bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralocorticoid Receptor Antagonists and Clinical Outcomes in
Primary Aldosteronism: As Good as Surgery?
Authors: Colussi G. L. , Novello M. , Uzzau A. , Catena C. , Sechi L. A.
Published: December 2015

Primary aldosteronism (PA) is detected with increasing frequency in hypertensive
patients and is associated with excess cardiovascular, renal, and metabolic
complications. For these reasons, appropriate choices for treatment of this
endocrine condition are mandatory. Adrenalectomy is safely performed in PA
patients when adrenal venous sampling (AVS) demonstrates lateralized aldosterone
secretion. AVS, however, is a complex procedure and even among worldwide
referral centers there are substantial discrepancies for interpretation of
results. Also, in the majority of PA patients with lateralized aldosterone
secretion, hypertension may persist after adrenalectomy requiring use of
additional antihypertensive agents. Treatment with mineralocorticoid receptor
antagonists (MRAs) is currently recommended for PA patients with bilateral
adrenal disease, but these agents effectively decrease blood pressure also in
patients with unilateral disease, although concern remains for possible
sex-related side effects. Prospective studies indicate that MRAs have
therapeutic values comparable to surgery in the long-term, inasmuch as they
effectively correct metabolic abnormalities and subclinical organ damage and
reduce the risk of cardiovascular events and renal disease progression. This
article overviews the clinical outcomes obtained in patients with PA with use of
MRAs.
Glucose Metabolism in Primary Aldosteronism
Authors: Remde H. , Hanslik G. , Rayes N. , Quinkler M.
Published: December 2015

In recent years, an increasing number of studies have revealed deleterious effects of aldosterone via the mineralocorticoid receptor (MR). Especially in patients with primary aldosteronism (PA) a significant higher estimated risk of developing cardiovascular comorbidities and comortalities compared to essential hypertensives was reported. As diabetes mellitus and the metabolic syndrome are one of the major contributors to cardiovascular morbidity and mortality their connection to aldosterone excess became a focus of research in PA patients. Several studies assessed the effect of PA on glucose metabolism, the prevalence of diabetes mellitus, and the effect of PA treatment on both revealing different results. Therefore, we performed an extensive literature research. This review focuses on the current knowledge of the connection between aldosterone excess, glucose homeostasis, and diabetes mellitus in patients with PA. We have highlighted this topic from a pro and contra perspective followed by a summarizing concluding remark. Additionally, we have briefly reviewed the data on possible underlying mechanisms and indicated future considerations on the possible impact of cortisol co-secretion in PA.
Parathyroid Gland Function in Primary Aldosteronism
Authors: Bekeran M. , Reincke M. , Asbach E.
Published: December 2015

Primary aldosteronism (PA) is the most frequent cause of secondary arterial
hypertension. Beyond its effects on intravascular volume and blood pressure,
PA causes metabolic alterations and a higher cardiovascular morbidity, which
is reduced by PA-directed therapy. Experimental studies demonstrated that
mineralocorticoid excess may also influence mineral homeostasis. A role in
cardiovascular disease has also been attributed to parathyroid hormone
(PTH). Increasing evidence supports a bidirectional interaction between
aldosterone and PTH.

Primary hyperparathyroidism is associated with arterial hypertension and an
increased cardiovascular morbidity and mortality, which might be associated
to higher aldosterone values; parathyreoidectomy results in lowered
aldosterone and blood pressure levels. PA leads to secondary
hyperparathyroidism, which is reversible by PA-directed therapy. A lower
bone mineral density and a higher fracture rate were also shown to be
reversible by PA-directed therapy. There is a suspicion of a bidirectional
interaction between aldosterone and PTH, which might lead to a higher
cardiovascular risk. There are more and more reports about coincident PA and
primary hyperparathyroidism. From a pathophysiologic point of view this
constellation is best characterized as tertiary hyperparathyroidism. Future
aspects should further clarify the extent of these endocrine interactions
and analyze the influence of this interplay on cardiovascular morbidity and
mortality and bone health.
Steroid Hormone Production in Patients with Aldosterone Producing
Adenomas
Authors: Moors M. , Williams T. A. , Deinum J. , Eisenhofer G. , Reincke M. , Lenders J. W. M.
Published: December 2015

Primary aldosteronism encompasses 2 major underlying causes: (1) aldosterone
producing adenoma and (2) bilateral adrenal hyperplasia. In addition to the
aldosterone excess, increased production of other compounds of the steroidogenic
pathways may be involved. Until recently, most studies examined the production
of steroids other than aldosterone in tumor tissue, urine, or peripheral plasma
samples, but several new studies have also addressed steroid levels in adrenal
venous blood samples using liquid chromatography tandem mass spectrometry.
Plasma and tissue levels of several precursors of aldosterone with
mineralocorticoid activity are higher in patients with aldosterone producing
adenomas than in those with bilateral hyperplasia. These include corticosterone,
deoxycorticosterone, and their 18-hydroxylated metabolites. Similarly, urinary,
peripheral, and adrenal venous concentrations of the hybrid steroids
18-oxocortisol and 18-hydroxycortisol are higher in patients with aldosterone
producing adenomas than in bilateral hyperplasia. Differences in the
pathophysiology and in clinical and biochemical phenotypes caused by aldosterone
producing adenomas and bilateral adrenal hyperplasia may be related to the
differential expression of steroidogenic enzymes, and associated to specific
underlying somatic mutations. Correct appreciation of differences in steroid
profiling between aldosterone producing adenomas and bilateral adrenal
hyperplasia may not only contribute to a better understanding of the
pathogenesis of primary aldosteronism but may also be helpful for future
subtyping of primary aldosteronism.
Retrograde Endovascular Approach for Treating Unruptured Basilar Apex Aneurysms: Two Case Reports and Review of Literature
Authors: Rotta Marcus , Dias Guilherme , Rezende André , Pahl Felix , Oliveira Matheus , Rotta José
Published: December 2015

Background Treatment of target lesions when parent vessels are injured or diseased may be quite difficult. Moret et al have proposed an endovascular technique based on retrograde transcirculation approach through communicating vessels.

Methods We report on the first Brazilian experience with retrograde endovascular approach, to the best of our knowledge.

Results The two cases illustrate difficult anterograde approach techniques to treat basilar apex aneurysms. In the first case, tortuosity and angulation of both vertebral arteries associated to stenosis did not allow an anterograde approach. In the second case, after a SAH of a basilar apex aneurysm treated more than a decade ago with bilateral vertebral artery trapping, the patient underwent a retrograde approach.

Conclusion For this approach, follow-up data are still lacking and complications are usually more common than in anterograde approach. Nevertheless, in select cases, it may be applied by experienced hands with acceptable risks when no other treatment option (surgical or endovascular) is available.
Patientenzufriedenheit als Maßeinheit im Qualitätsmanagement – ein Vergleich zwischen einem Universitätsklinikum und einem Krankenhaus der Regelversorgung
Authors: Eichhorn L. , Murday A.-K. , Kohnen B. , Guttenthaler V. , Türler A. , Baumgarten G. , Wittmann M.
Published: December 2015

Ziel der Studie: Ziel der Studie war der Vergleich der Zufriedenheit von Patienten eines Regelversorgers mit der eines Universitätsklinikums. Aus Wichtigkeit des Parameters und ermittelter Zufriedenheit wurde ein Patientenzufriedenheits-Index berechnet. Mittel- bis langfristig soll so die Wettbewerbsfähigkeit und Auslastung des Krankenhauses optimiert werden sowie vorhandene Ressourcen kosteneffizient zur Steigerung der Attraktivität eingesetzt werden.

Methode: Die Autoren führten eine fragebogengestützte Erhebung in einem Universitätsklinikum (Universitätsklinikum Bonn, UKB, 1 224 Betten) und einem Krankenhaus der Regelversorgung (Johanniterkrankenhaus Bonn, JKH, 364 Betten) durch. Darin konnten Patienten anonymisiert Fragen zu unterschiedlichen Gesichtspunkten ihres Krankenhausaufenthalts beantworten. Es wurde sowohl die Zufriedenheit der Patienten mit den einzelnen Aspekten als auch die Einschätzung der Wichtigkeit erfasst. Hieraus wurde ein Patientenzufriedenheitsindex (PZI) ermittelt und statistisch ausgewertet.

Ergebnis: Die Ansprüche und Wünsche der Patienten beider Krankenhäuser, deren Zufriedenheit und die Gewichtung der einzelnen Gesichtspunkte unterscheiden sich in allen abgefragten Bereichen (Informations-, Beteiligungs-, Kontakt- und Komfortaspekt während des Krankenhausaufenthaltes) nicht signifikant. Die Studie ergab, dass den Patienten die Kommunikation beziehungsweise der Kontakt mit Ärzten und Pflegern an beiden Kliniken signifikant wichtiger ist als der Komfort (jeweils p<0,001). Die höchsten PZI-Werte ergaben sich beim Unterhaltungsangebot (UKB 1,02; JKH 1,25) und dem Kontakt zum Pflegepersonal (UKB 0,94; JKH 0,96). Auch mit der medizinisch-technischen Versorgungsqualität (UKB 0,93; JKH 0,95) zeigen sich die Patienten in beiden Kliniken sehr zufrieden. Verbesserungsbedarf besteht vor allem in der Kommunikation von Fehlern (PZI UKB 0,33; PZI JKH 0,31).

Schlussfolgerung: Durch das Erfassen der Ansprüche und Kritikpunkte der Patienten wird die patientenorientierten Gestaltung des Klinikalltages verbessert. Dadurch können personelle und materielle Ressourcen effizienter genutzt und durch konsequente Hinterfragung der eingesetzten Mittel die Attraktivität der Klinik gesteigert werden.
Multiple interests or unified voice? Online communities as intermediary spaces for development
Authors: Ferguson Julie E , Soekijad Maura
Published: December 2015

While the uptake of online communities toward development purposes continues to grow, many are characterized by an unresolved tension. On the one hand, they benefit from participation of heterogeneous stakeholders in their efforts to strengthen their expertise. On the other hand, these stakeholders represent highly diverging interests, which makes collective strategic action very challenging. To understand how online communities cope with this tension, we conducted a longitudinal, mixed method case study of an online community focused on development transportation. We argue that online communities are uniquely equipped, through their fluidity and open-endedness, to enable knowledge creation and agenda-setting. In so doing, online communities afford an ‘intermediary space’ that simultaneously accommodates both convergence and divergence of interests. Our study strengthens the bridge between information systems research and development studies, by highlighting the potential of ICT uptake toward ‘remaking participation’ in development debate, while including the perspectives of heterogeneous interest groups.
The Long and Winding Road of Enterprise System Implementation: Finding Success or Failure?
Authors: Grainger Nick , McKay Judy
Published: December 2015

A global manufacturing company needing to upgrade its IT to support rapid growth decided to pilot an enterprise system (ES) implementation in one of its European businesses. This was unsuccessful, but a second attempt in Australia, drawing on the many lessons learnt was regarded as successful. Subsequently, 14 implementations proceeded all over the Asia Pacific region and elsewhere in Europe with excellent outcomes. But the next implementation of the ES into a recently acquired business in New Zealand (NZ) proved problematic. The NZ management team and users were highly critical of the system and appeared to strongly resist its implementation. Cutover was eventually mandated and did occur, but the business almost failed because of problems with the new system. Following months of complaints and lobbying, the CIO in Head Office dispatched a small experienced team to NZ to review the situation. This case raises two fundamental challenges of IT management. It supports discussion of the many issues associated with the implementation of new systems and technologies, deepening appreciation of the challenges (particularly social, cultural and political) of IT implementation. It also supports learning about the phenomenon of resistance to change in the context of IT implementation.1
Mapping bilateral information interests using the activity of Wikipedia editors
Authors: Karimi Fariba , Bohlin Ludvig , Samoilenko Anna , Rosvall Martin , Lancichinetti Andrea
Published: December 2015

We live in a global village where electronic communication has eliminated the geographical barriers of information exchange. The road is now open to worldwide convergence of information interests, shared values and understanding. Nevertheless, interests still vary between countries around the world. This raises important questions about what today’s world map of information interests actually looks like and what factors cause the barriers of information exchange between countries. To quantitatively construct a world map of information interests, we devise a scalable statistical model that identifies countries with similar information interests and measures the countries’ bilateral similarities. From the similarities we connect countries in a global network and find that countries can be mapped into 18 clusters with similar information interests. Through regression we find that language and religion best explain the strength of the bilateral ties and formation of clusters. Our findings provide a quantitative basis for further studies to better understand the complex interplay between shared interests and conflict on a global scale. The methodology can also be extended to track changes over time and capture important trends in global information exchange.
Complex-time singularity and locality estimates for quantum lattice systems
Authors: Bouch Gabriel
Published: December 2015

We present and prove a well-known locality bound for the complex-time dynamics of a general class of one-dimensional quantum spin systems. Then we discuss how one might hope to extend this same procedure to higher dimensions using ideas related to the Eden growth process and lattice trees. Finally, we demonstrate with a specific family of lattice trees in the plane why this approach breaks down in dimensions greater than one and prove that there exist interactions for which the complex-time dynamics blows-up in finite imaginary time.
Hard convex lens-shaped particles: Densest-known packings and phase behavior
Authors: Cinacchi Giorgio , Torquato Salvatore
Published: December 2015

By using theoretical methods and Monte Carlo simulations, this work investigates dense ordered packings and equilibrium phase behavior (from the low-density isotropic fluid regime to the high-density crystalline solid regime) of monodisperse systems of hard convex lens-shaped particles as defined by the volume common to two intersecting congruent spheres. We show that, while the overall similarity of their shape to that of hard oblate ellipsoids is reflected in a qualitatively similar phase diagram, differences are more pronounced in the high-density crystal phase up to the densest-known packings determined here. In contrast to those non-(Bravais)-lattice two-particle basis crystals that are the densest-known packings of hard (oblate) ellipsoids, hard convex lens-shaped particles pack more densely in two types of degenerate crystalline structures: (i) non-(Bravais)-lattice two-particle basis body-centered-orthorhombic-like crystals and (ii) (Bravais) lattice monoclinic crystals. By stacking at will, regularly or irregularly, laminae of these two crystals, infinitely degenerate, generally non-periodic in the stacking direction, dense packings can be constructed that are consistent with recent organizing principles. While deferring the assessment of which of these dense ordered structures is thermodynamically stable in the high-density crystalline solid regime, the degeneracy of their densest-known packings strongly suggests that colloidal convex lens-shaped particles could be better glass formers than colloidal spheres because of the additional rotational degrees of freedom.
Effect of the cation model on the equilibrium structure of poly-L-glutamate in aqueous sodium chloride solution
Authors: Marchand Gabriel , Soetens Jean-Christophe , Jacquemin Denis , Bopp Philippe A.
Published: December 2015

We demonstrate that different sets of Lennard-Jones parameters proposed for the Na+ ion, in conjunction with the empirical combining rules routinely used in simulation packages, can lead to essentially different equilibrium structures for a deprotonated poly-L-glutamic acid molecule (poly-L-glutamate) dissolved in a 0.3M aqueous NaCl solution. It is, however, difficult to discriminate a priori between these model potentials; when investigating the structure of the Na+-solvation shell in bulk NaCl solution, all parameter sets lead to radial distribution functions and solvation numbers in broad agreement with the available experimental data. We do not find any such dependency of the equilibrium structure on the parameters associated with the Cl− ion. This work does not aim at recommending a particular set of parameters for any particular purpose. Instead, it stresses the model dependence of simulation results for complex systems such as biomolecules in solution and thus the difficulties if simulations are to be used for unbiased predictions, or to discriminate between contradictory experiments. However, this opens the possibility of validating a model specifically in view of analyzing experimental data believed to be reliable.
Magnetostatic nearest neighbor interactions in a Co48Fe52 nanowire array probed by in-field magnetic force microscopy
Authors: Vock S. , Tschulik K. , Uhlemann M. , Hengst C. , Fähler S. , Schultz L. , Neu V.
Published: December 2015

The magnetization behavior of nanowires embedded in an array is influenced by the sum of the dipolar fields produced by all surrounding nanowires. These magnetostatic interactions largely modify the array properties and thus complicate the reconstruction of the ensemble averaged behavior of the individual nanowires, such as the intrinsic switching field distribution. Simply correcting the shearing of the hysteresis in a mean-field approach does not account for the locally fluctuating demagnetizing field, which originates from the individual magnetization configuration in the close surrounding of each nanowire. We present an in-field Magnetic Force Microscopy study of electrochemically produced Co48Fe52 nanowires, in which the influence of the magnetic nearest neighbor configuration on the switching behavior of the individual embedded nanowires is clearly detected. Based on this finding, a statistical evaluation method of nearest neighbor histograms is proposed, which potentially allows to judge the strength of the local magnetostatic interactions against the magnitude of the intrinsic switching field distribution.
Near unity ideality factor and Shockley-Read-Hall lifetime in GaN-on-GaN p-n diodes with avalanche breakdown
Authors: Hu Zongyang , Nomoto Kazuki , Song Bo , Zhu Mingda , Qi Meng , Pan Ming , Gao Xiang , Protasenko Vladimir , Jena Debdeep , Xing Huili Grace
Published: December 2015

Textbook-like device characteristics are demonstrated in vertical GaN p-n diodes grown on bulk GaN substrates. These devices show simultaneously an avalanche breakdown voltage (BV) of >1.4 kV under reverse bias, an ideality factor plateau of ∼2.0 in a forward bias window followed by a near unity ideality factor of 1.1, which are consistently achieved over a temperature range of 300–400 K. At room temperature (RT), the diode with a mesa diameter of 107 μm showed a differential on-resistance Ron of 0.12 mΩcm2, thus resulting in a record figure-of-merit BV2/Ron of ∼16.5 GW/cm2, which is the highest ever demonstrated in any semiconductors. Analytical models are used to fit experimental I-Vs; based on the recombination current with an ideality factor of ∼2.0, a Shockley-Read-Hall lifetime of 12 ns is extracted at RT with an estimated recombination center concentration of 3 × 1015 cm−3.
Stochastic multi-objective scheduling of a combined cooling, heating and power microgrid containing a fuel cell
Authors: Sheng Wanxing , Peng Shuyong , Tang Yiyuan , Meng Xiaoli , Wang Delin , Wu Zhi , Gu Wei
Published: December 2015

Combined cooling, heating and power (CCHP) microgrids that use fuel cells have a promising future, because they are energy efficient, have low emissions, and consume less energy. This study investigates the optimal energy management of a CCHP microgrid that includes a photovoltaic, a battery, a fuel cell, a gas boiler, a thermal storage tank, an absorption chiller, and an electric chiller, with a cooling, heating and power load. A multi-objective chance-constrained programming model is proposed, which aims to minimize the total running costs, and SO2 and NOx emissions. A Monte-Carlo stochastic simulation technique is applied to deal with the stochastic characteristics of the PV cells, and the cooling, heating and power loads. An improved multi-objective particle swarm optimization with Pareto set is proposed to solve the model. Simulation results of a hotel building show that the proposed approach can reduce the emissions of the pollutants, and effectively improve the system's efficiency.
Influence of anisotropic magnetoelectric interaction on the spontaneous magnetocapacitance in TbMnO3
Authors: Chupis I. E. , Kovtun H. A.
Published: December 2015

The spontaneous magnetocapacitance (i.e., the temperature dependence of dielectric constant in the absence of a magnetic field) of the orthorhombic ferroelectromagnet TbMnO3 in the incommensurable antiferromagnetic states is phenomenologically and numerically analyzed. It is shown that both the inhomogeneous magnetoelectric (ME) energy of the third order, which creates the electric polarization, and the ME anisotropy of the fourth order must be considered to get qualitative agreement with the experiment. The inhomogeneous ME energy induces the peak on the εzz(T) which satisfies the Curie law, and a small peak on the εxx(T) at the vicinity of the temperature of the ferroelectric (FE) ordering. The anisotropic ME energy of the fourth order is responsible for the appearance and character of the breaks on the εzz and εxx temperature dependences at the Néel temperature, namely, a decrease in εzz and an increase in εxx in the event of antiferromagnetic ordering. It is shown that the competition of the anisotropic ME energies of the fourth and third orders leads to the minimum on εzz(T) near the FE-transition temperature. The numerical calculation of spontaneous magnetocapacitance with the use of experimental data was performed. The signs and the orders of the constants of anisotropic ME-interactions in TbMnO3 were determined.
Protonic/electronic hybrid oxide transistor gated by chitosan and its full-swing low voltage inverter applications
Authors: Chao Jin Yu , Zhu Li Qiang , Xiao Hui , Yuan Zhi Guo
Published: December 2015

Modulation of charge carrier density in condensed materials based on ionic/electronic interaction has attracted much attention. Here, protonic/electronic hybrid indium-zinc-oxide (IZO) transistors gated by chitosan based electrolyte were obtained. The chitosan-based electrolyte illustrates a high proton conductivity and an extremely strong proton gating behavior. The transistor illustrates good electrical performances at a low operating voltage of ∼1.0 V such as on/off ratio of ∼3 × 107, subthreshold swing of ∼65 mV/dec, threshold voltage of ∼0.3 V, and mobility of ∼7 cm2/V s. Good positive gate bias stress stabilities are obtained. Furthermore, a low voltage driven resistor-loaded inverter was built by using an IZO transistor in series with a load resistor, exhibiting a linear relationship between the voltage gain and the supplied voltage. The inverter is also used for decreasing noises of input signals. The protonic/electronic hybrid IZO transistors have potential applications in biochemical sensors and portable electronics.
Frequency-dependent photothermal measurement of transverse thermal diffusivity of organic semiconductors
Authors: Brill J. W. , Shahi Maryam , Payne Marcia M. , Edberg Jesper , Yao Y. , Crispin Xavier , Anthony J. E.
Published: December 2015

We have used a photothermal technique, in which chopped light heats the front surface of a small (∼1 mm2) sample and the chopping frequency dependence of thermal radiation from the back surface is measured with a liquid-nitrogen-cooled infrared detector. In our system, the sample is placed directly in front of the detector within its dewar. Because the detector is also sensitive to some of the incident light, which leaks around or through the sample, measurements are made for the detector signal that is in quadrature with the chopped light. Results are presented for layered crystals of semiconducting 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pn) and for papers of cellulose nanofibrils coated with semiconducting poly(3,4-ethylene-dioxythiophene):poly(styrene-sulfonate) (NFC-PEDOT). For NFC-PEDOT, we have found that the transverse diffusivity, smaller than the in-plane value, varies inversely with thickness, suggesting that texturing of the papers varies with thickness. For TIPS-pn, we have found that the interlayer diffusivity is an order of magnitude larger than the in-plane value, consistent with previous estimates, suggesting that low-frequency optical phonons, presumably associated with librations in the TIPS side groups, carry most of the heat.
Radiative rate modification in CdSe quantum dot-coated microcavity
Authors: Veluthandath Aneesh V. , Bisht Prem B.
Published: December 2015

Whispering gallery modes (WGMs) of the microparticles with spherical or cylindrical symmetry have exceptionally high quality factors and small mode volume. Quantum dots (QDs) are zero dimensional systems with variable band gap as well as luminescent properties with applications in photonics. In this paper, the WGMs have been observed in the luminescence spectra of CdSe QD-coated single silica microspheres. Theoretical estimations of variation of resonance frequency, electric field, and Q-values have been done for a multilayer coating of QDs on silica microspheres. Observed WGMs have been identified for their mode number and polarization using Mie theory. Broadening of modes due to material absorption has been observed. Splitting of WGMs has also been observed due to coherent coupling of counter propagating waves in the microcavity due to the presence of QDs. At room temperature, the time-resolved study indicates the modification of the radiative rate due to coupling of WGMs of the microcavity-QD hybrid system.
Attosecond beamline with actively stabilized and spatially separated beam paths
Authors: Huppert M. , Jordan I. , Wörner H. J.
Published: December 2015

We describe a versatile and compact beamline for attosecond spectroscopy. The setup consists of a high-order harmonic source followed by a delay line that spatially separates and then recombines the extreme-ultraviolet (XUV) and residual infrared (IR) pulses. The beamline introduces a controlled and actively stabilized delay between the XUV and IR pulses on the attosecond time scale. A new active-stabilization scheme combining a helium-neon-laser and a white-light interferometer minimizes fluctuations and allows to control delays accurately (26 as rms during 1.5 h) over long time scales. The high-order-harmonic-generation region is imaged via optical systems, independently for XUV and IR, into an interaction volume to perform pump-probe experiments. As a consequence of the spatial separation, the pulses can be independently manipulated in intensity, polarization, and frequency content. The beamline can be combined with a variety of detectors for measuring attosecond dynamics in gases, liquids, and solids.
Shape-tunable wax microparticle synthesis via microfluidics and droplet impact
Authors: Lee Doojin , Beesabathuni Shilpa N. , Shen Amy Q.
Published: December 2015

Spherical and non-spherical wax microparticles are generated by employing a facile two-step droplet microfluidic process which consists of the formation of molten wax microdroplets in a flow-focusing microchannel and their subsequent off-chip crystallization and deformation via microdroplet impingement on an immiscible liquid interface. Key parameters on the formation of molten wax microdroplets in a microfluidic channel are the viscosity of the molten wax and the interfacial tension between the dispersed and continuous fluids. A cursory phase diagram of wax morphology transition is depicted depending on the Capillary number and the Stefan number during the impact process. A combination of numerical simulation and analytical modeling is carried out to understand the physics underlying the deformation and crystallization process of the molten wax. The deformation of wax microdroplets is dominated by the viscous and thermal effects rather than the gravitational and buoyancy effects. Non-isothermal crystallization kinetics of the wax illustrates the time dependent thermal effects on the droplet deformation and crystallization. The work presented here will benefit those interested in the design and production criteria of soft non-spherical particles (i.e., alginate gels, wax, and polymer particles) with the aid of time and temperature mediated solidification and off-chip crosslinking.
Enhancing conjugation rate of antibodies to carboxylates: Numerical modeling of conjugation kinetics in microfluidic channels and characterization of chemical over-exposure in conventional protocols by quartz crystal microbalance
Authors: Asiaei Sasan , Smith Brendan , Nieva Patricia
Published: December 2015

This research reports an improved conjugation process for immobilization of antibodies on carboxyl ended self-assembled monolayers (SAMs). The kinetics of antibody/SAM binding in microfluidic heterogeneous immunoassays has been studied through numerical simulation and experiments. Through numerical simulations, the mass transport of reacting species, namely, antibodies and crosslinking reagent, is related to the available surface concentration of carboxyl ended SAMs in a microchannel. In the bulk flow, the mass transport equation (diffusion and convection) is coupled to the surface reaction between the antibodies and SAM. The model developed is employed to study the effect of the flow rate, conjugating reagents concentration, and height of the microchannel. Dimensionless groups, such as the Damköhler number, are used to compare the reaction and fluidic phenomena present and justify the kinetic trends observed. Based on the model predictions, the conventional conjugation protocol is modified to increase the yield of conjugation reaction. A quartz crystal microbalance device is implemented to examine the resulting surface density of antibodies. As a result, an increase in surface density from 321 ng/cm2, in the conventional protocol, to 617 ng/cm2 in the modified protocol is observed, which is quite promising for (bio-) sensing applications.
Solutions for the electric potential and field distribution in cylindrical core-shell nanoparticles using the image charge method
Authors: Daneshfar Nader , Moradbeigi Nasrin
Published: December 2015

This article considers the problem of finding the electrostatic potential that is given in terms of a scalar function called Green function in dielectric cylindrical nanoparticles with core-shell structure using the image charge method. By using this method that allows us to solve differential form of electric potential problem by the Green function, we investigate the distribution of the electric field in the configuration of a cylindrical nanoparticle surrounded by a continuum dielectric medium. By utilizing this well-known method, we obtain exact analytical formulas for the electrostatic potential and the electric field inside the shell, core and surrounding space of nanoparticle that can be applied to analysis of electromagnetic problems, electrostatic interactions in biomolecular simulations and also computer simulations of condensed-matter media.
The effect of fire on tree–grass coexistence in savannas: a simulation study
Authors: Lehsten Veiko , Arneth Almut , Spessa Allan , Thonicke Kirsten , Moustakas Aristides
Published: December 2015

The savanna biome has the greatest burned area globally. Whereas the global distribution of most biomes can be predicted successfully from climatic variables, this is not so for savannas. Attempts to dynamically model the distribution of savannas, including a realistically varying tree : grass ratio are fraught with difficulties. In a simulation study using the dynamic vegetation model LPJ-GUESS we investigate the effect of fire on the tree : grass ratios as well as the biome distribution on the African continent. We performed simulations at three spatial scales: locally, at four sites inside Kruger National Park (South Africa); regionally, along a precipitation gradient; and for the African continent. We evaluated the model using results of a fire experiment and found that the model underestimates the effect of fire on tree cover slightly. On a regional scale, high frequencies were able to prevent trees from outcompeting grasses in mesic regions between ~700 and 900 mm mean annual precipitation. Across the African continent, incorporation of fire improved notably the simulated distribution of the savanna biome. Our model results confirm the role of fire in determining savanna distributions, a notion that has been challenged by competing theories of tree–grass coexistence.
Hyperpolarization-activated, cyclic nucleotide-gated cation channels in
Aplysia
: Contribution to classical conditioning
Authors: Yang Qizong , Kuzyk Pavlo , Antonov Igor , Bostwick Caleb J. , Kohn Andrea B. , Moroz Leonid L. , Hawkins Robert D.
Published: December 2015

Significance

We characterize the channel properties, distribution, and behavioral function of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the mollusc
Aplysia. Aplysia
has one HCN gene, which has overall similarities to HCN homologs from other species. The acHCN channel also has functional properties that closely resemble vertebrate homologs and is expressed in neurons including siphon motor neurons. HCN channels contribute to an associative form of learning (classical conditioning) but not to two nonassociative forms of learning (intermediate-term sensitization and unpaired training) of the siphon withdrawal reflex. The HCN current is enhanced by NO and in turn enhances the NMDA-like current in the motor neurons, suggesting that HCN channels contribute to conditioning through this pathway.
Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer
Authors: Houghton Jacob L. , Zeglis Brian M. , Abdel-Atti Dalya , Aggeler Robert , Sawada Ritsuko , Agnew Brian J. , Scholz Wolfgang W. , Lewis Jason S.
Published: December 2015

Significance

Pancreatic cancer will soon be the second leading cause of cancer deaths annually, yet no adequate molecular imaging tools exist to aid in the staging, monitoring, and treatment of the disease. Here we describe the development and preclinical evaluation of three unique immunoconjugates for positron emission tomography, near-infrared fluorescent optical imaging, and multimodal imaging of pancreatic ductal adenocarcinoma (PDAC). The probes were developed using a site-specific, chemoenzymatic methodology that is robust, reproducible, and modular. By targeting CA19.9, the most abundant antigen in >90% of PDAC tumors, we were able to obtain high-quality images in multiple murine models of PDAC, suggesting these constructs could be the core of a molecular imaging toolkit aimed at improving outcomes for patients with PDAC.
Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1
Authors: El Rayes Tina , Catena Raúl , Lee Sharrell , Stawowczyk Marcin , Joshi Natasha , Fischbach Claudia , Powell Charles A. , Dannenberg Andrew J. , Altorki Nasser K. , Gao Dingcheng , Mittal Vivek
Published: December 2015

Significance

Lungs are highly susceptible to inflammation. However, molecular insights into how external inflammation enhances metastatic outgrowth in the lungs remain lacking. Clinically, approaches are required to block tumor outgrowth in secondary organs for effective treatment of metastatic cancers. We demonstrate a previously unidentified mechanism of thrombospondin-1 (Tsp-1) regulation by inflammatory neutrophil proteases in the metastatic organ. Our findings suggest the potential of using neutrophil protease inhibitors as antimetastatic therapies.
Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation
Authors: Knies Nathalie , Alankus Begüm , Weilemann Andre , Tzankov Alexandar , Brunner Kristina , Ruff Tanja , Kremer Marcus , Keller Ulrich B. , Lenz Georg , Ruland Jürgen
Published: December 2015

Significance

The activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) has a poor clinical outcome and is characterized by constitutive caspase recruitment domain-containing protein 11 (CARD11)/B-cell CLL/lymphoma 10 (BCL10)/mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) signaling and nuclear factor kappa-B (NF-κB) activation, which is essential for tumor cell survival. However, NF-κB inhibitors have not reached the clinic due to high toxicity, and alternative strategies for targeted therapies are needed. Using mouse genetics, we demonstrate that forced CARD11/BCL10/MALT1 signaling drives lethal lymphoproliferation through simultaneous NF-κB and c-Jun N-terminal kinase (JNK) activation. Pharmacological inhibition of JNK was similar to NF-κB blockage and toxic to autonomously proliferating murine B cells, and constitutive JNK activity was observed in human ABC-DLBCL cells, which are also sensitive to JNK inhibitors. Our results identify the JNK pathway as a therapeutic target for DLBCL.
Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment
Authors: Burgoyne Thomas , Meschede Ingrid P. , Burden Jemima J. , Bailly Maryse , Seabra Miguel C. , Futter Clare E.
Published: December 2015

Significance

Photoreceptors of the vertebrate retina contain specialized outer segments (OSs) where phototransduction begins. Rod OSs contain stacks of ordered membranous discs that undergo a daily renewal process essential for vision. Mechanisms underlying disc renewal are unclear. The biosynthetic machinery resides in the inner segment (IS), which is connected to the OS via a connecting cilium. Here, we use electron microscopy and tomography to show that the visual pigment, rhodopsin, traffics to the OS via the ciliary plasma membrane, which evaginates to form discs that are initially extracellularly exposed and that make novel contacts with the IS. Leading edges of adjacent evaginations then fuse to form discrete discs. Tomographic analysis leads us to propose a potential mechanism underlying the evagination process.
Origin and diversification of wings: Insights from a neopteran insect
Authors: Medved Victor , Marden James H. , Fescemyer Howard W. , Der Joshua P. , Liu Jin , Mahfooz Najmus , Popadić Aleksandar
Published: December 2015

Significance

De-repressing appendage growth induces development of ectopic wings on the dorsal prothorax (T1) of the neopteran insect
Oncopeltus
. These T1 wings, albeit fully developed, are small and of primarily dorsal origin. Transcriptome data indicate that incorporation of ventrally originating tissue was a key evolutionary innovation for generating large and useful T2 and T3 wings. Complimentary functional experiments reveal that wings and an adjacent thoracic plate are not developmentally distinct structures, and are coregulated to create tight wing folding that arose during the transition from paleopteran to neopteran insects. Finally,
Ultrabithorax
regulates the divergence of fore- and hindwing morphology, a culminating but also ancient feature of insect wing diversity. These innovations account for major features of insect wing origin and diversification.
Data contradict common perceptions about a controversial provision of the US Endangered Species Act
Authors: Malcom Jacob W. , Li Ya-Wei
Published: December 2015

Significance

The US Endangered Species Act is the most comprehensive law any nation has enacted to protect imperiled species. Many of its protections come from section 7 of the Act, but how government regulators use this tool is poorly understood. Our analysis is the first to systematically evaluate how the US Fish and Wildlife Service has implemented section 7 over an extend timeframe and across all listed species. The results inform current efforts to improve the conservation effectiveness of section 7 and rebut certain claims about the regulatory burdens of complying with section 7.
Oscillatory phase shapes syllable perception
Authors: ten Oever Sanne , Sack Alexander T.
Published: December 2015

Significance

The environment is full of temporal information that links specific auditory and visual representations to each other. Especially in speech, this is used to guide perception. The current paper shows that syllables with varying visual-to-auditory delays get preferably processed at different oscillatory phases. This mechanism facilitates the separation of different representations based on consistent temporal patterns in the environment and provides a way to categorize and memorize information, thereby optimizing a wide variety of perceptual processes.
Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity
Authors: Yin Jie , Leavenworth Jianmei W. , Li Yang , Luo Qi , Xie Huafeng , Liu Xinhua , Huang Shan , Yan Han , Fu Zheng , Zhang Liyun Y. , Zhang Litao , Hao Junwei , Wu Xudong , Deng Xianming , Roberts Charles W. M. , Orkin Stuart H. , Cantor Harvey , Wang Xi
Published: December 2015

Significance

How NK cell development diverges from T/B cell commitment at the common lymphoid progenitor stage is poorly understood. Histone modification near critical gene loci often influences lineage determination. Ezh2 is a histone methyltransferase frequently associated with gene repression. Here we observed that Ezh2-null hematopoietic stem and progenitor cells (HSPCs) or HSPCs treated with Ezh2 inhibitors gave rise to increased NK precursors and mature progeny that display enhanced cytotoxicity against tumor cells. The latter effects were associated with up-regulation of IL-15R (CD122) and the NKG2D-activating receptor. These findings may provide insight into the contribution of epigenetic regulation to the genesis of NK cells and suggest that Ezh2 inhibitors may inhibit tumor growth directly and indirectly through mobilization of NK cells.
The courage of conviction
Authors: Paul Sarah K.
Published: December 2015

Is there a sense in which we exercise direct volitional control over our beliefs? Most agree that there is not, but discussions tend to focus on control in forming a belief. The focus here is on sustaining a belief over time in the face of ‘epistemic temptation’ to abandon it. It is argued that we do have a capacity for ‘doxastic self-control’ over time that is partly volitional in nature, and that its exercise is rationally permissible.
The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling
Authors: Giampietro Costanza , Disanza Andrea , Bravi Luca , Barrios-Rodiles Miriam , Corada Monica , Frittoli Emanuela , Savorani Cecilia , Lampugnani Maria Grazia , Boggetti Barbara , Niessen Carien , Wrana Jeff L. , Scita Giorgio , Dejana Elisabetta
Published: December 2015

Vascular endothelial (VE)–cadherin transfers intracellular signals contributing to vascular hemostasis. Signaling through VE-cadherin requires association and activity of different intracellular partners. Yes-associated protein (YAP)/TAZ transcriptional cofactors are important regulators of cell growth and organ size. We show that EPS8, a signaling adapter regulating actin dynamics, is a novel partner of VE-cadherin and is able to modulate YAP activity. By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14–3-3–YAP associates with the VE–cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity.
Whole-proteome genetic analysis of dependencies in assembly of a vertebrate kinetochore
Authors: Samejima Itaru , Spanos Christos , Alves Flavia de Lima , Hori Tetsuya , Perpelescu Marinela , Zou Juan , Rappsilber Juri , Fukagawa Tatsuo , Earnshaw William C.
Published: December 2015

Kinetochores orchestrate mitotic chromosome segregation. Here, we use quantitative mass spectrometry of mitotic chromosomes isolated from a comprehensive set of chicken DT40 mutants to examine the dependencies of 93 confirmed and putative kinetochore proteins for stable association with chromosomes. Clustering and network analysis reveal both known and unexpected aspects of coordinated behavior for members of kinetochore protein complexes. Surprisingly, CENP-T depends on CENP-N for chromosome localization. The Ndc80 complex exhibits robust correlations with all other complexes in a “core” kinetochore network. Ndc80 associated with CENP-T interacts with a cohort of Rod, zw10, and zwilch (RZZ)–interacting proteins that includes Spindly, Mad1, and CENP-E. This complex may coordinate microtubule binding with checkpoint signaling. Ndc80 associated with CENP-C forms the KMN (Knl1, Mis12, Ndc80) network and may be the microtubule-binding “workhorse” of the kinetochore. Our data also suggest that CENP-O and CENP-R may regulate the size of the inner kinetochore without influencing the assembly of the outer kinetochore.
Thirty years of search and capture: The complex simplicity of mitotic spindle assembly
Authors: Heald Rebecca , Khodjakov Alexey
Published: December 2015

Cell division is enacted by a microtubule-based, self-assembling macromolecular machine known as the mitotic spindle. In 1986, Kirschner and Mitchison proposed that by undergoing dynamic cycles of growth and disassembly, microtubules search for chromosomes. Capture of microtubules by the kinetochores progressively connects chromosomes to the bipolar spindle. 30 years later, “search and capture” remains the cornerstone of spindle assembly. However, a variety of facilitating mechanisms such as regulation of microtubule dynamics by diffusible gradients, spatially selective motor activities, and adaptive changes in chromosome architecture have been discovered. We discuss how these mechanisms ensure that the spindle assembles rapidly and with a minimal number of errors.