Vista Research Articles

Simultaneous non-polar and polar lipid analysis by on-line combination of HILIC, RP and high resolution MS.

Given the chemical diversity of lipids and their biological relevance, suitable methods for lipid profiling and quantification are demanded to reduce sample complexity and analysis times. In this work, we present a novel on-line chromatographic method coupling hydrophilic interaction liquid chromatography (HILIC) dedicated to class-specific separation of polar lipid to reversed-phase chromatography (RP) for non-polar lipid analysis. More specifically, the void volume of the HILIC separation-consisting of non-polar lipids- is transferred to the orthogonal RP column enabling the on-line combination of HILIC with RP without any dilution in the second dimension. In this setup the orthogonal HILIC and RP separations were performed in parallel and the effluents of both columns were combined prior to high-resolution MS detection, offering the full separation space in one analytical run. Rapid separation for both polar and non-polar lipids within only 15 min (including reequilibration time) was enabled using sub-2 μm particles and UHPLC. The method proved to be robust with excellent retention time stability (RSDs < 1%) and LODs in the fmol to pmol (absolute on column) range even in the presence of complex biological matrix such as human plasma. The presented high-resolution LC-MS/MS method leads to class-specific separation of polar lipids and separation of non-polar lipids which is lost in conventional HILIC separations. HILIC-RP-MS is a promising tool for targeted and untargeted lipidomics workflows as three interesting features are combined namely (1) the decreased run time of state of the art shotgun MS methods, (2) the elevated linear dynamic range inherent to chromatographic separation and (3) increased level of identification by separation of polar and non-polar lipid classes.

Design and implementation of Guillain-Barré syndrome clinical date management and analysis system

Objective To design a scientific, standardized, fully functional, easy-to-use Guillain-Barre syndrome (GBS) clinical informatization management system, with the purpose to meet the needs of diagnosis and clinical research in patients with GBS. This system can manage and excavate clinical data and provide a platform for clinical research of GBS. Methods The clinical data items of GBS were identified. The Visual Basic 6.0 and Vista DB software development environment was used to develop the system and the related database based on embedded database. Results A GBS database including 560 clinical indicators were set up. Through the built-in data mining and analysis functions, the system can realize the functions of visualized data input, combination search, statistical analysis, data exchange and literature update. This system has been used in Xijing Hospital, and a total 274 clinical and prognostic records were recorded from the patients with GBS. The practical results proved that the system can achieve the design goals. Conclusions Based on the information technology and GBS-related clinical epidemiology and neurology expertise, a standard GBS clinical data management and analysis system and related database were established, which could provide a basis for GBS information storage, update, epidemiological investigation and prognosis. Key words: Guillain-Barre syndrome; Clinical date; Data mining; Date management; Database

How to View the Parthenon through the Camera Obscura of the Tortoise

Visiting ruins, I enjoy the texture of the weathered stones. The wide space, colored in spring by wildflowers. Open space and vistas, the heady smell of grasses drying in the hot sun. Birds sing as they have since Plato's cicadas. Once, alone near the ruins, I heard a strange rhythmic clicking in the grass: two tortoises making love. The ruins that I visit remind me of antiquity not because I picture Socrates walking through the Stoa, but because I picture him walking along the still undeveloped riverbank, smelling these grasses, listening to these birds. The simplicity that I long for, however, is not millennia away, but only centuries. It is almost at arms’ length, but just out of view. What I find there is nature in a frame of culture. Like most tourists, I cannot transform the stones into the imaginary film of antiquity that the European brain of the nineteenth century, steeped in a classical education, projected onto them. Yet their vision was no more authentic than mine: in order to project the past onto stones, they had to erase the present.

ISHO Real Estate Regenerating Timişoara. The non-metropolitan city of Timişoara elected as European Capital of Culture for 2021

Timisoara is a major city situated in western Romania. In 2021, it will be European Capital of Culture. The city evolved around a fortified citadel surrounded by satellite settlements. After the demolition of the fortification (the XIXth century) a consistent urban tissue developed between the core and satellites. During the years, our office produced projects situated in these intermediate areas, developing an ”urban landscape” perspective, managing to attribute to the interventions a connecting role between the existing landmarks and poles; an important role was given to the ”modelling” of the volumes in order to open vistas and visual cones, as well as to the choice of forms and textures in order to ”stitch” the existing fabric and to offer a new reading of the city. We have selected one project in order to illustrate the methodology: the ”ISHO” Real Estate development.

Pedidos De Vista No Tribunal Superior Eleitoral (Requests to View the Case at the Brazilian Superior Electoral Court)

Portuguese Abstract: O artigo e o resultado de pesquisa quantitativa com objetivo de responder duas perguntas: 1) os pedidos de vista no TSE sao comuns? 2) Os pedidos de vista no TSE sao curtos? Foram capturados os dados basicos, incluindo informacoes de andamentos processuais, de 235.416 casos ingressados no tribunal entre janeiro de 2006 e maio de 2017. Os dados mostram que os pedidos de vista nao sao comuns no TSE. Apenas 1.17% dos processos no periodo tiveram um pedido de vista. Os dados tambem mostram que os pedidos de vista nao sao curtos. A media geral e de 66.97 dias, sendo que aproximadamente 1/5 dos pedidos ultrapassa 100 dias – 5 vezes o prazo mais alongado, pelo novo CPC. English Abstract: The paper is the result of quantitative research aimed at answering two questions: 1) are requests to view the case at the Brazilian Electoral Court (TSE) common? 2) Are requests to view the case at the TSE short in duration? We captured basic data, including docket entries, for 235.416 cases admitted to the court between January 2006 and May 2017. The data shows that requests to view the case are not common at the TSE. Only 1.17% of cases during this time were the object of a request. The data also shows that requests are not short. The overall average is 66.97 days, while approximately 1/5 of requests is returned after more than 100 days – 5 times the longest deadline, that of the new Civil Procedure Code.

A vista particular, de Ricardo Lísias

Nesta resenha de A vista particular (2016), concentro-me na manipulação que caracteriza toda arte, para entender como o romance lida com essa questão, politizando-a.

Effect of Nerve Growth Factor on Neural Differentiation of Mouse Embryonic Stem Cells.

The cholinergic, GABAergic, and catecholaminergic neurons derived from mouse embryonic stem cells in a culture medium supplemented with recombinant NGF were phenotyped and scored. NGF stimulated generation of neurons, but not neuronal progenitors from embryonic stem cells and affected the proportion of specific types of neurons in cultures of differentiating embryonic stem cells. These findings open vista to employ NGF for generation of specific neuron types from embryonic stem cells for fundamental and toxicological studies.

Mapping the ecosystem service delivery chain: Capacity, flow, and demand pertaining to aesthetic experiences in mountain landscapes

Accounting for the spatial connectivity between the provision of ecosystem services (ES) and their beneficiaries (supply–benefit chain) is fundamental to understanding ecosystem functioning and its management. However, the interrelationships of the specific chain links within ecosystems and the actual benefits that flow from natural landscapes to surrounding land have rarely been analyzed. We present a spatially explicit model for the analysis of one cultural ecosystem service (aesthetic experience), which integrates the complete ecosystem service delivery chain for Puez-Geisler Nature Park (Italy): (1) The potential service stock (ES capacity) relies on an expert-based land use ranking matrix, (2) the actual supply (ES flow) is based on visibility properties of observation points along recreational routes, (3) the beneficiaries of the service (ES demand) are derived from socioeconomic data as a measure of the visitation rate to the recreation location, and (4) the supply–demand relationship (ES budget) addresses the spatially explicit oversupply and undersupply of ES. The results indicate that potential ES stocks are substantially higher in core and buffer zones of protected areas than in surrounding land owing to the specific landscape composition. ES flow maps reveal service delivery to 80% of the total area studied, with the highest actual service supply to locations with long and open vistas. ES beneficiary analyses show the highest demand for aesthetic experiences in all-season tourist destinations like Val Badia and Val Gardena, where both recreational amenity and overnight stays are equally high. ES budget maps identify ES hot and cold spots in terms of ES delivery, and they highlight ES undersupply in nature protection buffer zones although they are characterized by highest ES capacity. We show how decision/policy makers can use the presented methodology to plan landscape protection measures and develop specific regulation strategies for visitors based on the ES delivery chain concept.

On the Possibility of Retrieving Near-Surface Rain Rate from the Microwave Sounder Saphir of the Megha-Tropiques Mission

In this study, ab initio atmospheric profiles generated through high-resolution calculations from the community weather model WRF, suitably matched up with both TRMM Microwave Imager (TMI) and Precipitation Radar (PR) instruments of the TRMM satellite were used to compute simulated brightness temperatures (BTs) corresponding to SAPHIR frequencies, through an in-house polarized radiative transfer code. An artificial neural network was then constructed and trained to return the near-surface rain (NSR) rate given the six BTs corresponding to SAPHIR. For accomplishing the retrievals, measured BTs of SAPHIR (level 1 data) were used. NSR rates were calculated for two precipitating systems, namely (i) cyclone Neelam and (ii) cyclone Phailin. Rain rates thus estimated were then validated with the TMI-PR combined rain product of TRMM (2A12). The results showed that there is good agreement between the two. An inter-comparison between rain rates derived from MADRAS and SAPHIR was also done. This unexpected ability of the SAPHIR radiances provide us with the rainfall signature opens up new vistas in achieving the mission objectives of Megha-Tropiques.

Preparing the PPP Phoenix to Fly: Redesigning Frameworks to Match Emerging Vistas

Preparing the PPP Phoenix to Fly: Redesigning Frameworks to Match Emerging Vistas

A Novel Algorithmic Approach for an Automatic Data Placement for NUMA Based Design

Scalability is a key concern for SMP based architecture in the current context. NUMA based architecture design seems to be a promising hope addressing this key concern. At the same time CC-NUMA based design architecture demands a deeper understanding and open vistas for key areas of improvement. Our proposed research tries to investigate, evolve and analyze one of the key design issues for NUMA machine and proposes an innovative solution to address this key design issue under investigation in the current phase of our work.

Prospects of herbal gardens as new vistas of medical tourism inNorth East India

Address for correspondence : BINA PANI DEKA, Krishi Vigyan Kendra (A.A.U.) Teok, JORHAT (ASSAM) INDIA Email : dekabinapani@gmail.com; dbinapani@ymail.co Coopted auhors : RUPAM BORGOHAIN AND DIBYAJYOTI BHARALI, Krishi Vigyan Kendra (A.A.U.) Teok, JORHAT (ASSAM) INDIA Prospects of herbal gardens as new vistas of medical tourism in North East India BINA PANI DEKA, RUPAM BORGOHAIN AND DIBYAJYOTI BHARALI MEMBERS OF THE RESEARCH FORUM  e ISSN–2230–9438 DOI:10.15740/HAS/APPS/6.1and2/46-49 Visit us :www.researchjournal.co.in Click www.researchjournal.co.in/online/subdetail.html to purchase.

Probing Microenvironment in Ionic Liquids by Time-Resolved EPR of Photoexcited Triplets.

Unusual physicochemical properties of ionic liquids (ILs) open vistas for a variety of new applications. Herewith, we investigate the influence of microviscosity and nanostructuring of ILs on spin dynamics of the dissolved photoexcited molecules. We use two most common ILs [Bmim]PF6 and [Bmim]BF4 (with its close analogue [C10mim]BF4) as solvents and photoexcited Zn tetraphenylporphyrin (ZnTPP) as a probe. Time-resolved electron paramagnetic resonance (TR EPR) is employed to investigate spectra and kinetics of spin-polarized triplet ZnTPP in the temperature range 100-270 K. TR EPR data clearly indicate the presence of two microenvironments of ZnTPP in frozen ILs at 100-200 K, being manifested in different spectral shapes and different spin relaxation rates. For one of these microenvironments TR EPR data is quite similar to those obtained in common frozen organic solvents (toluene, glycerol, N-methyl-2-pyrrolidone). However, the second one favors the remarkably slow relaxation of spin polarization, being much longer than in the case of common solvents. Additional experiments using continuous wave EPR and stable nitroxide as a probe confirmed the formation of heterogeneities upon freezing of ILs and complemented TR EPR results. Thus, TR EPR of photoexcited triplets can be effectively used for probing heterogeneities and nanostructuring in frozen ILs. In addition, the increase of polarization lifetime in frozen ILs is an interesting finding that might allow investigation of short-lived intermediates inaccessible otherwise.

To Infinity – And Beyond

From the vantage point of my small corner of the world, the field of clinical research has always dazzled me with its vistas of endless possibility, creativity, and constant re-invention. In this issue of Clinical Researcher , we have collected a mix of articles from authors involved in a myriad of

Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase.

The objective of this investigation was to screen for potential endogenous substrates for CYP2D6. Using recombinant CYP2D6, together with hepatic microsomes from CYP2D6-transgenic mice, human liver microsomes, and a specific anti-CYP2D6 monoclonal antibody, it was ascertained that CYP2D6 does not significantly metabolize the endogenous phenylethylamines 2-phenylethylamine, octopamine, synephrine, 3-methoxy-p-tyramine, 4-methoxy-m-tyramine, metanephrine, and normetanephrine, nor the indolethylamines tryptamine, serotonin, 6-methoxytryptamine, and melatonin, nor the beta-carbolines harman, norharman and tryptoline. However, the indolethylamines 5-methoxy-N,N-dimethyltryptamine (5-MDMT) and pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) showed relatively high affinity for CYP2D6 in a spectral binding assay (K(s) 28 +/- 5, and 0.5 +/- 0.3 microm (mean +/- SEM), respectively) and were O-demethylated only by CYP2D6 in a panel of 15 recombinant common human P450s. Pinoline and 5-MDMT O-demethylase activities were 35- and 11-fold greater in liver microsomes from CYP2D6-humanized mice, respectively, than those in liver microsomes from control mice. Moreover, the increased activities were completely inhibited by an anti-CYP2D6 monoclonal antibody. Kinetic analysis with recombinant CYP2D6 gave K(m) and k(cat) values for 5-MDMT and pinoline O-demethylations of 12 +/- 1 microm and 65 +/- 1 min(-1) and 1.8 +/- 0.3 microm and 26 +/- 1 min(-1), respectively. These two substrates can be added to 5-methoxytryptamine, which we have recently reported to be an endogenous CYP2D6 substrate. CYP2D6 is therefore a relatively highly specific, high-affinity, high-capacity 5-methoxyindolethylamine O-demethylase. Polymorphic cytochrome CYP2D6 may therefore exert an influence on mood and behavior by the O-demethylation of these 5-methoxyindolethylamines found in the brain and pineal gland. These processes may also impact on mental and neurological health. The findings may open new vistas for the determination of CYP2D6 phenotype.

FICTION IN REVIEW

1 6 3 R F I C T I O N I N R E V I E W T I M O T H Y Y O U N G Stories come to us in many shapes. Nearly every art form, utilitarian or not, is at some point bound to a critical reading that asserts that it is narrative: dance, music, painting, even architecture have been saddled with that ennobling but burdensome label. As much as we as viewers or listeners can learn to appreciate abstraction, our minds tend to seek a storyline. The most common systems for telling stories, of course, are language and art. If we agree that these two principal expressions of human creative intellectual e√ort, picture making and language, evolved simultaneously – in the form of pictograms, cuneiform, hieroglyphics – then it is interesting (or at least intriguing) to ponder how one form gained supremacy over the other as our primary system for expressing narratives. What I am really talking about is one speci fic and vexing issue that persists in our modern world: why so few people give comic books and graphic novels the respect they are due. Yes, Art Spiegelman’s Maus won a Pulitzer Prize and Alison Bechdel’s Fun Home was one of the best-reviewed books of H e r e , by Richard McGuire (Pantheon, 304 pp., $35) 1 6 4 Y O U N G Y its decade, but by and large stories told with pictures have not made significant ingress onto best-seller lists. Ever since comic books were excoriated as instruments intended to seduce the innocent by the psychologist Fredric Wertham in the 1950s, there have been rallying movements by artists and cartoonists to reclaim the value of the serial graphic narrative form. One of the most important outlets for experimental comic art over the past forty years was RAW, the brainchild of Spiegelman and Françoise Mouly, which aimed to express and elicit an intellectual appreciation of alternative graphic art. This selfproclaimed ‘‘graphix magazine of postponed suicides’’ eventually came to focus on long-form comic stories, launching or supporting the careers of artists such as Sue Coe, Gary Panter, Julie Doucet, and Charles Burns. The most influential work to appear in RAW may have been ‘‘Here’’ by Richard McGuire, published in volume 2, issue 1, in 1989. This six-page, thirty-six-panel story, in black and white, looked at first glance as if it were just another avant-garde comic tale. Instead, it was a startling experiment with time and space. It had a single setting – the corner of a suburban house. It had characters, but in the fifth panel another scene popped up in front of the narrative, then another pair of ‘‘windows’’ appeared – all of these distinguished by years noted at their top left corners. The story being told seemed to be multiplied across time but not space. It was all happening in the same room – or, more accurately, at the extremes of the scale of time in the same open vista. A first-time viewing of McGuire’s original ‘‘Here’’ in 2015 might call to mind the work of one of our other great national comic artists, Chris Ware, creator of an ever-expanding universe of brilliant illustrative expression. That connection would not be incorrect, but the chronology of influence must be kept in order. Ware credits McGuire with opening his eyes to the temporal and spatial possibilities of graphic storytelling when he was a young artist, something Ware himself has explored with great success. Ware, in an essay expressing his admiration for McGuire, calls him a genius for breaking the traditional hold that linearity had on comic stories – and making a work that functions ‘‘closer to real memory and experience than anything that had come before in comics.’’ That appreciation, shared by a great number of readers F I C T I O N I N R E V I E W 1 6 5 R and other artists, had to be leavened by a large measure of patience , as McGuire worked on an expanded, color version of his story over the years. The fully realized version of Here...

L’abolitionnisme britannique dans les relations anglo–portugaises: le cas de la colonie portugaise du Cap-Vert

Maria Rosaria Turano (1945-2009) wrote an article taking stock of the situation in Cape Verde concerning the issues of slavery and slave trade. She focused on the relations between Portugal and Great Britain, whose Parliament had outlawed the slave trade in 1807. The British tried to control the illegal trade across the Atlantic Ocean, and to this end they created a number of Anglo-Portuguese mixed commissions. One of these commissions was set up in Boa Vista, and here, Henry William Macaulay, the British commissary judge, played an important role. Hence, the publication of his letter to the Portuguese Governor General as an appendix for the essay: a letter that is important to the understanding of the relations between Portugal and Great Britain, as well as relations within Cape Verde society in the 19th-century

Shantytowns and Pioneers beyond the City Wall: Berlin's Urban Frontier in the Nineteenth Century

In 1783, Friedrich Gedike wondered whether the city of Berlin was growing disproportionately to the rest of the country. Like any good enlightened observer of the city, Gedike praised the open vistas of newly planned suburbs over the cramped streets of the medieval city core. But, though a spacious city allowed for healthy use and recreation and Berlin remained much smaller than great capitals such as Paris and London, Gedike feared that Berlin's growth was becoming too rapid to control. Something, he worried, was out of proportion. Hundreds of buildings had been erected in place of the city's now demolished ramparts. This newly won land had not sufficed, however, and new suburbs with thousands of new buildings arose, streets irregularly placed, without adequate linkages to the inner city. This immoderate growth was evident in the failure to overcome the boundary between the city core and newly developed suburbs. The number of streets broken through the former fortifications land proved inadequate. This continued division, Gedike feared, would impede the city's ongoing development.

Hyperpolarized Functional Magnetic Resonance of Murine Skeletal Muscle Enabled by Multiple Tracer-Paradigm Synchronizations

Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic functional magnetic resonance studies in muscle, the simplicity of our approach makes this technique amenable to a wide range of functional metabolic tracer studies.

Analytical characterization of NOTA-modified somatropins

Chemical modification of biomolecules like the introduction of metal-chelators into proteins can lead to heterogeneous product formation. The nature and extend of the modification is important in interpreting the biological properties of the bioconjugate, given their possible influence on the pharmacokinetics as well as on the binding affinity to the target. The present study describes the synthesis and analytical characterization of somatropin modified on its lysine's ɛ-amino groups with the acylating chelator S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA). Direct separation and identification techniques (i.e. RP–MS and CE–MS) and peptide mapping after trypsin and chymotrypsin digestion demonstrated that the use of higher amounts of p-SCN-Bn-NOTA during synthesis leads to a complex product composition with higher order substitution degrees (i.e. multiple NOTA-moieties per somatropin molecule), as well as the presence of different position isomers. From the nine lysine (Lys) residues in somatropin, Lys-70 was experimentally found to be the modification hotspot under our synthesis conditions (pH=9.0). This was supported by the in silico calculated lowest pKa value of 8.3 for Lys-70. Based on the crystal structure of somatropin in complex with the extracellular parts of the growth hormone receptor, the Lys-70 residue is positioned outside the binding pockets and will therefore not directly interfere with receptor binding. Gallium chelation by NOTA-somatropin resulted in a 100% complexation. The synthesis of NOTA-somatropin using p-SCN-Bn-NOTA and somatropin under our operational conditions is therefore a suitable synthesis procedure for the production of a target-specific radiopharmaceutical for further investigation toward treatment and visualization of growth hormone-specific cancers.