bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery
Authors: Gupta Rishi , Sun Chung-Huan Johnny , Rochestie Dustin , Owada Kumiko , Khaldi Ahmad , Johnson Andrew K , Horn Christopher M
Published: June 2016

Background

Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood–brain barrier and reperfusion injury.

Objective

To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy.

Methods

We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours.

Results

The 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9–20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67).

Conclusions

This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.
Ten‐minute chat
Authors: Day Liz Edmondson
Published: June 2016

Liz Edmondson Day is the practice manager at Stanley House Veterinary Group, which recently won the Employer of the Year category in the 2016 Pendle Business Awards, which are intended to recognise high achieving businesses in the area.
Characterization of surge superposition following 2-stage load rejection in hydroelectric power plant
Authors: Chen Sheng , Zhang Jian , Wang Xichen
Published: June 2016

When calculating the maximum upsurge in surge tank due to load rejection in a hydroelectric power plant, it has been natural and customary to believe that the maximum surge amplitude occurs in simultaneous load rejection of all units at 100% load. As 2-stage load rejection (2-stage LR), involving a step-wise reduction in load, is not considered since it is assumed to produce less severe surge conditions. This study formulates the surge superposition associated with 2-stage LR and shows, surprisingly but significantly, that such 2-stage LR sometimes produces more severe surge conditions than simultaneous and complete load rejection (SCLR). The results indicate that this unexpected phenomenon is ascribable to the resistant effect of throttled surge tank, whose increase will lead to a greater difference in the maximum upsurges between 2-stage LR and SCLR conditions. Different time intervals during 2-stage LR correspond to different maximum upsurges. The analytical formula predicting the worst interval time is derived exactly and verified with two numerical cases.
Measuring the trilinear neutral Higgs boson couplings in the minimal supersymmetric standard model at e+e− colliders in the light of the discovery of a Higgs boson
Authors: Khosa Charanjit K. , Pandita P. N.
Published: June 2016

We consider the measurement of the trilinear couplings of the neutral Higgs bosons in the minimal supersymmetric standard model (MSSM) at a high energy [Formula: see text] linear collider in the light of the discovery of a Higgs boson at the CERN Large Hadron Collider (LHC). We identify the state observed at the LHC with the lightest Higgs boson [Formula: see text] of the MSSM, and impose the constraints following from this identification, as well as other experimental constraints on the MSSM parameter space. In order to measure trilinear neutral Higgs couplings, we consider different processes where the heavier Higgs boson [Formula: see text] of the MSSM is produced in electron–positron collisions, which subsequently decays into a pair of lighter Higgs boson. We identify the regions of the MSSM parameter space where it may be possible to measure the trilinear couplings of the Higgs boson at a future electron–positron collider. A measurement of the trilinear Higgs couplings is a crucial step in the construction of the Higgs potential, and hence in establishing the phenomena of spontaneous symmetry breaking in gauge theories.
Cascading failures of interdependent modular small-world networks
Authors: Zhu Guowei , Wang Xianpei , Tian Meng , Dai Dangdang , Long Jiachuan , Zhang Qilin
Published: June 2016

Much empirical evidence shows that many real-world networks fall into the broad class of small-world networks and have a modular structure. The modularity has been revealed to have an important effect on cascading failure in isolated networks. However, the corresponding results for interdependent modular small-world networks remain missing. In this paper, we investigate the relationship between cascading failures and the intra-modular rewiring probabilities and inter-modular connections under different coupling preferences, i.e. random coupling with modules (RCWM), assortative coupling in modules (ACIM) and assortative coupling with modules (ACWM). The size of the largest connected component is used to evaluate the robustness from global and local perspectives. Numerical results indicate that increasing intra-modular rewiring probabilities and inter-modular connections can improve the robustness of interdependent modular small-world networks under intra-attacks and inter-attacks. Meanwhile, experiments on three coupling strategies demonstrate that ACIM has a better effect on preventing the cascading failures compared with RCWM and ACWM. These results can be helpful to allocate and optimize the topological structure of interdependent modular small-world networks to improve the robustness of such networks.
Output Voltage Sampling Circuit for Discontinuous Conduction Mode Flyback Pulse-Width Modulation Controller
Authors: Shi Ling-Feng , Shi Zhen-Bo , Chen Sen , Xun Jian-Hui
Published: June 2016

Primary-side controlled pulse-width modulation (PWM) flyback converter has been widely used in low-power and low-voltage products for its simple structure and low cost. This paper presents a novel output voltage sampling circuit which considers the influence of the rectifier diode current on the output voltage sampling. The output voltage sampling circuit samples the output voltage at 85% of the secondary inductance discharge time [Formula: see text] of last cycle, which improves the accuracy of the output voltage sampling circuit. Besides, the circuit can also sample the secondary inductance discharge time [Formula: see text]. Finally, a chip has been fabricated in 0.6[Formula: see text][Formula: see text]m complementary metal-oxide semiconductor (CMOS) process, which is used in the presented output voltage sampling circuit in its internal circuit to simple output voltage and achieve constant output voltage.
Minimal Buffer Insertion Based Low Power Clock Tree Synthesis for 3D Integrated Circuits
Authors: Sumanth Kumar Kamineni , Reuben John
Published: June 2016

Three-Dimensional (3D) Integrated Circuits (ICs) offers integrating capabilities of ‘More than Moore’ while overcoming CMOS scaling limitations, providing the advantages of low power, high performance and reduced costs. The design of the Clock Distribution Network (CDN) for a 3D IC has to be done meticulously to guarantee reliable operation. In the design of the CDN, clock buffers are crucial units that affect the clock skew, slew and power dissipated by the clock tree. In this paper, we propose a two-stage buffering technique that inserts clock buffers for slew control and skew minimization. Such a buffering technique decreases the number of buffers and power dissipated in the clock tree when compared to previous works which were inserting buffers primarily for slew control. We incorporate the proposed buffering technique into the 3D clock tree synthesis algorithm of previous work and evaluate the performance of the clock tree for both single Through-Silicon Vias (TSV) and mutiple TSV approach. When evaluated on IBM benchmarks (r1-r5), our buffering technique results in 25–28% reduction in buffer count and 25–29% reduction in power for single TSV-based 3D CDN. For multi-TSV approach, the performance of our work is even better:around 31–38% reduction in buffer count and 32–39% reduction in power.
Improvement in a phenomenological formula for ground state binding energies
Authors: Gangopadhyay G.
Published: June 2016

The phenomenological formula for ground state binding energy derived earlier [G. Gangopadhyay, Int. J. Mod. Phys. E 20 (2011) 179] has been modified. The parameters have been obtained by fitting the latest available tabulation of experimental values. The major modifications include a new term for pairing and introduction of a new neutron magic number at N = 160. The new formula reduced the root mean square deviation to 363[Formula: see text]keV, a substantial improvement over the previous version of the formula.
Two coloring problems on matrix graphs
Authors: Han Zhe , Lu Mei
Published: June 2016

In this paper, we propose a new family of graphs, matrix graphs, whose vertex set [Formula: see text] is the set of all [Formula: see text] matrices over a finite field [Formula: see text] for any positive integers [Formula: see text] and [Formula: see text]. And any two matrices share an edge if the rank of their difference is [Formula: see text]. Next, we give some basic properties of such graphs and also consider two coloring problems on them. Let [Formula: see text] (resp., [Formula: see text]) denote the minimum number of colors necessary to color the above matrix graph so that no two vertices that are at a distance at most [Formula: see text] (resp., exactly [Formula: see text]) get the same color. These two problems were proposed in the study of scalability of optical networks. In this paper, we determine the exact value of [Formula: see text] and give some upper and lower bounds on [Formula: see text].
Grid-free petroleum reservoir characterization with truncated pluri-Gaussian simulation: Hekla case study
Authors: Zagayevskiy Yevgeniy , Deutsch Clayton V.
Published: June 2016

A new geostatistical grid-free simulation (GFS) method has been developed recently that represents simulated continuous attributes of the natural phenomena, such as stratigraphic surface boundaries or petrophysical properties, as an analytical function of the coordinates of the simulation locations. Thus, GFS resolves challenges related to model regridding, increasing resolution around already simulated locations and integration of newly available data in a consistent manner. The present paper contains further developments in simulation of categorical variables, such as facies, in a grid-free fashion based on the truncated pluri-Gaussian simulation (TPG) paradigm. The resultant simulation engine allows the entire reservoir system to be represented as an analytical stochastic function: that is, values of any reservoir properties are simulated on demand at requested locations in space. The selection of proper variograms of Gaussian continuous variables for simulation of categorical variables in a TPG framework is proposed through a methodology based on Monte Carlo simulation. The variogram models of the underlying Gaussian continuous variables are obtained by minimizing the difference between numerically computed and target indicator variograms. A local optimization approach is suggested for a fast precise derivation of the variograms. The stable variogram model leads to the closest fit to the experimental variograms of the continuous variables. The automatic establishment of a truncation mask based on multidimensional scaling to convert Gaussian continuous variables to categories is also explained. Finally, the proposed GFS algorithm for petroleum reservoir characterization is demonstrated in its full-scale applicability to the Hekla offshore petroleum reservoir located in the North Sea. The results look promising, and should be beneficial to petroleum reservoir modelling in practice.
The Messinian sea-level fall in the western Black Sea: small or large? Insights from offshore Romania
Authors: Krezsek C. , Schleder Z. , Bega Z. , Ionescu G. , Tari G.
Published: June 2016

The Messinian sea-level fall in the western Black Sea is poorly understood and often debated. We provide evidence for the sea-level fall, offshore Romania. There, the Messinian sedimentation is closely related to the gravitational collapse of the basin margin above the Maykop shales. This thin-skinned system controlled the Messinian lowstand depocentres. We estimated about 500–600 m of sea-level drop based on the erosional valleys cut into the formed lower Pontian slope and the Messinian erosional surface (MES).

The Messinian lowstand sediments are delimited by the basal erosional surface (BES) formed at the onset of the sea-level fall and by the MES related to transgressive wave erosion during the initial slow rise in sea level. Subsequent rapid sea-level rise drowned the remaining erosional topography on the lower Pontian palaeo-shelf. Similar features have been described in the Mediterranean Basin.
Early geological studies and mapping in Sweden
Authors: Sundquist Björn
Published: June 2016

Geological research and teaching in a modern sense started in Sweden around 1820 with the establishment of a school of mining in Falun, central Sweden. Before that time, geology-related studies were carried out by individual people at the Board of Mines and the universities in Uppsala, Lund and Åbo, along with studies in chemistry, mining, mineralogy, agriculture, or just by curiosity triggered by natural phenomena, such as the enigmatic ‘diminution of water’. In 1694, Urban Hiärne wrote and initiated the distribution of a questionnaire with the purpose of collecting information about Sweden's natural resources, some results of which he summarized a decade later. Hiärne, Magnus von Bromell, Christopher Polhem, Emanuel Swedenborg and others were the precursors who, in a sense, prepared the way for the following decades or even century of chemical, mineralogical and, eventually, geological research. The followers were Georg Brandt, Anton von Swab, Carl von Linné, Johan Gottschalk Wallerius, Axel Fredrik Cronstedt, Torbern Bergman, Carl Wilhelm Scheele, Johan Gottlieb Gahn and Wilhelm Hisinger, just to mention some of the most renowned. Samuel Gustaf Hermelin was the first person in Sweden to publish a geological map (1767), followed in 1797 by Wilhelm Hisinger, who was the first to publish an illuminated geological map.
Stratigraphic evolution of an estuarine fill succession and the reservoir characterization of inclined heterolithic strata, Cretaceous of southern Utah, USA
Authors: Johnson Cari L. , Stright L. , Purcell R. , Durkin P.
Published: June 2016

This study documented the architecture of a paralic succession using outcrops of the Upper Cretaceous John Henry Member of the Straight Cliffs Formation, southern Utah (USA). The 65 m thick interval of interest includes a basal succession of elongate tidal bars, which sits unconformably on the Calico Bed of the Smoky Hollow Member. These barforms are overlain by carbonaceous estuarine bay fill with tidal deposits, a bayhead delta and, ultimately, a coastal plain succession. The estuarine succession demonstrates a decreasing tidal influence through time and this is interpreted to reflect evolution from a mixed-energy to a wave-dominated estuary as a result of the changing morphology of the estuary and/or the migration of barrier islands across its mouth. The regional correlations are also discussed, with implications for sequence stratigraphic interpretations. A detailed interpretation of the ancient bayhead delta highlights the internal architecture and provides data for statistical comparison between this feature, which is dominated by inclined heterolithic strata, and a previously published study of fluvial point bar inclined heterolithic strata. The results emphasize distinct grain size trends from these two examples, as well as differences in the continuity and spatial distribution of mudstone drapes, which act as both baffles and barriers to fluid flow.
Transgressive successions of the Mahakam Delta Province, Indonesia
Authors: Lambiase Joseph J. , Riadi Ridha S. , Nirsal Nadia , Husein Salahuddin
Published: June 2016

Sedimentological and stratigraphic analysis of outcrops and subsurface data in the Mahakam Delta province, combined with concepts of transgressive sedimentary processes derived from a study of the modern Mahakam Delta, indicate that a significant portion of the palaeo-Mahakam Delta succession was deposited during transgressive phases. Some of the transgressive successions resulted from major transgressions and are regionally extensive, but many reflect small, short-lived transgressions within dominantly progradational phases.

Two sandstone facies with significant reservoir potential are common within the transgressive successions. Backfilled distributary sandstones occur in outcrop as 10–20 m thick, fining-upward channel sands that become more marine upward and in the subsurface as elongate, coastline-perpendicular sand bodies with a back-stepping stratigraphic architecture and highly variable thickness. Transgressive shoreline sandstones also fine upward, but they are shoreline-parallel, their lateral extent is controlled by the pre-transgression delta morphology and their thickness depends on the rate of relative sea-level rise.

Both types of transgressive sandstone can be difficult to distinguish from specific progradational sandstones with wireline log data, especially when they occur within predominantly progradational successions. However, their sand body geometries, volumetrics and connectivity are much different from the stratigraphically adjacent sandstones deposited during progradational phases of deltaic deposition.
Analysis of floodplain sedimentation, avulsion style and channelized fluvial sandbody distribution in an upper coastal plain reservoir: Middle Jurassic Ness Formation, Brent Field, UK North Sea
Authors: Flood Yvette S. , Hampson Gary J.
Published: June 2016

Numerical models and recent outcrop case studies of alluvial-to-coastal-plain strata suggest that autogenic avulsion can control the stacking density and architecture of channelized fluvial sandbodies. The application of these models to subsurface well data was tested by the analysis of upper coastal plain deposits of the late Bajocian Ness Formation in the Brent Field reservoir, UK North Sea. These coastal plain deposits accumulated during the progradation and retrogradation of the wave-dominated ‘Brent Delta’. Sedimentological facies analysis and palaeosol characterization in cores were used to interpret the styles of palaeochannel avulsion. These results were then compared with the dimensions and distributions of channelized fluvial sandbodies that had been quantified by spatial statistical tools (lacunarity, Besag's
L
function) applied to interpretative correlation panels between closely spaced wells. The results indicate that the distributions of channelized sandbodies may plausibly have been generated by avulsions and that they influence sandbody connectivity and pressure depletion patterns. Intervals of upper coastal plain strata with relatively wide sandbodies that display some clustering in their stratigraphic architecture are associated with a high proportion of avulsions by incision and annexation in core samples. Such intervals display relatively good vertical pressure communication and relatively slow, uniform pressure depletion.
Biomarker Records Associated with Mass Extinction Events
Authors: Whiteside Jessica H. , Grice Kliti
Published: June 2016

The history of life on Earth is punctuated by a series of mass extinction episodes that vary widely in their magnitude, duration, and cause. Biomarkers are a powerful tool for the reconstruction of historical environmental conditions and can therefore provide insights into the cause and responses to ancient extinction events. In examining the five largest mass extinctions in the geological record, investigators have used biomarkers to elucidate key processes such as eutrophy, euxinia, ocean acidification, changes in hydrological balance, and changes in atmospheric CO2. By using these molecular fossils to understand how Earth and its ecosystems have responded to unusual environmental activity during these extinctions, models can be made to predict how Earth will respond to future changes in its climate.
Recent Advances in Understanding of Thermal Expansion Effects in Premixed Turbulent Flames
Authors: Sabelnikov Vladimir A. , Lipatnikov Andrei N.
Published: June 2016

When a premixed flame propagates in a turbulent flow, not only does turbulence affect the burning rate (e.g., by wrinkling the flame and increasing its surface area), but also the heat release in the flame perturbs the pressure field, and these pressure perturbations affect the turbulent flow and scalar transport. For instance, the latter effects manifest themselves in the so-called countergradient turbulent scalar flux, which has been documented in various flames and has challenged the combustion community for approximately 35 years. Over the past decade, substantial progress has been made in investigating (a) the influence of thermal expansion in a premixed flame on the turbulent flow and turbulent scalar transport within the flame brush, as well as (b) the feedback influence of countergradient scalar transport on the turbulent burning rate. The present article reviews recent developments in this field and outlines issues to be solved in future research.
Defining the Clinical Value of a Genomic Diagnosis in the Era of Next-Generation Sequencing
Authors: Strande Natasha T. , Berg Jonathan S.
Published: June 2016

As with all fields of medicine, the first step toward medical management of genetic disorders is obtaining an accurate diagnosis, which often requires testing at the molecular level. Unfortunately, given the large number of genetic conditions without a specific intervention, only rarely does a genetic diagnosis alter patient management—which raises the question, what is the added value of obtaining a molecular diagnosis? Given the fast-paced advancement of genomic technologies, this is an important question to address in the context of genome-scale testing. Here, we address the value of establishing a diagnosis using genome-scale testing and highlight the benefits and drawbacks of such testing. We also review and compare recent major studies implementing genome-scale sequencing methods to identify a molecular diagnosis in cohorts manifesting a broad range of Mendelian monogenic disorders. Finally, we discuss potential future applications of genomic sequencing, such as screening for rare conditions.
Old Dogs, New Tricks: Monogenic Autoinflammatory Disease Unleashed
Authors: Stoffels Monique , Kastner Daniel L.
Published: June 2016

Autoinflammatory diseases are inborn disorders of the innate immune system characterized by episodes of systemic inflammation that are mediated largely by myeloid cells. The field of autoinflammatory diseases has been established since 1999, following the identification of the first genes underlying periodic fever syndromes. This review focuses on developments that have transformed the field in the last two years. We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever (FMF). Finally, the new monogenic autoinflammatory disease haploinsufficiency of A20 (HA20) underscores the placement of monogenic diseases in the firmament of common autoinflammatory phenotypes. The advances in the last two years have shed light on the pathophysiology of several autoinflammatory diseases and have elucidated new pathways that play a role in innate immunity.
“Be Operational, or Disappear”: Thoughts on a Present Discontent
Authors: Tomlins Christopher
Published: June 2016

Considered as regimes of interpellation, history and law separately and jointly observe and insist upon realities often antagonistic to distinct realities that arise from their alternate incarnation as memory and right. Because it exists at the intersection of history and law, legal history has a responsibility to resolve, or at least reveal, these cross-purposes. This essay summarizes the development of the field of legal history and reviews the origins of its current leading sector, critical historicism. Using examples from Australian Native title jurisprudence, it argues that critical historicism cannot meet its responsibilities. The essay points elsewhere, to philosophies of history that may perform better.
Corporate Lawyers in Emerging Markets
Authors: Garth Bryant G.
Published: June 2016

The growth of corporate law firms in emerging markets is mainly followed by practitioner journals reporting new offices and mergers, the openness of markets to non-national lawyers, and various rankings of local and transnational law firms. There is a small but growing academic literature that, for the most part, relies on US theoretical models, asking whether the corporate law firms are converging toward a global standard or what form of global/local hybrid is taking root. This literature fits well with the practical concerns about the specific spread of corporate lawyers. A complementary approach looks more into the global processes that produce the expectation that corporate lawyers will evolve into some modern model resembling the US corporate lawyer. For this more general line of research the position of corporate lawyers in relation to the state becomes more important, as do the hierarchical and imperial relationships that are manifested in different roles and statuses for those from the core and those from the periphery.
Xenogeneic Silencing and Its Impact on Bacterial Genomes
Authors: Singh Kamna , Milstein Joshua N. , Navarre William Wiley
Published: June 2016

The H-NS (heat-stable nucleoid structuring) protein affects both nucleoid compaction and global gene regulation. H-NS appears to act primarily as a silencer of AT-rich genetic material acquired by horizontal gene transfer. As such, it is key in the regulation of most genes involved in virulence and in adaptation to new environmental niches. Here we review recent progress in understanding the biochemistry of H-NS and how xenogeneic silencing affects bacterial evolution. We highlight the strengths and weaknesses of some of the models proposed in H-NS-mediated nucleoprotein complex formation. Based on recent single-molecule studies, we also propose a novel mode of DNA compaction by H-NS termed intrabridging to explain over two decades of observations of the H-NS molecule.
Kin Recognition in Bacteria
Authors: Wall Daniel
Published: June 2016

The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the individual. Kin recognition involves specific biochemical interactions between a receptor(s) and an identification molecule(s). Recognition specificity, ensuring that nonkin are excluded and kin are included, is critical and depends on the number of loci and polymorphisms involved. After recognition and biochemical perception, the common ensuing cooperative behaviors include biofilm formation, quorum responses, development, and swarming motility. Although kin recognition is a fundamental mechanism through which cells might interact, microbiologists are only beginning to explore the topic. This review considers both molecular and theoretical aspects of bacterial kin recognition. Consideration is also given to bacterial diversity, genetic relatedness, kin selection theory, and mechanisms of recognition.
Quantitative deep mapping of the cultured podocyte proteome uncovers shifts in proteostatic mechanisms during differentiation
Authors: Rinschen Markus M. , Schroeter Christina B. , Koehler Sybille , Ising Christina , Schermer Bernhard , Kann Martin , Benzing Thomas , Brinkkoetter Paul T.
Published: June 2016

The renal filtration barrier is maintained by the renal podocyte, an epithelial postmitotic cell. Immortalized mouse podocyte cell lines—both in the differentiated and undifferentiated state—are widely utilized tools to estimate podocyte injury and cytoskeletal rearrangement processes in vitro. Here, we mapped the cultured podocyte proteome at a depth of more than 8,800 proteins and quantified 7,240 proteins. Copy numbers of proteins mutated in forms of hereditary nephrotic syndrome or focal segmental glomerulosclerosis (FSGS) were assessed. We found that cultured podocytes express abundant copy numbers of endogenous receptors, such as tyrosine kinase membrane receptors, the G protein-coupled receptor (GPCR), NPR3 (ANP receptor), and several poorly characterized GPCRs. The data set was correlated with deep mapping mRNA sequencing (“mRNAseq”) data from the native mouse podocyte, the native mouse podocyte proteome and staining intensities from the human protein atlas. The generated data set was similar to these previously published resources, but several native and high-abundant podocyte-specific proteins were not identified in the data set. Notably, this data set detected general perturbations in proteostatic mechanisms as a dominant alteration during podocyte differentiation, with high proteasome activity in the undifferentiated state and markedly increased expression of lysosomal proteins in the differentiated state. Phosphoproteomics analysis of mouse podocytes at a resolution of more than 3,000 sites suggested a preference of phosphorylation of actin filament-associated proteins in the differentiated state. The data set obtained here provides a resource and provides the means for deep mapping of the native podocyte proteome and phosphoproteome in a similar manner.
Regulation of membrane KCNQ1/KCNE1 channel density by sphingomyelin synthase 1
Authors: Wu Meikui , Takemoto Makoto , Taniguchi Makoto , Takumi Toru , Okazaki Toshiro , Song Wen-Jie
Published: June 2016

Sphingomyelin synthase (SMS) catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. We previously showed that SMS1 deficiency leads to a reduction in expression of the K+ channel KCNQ1 in the inner ear (Lu MH, Takemoto M, Watanabe K, Luo H, Nishimura M, Yano M, Tomimoto H, Okazaki T, Oike Y, and Song WJ. J Physiol 590: 4029–4044, 2012), causing hearing loss. However, it remains unknown whether this change in expression is attributable to a cellular process or a systemic effect in the knockout animal. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in individual cells. To this end, we expressed the KCNQ1/KCNE1 channel in human embryonic kidney 293T cells and evaluated the effect of SMS1 manipulations on the channel using whole cell recording. Application of tricyclodecan-9-yl-xanthogenate, a nonspecific inhibitor of SMSs, significantly reduced current density and altered channel voltage dependence. Knockdown of SMS1 by a short hairpin RNA, however, reduced current density alone. Consistent with this, overexpression of SMS1 increased the current density without changing channel properties. Furthermore, application of protein kinase D inhibitors also suppressed current density without changing channel properties; this effect was nonadditive with that of SMS1 short hairpin RNA. These results suggest that SMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner.
Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle
Authors: Kuhlenhoelter Alisha M. , Kim Kyoungrae , Neff Dustin , Nie Yaohui , Blaize A. Nicole , Wong Brett J. , Kuang Shihuan , Stout Julianne , Song Qifan , Gavin Timothy P. , Roseguini Bruno T.
Published: June 2016

Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH ( n = 18) increased core temperature (Tc) from 36.9 ± 0.1 to 37.4 ± 0.1°C ( P < 0.01) and average leg skin temperature (Tleg) from 33.1 ± 0.1 to 39.6 ± 0.1°C ( P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34+CD133+). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH ( n = 11) compared with the control group ( n = 12). LBH also reduced the expression of transcription factor FOXO1 ( P = 0.03). Exposure to TH ( n = 14) increased Tlegfrom 32.8 ± 0.2 to 40.3 ± 0.1°C ( P < 0.05) but Tcremained unaltered (36.8 ± 0.1°C at baseline and 36.9 ± 0.1°C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.
The influence of altitude hypoxia on uroflowmetry parameters in women
Authors: Verratti Vittore , Paulesu Luana , Pietrangelo Tiziana , Doria Christian , Di Giulio Camillo , Aloisi Anna Maria
Published: June 2016

There is scientific evidence to suggest a correlation between hypoxia and the physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3 ± 7.1 yr) from normoxic [1,340 meters above sea level (m a.s.l.)] to hypoxic conditions (up to 5,050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2). As expected, SpO2 decreased from 97.7 to 77.8% with increasing altitude. Micturition flow time, flow volume, and voiding time increased with altitude ( P < 0.04 for all), indicating a negative correlation with SpO2. In conclusion, in young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes. These data could help to support the design of new strategies for both prevention and medical treatment. An example of the latter might be hyperbaric oxygen therapy, which in some studies has proved able to reduce the symptoms in patients with hypoxic bladder.
The epoxyeicosatrienoic acid analog PVPA ameliorates cyclosporine-induced hypertension and renal injury in rats
Authors: Yeboah Michael M. , Hye Khan Md Abdul , Chesnik Marla A. , Sharma Amit , Paudyal Mahesh P. , Falck John R. , Imig John D.
Published: June 2016

The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patients at risk of allograft rejection. Cytochrome P-450 epoxygenase metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), have potent vasodilator and antihypertensive properties in addition to many cytoprotective effects, but their effects on CNI-induced nephrotoxicity have not been explored. Here, we show that PVPA, a novel, orally active analog of 14,15-EET, effectively prevents the development of hypertension and ameliorates kidney injury in cyclosporine-treated rats. PVPA treatment reduced proteinuria and renal dysfunction induced by cyclosporine. PVPA inhibited inflammatory cell infiltration into the kidney and decreased renal fibrosis. PVPA also reduced tubular epithelial cell apoptosis, attenuated the generation of reactive oxygen species, and modulated the unfolded protein response that is associated with endoplasmic reticulum stress. Consistent with the in vivo data, PVPA attenuated cyclosporine-induced apoptosis of NRK-52E cells in vitro. These data indicate that the cytochrome P-450/EET system offers a novel therapeutic strategy to treat or prevent CNI-induced nephrotoxicity.
Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria
Authors: Contreras-Sanz Alberto , Krska Louise , Balachandran Aswini A. , Curtiss Natasha L. , Khasriya Rajvinder , Kelley Stephen , Strutt Matthew , Gill Hardyal S. , Taylor Kevin M. , Mansfield Kylie J. , Wu Changhao , Peppiatt-Wildman Claire M. , Malone-Lee James , Duckett Jonathan , Wildman Scott S.
Published: June 2016

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/μl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients.
A methodological approach for quantifying and characterizing the stability of agitated saline contrast: implications for quantifying intrapulmonary shunt
Authors: Hackett Heather K. , Boulet Lindsey M. , Dominelli Paolo B. , Foster Glen E.
Published: June 2016

Agitated saline contrast echocardiography is often used to determine blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA). We applied indicator dilution theory to time-acoustic intensity curves obtained from a bolus injection of hand-agitated saline contrast to acquire a quantitative index of contrast mass. Using this methodology and an in vitro model of the pulmonary circulation, the purpose of this study was to determine the effect of transit time and gas composition [air vs. sulphur hexafluoride (SF6)] on contrast conservation between two detection sites separated by a convoluted network of vessels. We hypothesized that the contrast lost between the detection sites would increase with transit times and be reduced by using contrast bubbles composed of SF6. Changing the flow and/or reducing the volume of the circulatory network manipulated transit time. Contrast conservation was measured as the ratio of outflow and inflow contrast masses. For air, 53.2 ± 3.4% (SE) of contrast was conserved at a transit time of 9.25 ± 0.02 s but dropped to 16.0 ± 1.0% at a transit time of 10.17 ± 0.06 s. Compared with air, SF6 contrast conservation was significantly greater ( P < 0.05) with 114.3 ± 2.9% and 73.7 ± 3.3% of contrast conserved at a transit time of 10.39 ± 0.02 s and 13.46 ± 0.04 s, respectively. In summary, time-acoustic intensity curves can quantify agitated saline contrast, but loss of contrast due to bubble dissolution makes measuring Q̇IPAVA across varying transit time difficult. Agitated saline composed of SF6 is stabilized and may be a suitable alternative for Q̇IPAVA measurement.
Effect of a Deep Cryogenic Treatment on Wear and Microstructure of a 6101 Aluminum Alloy
Authors: Franco Steier Volker , Ashiuchi Edgar Sobral , Reißig Lutz , Araújo José Alexander
Published: June 2016

The aim of this work is to evaluate the effect of a deep cryogenic treatment (DCT) on the wear behavior and on the microstructure of an aluminum alloy. In order to compare the level of improvement on the wear resistance provided by the DCT with a more traditional technique, a test matrix which included DCT, CrN coated specimens, and combinations of both modification methods was conducted. The wear behavior was investigated using microabrasive wear tests. The cryogenic treated specimens proved to have similar low wear rates as the specimens coated with CrN. The most distinct improvement was reached with a combination of both techniques. In the case of the DCT, the performed microstructural analysis identified the generation of additional GP-zones as the reason for the improved wear resistance.
Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm
Authors: Zhang Lei , Wang Linlin , Du Bochuan , Wang Tianjiao , Tian Pu , Tian Suyan
Published: June 2016

Among non-small cell lung cancer (NSCLC), adenocarcinoma (AC), and squamous cell carcinoma (SCC) are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR), can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.
Intraventricular Neurilemmoma (Schwannoma): Shall GFAP Immunostaining Be Regarded as a Histogenetical Tag or as a Mere Histomimetical Trait?
Authors: Salazar Miguel Fdo. , Tena Suck Martha Lilia , Rembao Bojórquez Daniel , Salinas Lara Citlaltepetl
Published: June 2016

Neurilemmomas are benign neoplasms presumedly derived from Schwann cells which rarely originate within the central nervous system. Moreover, their intraventricular location has been seldom noticed with less than 30 cases reported worldwide. Here, we add another case study to the record as well as the fifth one in Latin American population. A 16-year-old boy without significant past clinical data debuted with headache and progressive left eye blindness during six months. Neuroimaging scans showed a bulky, multiloculated, intraventricular tumour emerging from the posterior horn of the left lateral ventricle. Microscopically, the lesion put on view the classical schwannian histology: spindle cells arranged in both compact and loosely textured areas. Verocay bodies were not present but vessel hyalinisation, pericellular reticulin, and senescent atypia were observed. The immunoperoxidase reactions were also consistent with neurilemmal differentiation; however, glial fibrillary acidic protein expression was widespread and unexpectedly seen. Traditionally conceived as “nerve sheath tumours” the dual immunophenotype herein demonstrated points to a different histogenetical pathway other than sheer Schwann cell derivation. As previously advised by some authors, neoplastic transformation from a multipotent stem cell may explain the occasional finding of these tumours in unconventional intracranial compartments.
The Importance of Risk and Subgroup Analysis of Nonparticipants in a Geriatric Intervention Study
Authors: Rosted Elizabeth , Poulsen Ingrid , Hendriksen Carsten , Wagner Lis
Published: June 2016

Background. A major concern in intervention studies is the generalizability of the findings due to refusal of intended participants to actually take part. In studies including ill older people the number of those declining to participate may be large and the concern is therefore relevant.Objectives. To compare patients characteristics, rates of acute readmission, and mortality after one and six months among older persons who agreed and those who declined to participate in a randomized controlled trial and to describe subgroups of nonparticipants.Design. Comparative study based on a randomized controlled trial.Setting. University hospital in the Capital Region of Denmark.Participants. Patients ≥70 years discharged home after a short Emergency Department stay. 399 were requested to participate; 271 consented, whereas 128 refused.Results. Refusers were more likely to be readmitted (p<0.001) or die (p=0.006). The largest subgroup of refusers described as “too ill” had the highest risk of readmission (OR = 3.00, 95% CI = 1.61–5.47,p=0.001) and of mortality within six months (OR = 3.50, 95% CI = 1.64–7.49,p=0.002). However, this seems not to have affected the results of our randomized study.Conclusion. We recommend that intervention studies among older people or other fragile patient groups include analysis of relevant risk and subgroup analyses of refusers.
MD Study of Solution Concentrations on Ion Distribution in a Nanopore-Based Device Inspired from Red Blood Cells
Authors: Ge Yanyan , Xian Jieyu , Kang Min , Li Xiaolin , Jin Meifu
Published: June 2016

A molecular dynamics model of a nanopore-based device, which is similar to the nanopores in a cell membrane, was used to determine the influence of solution concentration on radial ion distribution, screening effects, and the radial potential profile in the nanopore. Results from these simulations indicate that as the solution concentration increases, the density peaks for both the counterion and coion near the charged wall increase at different speeds as screening effects appeared. Consequently, the potential near the charged wall of the nanopore changed from negative to positive during the simulation. The detailed understanding of ion distribution in nanopores is important for controlling the ion permeability and improving the cell transfection and also the design and application of nanofluidic devices.