin discussions on how best to create an empirically based model of its global morphology. Here we use nearly 113,000 values of maximum electron density (Nmax) obtained from 2005 to 2012 by the Mars Advanced Radar for Subsurface and Ionospheric Sounding on board the Mars Express satellite. At the altitude of peak density, photochemical processes dominate over dynamical effects, and thus values of Nmax can be organized using three basic parameters: solar flux, solar zenith angle, and orbital distance. The model can be used retrospectively to provide Nmax values for any date starting in 1965. Forecasts are possible using predicted solar flux values extending to the end of solar cycle 24. Validations using Viking in situ observations and radio occultation measurements from several satellite missions provide encouraging results for a useful semiempirical climatological model.
NAO implicated as a predictor of Northern Hemisphere mean temperature multidecadal variability
Authors: Li Jianping , Sun Cheng , Jin Fei‐Fei
Published: October 2013

The twentieth century Northern Hemisphere mean surface temperature (NHT) is characterized by a multidecadal warming‐cooling‐warming pattern followed by a flat trend since about 2000 (recent warming hiatus). Here we demonstrate that the North Atlantic Oscillation (NAO) is implicated as a useful predictor of NHT multidecadal variability. Observational analysis shows that the NAO leads both the detrended NHT and oceanic Atlantic Multidecadal Oscillation (AMO) by 15–20 years. Theoretical analysis illuminates that the NAO precedes NHT multidecadal variability through its delayed effect on the AMO due to the large thermal inertia associated with slow oceanic processes. An NAO‐based linear model is therefore established to predict the NHT, which gives an excellent hindcast for NHT in 1971–2011 with the recent flat trend well predicted. NHT in 2012–2027 is predicted to fall slightly over the next decades, due to the recent NAO decadal weakening that temporarily offsets the anthropogenically induced warming.
Ionospheric symmetry caused by geomagnetic declination over North America
Authors: Zhang Shun‐Rong , Chen Ziwei , Coster Anthea J. , Erickson Philip J. , Foster John C.
Published: October 2013

We describe variations in total electron content (TEC) in the North American sector exhibiting pronounced longitudinal progression and symmetry with respect to zero magnetic declination. Patterns were uncovered by applying an empirical orthogonal function (EOF) decomposition procedure to a 12 year ground‐based American longitude sector GPS TEC data set. The first EOF mode describes overall average TEC, while the strong influence of geomagnetic declination on the midlatitude ionosphere is found in the second EOF mode (or the second most significant component). We find a high degree of correlation between spatial variations in the second EOF mode and vertical drifts driven by thermospheric zonal winds, along with well‐organized temporal variation. Results strongly suggest a causative mechanism involving varying declination with longitude along with varying zonal wind climatology with local time, season, and solar cycle. This study highlights the efficiency and key role played by the geomagnetic field effect in influencing mesoscale ionospheric structures over a broad midlatitude range.
Rippled quasi‐perpendicular collisionless shocks: Local and global normals
Authors: Ofman L. , Gedalin M.
Published: October 2013

Proper determination of the shock normal is necessary for reliable determination of observed heliospheric shock parameters and comparison of observations with theory. The existing methods work sufficiently well for low and moderate Mach numbers one‐dimensional stationary shocks. Higher‐Mach‐number shocks are no longer planar at the scales of the ion convective gyroradius or smaller. In rippled shock fronts, the local shock normal may differ substantially from the global normal. The former is determined by the local direction of the fastest variation of the magnetic field, while the latter is determined by the far upstream and far downstream plasma conditions. Here we use 2‐D hybrid modeling of quasi‐perpendicular collisionless shocks with moderate and high Mach numbers to quantify the difference between the directions of the two normals. We find that the angle between the local normal and the global normal may be as large as 40° within the front of a rippled heliospheric shock. The coplanarity method of the shock normal determination is sensitive to the choice of the region for the magnetic field averaging. We also find that the usage of the sliding averaging region in the close vicinity of the shock transition provides satisfactory estimates of the global normal.
Solar irradiance reduction via climate engineering: Impact of different techniques on the energy balance and the hydrological cycle
Authors: Niemeier U. , Schmidt H. , Alterskjær K. , Kristjánsson J. E.
Published: October 2013

Different techniques of solar radiation management (SRM) have been suggested to counteract global warming, among them the injection of sulfur into the stratosphere, mirrors in space, and marine cloud brightening through artificial emissions of sea salt. This study focuses on to what extent climate impacts of these three methods would be different. We present results from simulations with an Earth system model where the forcing from the increase of greenhouse gases in a transient scenario (RCP4.5) was balanced over 50 years by SRM. While global mean temperature increases slightly due to the inertia of the climate system and evolves similar with time for the different SRM methods, responses of global mean precipitation differ considerably among the methods. The hydrological sensitivity is decreased by SRM, most prominently for aerosol‐based techniques, sea salt emissions, and injection of sulfate into the stratosphere. Reasons for these differences are discussed through an analysis of the surface energy budget. Furthermore, effects on large‐scale tropical dynamics and on regional climate are discussed.
Seasonal cycle of orographic gravity wave occurrence above small islands in the Southern Hemisphere: Implications for effects on the general circulation
Authors: Alexander M. J. , Grimsdell A. W.
Published: October 2013

Orographic gravity waves generated by flow over the topography of small islands in the southern oceans have been observed from orbit with the Atmospheric Infrared Sounder on the Aqua satellite. We examine the occurrence frequencies of these waves in the stratosphere at ∼40km above 14 islands and examine geographical and seasonal changes. Our results show that these small island mountain waves occur commonly in the stratosphere in the May–September season, though not every day. Differing seasonal variations are evident at different islands, and the seasonal variations are closely related to latitude and prevailing wind patterns. We also examine interannual variability in 2years of data and the relationships between occurrence frequencies, momentum fluxes, and stratospheric and surface winds. The results suggest that stratospheric winds have a first‐order limiting effect on the observations of these island mountain waves in Atmospheric Infrared Sounder (AIRS) data. Surface wind direction and island orographic relief have an additional but secondary influence on the island mountain wave occurrence frequencies in AIRS data. The implications are that these wave events are extremely common and that on many days when the waves are not observed in AIRS data they have likely dissipated and induced a drag force on the atmosphere below the 40km observation level. Observations of momentum flux during these wave events also permit a first estimate of their importance to the general circulation of the Southern Hemisphere.
Treatment With Anti–Tumor Necrosis Factor Biologic Agents in Human T Lymphotropic Virus Type I–Positive Patients With Rheumatoid Arthritis
Authors: Umekita Kunihiko , Hidaka Toshihiko , Miyauchi Shunichi , Ueno Shiro , Kubo Kazuyoshi , Takajo Ichiro , Hashiba Yayoi , Kai Yasufumi , Nagatomo Yasuhiro , Okayama Akihiko
Published: October 2013

Objective

To investigate the response to and safety of anti–tumor necrosis factor (anti‐TNF) therapy in human T lymphotropic virus type I (HTLV‐I)–positive patients with rheumatoid arthritis (RA).

Methods

Therapeutic response was evaluated in 10 HTLV‐I–positive and 20 HTLV‐I–negative patients with RA (sex and age matched) at 3 months after the beginning of anti‐TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti‐TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2‐year period.

Results

Significantly higher baseline levels of C‐reactive protein (CRP) were observed in HTLV‐I–positive patients than in HTLV‐I–negative patients (P = 0.0003). The response rate to anti‐TNF therapy was lower in HTLV‐I–positive patients than in HTLV‐I–negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti‐TNF treatment in HTLV‐I–positive patients were significantly higher than in HTLV‐I–negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV‐I–positive patients than in HTLV‐I–negative patients (P = 0.013). During the 2‐year observation period, no patients developed ATL.

Conclusion

These data suggest that HTLV‐I–positive patients with RA had higher inflammation and greater resistance to anti‐TNF treatment than HTLV‐I–negative patients. Further study is necessary to determine whether HTLV‐I infection should be measured when anti‐TNF agents are administered to patients with RA, especially in areas were HTLV‐I is endemic.
State and parameter estimation of state‐space model with entry‐wise correlated uniform noise
Authors: Pavelková Lenka , Kárný Miroslav
Published: October 2013

Joint parameter and state estimation is proposed for linear state‐space model with uniform, entry‐wise correlated, state and output noises (LSU model for short). The adopted Bayesian modelling and approximate estimation produce an estimator that (a) provides the maximum a posteriori estimate enriched by information on its precision, (b) respects correlated noise entries without demanding the user to tune noise covariances, and (c) respects bounded nature of real‐life variables. Copyright © 2013 John Wiley & Sons, Ltd.
Sand Supported Mixed‐Phase TiO2 Photocatalysts for Water Decontamination Applications
Authors: Hanaor Dorian A. H. , Sorrell Charles C.
Published: October 2013

Using an organometallic precursor, TiO2 coatings were fabricated on surfaces of quartz, zircon, and rutile sands. X‐ray diffraction, X‐ray fluorescence, UV–vis spectroscopy, and surface area measurement were used to characterize support materials. The phase composition and morphology of the coatings were characterized by laser Raman microspectroscopy and scanning electron microscopy, respectively. A packed bed reactor was used to study the inactivation of Escherichia coli in recirculating water by the supported photocatalysts. It was found that the sand grains were well coated with a homogenous layer of TiO2 and coatings were well adhered, exhibiting a mixed anatase‐rutile composition after firing at 850 °C. Photocatalytic activity was highest in coatings applied to quartz sand, although sterilization of the recirculating water was not achieved with any of the materials investigated. The advantages of quartz as a TiO2 photocatalyst support material are likely a result of this material's higher purity and optical transmittance. Potential enhancement through Si doping cannot be ruled out.
Subtree Reuse in Multi‐Frontal Solvers for Regular Grids in Step‐and‐Flash Imprint Nanolithography Modeling
Authors: Sieniek Marcin , Paszynski Maciej
Published: October 2013

The paper presents multi‐scale modeling of the step‐and‐flash imprint lithography, a modern patterning process, which depends on photopolymerization in order to replicate the topography of a template onto a substrate [Colbum et al., J. Vac. Sci. Technol. B 2001, 19, 6]. Multi‐scale modeling presented in this paper corresponds to densification of the feature inside the template as well as deformation of the feature after removal of the template. Linear elasticity with thermal expansion coefficient, discretized with the finite element method (FEM) [Paszynski et al., IOP Conf. Series: Mat. Sci. Eng. 2010, 10, 012247] is utilized as the macro‐scale model. Molecular statics (MS) with quadratic and Lennard‐Jones potentials is utilized as the nano‐scale model [Paszynski et al., ICES Report, 2005, 05‐38]. Degrees of freedom from the macro‐scale model located on the interface have been identified with particles from nano‐scale domain. In order to improve the performance of the traditional approach, we propose an optimization technique for multi‐frontal direct solvers with constant coeffcients. The technique consists in reuse of sub‐branches of elimination trees over regular cube‐shaped grids built with hexahedral finite elements. To obtain an efficient reuse scheme, we construct an elimination tree in a specific way, so that all frontal matrices at certain level of the tree are identical. It is based on an observation that the solver tree for a uniform, fine 3D finite element grid is very regular, provided that introduction of boundary conditions as well as macro–nano‐scale interface conditions is postponed to the root of the tree (as opposed to applying them at the bottom nodes). Apart from a detailed description of the optimization, we offer a comprehensive estimation of the computational cost and memory usage benefits and showcase its accuracy.
Mechanical Properties of Conjugated Polymers and Polymer‐Fullerene Composites as a Function of Molecular Structure
Authors: Savagatrup Suchol , Makaram Aditya S. , Burke Daniel J. , Lipomi Darren J.
Published: October 2013

Despite the importance of mechanical compliance in most applications of semiconducting polymers, the effects of structural parameters of these materials on their mechanical properties are typically not emphasized. This paper examines the effect of length of the pendant group on the tensile modulus and brittleness for a series of regioregular poly(3‐alkylthiophenes) (P3ATs) and their blends with a soluble fullerene derivative, PCBM. The tensile modulus decreases with increasing length of the alkyl side‐chain, from 1.87 GPa for butyl side chains to 0.16 GPa for dodecyl chains. The moduli of P3AT:PCBM blends films are greater than those of the pure polymers by factors of 2–4. A theoretical model produces a trend in the effect of alkyl side chain on tensile modulus that follows closely to the experimental measurements. Tensile modulus correlates with brittleness, as the strain at which cracks appear is 6% for P3BT and >60% for P3OT. Adhesion of the P3AT film to a polydimethylsiloxane (PDMS) substrate is believed to play a role in an apparent increase in brittleness from P3OT to P3DDT. The additive 1,8‐Diiodooctane (DIO) reduces the modulus of P3HT:PCBM blend by a factor of 3. These results could enable mechanically robust, flexible, and stretchable electronics.
Solids transport models comparison and fine‐tuning for horizontal, low concentration flow in single‐phase carrier fluid
Authors: Soepyan Frits Byron , Cremaschi Selen , Sarica Cem , Subramani Hariprasad J. , Kouba Gene E.
Published: October 2013

We determined and fine‐tuned the solids transport models appropriate for predicting the single‐phase carrier fluid velocity to transport solid particles in conduits for horizontal, low concentration flow. A database with 538 experimental data points was compiled. A literature review was performed to determine the data ranges, forces, and mechanisms used to develop 44 models, and their velocity predictions were compared against the database using statistics. Using the dimensionless forms of the models and the data, the model parameters were adjusted to improve their accuracy and identify the dominant forces. At low concentrations: for liquid/solid flow from a bed of solids and gas/solid flow from the bottom of pipelines, the particle weight, and inertial and viscous forces dominate; for gas/solid flow from a bed of solids, the particle weight, and inertial, viscous, and adhesive forces play a role; and gaps exist in the data for large‐diameter pipes and high‐density gases. © 2013 American Institute of Chemical Engineers AIChE J, 60: 76–122, 2014
Comparison of DEM results and Lagrangian experimental data for the flow and mixing of granules in a rotating drum
Authors: Alizadeh Ebrahim , Bertrand Francois , Chaouki Jamal
Published: October 2013

This work assesses the accuracy of the discrete element method (DEM) for the simulation of solids mixing using non‐intrusive Lagrangian radioactive particle tracking data, and explains why it may provide physically sound results even when non‐real particle properties are used. The simulation results concern the size segregation of polydisperse granules in a rotating drum operated in rolling mode. Given that the DEM is sensitive to simulation parameters, the granule properties were measured experimentally or extracted from the literature. Several flow phenomena are investigated numerically and experimentally, including the particle residence time, the radial segregation, and the radial variation of the axial dispersion coefficient. An analysis of the DEM model is then presented, with an emphasis on the Young's modulus and friction coefficients. Finally, dimensionless motion equations and corresponding dimensionless numbers are derived to investigate the effect of simulation parameters on particle dynamics. © 2013 American Institute of Chemical Engineers AIChE J, 60: 60–75, 2014
Database monitoring index for adaptive soft sensors and the application to industrial process
Authors: Kaneko Hiromasa , Funatsu Kimito
Published: October 2013

In chemical plants, soft sensors are used to predict difficult‐to‐measure process variables. Soft sensor models must adapt to process changes by using new measured data. However, when a model is reconstructed with data that have low variation, the model cannot predict abrupt changes of process characteristics. The predictive performance of adaptive models depends on databases. We therefore propose an index to monitor database, that is, database monitoring index (DMI), and a database monitoring method using the DMI. The DMI is based on similarity between two data. The more similar two data are the smaller value the DMI has. New data are stored when the minimum DMI‐value of the data exceeds a threshold. Through the analysis of simulation data and real industrial data, we confirmed that databases can be appropriately managed and the predictive accuracy of adaptive soft sensor models increased by using the proposed method. © 2013 American Institute of Chemical Engineers AIChE J, 60: 160–169, 2014
Clinical implications of the SETBP1 mutation in patients with primary myelodysplastic syndrome and its stability during disease progression
Authors: Hou Hsin‐An , Kuo Yuan‐Yeh , Tang Jih‐Luh , Chou Wen‐Chien , Yao Ming , Lai Yan‐Jun , Lin Chien‐Chin , Chen Chien‐Yuan , Liu Chieh‐Yu , Tseng Mei‐Hsuan , Huang Chi‐Fei , Chiang Ying‐Chieh , Lee Fen‐Yu , Liu Ming‐Chih , Liu Chia‐Wen , Huang Shang‐Yi , Ko Bor‐Sheng , Wu Shang‐Ju , Tsay Woei , Chen Yao‐Chang , Tien Hwei‐Fang
Published: October 2013

Mutations of the SET binding protein 1 (SETBP1) gene have been identified in patients with myeloid neoplasms, but the clinical relevance of this mutation and its association with other gene mutations in myelodysplastic syndrome (MDS) and the stability during disease progression remains unclear. Mutations in SETBP1 gene at exon 4 were analyzed by polymerase chain reaction and direct sequencing in 430 MDS patients. The results were correlated with clinical features, cytogenetics, gene mutations and treatment outcomes. SETBP1 mutations were identified in 14 (3.3%) of the 430 patients with primary MDS based on the FAB classification and 8 (2.4%) of the 333 patients based on the WHO classification. The SETBP1 mutation was closely associated with higher white blood cell counts, isochromosome of 17q, monosomy 7, and mutations of ASXL1, EZH2 and SRSF2. With a median follow‐up of 43.9 months, MDS patients, based on either the FAB or WHO classification, had a significantly poorer overall survival (OS) if they harbored SETBP1 mutation. Further, SETBP1 mutation was an independent poor prognostic factor for OS (HR = 1.842, CI 95%, 1.1018–3.332, P = 0.043) irrespective of age, sex, and the International Prognostic Scoring System. Sequential analysis showed that the original SETBP1 mutations in the eight SETBP1‐mutated patients studied were retained while two of the 101 SETBP1‐wild patients acquired novel SETBP1 mutations during follow‐ups. The SETBP1 mutation is associated with poor prognosis in MDS. The mutation can be acquired during the clinical course suggesting it may play a role in disease progression. Am. J. Hematol. 89:181–186, 2014. © 2013 Wiley Periodicals, Inc.
Laboratory tests for paroxysmal nocturnal hemoglobinuria
Authors: Preis Meir , Lowrey Christopher H.
Published: October 2013

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder that is often suspected in a patient presenting with non‐immune hemolytic anemia associated with pancytopenia or venous thrombosis. This disorder is a consequence of acquired somatic mutations in the phosphatidylinositol glycan class A (PIG‐A)gene in the hematopoietic stem cells (HSC) of patients. The presence of these mutations leads to production of blood cells with decreased glycosyl phosphatidylinositol‐anchored cell surface proteins, making red blood cells derived from the clone more sensitive to complement mediated hemolysis. The diagnosis of PNH may be difficult in some cases due a low proportion of PNH cells in the blood and occasionally due to difficulties in selecting the most appropriate diagnostic studies. The latest generation of tests allow for detection of very small populations of PNH cells, for following the natural course and response to therapy of the disease, and for helping to decide when to initiate therapy with monoclonal antibody targeting the terminal complement protein C5 (Eculizumab), anticoagulation, and in some cases allogeneic HSC transplant. In this article, we review the different diagnostic tests available to clinicians for PNH diagnosis. Am. J. Hematol. 89:339–341, 2014. © 2013 Wiley Periodicals, Inc.
Genotype and clinical care correlations in craniosynostosis: Findings from a cohort of 630 Australian and New Zealand patients
Authors: Roscioli T. , Elakis G. , Cox T.C. , Moon D.J. , Venselaar H. , Turner A.M. , Le T. , Hackett E. , Haan E. , Colley A. , Mowat D. , Worgan L. , Kirk E.P. , Sachdev R. , Thompson E. , Gabbett M. , McGaughran J. , Gibson K. , Gattas M. , Freckmann M‐L. , Dixon J. , Hoefsloot L. , Field M. , Hackett A. , Kamien B. , Edwards M. , Adès L.C. , Collins F.A. , Wilson M.J. , Savarirayan R. , Tan T.Y. , Amor D.J. , McGIllivray G. , White S.M. , Glass I.A. , David D.J. , Anderson P.J. , Gianoutsos M. , Buckley M.F.
Published: October 2013

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1‐3/TWIST1‐associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis. © 2013 Wiley Periodicals, Inc.
Progress in Designing Artificial Proteases: A New Therapeutic Option for Amyloid Diseases
Authors: Suh Junghun
Published: October 2013

This Focus Review describes the evolution of artificial proteases, which are synthetic catalysts for peptide hydrolysis that mimic the action of natural proteases. The evolution took place through discovery of catalytic centers for peptide hydrolysis, attachment of substrate‐recognition sites to the catalytic centers, and the advent of target‐selective artificial proteases. Application of the target‐selective artificial proteases led to a therapeutic option for amyloid diseases, such as Alzheimer’s disease and diabetes.
Graphen‐analoge anorganische Schichtmaterialien
Authors: Rao C. N. R. , Ramakrishna Matte H. S. S. , Maitra Urmimala
Published: October 2013

Die Entdeckung von Graphen war eine Sensation für die Chemie, aber auch für die Physik, die Materialwissenschaften und verwandte Gebiete. Die ungewöhnlichen Eigenschaften des Graphens weckten auch ein Interesse an anderen Schichtmaterialien wie Molybdänsulfid und Bornitrid. So sind in den letzten Jahren verschiedene ein‐ und mehrlagige Chalkogenide und andere anorganische Materialien mit interessanten Eigenschaften und Anwendungsmöglichkeiten hergestellt und charakterisiert worden. Dieser Aufsatz gibt eine Übersicht über neue zweidimensionale Nanomaterialien. Dabei behandeln wir nicht nur Synthese und Charakterisierung, sondern auch spektroskopische und optische, magnetische und elektrische Eigenschaften und mögliche Anwendungen. Außerdem werden Kompositmaterialien aus anorganischen Schichtstrukturen mit Graphen und Polymeren und schließlich Borcarbonitride behandelt.
India's Demographic Transition: Boon or Bane?
Authors: Kumar Utsav
Published: October 2013

Age structure and its dynamics are critical in understanding the impact of population growth on a country's growth prospects. Using state‐level data from India, we show that the pace of demographic transition varies across states, and that these differences are likely to be exacerbated over the period 2011–26. We show that the so‐called BIMARU states (Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh) are likely to see a continuing increase in the share of the working‐age population in total population. The BIMARU states are expected to contribute 58 per cent of the increase in India's working‐age population. The BIMARU states have traditionally been the slow‐growing states and have performed poorly on different accounts of social and physical infrastructure. The article argues that whether the demographic window of opportunity will be utilised and turned into a boon or be wasted and result in a bane will rest critically on the ability of the BIMARU states to exploit the bulge in the working‐age population.
Synthesis and Evaluation as Antitumor Agents of 1,4‐Naphthohydroquinone Derivatives Conjugated with Amino Acids and Purines
Authors: Molinari Aurora , Oliva Alfonso , Ojeda Claudia , Miguel del Corral José M. , Castro Maria A. , Mollinedo Faustino , San Feliciano Arturo
Published: October 2013

We report on the synthesis of two series of 1,4‐naphthohydroquinone derivatives conjugated with amino acids (Gly, Ala, Phe, and Glu) and with substituted purines linked by an aliphatic chain. The compounds were obtained through Diels–Alder cycloaddition between myrcene and 1,4‐benzoquinone and evaluated in vitro for their cytotoxicity (GI50) against cultured human cancer cells of A‐549 lung carcinoma, HT‐29 colon adenocarcinoma, and MCF‐7 breast carcinoma. The GI50 values found for some hydroquinone–amino acid and hydroquinone–purine hybrids against MCF‐7 are in an activity range comparable to that of the reference drug doxorubicin.
Effectiveness of Chloroquine and Inflammatory Cytokine Response in Patients With Early Persistent Musculoskeletal Pain and Arthritis Following Chikungunya Virus Infection
Authors: Chopra Arvind , Saluja Manjit , Venugopalan Anuradha
Published: October 2013

Objective

To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection.

Methods

During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/IgG anti‐CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24‐week, 2‐arm, parallel efficacy trial of CQ (250 mg/day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin‐6 [IL‐6], interferon‐γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ‐inducible protein 10, and IL‐13). Twenty‐two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent‐to‐treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched.

Results

There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain −3.9 and −4.2, respectively). Patients improved significantly. Cytokine levels remained several‐fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent.

Conclusion

This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.
An Essential Role of Caspase 1 in the Induction of Murine Lupus and Its Associated Vascular Damage
Authors: Kahlenberg J. Michelle , Yalavarthi Srilakshmi , Zhao Wenpu , Hodgin Jeffrey B. , Reed Tamra J. , Tsuji Noriko M. , Kaplan Mariana J.
Published: October 2013

Objective

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome associated with organ damage and an elevated risk of cardiovascular disease resulting from activation of both innate and adaptive immune pathways. Recently, increased activation of the inflammasome machinery in SLE has been described. Using the mouse model of pristane‐induced lupus, we undertook this study to explore whether caspase 1, the central enzyme of the inflammasome, plays a role in the development of SLE and its associated vascular dysfunction.

Methods

Eight‐week‐old wild‐type (WT) or caspase 1−/− mice were injected intraperitoneally with phosphate buffered saline or pristane. Six months after injection, mice were euthanized, and the development of a lupus phenotype and vascular dysfunction was assessed.

Results

While WT mice exposed to pristane developed autoantibodies and a strong type I interferon response, mice lacking caspase 1 were significantly protected against these features as well as against pristane‐induced vascular dysfunction. Further, the development of immune complex glomerulonephritis, which was prominent after pristane exposure in WT mice, was significantly abrogated in caspase 1−/− mice.

Conclusion

These results indicate that caspase 1 is an essential component in the development of lupus and its associated vascular dysfunction and that it may play an important role in the cross‐talk between environmental exposures and autoimmunity development, thus identifying a novel pathway for therapeutic targeting.
Modified Gaussian estimation for correlated binary data
Authors: Zhang Xuemao , Paul Sudhir
Published: October 2013

In this paper, we develop a Gaussian estimation (GE) procedure to estimate the parameters of a regression model for correlated (longitudinal) binary response data using a working correlation matrix. A two‐step iterative procedure is proposed for estimating the regression parameters by the GE method and the correlation parameters by the method of moments. Consistency properties of the estimators are discussed. A simulation study was conducted to compare 11 estimators of the regression parameters, namely, four versions of the GE, five versions of the generalized estimating equations (GEEs), and two versions of the weighted GEE. Simulations show that (i) the Gaussian estimates have the smallest mean square error and best coverage probability if the working correlation structure is correctly specified and (ii) when the working correlation structure is correctly specified, the GE and the GEE with exchangeable correlation structure perform best as opposed to when the correlation structure is misspecified.
Study on the synthesis and structure–effect relationship of multi‐aryl imidazoles with their fluorescence properties
Authors: Tian Mi , Wang Chao , Wang LiGong , Luo Kai , Zhao An , Guo CanCheng
Published: October 2013

In this paper, 23 multi‐aryl imidazole derivatives were synthesized and identified by nuclear magnetic resonance, ultraviolet‐visible and elemental analysis. At the same time, their ultraviolet‐visible maximum absorption (λabmax), fluorescence emission maximum (λemmax) and quantum yields (Фf) were measured. The relationships between the optical behaviors and structures for these compounds were assessed. The results show that the λmaxab and λmaxem are red‐shifted and the fluorescence Фf are increased by the introduction of electron‐withdrawing substituents and the increase in the planarity of multi‐aryl imidazole molecules. The results also showed that the fluorescence quantum yields of the compounds containing two imidazole nuclei are double the corresponding mono‐imidazole nucleus compounds. Copyright © 2013 John Wiley & Sons, Ltd.
Revealing interaction between sulfobutylether‐β‐cyclodextrin and reserpine by chemiluminescence and site‐directed molecular docking
Authors: Xiong Xunyu , Wu Min , Zhao Xinfeng , Song Zhenghua
Published: October 2013

The host–guest interaction between sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD) and reserpine (RSP) is described using flow injection‐chemiluminescence (FI‐CL) and site‐directed molecular docking methods. It was found that RSP could inhibit the CL intensity produced by a luminol/SBE‐β‐CD system. The decrease in CL intensity was logarithmic over an RSP concentration range of 0.03 to 700.0 nM, giving a regression equation of ∆I = 107.1lgCRES + 186.1 with a detection limit of 10 pM (3σ). The CL assay was successfully applied in the determination of RSP in injection, saliva and urine samples with recoveries in the range 93.5–106.1%. Using the proposed CL model, the binding constant (KCD‐R) and the stoichiometric ratio of SBE‐β‐CD/RSP were calculated to be 7.4 × 106 M‐1 and 1 : 1, respectively. Using molecular docking, it was confirmed that luminol binds to the small cavity of SBE‐β‐CD with a nonpolar interaction, while RSP targeted the larger cavity of SBE‐β‐CD and formed a 1 : 1 complex with hydrogen bonds. The proposed new CL method has the potential to become a powerful tool for revealing the host–guest interaction between CDs and drugs, as well as monitoring drugs with high sensitivity. Copyright © 2013 John Wiley & Sons, Ltd.
Infants' object location and identity processing in spatial scenes: an ERP study
Authors: van Hoogmoed Anne H. , van den Brink Danielle , Janzen Gabriele
Published: October 2013

Background

Fast detection and identification of objects in an environment is important for using objects as landmarks during navigation. While adults rapidly process objects within an environment and use landmarks during navigation, infants do not routinely use distal landmarks below the age of 18 months. In the current event‐related potential (ERP) study we adopted an oddball paradigm to examine whether infants are capable of processing objects in environments, which is a prerequisite for using objects as landmarks.

Methods

We measured the electrophysiological correlates and time courses related to the processing of changes in object location, object identity, and a switch of two objects.

Results

Twelve‐month‐old infants showed an Nc (negative central) effect reflecting increased attention likely caused by initial change detection within 300 msec for all three manipulations. In addition, they showed conscious processing of an object change and a location change as evidenced by a positive slow wave (PSW).

Conclusion

This study is the first to show that infants are capable of rapidly detecting changes in single objects when these are presented in an environment, but lack conscious detection of a switch. These results indicate that 12‐month‐old infants as yet lack the ability to rapidly bind the identity and location of multiple objects within an environment.
Person re‐identification with local descriptors across multicameras
Authors: Huang Qiao , Yang Jie
Published: October 2013

Tracking the same person across multiple cameras is an important task in human motion analysis systems. It is also desirable to re‐identify the individuals who have been previously seen with a single camera. This paper addresses this problem by the re‐identification of the same individual in two different datasets, which are both challenging situations from human motion analysis systems. In this paper, local descriptors are introduced for image description, and support vector machines are employed for high classification performance and so an efficient bag‐of‐features approach for image presentation. In this way, robustness against low resolution, occlusion, and pose, viewpoint and illumination changes is achieved in a very fast way. We obtain promising results from the evaluation with situations where a number of individuals vary continuously from a multicamera system. Copyright © 2013 John Wiley & Sons, Ltd.
A faster triangle‐to‐triangle intersection test algorithm
Authors: Ling‐yu Wei
Published: October 2013

The triangle‐to‐triangle intersection test is the most basic component of collision detection. And our algorithm, which firstly computes the line segment between triangle A and the plane of triangle B and uses a new method to detect the intersection between this line and triangle B, can reduce about 10% of time on average, compared with the previous fastest algorithm. Our new method divides the plane of triangle B into four quarter planes by two edges of B, and detects intersection depending on the location of the two endpoints of the segment. After using some techniques like avoiding division and projecting the segment and triangle B on XY, YZ, or ZX plane, the total number of arithmetic operations is reduced to at most 87, which is less than any existing algorithms. Copyright © 2013 John Wiley & Sons, Ltd.