bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Organic NPK Granules and Inorganic Fertilizers on Growth, Yield and Economics of Rice
Authors: Reshma M. S. , Jawahar S. , Kalaiyarasan C. , Suseendran K. , Elayaraja D.
Published: July 2024

Modern intensive agriculture, which sparked the "Green Revolution" in the early 1970s, degraded the environment, which decreased productivity and had other negative impacts on the environment and public health. In order to improve the health of the agricultural environment, organic farming, which primarily forgoes the use of chemicals in agriculture, depends on a comprehensive production and management system. The multitude of microorganisms in the soil under this holistic management method ensures that the soil is alive, active, and productive by keeping it biologically active. It is a reality that plants can and do absorb huge amounts of big organic molecules, such as vitamins, chelated minerals, hormones, and other substances that are advantageous to them, refuting the claim that plants only ever take up nutrients in inorganic form. To investigate further, a field experiment was conducted at the Experimental Farm, Department of Agronomy, Annamalai University, Annamalai Nagar, Cuddalore District of Tamil Nadu from June to September 2023 to study the effect of combined application of graded levels of inorganic fertilizers along with organic NPK granules on growth, yield and economics of rice. The experiment was laid out in randomized block design with seven treatments, comprised of different levels of inorganic fertilizers and organic NPK granules. Among the treatments evaluated, application of 70% NPK through inorganic fertilizers and 30% NPK through organic NPK granules registered higher growth, yield attributes and yield of rice. However the net income and benefit cost ratio was observed under application of 100% NPK through inorganic fertilizers which was comparable with application of 70% NPK through inorganic fertilizers and 30% NPK through organic granules. Therefore it can be concluded that combined application of 70% NPK through inorganic fertilizers and 30% NPK through organic granules is an environmental safe and economically viable nutrient management practice for getting higher yield and income from rice and it can be recommended to the rice growers.
Daylighting Evaluation of Perforated Screen Façade with Light Shelf in the Tropics
Authors: Elsiana Feny , S Arifin Lilianny
Published: July 2024

The use of large glass facades in buildings without external shading devices leads to a high daylight level, uneven daylight distribution, and glare. A perforated screen facade (PSF) is one of the shading systems that can provide daylight and view and prevent direct solar radiation into a building. More research is needed about the daylight performance of PSF in integration with daylighting systems in the tropics. A combination of PSF and light shelf (LS), a daylighting system that can redirect daylight to the ceiling and enhance daylight distribution, is proposed to improve daylight levels and reduce glare. The research aims to evaluate the daylight performance of PSF and LS in the tropics. The research method is experimental with simulation utilizing IES-VE Radiance IES. Average Daylight Factor (DFavg), Useful Daylight Illuminance (UDI), and Daylight Glare Probability (DGP) of a room with a side window were compared with a room with PSF and LS. The results showed that implementing PSF and LS improved daylight performance by lowering the DFavg by 55%, increasing the UDI, and reducing the DGP.
Personenbezug von Large Language Models — Eine datenschutzrechtliche Grundsatzfrage bei der Nutzung generativer KI-Modelle
Authors: Moos Flemming
Published: July 2024

Seit der Veröffentlichung von ChatGPT im November 2022 ist der Markt für generative KI-Modelle sprichwörtlich explodiert. Das gilt auch und ganz maßgeblich für Einsatzszenarien im Unternehmenskontext; etwa in Gestalt von Assistenzfunktionen für Office-Programme, maschinelle Übersetzungen oder auch die automatisierte Generierung von Content jeglicher Art, z.B. durch Chatbots. Es ist deshalb sicherlich nicht übertrieben zu konstatieren, dass derzeit jedes Unternehmen für sich bewertet, ob und für welche Zwecke es sinnvoll und rechtskonform generative KI-Modelle, vor allem in der Form sog. Large Language Models (LLMs) einsetzen kann. Dass hierbei prinzipiell auch das Datenschutzrecht zu beachten ist, ist klar. Unklar ist aber bisher in welchem Umfang und in welcher Phase der Einführung und Nutzung eines LLM im Unternehmen. Das hängt maßgeblich von der Frage ab, ob ein LLM an sich bereits aus personenbezogenen Daten besteht. Dieser Frage geht der Beitrag nach.
Gedanken zur Personengesellschaftsbesteuerung im Jahre 2024
Authors: Prinz Ulrich
Published: July 2024

Gottfried E. Breuninger, dem dieser Betrag in hoher Wertschätzung und jahrzehntelanger kollegialer Zusammenarbeit gewidmet ist, hat sich in seiner im Jahre 1991 veröffentlichten Doktorarbeit an der Juristischen Fakultät der Eberhard-Karls-Universität Tübingen mit der „BGB-Gesellschaft als Rechtssubjekt im Wirtschaftsverkehr“ befasst. Der Streit um die Rechtsnatur der Gesamthandsgesellschaft mit ihren mitgliedschaftsrechtlichen und vermögensrechtlichen Aspekten sowie den sehr facettenreichen rechtstatsächlichen Erscheinungsformen stand im Mittelpunkt. Mehr als 30 Jahre später hat seine damalige Doktorarbeit weiter und erneut hohe Aktualität. Denn der gesellschaftsrechtliche Gesetzgeber hat mit dem „Gesetz zur Modernisierung des Personengesellschaftsrechts (MoPeG)“ vom 10.8.2021 vor allem das Recht der GbR als Grundform gemeinsamer wirtschaftlicher Zweckverfolgung mit Wirkung ab dem Jahre 2024 auf die Höhe der Zeit gebracht und im Zuge dessen das gesellschaftsrechtliche Gesamthandsprinzip aufgegeben. Zugleich wurde dadurch bei den in der Gedankenwelt der transparenten Mitunternehmerbesteuerung verwurzelten Steuerrechtlern einiges an Unruhe geschaffen. Denn die gesellschaftsrechtliche Gesamthand findet in etlichen Steuernormen wegweisend Erwähnung, was zu Verständnisfriktionen zwischen Gesellschafts- und Steuerrecht führen könnte und zudem den Dualismus der Unternehmensbesteuerung mit Trennungs- und Transparenzprinzip berührt. Manche Kommentatoren der Entwicklung vermuten dagegen mit Blick auf das Infragestellen steuerrechtlicher Grundlagen der Personengesellschaften einen „Sturm im Wasserglas“. Der Steuergesetzgeber hat nun klugerweise im Kreditzweitmarktförderungsgesetz vom 22.12.2023 einige steuerliche MoPeG-Folgefragen gelöst. Dies ist Anlass, zu Ehren von Gottfried Breuninger einen Blick auf die Personengesellschaftsbesteuerung im Jahre 2024 zu werfen.
Vom Mittelpunkt über die Willensbildung zur Betriebsstätte
Authors: Töben Thomas , Schrepp Caroline
Published: July 2024

Die Verfasser analysieren die Rechtsprechung zur Auslegung des Begriffs des Ortes der Geschäftsleitung. Diese nimmt Bezug auf das Zivilrecht, namentlich § 17 Abs. 1 Satz2 ZPO betreffend den Gerichtsstand juristischer Personen. Die seit 1977 in § 10 AO enthaltene Legaldefinition „Geschäftsleitung ist der Mittelpunkt der geschäftlichen Oberleitung“ geht darüber hinaus auf Vorschriften zur Zuständigkeit der Finanzämter zurück. Der Ort der Geschäftsleitung liegt daher grundsätzlich dort, wo der Gesellschaft ein Büro zur Verfügung steht, wo die satzungsmäßigen Geschäftsführer erreichbar sind und wo die Verwaltung, das sog. Tagesgeschäft, der Gesellschaft geführt wird.
Die Entwicklungen in der Rechtsprechung zum Bauprozessrecht — Übersicht für das Jahr 2023
Authors: Schmeel Günter
Published: July 2024

Die Rechtsprechungsübersicht knüpft an den Überblick in MDR 2023, 683 zu den prozessrechtlichen Besonderheiten im Bauvertragsrecht an und behandelt die einschlägigen Entscheidungen aus dem Jahre 2023.
Turbulent kinetic energy and coherent structures in a tidal river
Authors: Talke S. A. , Horner‐Devine A. R. , Chickadel C. C. , Jessup A. T.
Published: November 2013

We investigate the relationship between turbulence statistics and coherent structures (CS) in an unstratified reach of the Snohomish River estuary using in situ velocity measurements and surface infrared (IR) imaging. Sequential IR images are used to estimate surface flow characteristics via a particle‐image‐velocimetry (PIV) technique, and are conditionally sampled to delineate the surface statistics of bottom‐generated CS, or boils. In the water column, we find that turbulent kinetic energy (TKE) production exceeds dissipation near the bed but is less than dissipation in the midwater column and that TKE flux divergence closes a significant portion of the measured imbalance. The surface boundary leads to divergence in upwelling CS, and leads to the redistribution of vertical TKE to the horizontal. Very near the surface, statistical anisotropy is observed at length scales larger than the depth H (3–5 m), while boil‐scale motions of O(1)m are nearly isotropic and exhibit a −5/3 turbulent cascade to smaller scales. Conditional sampling suggests that TKE dissipation in boils is approximately 2 times greater on average than dissipation in ambient flow. Similarly, surface boils are marked by significantly greater velocity variance, upwelling, divergence, and TKE flux divergence than ambient flow regions. Coherent structures and their surface manifestation, therefore, play an important role in the vertical transport of TKE and the water column distribution of dissipation, and are an important component of the TKE budget.
Critical taper analysis reveals lithological control of variations in detachment strength: An analysis of the Alpine basal detachment (Swiss Alps)
Authors: von Hagke C. , Oncken O. , Evseev S.
Published: November 2013

Although evidence for weak detachments underlying foreland thrust belts exists, very little is known about the lateral variations in effective strength, as well as the geological nature of such variations. Using critical taper analysis, we show that a detailed and systematic measurement of surface slope of the Central European Alps reveals variations in strength parameter F along the detachment, based on the argument that the Alps are close to the critical state. We show that the basal detachment is very weak near the deformation front but strengthens toward the hinterland. Very low F (effective coefficient of friction plus normalized cohesion) values of <0.1 and even 0.05 occur within evaporites and within shales in Triassic (west) or Upper Cretaceous/Lower Tertiary sequences (east) used by the Alpine sole detachment. These very low values in shales—comparably low values are reported from other orogens—are caused partly by slightly elevated pore pressures (λ > 0.54) but may also require additional mechanisms of dynamic weakening.
A fast and sensitive new satellite SO2 retrieval algorithm based on principal component analysis: Application to the ozone monitoring instrument
Authors: Li Can , Joiner Joanna , Krotkov Nickolay A. , Bhartia Pawan K.
Published: November 2013

We describe a new algorithm to retrieve SO2 from satellite‐measured hyperspectral radiances. We employ the principal component analysis technique in regions with no significant SO2 to capture radiance variability caused by both physical processes (e.g., Rayleigh and Raman scattering and ozone absorption) and measurement artifacts. We use the resulting principal components and SO2 Jacobians calculated with a radiative transfer model to directly estimate SO2 vertical column density in one step. Application to the Ozone Monitoring Instrument (OMI) radiance spectra in 310.5–340 nm demonstrates that this approach can greatly reduce biases in the operational OMI product and decrease the noise by a factor of 2, providing greater sensitivity to anthropogenic emissions. The new algorithm is fast, eliminates the need for instrument‐specific radiance correction schemes, and can be easily adapted to other sensors. These attributes make it a promising technique for producing long‐term, consistent SO2 records for air quality and climate research.
Modeling soil moisture‐precipitation feedback in the Sahel: Importance of spatial scale versus convective parameterization
Authors: Taylor Christopher M. , Birch Cathryn E. , Parker Douglas J. , Dixon Nick , Guichard Françoise , Nikulin Grigory , Lister Grenville M. S.
Published: November 2013

Feedback between soil moisture and precipitation influence climate variability in semiarid regions. However, serious concerns exist about the ability of coarse‐scale global atmospheric models to depict one key aspect of the feedback loop, namely the sensitivity of daytime convection to soil moisture. Here we compare regional simulations using a single model, run at different spatial resolutions, and with convective parameterizations switched on or off against Sahelian observations. Convection‐permitting simulations at 4 and 12 km capture the observed relationships between soil moisture and convective triggering, emphasizing the importance of surface‐driven mesoscale dynamics. However, with the inclusion of the convection scheme at 12 km, the behavior of the model fundamentally alters, switching from negative to positive feedback. Similar positive feedback is found in 9 out of 10 Regional Climate Models run at 50 km. These results raise questions about the accuracy of the feedback in regional models based on current convective parameterizations.
Frost flower aerosol effects on Arctic wintertime longwave cloud radiative forcing
Authors: Xu Li , Russell Lynn M. , Somerville Richard C. J. , Quinn Patricia K.
Published: November 2013

Frost flowers are clusters of highly saline ice crystals growing on newly formed sea ice or frozen lakes. Based on observations of particles derived from frost flowers in the Arctic, we formulate an observation‐based parameterization of salt aerosol source function from frost flowers. The particle flux from frost flowers in winter has the order of 106 m−2 s−1 at the wind speed of 10 m s−1, but the source flux is highly localized to new sea ice regions and strongly dependent on wind speed. We have implemented this parameterization into the regional Weather Research and Forecasting model with Chemistry initialized for two wintertime scenarios. The addition of sea salt aerosol emissions from frost flowers increases averaged sea salt aerosol mass and number concentration and subsequent cloud droplet number. This change of cloud droplet number concentration increases downward longwave cloud radiative forcing through enhanced cloud optical depth and emissivity. The magnitude of this forcing of sea salt aerosols from frost flowers on clouds and radiation, however, contributes negligibly to surface warming in Barrow, Alaska, in the wintertime scenarios studied here.
Motivational Incentives Improve Unfamiliar Face Matching Accuracy
Authors: Moore Rachel M. , Johnston Robert A.
Published: November 2013

Unfamiliar face matching is the process of simultaneously verifying the equivalence of two faces. Accuracy within this task is crucial given its importance and prevalence in security domains. However, research has consistently demonstrated that unfamiliar face matching is error prone, suggesting the need for improvement techniques. Motivational incentives have been shown to reliably enhance performance on a wide array of cognitive tasks. Therefore, the current study examined the effect of motivational incentives on unfamiliar face matching. Experiment 1 showed increased accuracy in mismatch trials with the addition of a motivational incentive. The improvement was associated with an increase in reaction time and bias towards making a mismatch response. This bias, however, did not produce a decrease in accuracy on match trials. Experiment 2 replicated this result with a more ecologically valid methodology. The results suggest motivational incentives to be effective at improving performance on mismatch trials, arguably the most important aspect of real‐world unfamiliar face matching. Copyright © 2013 John Wiley & Sons, Ltd.
On the Relation between Morphology and FET Mobility of Poly(3‐alkylthiophene)s at the Polymer/SiO2 and Polymer/Air Interface
Authors: Oosterbaan Wibren D. , Bolsée Jean‐Christophe , Wang Linjun , Vrindts Veerle , Lutsen Laurence J. , Lemaur Vincent , Beljonne David , McNeill Christopher R. , Thomsen Lars , Manca Jean V. , Vanderzande Dirk J. M.
Published: November 2013

The influence of the interface of the dielectric SiO2 on the performance of bottom‐contact, bottom‐gate poly(3‐alkylthiophene) (P3AT) field‐effect transistors (FETs) is investigated. In particular, the operation of transistors where the active polythiophene layer is directly spin‐coated from chlorobenzene (CB) onto the bare SiO2 dielectric is compared to those where the active layer is first spin‐coated then laminated via a wet transfer process such that the film/air interface of this film contacts the SiO2 surface. While an apparent alkyl side‐chain length dependent mobility is observed for films directly spin‐coated onto the SiO2 dielectric (with mobilities of ≈10−3 cm2 V−1 s−1 or less) for laminated films mobilities of 0.14 ± 0.03 cm2 V−1 s−1 independent of alkyl chain length are recorded. Surface‐sensitive near edge X‐ray absorption fine structure (NEXAFS) spectroscopy measurements indicate a strong out‐of‐plane orientation of the polymer backbone at the original air/film interface while much lower average tilt angles of the polymer backbone are observed at the SiO2/film interface. A comparison with NEXAFS on crystalline P3AT nanofibers, as well as molecular mechanics and electronic structure calculations on ideal P3AT crystals suggest a close to crystalline polymer organization at the P3AT/air interface of films from CB. These results emphasize the negative influence of wrongly oriented polymer on charge carrier mobility and highlight the potential of the polymer/air interface in achieving excellent “out‐of‐plane” orientation and high FET mobilities.
A Magnetoclick Imidazolidinone Nanocatalyst for Asymmetric 1,3‐Dipolar Cycloadditions
Authors: Pagoti Sreenivasarao , Dutta Debasish , Dash Jyotirmayee
Published: November 2013

A 1,3‐dipolar azide–alkyne cycloaddition has been used to prepare a magnetic nanoparticle immobilized MacMillan catalyst that catalyzes the enantioselective 1,3‐dipolar cycloaddition between nitrones and α,β‐unsaturated aldehydes. The catalyst can be recovered and recycled for five consecutive runs without any significant loss in yields and diastereo‐ and enantioselectivities of the isoxazolidines.

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Lithiation‐Induced Dilation Mapping in a Lithium‐Ion Battery Electrode by 3D X‐Ray Microscopy and Digital Volume Correlation
Authors: Eastwood David S. , Yufit Vladimir , Gelb Jeff , Gu Allen , Bradley Robert S. , Harris Stephen J. , Brett Daniel J. L. , Brandon Nigel P. , Lee Peter D. , Withers Philip J. , Shearing Paul R.
Published: November 2013

Recent advances in high‐resolution 3D X‐ray computed tomography (CT) allow detailed, non‐destructive 3D structural mapping of a complete lithium‐ion battery. By repeated 3D image acquisition (time lapse CT imaging) these investigations of material microstructure are extended into the fourth dimension (time) to study structural changes of the device in operando. By digital volume correlation (DVC) of successive 3D images the dimensional changes taking place during charge cycling are quantified at the electrode level and at the Mn2O4 particle scale. After battery discharging, the extent of lithiation of the manganese (III/IV) oxide grains in the electrode is found to be a function of the distance from the battery terminal with grains closest to the electrode/current collector interface having the greatest expansion (≈30%) and grains furthest from the current collector and closest to the counter electrode showing negligible dilation. This implies that the discharge is limited by electrical conductivity. This new CT+DVC technique is widely applicable to the 3D exploration of the microstructural degradation processes for a range of energy materials including fuel cells, capacitors, catalysts, and ceramics.
The effect of system pressure on gas‐liquid slug flow in a microchannel
Authors: Yao Chaoqun , Dong Zhengya , Zhao Yuchao , Chen Guangwen
Published: November 2013

Characteristics of gas‐liquid two‐phase flow under elevated pressures up to 3.0 MPa in a microchannel are investigated to provide the guidance for microreactor designs relevant to industrial application. The results indicate that a strong leakage flow through the channel corners occurs although the gas bubbles block the channel. With a simplified estimation, the leakage flow is shown to increase with an increase in pressure, leading to a bubble formation shifting from transition regime to squeezing regime. During the formation process, the two‐phase dynamic interaction at the T‐junction entrance would have a significant influence on the flow in the main channel as the moving velocity of generated bubbles varies periodically with the formation cycle. Other characteristics such as bubble formation frequency, bubble and slug lengths, bubble velocities, gas hold‐up, and the specific surface area are also discussed under different system pressures. © 2013 American Institute of Chemical Engineers AIChE J, 60: 1132–1142, 2014
Optimum heat storage design for solar‐driven absorption refrigerators integrated with heat exchanger networks
Authors: Lira‐Barragán Luis Fernando , Ponce‐Ortega José María , Serna‐González Medardo , El‐Halwagi Mahmoud M.
Published: November 2013

A methodology is presented for optimizing hybrid renewable energy‐fossil fuel systems with short‐term heat storage. The considered system is an absorption‐refrigeration (AR) cycle integrated with a heat exchanger network (HEN) requiring cooling below ambient temperature. The AR cycle can be driven by multiple energy sources including excess energy from hot process streams, renewable energy sources (solar and biofuels), and fossil fuels. A two‐step approach based on mixed integer nonlinear programming methods is used for the optimization. First, the problem of optimal energy integration in the hybrid energy system without heat storage is solved on a monthly basis by minimizing simultaneously the total annual cost and the overall greenhouse gas emissions. In the second step, the multi‐tank thermal energy storage (TES) design problem is solved. The design involves the identification of the optimal number of storage tanks, their sizes, configuration and operation policies. The TES optimization is carried out on an hourly basis while incorporating the design targets determined by the first step. © 2013 American Institute of Chemical Engineers AIChE J, 60: 909–930, 2014
A 2‐Benzothiazolylphenyl Group Accelerates the Intramolecular [2+2] Cycloaddition of Allene‐Ynes
Authors: Hori Hiroto , Arai Shigeru , Nishida Atsushi
Published: November 2013

A [2+2] cycloaddition reaction of allene‐ynes under thermal conditions with/without a metal complex is described. A key feature of this reaction is that a 2‐benzothiazolylphenyl group bearing a CC triple bonds remarkably promotes the reaction to give the corresponding cyclobutenes with or without metal catalysts.
Fecal microbiomes of non‐human primates in Western Uganda reveal species‐specific communities largely resistant to habitat perturbation
Authors: McCord Aleia I. , Chapman Colin A. , Weny Geoffrey , Tumukunde Alex , Hyeroba David , Klotz Kelly , Koblings Avery S. , Mbora David N.M. , Cregger Melissa , White Bryan A. , Leigh Steven R. , Goldberg Tony L.
Published: November 2013

Primate gastrointestinal microbial communities are becoming increasingly appreciated for their relevance to comparative medicine and conservation, but the factors that structure primate “microbiomes” remain controversial. This study examined a community of primates in Kibale National Park, Uganda, to assess the relative importance of host species and location in structuring gastrointestinal microbiomes. Fecal samples were collected from primates in intact forest and from primates in highly disturbed forest fragments. People and livestock living nearby were also included, as was a geographically distant population of related red colobus in Kenya. A culture‐free microbial community fingerprinting technique was used to analyze fecal microbiomes from 124 individual red colobus (Procolobus rufomitratus), 100 individual black‐and‐white colobus (Colobus guereza), 111 individual red‐tailed guenons (Cercopithecus ascanius), 578 human volunteers, and 364 domestic animals, including cattle (Bos indicus and B. indicus × B. taurus crosses), goats (Caprus hircus), sheep (Ovis aries), and pigs (Sus scrofa). Microbiomes sorted strongly by host species, and forest fragmentation did not alter this pattern. Microbiomes of Kenyan red colobus sorted distinctly from microbiomes of Ugandan red colobus, but microbiomes from these two red colobus populations clustered more closely with each other than with any other species. Microbiomes from red colobus and black‐and‐white colobus were more differentiated than would be predicted by the phylogenetic relatedness of these two species, perhaps reflecting heretofore underappreciated differences in digestive physiology between the species. Within Kibale, social group membership influenced intra‐specific variation among microbiomes. However, intra‐specific variation was higher among primates in forest fragments than among primates in intact forest, perhaps reflecting the physical separation of fragments. These results suggest that, in this system, species‐specific processes such as gastrointestinal physiology strongly structure microbial communities, and that primate microbiomes are relatively resistant to perturbation, even across large geographic distances or in the face of habitat disturbance. Am. J. Primatol. 76:347–354, 2014. © 2013 Wiley Periodicals, Inc.
Ontogeny of material stiffness heterogeneity in the macaque mandibular corpus
Authors: Daegling David J. , Granatosky Michael C. , McGraw W. Scott
Published: November 2013

Evidence is accumulating that bone material stiffness increases during ontogeny, and the role of elastic modulus in conditioning attributes of strength and toughness is therefore a focus of ongoing investigation. Developmental changes in structural properties of the primate mandible have been documented, but comparatively little is known about changes in material heterogeneity and their impact on biomechanical behavior.

We examine a cross‐sectional sample of Macaca fascicularis (N = 14) to investigate a series of hypotheses that collectively evaluate whether the patterning of material stiffness (elastic modulus) heterogeneity in the mandible differs among juvenile, subadult and adult individuals. Because differences in age‐related activity patterns are known to influence bone stiffness and strength, these data are potentially useful for understanding the relationship between feeding behavior on the one hand and material and structural properties of the mandible on the other.

Elastic modulus is shown to be spatially dependent regardless of age, with this dependence being explicable primarily by differences in alveolar versus basal cortical bone. Elastic modulus does not differ consistently between buccal and lingual cortical plates, despite likely differences in the biomechanical milieu of these regions. Since we found only weak support for the hypothesis that the spatial patterning of heterogeneity becomes more predictable with age, accumulated load history may not account for regional differences in bone material properties in mature individuals with respect to the mandibular corpus. Am J Phys Anthropol 153:297–304, 2014. © 2013 Wiley Periodicals, Inc.
Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis
Authors: Christmann Romy B. , Sampaio‐Barros Percival , Stifano Giuseppina , Borges Claudia L. , de Carvalho Carlos R. , Kairalla Ronaldo , Parra Edwin R. , Spira Avrum , Simms Robert , Capellozzi Vera L. , Lafyatis Robert
Published: November 2013

Objective

Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc‐related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease.

Methods

Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc‐related ILD and in 4 controls. High‐resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2–3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein.

Results

Lung microarray data distinguished patients with SSc‐related ILD from healthy controls. In the lungs of patients with SSc‐related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)– and interferon (IFN)–regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < −0.1), including IFN and macrophage markers, chemokines, and heat‐shock proteins.

Conclusion

These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc‐related ILD: macrophage emigration and activation, and up‐regulated expression of TGFβ‐ and IFN‐regulated genes.
Inhibition of Myogenic MicroRNAs 1, 133, and 206 by Inflammatory Cytokines Links Inflammation and Muscle Degeneration in Adult Inflammatory Myopathies
Authors: Georgantas Robert W. , Streicher Katie , Greenberg Steven A. , Greenlees Lydia M. , Zhu Wei , Brohawn Philip Z. , Higgs Brandon W. , Czapiga Meggan , Morehouse Christopher A. , Amato Anthony , Richman Laura , Jallal Bahija , Yao Yihong , Ranade Koustubh
Published: November 2013

Objective

The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics of chronic muscle inflammation and skeletal muscle wasting, are poorly understood. As such, effective targeted treatments for these diseases are lacking, resulting in critical unmet medical needs for these devastating diseases. The purpose of this study was to identify possible new targets for drug development by exploring the mechanism by which inflammation may play a role in the pathology of the inflammatory myopathies.

Methods

We compared expression levels of inflammatory cytokines and microRNAs (miRNAs) between muscle biopsy samples from patients with inflammatory myopathies and those from donors without myositis. In vitro human and mouse model systems were then used to characterize the role of these cytokines and microRNAs on myoblast‐to‐myocyte differentiation.

Results

We observed increased expression of inflammatory cytokines, including tumor necrosis factor α (TNFα), interferon‐α (IFNα), IFNβ, and interleukin‐1β, in different subtypes of inflammatory myopathies. We observed decreased expression of microRNA‐1 (miR‐1), miR‐133a, and miR‐133b in all of the inflammatory myopathy subtypes we evaluated, as well as decreased expression of miR‐206 in DM; these miRNAs are essential for adult skeletal muscle differentiation and maintenance. TNFα was significantly inversely correlated with decreased myogenic miRNA expression in the inflammatory myopathy subtypes. In mechanistic studies, TNFα inhibited the expression of myogenic miRNAs and suppressed the differentiation of C2C12 myoblasts to myocytes/myotubes in an NF‐κB–dependent manner. This block in differentiation by TNFα was relieved by overexpression of miR‐1, miR‐206, or miR‐133a/b.

Conclusion

Taken together, these results provide a new mechanistic link between the action of proinflammatory cytokines and the degenerative pathology of inflammatory myopathies, and suggest therapeutic approaches for these diseases.
Assessment of Joint and Fascia Manifestations in Chronic Graft‐Versus‐Host Disease
Authors: Inamoto Yoshihiro , Pidala Joseph , Chai Xiaoyu , Kurland Brenda F. , Weisdorf Daniel , Flowers Mary E. D. , Palmer Jeanne , Arai Sally , Jacobsohn David , Cutler Corey , Jagasia Madan , Goldberg Jenna D. , Martin Paul J. , Pavletic Steven Z. , Vogelsang Georgia B. , Lee Stephanie J. , Carpenter Paul A. ,   on behalf of the Chronic GVHD Consortium
Published: November 2013

Objective

To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft‐versus‐host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results.

Methods

In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P‐ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions.

Results

Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician‐ and patient‐perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician‐ and patient‐perceived worsening, but the P‐ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality.

Conclusion

Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P‐ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P‐ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases.
A Computer Simulation Approach to Assessing Therapeutic Intervention Points for the Prevention of Cytokine‐Induced Cartilage Breakdown
Authors: Proctor C. J. , Macdonald C. , Milner J. M. , Rowan A. D. , Cawston T. E.
Published: November 2013

Objective

To use a novel computational approach to examine the molecular pathways involved in cartilage breakdown and to use computer simulation to test possible interventions for reducing collagen release.

Methods

We constructed a computational model of the relevant molecular pathways using the Systems Biology Markup Language, a computer‐readable format of a biochemical network. The model was constructed using our experimental data showing that interleukin‐1 (IL‐1) and oncostatin M (OSM) act synergistically to up‐regulate collagenase protein levels and activity and initiate cartilage collagen breakdown. Simulations were performed using the COPASI software package.

Results

The model predicted that simulated inhibition of JNK or p38 MAPK, and overexpression of tissue inhibitor of metalloproteinases 3 (TIMP‐3) led to a reduction in collagen release. Overexpression of TIMP‐1 was much less effective than that of TIMP‐3 and led to a delay, rather than a reduction, in collagen release. Simulated interventions of receptor antagonists and inhibition of JAK‐1, the first kinase in the OSM pathway, were ineffective. So, importantly, the model predicts that it is more effective to intervene at targets that are downstream, such as the JNK pathway, rather than those that are close to the cytokine signal. In vitro experiments confirmed the effectiveness of JNK inhibition.

Conclusion

Our study shows the value of computer modeling as a tool for examining possible interventions by which to reduce cartilage collagen breakdown. The model predicts that interventions that either prevent transcription or inhibit the activity of collagenases are promising strategies and should be investigated further in an experimental setting.
Duration of the South America summer monsoon is increasing
Authors: Rao V. Brahmananda , Franchito Sergio H. , Gan Manoel A. , Gerolamo Renato O. P.
Published: November 2013

We studied the interannual variability of the beginning, end and duration of South American monsoon system (SAMS) for the period 1956–2006. The mean beginning date was 10 October, whereas the mean end date was 6 April, and the mean duration was 174 days. The beginning of SAMS showed a tendency to start earlier and the end date showed a tendency to delay; thus, the duration of SAMS showed a tendency to increase by about 7 days in 10 years. We found that the beginning and end dates of SAMS have significant positive correlation with sea surface temperature (SST) of an earlier period at southwest Africa in the South Atlantic Ocean. This suggests the potential of SST in the prediction of the beginning and end dates of SAMS.
Quercetin‐3‐rhamnoglucoside (rutin) stimulates transport of organic anion compounds mediated by organic anion transporting polypeptide 2B1
Authors: Ogura Jiro , Koizumi Takahiro , Segawa Masahiro , Yabe Keisuke , Kuwayama Kaori , Sasaki Shunichi , Kaneko Chihiro , Tsujimoto Takashi , Kobayashi Masaki , Yamaguchi Hiroaki , Iseki Ken
Published: November 2013

Quercetin‐3‐rhamnoglucoside (rutin) has a wide spectrum of biochemical and pharmacological activities. Rutin is absorbed mainly in its unmetabolized form. Organic anion transporting polypeptide (OATP) 2B1 is a major uptake transporter in the intestine. Thus, it is important for the prevention of adverse events to understand drug interactions mediated by OATP2B1 in the absorption process. This study assessed the effect of rutin on transport by OATP2B1. Rutin stimulated the uptake of estrone‐3‐sulfate (E‐3‐S), taurocholic acid (TCA), cholic acid (CA) and rosuvastatin by OATP2B1, but not p‐coumaric acid or ferulic acid. The EC50 of rutin for transport by OATP2B1 was 2.32 μm. The Km value of E‐3‐S for OATP2B1 in the presence of rutin (9.21 μm) was almost the same as that in the absence of rutin (8.53 μm). On the other hand, the Vmax of E‐3‐S transport by OATP2B1 in the presence of rutin (270 pmol/mg protein/min) was 1.2‐fold higher than that in the absence of rutin (218 pmol/mg protein/min). Moreover, the expression level of OATP2B1 on the cell membrane was increased by treatment with rutin for 5 min without alteration of the total OATP2B1 expression level. Moreover, the increase in the localization of OATP2B1 at the cell surface was detected by the immunocytochemistry. The stimulatory effect of rutin is a little weak but may affect the absorption of OATP2B1 substrates, because rutin is taken daily in foods and its intestinal concentration would reach the stimulatory range of OATP2B1. Copyright © 2014 John Wiley & Sons, Ltd.
Peroxynitrite, a potent macrophage‐derived oxidizing cytotoxin to combat invading pathogens
Authors: Prolo Carolina , Álvarez María Noel , Radi Rafael
Published: November 2013

Macrophages are among the first cellular actors facing the invasion of microorganisms. These cells are able to internalize pathogens and destroy them by means of toxic mediators, many of which are produced enzymatically and have strong oxidizing capacity. Indeed, macrophages count on the NADPH oxidase complex activity, which is triggered during pathogen invasion and leads to the production of superoxide radical inside the phagosome. At the same time, the induction of nitric oxide synthase results in the production of nitric oxide in the cytosol which is able to readily diffuse to the phagocytic vacuole. Superoxide radical and nitric oxide react at diffusion controlled rates with each other inside the phagosome to yield peroxynitrite, a powerful oxidant capable to kill micro‐organisms. Peroxynitrite toxicity resides on oxidations and nitrations of biomolecules in the target cell. The central role of peroxynitrite as a key effector molecule in the control of infections has been proven in a wide number of models. However, some microorganisms and virulent strains adapt to survive inside the potentially hostile oxidizing microenvironment of the phagosome by either impeding peroxynitrite formation or rapidly detoxifying it once formed. In this context, the outcome of the infection process is a result of the interplay between the macrophage‐derived oxidizing cytotoxins such as peroxynitrite and the antioxidant defense machinery of the invading pathogens. © 2013 BioFactors, 40(2):215–225, 2014
Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis
Authors: Calvanese Luisa , Falcigno Lucia , Maglione Cira , Marasco Daniela , Ruggiero Alessia , Squeglia Flavia , Berisio Rita , D'Auria Gabriella
Published: November 2013

PonA2 is one of the two class A penicillin binding proteins of Mycobacterium tuberculosis, the etiologic agent of tuberculosis. It plays a complex role in mycobacterial physiology and is spotted as a promising target for inhibitors. PonA2 is involved in adaptation of M. tuberculosis to dormancy, an ability which has been attributed to the presence in its sequence of a C‐terminal PASTA domain. Since PASTA modules are typically considered as β‐lactam antibiotic binding domains, we determined the solution structure of the PASTA domain from PonA2 and analyzed its binding properties versus a plethora of potential binders, including the β‐lactam antibiotics, two typical muropeptide mimics, and polymeric peptidoglycan. We show that, despite a high structural similarity with other PASTA domains, the PASTA domain of PonA2 displays different binding properties, as it is not able to bind muropeptides, or β‐lactams, or polymeric peptidoglycan. These results indicate that the role of PASTA domains cannot be generalized, as their specific binding properties strongly depend on surface residues, which are widely variable. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 712–719, 2014.
Model‐based derivation, analysis and control of unstable microaerobic steady‐states—Considering Rhodospirillum rubrum as an example
Authors: Carius Lisa , Rumschinski Philipp , Faulwasser Timm , Flockerzi Dietrich , Grammel Hartmut , Findeisen Rolf
Published: November 2013

Microaerobic (oxygen‐limited) conditions are critical for inducing many important microbial processes in industrial or environmental applications. At very low oxygen concentrations, however, the process performance often suffers from technical limitations. Available dissolved oxygen measurement techniques are not sensitive enough and thus control techniques, that can reliable handle these conditions, are lacking. Recently, we proposed a microaerobic process control strategy, which overcomes these restrictions and allows to assess different degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on the design of a control strategy for the automation of oxygen‐limited continuous cultures using the microaerobic formation of photosynthetic membranes (PM) in Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the considered phenomenon depends on the optimal availability of mixed‐carbon sources, hence on boundary conditions which make the process performance challenging. Empirically assessing these specific microaerobic conditions is scarcely practicable as such a process reacts highly sensitive to changes in the substrate composition and the oxygen availability in the culture broth. Therefore, we propose a model‐based process control strategy which allows to stabilize steady‐states of cultures grown under these conditions. As designing the appropriate strategy requires a detailed knowledge of the system behavior, we begin by deriving and validating an unstructured process model. This model is used to optimize the experimental conditions, and identify properties of the system which are critical for process performance. The derived model facilitates the good process performance via the proposed optimal control strategy. In summary the presented model‐based control strategy allows to access and maintain microaerobic steady‐states of interest and to precisely and efficiently transfer the culture from one stable microaerobic steady‐state into another. Therefore, the presented approach is a valuable tool to study regulatory mechanisms of microaerobic phenomena in response to oxygen limitation alone. Biotechnol. Bioeng. 2014;111: 734–747. © 2013 Wiley Periodicals, Inc.
Lipase‐catalyzed process for biodiesel production: Protein engineering and lipase production
Authors: Hwang Hyun Tae , Qi Feng , Yuan Chongli , Zhao Xuebing , Ramkrishna Doraiswami , Liu Dehua , Varma Arvind
Published: November 2013

Biodiesel is an environment‐friendly and renewable fuel produced by transesterification of various feedstocks. Although the lipase‐catalyzed biodiesel production has many advantages over the conventional alkali catalyzed process, its industrial applications have been limited by high‐cost and low‐stability of lipase enzymes. This review provides a general overview of the recent advances in lipase engineering, including both protein modification and production. Recent advances in biotechnology such as in protein engineering, recombinant methods and metabolic engineering have been employed but are yet to impact lipase engineering for cost‐effective production of biodiesel. A summary of the current challenges and perspectives for potential solutions are also provided. Biotechnol. Bioeng. 2014;111: 639–653. © 2013 Wiley Periodicals, Inc.
Early invasive versus selectively invasive strategy in patients with non‐ST‐segment elevation acute coronary syndrome: Impact of age
Authors: Angeli Fabio , Verdecchia Paolo , Savonitto Stefano , Morici Nuccia , De Servi Stefano , Cavallini Claudio
Published: November 2013

Background

It is unclear whether the benefits of an early invasive strategy (EIS) in patients with non‐ST‐segment elevation acute coronary syndromes (NSTEACS) equally apply to younger and older individuals. Elderly patients are generally less likely to undergo EIS when compared with younger patients.

Objectives

We conducted a meta‐analysis to compare the benefit of an EIS versus a selectively invasive strategy (SIS) in patients with NSTEACS. We tested the hypothesis that the magnitude of benefit of an EIS over a SIS mainly applies to older individuals.

Methods

We extracted data from randomized controlled trials (RCTs) identified through search methodology filters. The primary outcome of the analysis was the composite of all‐cause death and myocardial infarction (MI). Secondary outcomes were death and MI taken alone and re‐hospitalization.

Results

Nine trials (n = 9,400 patients) were eligible. The incidence of the composite end‐point of MI and all‐cause death was 16.0% with the EIS and 18.3% with the SIS (OR: 0.85, 95% CI: 0.76–0.95). The incidence of MI was 8.4% with the EIS and 10.9% with the SIS (OR: 0.75, 95% CI: 0.66–0.87). Similar results were obtained for rehospitalization (OR: 0.71, 95% CI: 0.55–0.90). The incidence of all‐cause death did not differ between the two groups. The EIS reduced the composite end‐point and re‐hospitalization to a greater extent in elderly than in younger patients (P for interaction = 0.044 and <0.0001, respectively). These findings were confirmed in meta‐regression analyses.

Conclusions

In patients with NSTEACS, a routine EIS reduces the risk of rehospitalization and the composite end point of recurrent MI and death to a greater extent in elderly than in younger individuals. © 2013 Wiley Periodicals, Inc.