143,991 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Sistema de gestão ambiental - uma proposta corporativa para a Embrapa.
No full textHistórico e contextualização; Estratégia de Ação para Implantação de um Sistema de Gestão Ambiental Corporativo; Objetivos Gerais e Específicos do Sistema de Gestão Ambiental Corporativo; Apresentação do Sistema de Gestão Ambiental Corporativo neste Documento
Mehanizem odpornosti proti azolom v kvasovki Candida glabrata v prisotnosti imunosupresiva mikofenolne kisline
No full textCandida glabrata is the second most common cause of Candidemia and other forms of invasive candidiasis in the western world. It has an intrinsic high tolerance and often develops resistance to various antifungals. Understanding the resistance mechanisms is of utmost importance to tackle this problem. The most studied among the yeast pathogens is Candida albicans, however C. glabrata and its pathogenic traits differ from it, especially the proficiency of C. glabrata to adapt to harsh environment and develop resistance. C. glabrata is a close relative to the ale yeast Saccharomyces cerevisiae, they share a high degree of homology, although the regulation and function of some genes can be different. Drug combinations are a valid strategy to combat the resistance, and many combinations are already present in the clinic. Unfortunately, the drug-drug interactions are still mostly only considered for their potentially toxic effect on the host, and their effects on pathogens are usually ignored. On this basis, we tested different combinations of immunosuppressive and antifungal drugs against C. glabrata and S. cerevisiae clinical isolates. We successfully confirmed the synergistic interaction between calcineurin inhibitors (cyclosporine A, Fk506) and antifungals (amphotericin B, itraconazole, and fluconazole). We also discovered clinically relevant antagonism between purine biosynthesis inhibitor mycophenolic acid (MPA) and azole antifungals and explored the mechanism behind it. MPA alleviates the effect of azoles through enhanced activity of efflux pumps, which lowers the bioavailability of azoles thus reducing their effect. The MPA induction of the efflux pumps comes as a cell response to weak lipophilic acid, and via dysfunctional mitochondria regulating the Hog1 osmotic/oxidative stress response and Pkc1 cell wall integrity pathways involving genes HSP12, SSA3, RCK2, ROX1, and YPK1. Ypk1 serine/threonine protein kinase seems to be an integral regulator for drug response and a potential connection between the signaling from the dysfunctional mitochondria, by sensing the sphingolipid homeostasis and triggering the cell wall integrity pathway and drug response. Ypk1 is a promising target for the drug development, since its deletion greatly reduces the tolerance to fluconazole and MPA and diminishes the suppressive antagonistic interaction between the drugs. We also discovered/confirmed 28 gene deletions that significantly change the susceptibility of C. glabrata to fluconazole, 26 for MPA and 17 for the combination of both drugs. All of these genes present potential for further drug development.Patogena kvasovka Candida glabrata je drugi najpogostejši vzrok kandidemij in drugih oblik invazivnih kandidoz. Ima prirojeno visoko toleranco do antimikotikov in pogosto do njih razvije odpornost. Za spopadanje s tem problemom je razumevanje mehanizmov odpornosti ključnega pomena. Mehanizmi virulence kvasovke C. glabrata se razlikujejo od glavne predstavnice patogenih kvasovk Candida albicans. C. glabrata je namreč bližnji sorodnik s pivsko kvasovko Saccharomyces cerevisiae, z njo si deli mnogo homolognih genov, vendar ti lahko nastopajo z malenkost spremenjeno funkcijo in načinom regulacije. Ena od strategij za borbo proti odpornosti je uporaba kombinirane terapije. Kombinacije zdravil so pogost pojav v kliničnem okolju, vendar se običajno vpliv njihovih interakcije preučuje zgolj za gostitelja. Kakšen učinek imajo te interakcije na patogene, pa je velikokrat spregledano. Na tej podlagi smo testirali učinek različnih kombinacij imunosupresivov in antimikotikov na klinične izolate kvasovk C. glabrata in S. cerevisiae. Potrdili smo sinergijo med kalcinurinskimi inhibitorji (ciklosporin A in Fk506) in antimikotiki (amfotericin B, flukonazol in itrakonazol). Poleg tega smo odkrili nov, klinično relevanten supresivni antagonizem, kjer inhibitor biosinteze purinov mikofenolna kislina (MPA) zmanjša učinkovitost azolov, in raziskali mehanizem, zakaj do tega pride. MPA zmanjša učinek azolov skozi širok stresni odziv s povečanjem aktivnost izlivnih črpalk, kar zmanjša biološko uporabnost azolov. Aktivacija črpalk s strani MPA pride kot odziv celice na šibke lipofilne kisline in z aktivacijo kaskad stresnih odzivov Hog1 (osmotski/oksidativni stres) ter Pkc1 (ohranitev integritete celične stene), verjetno reguliranih skozi disfunkcionalne mitohondrije. Pri tem sodelujejo geni HSP12, SSA3, RCK2, ROX1 in YPK1. Rezultati kažejo v smer, da je serin/treonin protein kinaza Ypk1 integralni regulator za odziv na različna zdravila in morebitna povezava med signalizacijo disfunkcionalnih mitohondrijev in jedra skozi zaznavanje sfingolipidne homeostaze in posledične aktivacije Pkc1 odziva za ohranitev integritete celične stene in odziva na zdravila. Za potrditev tega modela so potrebne še dodatne raziskave. Ypk1 tako predstavlja obetavno tarčo za razvoj novih zdravil/terapij, saj njena delecija močno poveča občutljivost tako na flukonazol kot tudi na MPA in pri tem odstrani supresivno antagonistično interakcijo med zdravili. Odkrili oz. potrdili smo 28 genskih delecij, ki signifikantno spremenijo občutljivost kvasovke C. glabrata na flukonazol, 26 delecij za MPA in 17 za kombinacijo obeh zdravil. Vsi te geni predstavljajo potencial za nadaljnji razvoj zdravil
Pragmatic Case Studies as a Source of Unity in Applied Psychology
No full textTo unify or not to unify applied psychology: that is the question. In this article we review pendulum swings in the historical efforts to answer this question—from a comprehensive, positivist, “top-down,” deductive yes between the 1930s and the early 60s, to a postmodern no since then. A rationale and proposal for a limited, “bottom-up,” inductive yes in applied psychology is then presented, employing a case-based paradigm that integrates both positivist and postmodern themes and components. This paradigm is labeled “pragmatic psychology” and, its specific use of case studies, the “Pragmatic Case Study Method” (“PCS Method”). We call for the creation of peer-reviewed journal-databases of pragmatic case studies as a foundational source of unifying applied knowledge in our discipline. As one example, the potential of the PCS Method for unifying different angles of theoretical regard is illustrated in an area of applied psychology, psychotherapy, via the case of Mrs. B. The article then turns to the broader historical and epistemological arguments for the unifying nature of the PCS Method in both applied and basic psychology.Peer reviewe
Development and optimization of HPLC methods in drug development using Quality by design approach
No full textRazvoj novega zdravila v farmacevtski industriji je sestavljen iz različnih procesov, med katere uvrščamo tudi razvoj analiznih metod. Rezultati, ki jih dobimo z njihovo uporabo, nam omogočajo odločitev glede strategije za nadaljnji razvoj zdravila oziroma podajo informacijo, ali je zdravilo primerno za sprostitev na trg. Zato je bistveno, da so analizne metode natančne, točne in zanesljive. Ključna analizna metoda za analizo in sproščanje zdravil je tekočinska kromatografija visoke ločljivosti (HPLC), katere razvoj je zaradi kompleksne sestave vzorcev tekom razvoja lahko zelo zahteven. S tradicionalnim pristopom (>>one factor at a time>sweet spot>central composite face design>design space>central composite face-centered design>design space<<) v odvisnosti od vrstnega reda elucije nečistote C in neznanega razkrojnega produkta. Za POVZETEK 3 končno metodo smo izbrali optimalno kombinacijo faktorjev, ki leži v robustnejšem območju ter potrdili ustrezno ponovljivost, točnost, linearnost in občutljivost razvite metode UHPLC. Z uporabo AQbD smo razvili dve novi robustni metodi in s tem odpravili težave obstoječih farmakopejskih metod. Z uporabo DoE smo zmanjšali število izvedenih eksperimentov, ki bi bili potrebni pri uporabi OFAT načina, matematični model pa nam je omogočil pridobitev podrobnih informacij glede vplivov faktorjev in faktorskih interakcij na posamezen odziv, česar z OFAT načinom ni mogoče ugotoviti. Na ta način smo določili območje robustnosti. V primeru ropinirolijevega klorida smo bistveno skrajšali čas analize in zmanjšali porabo organskih topil, kar je v skladu z aktualnimi trendi v analizni kemiji. Na obeh primerih smo dokazali učinkovitost uporabe AQbD pri razvoju in optimizaciji metod HPLC.The development of a new drug product in pharmaceutical industry consists of many processes, including analytical methods. The results obtained by using analytical methods allow us to determine the strategy for further development or provide information on whether the drug product may be released. It is therefore essential that analytical methods are precise, accurate and reliable. High performance liquid chromatography (HPLC) method is the key analytical method for drug product analysis and release. The development of HPLC method may be a challenge because of the complexity of the samples in development. Using the traditional approach (OFAT) the process of HPLC method development and optimization is time consuming and non-transparent, as well as it is impossible to determine factor interactions that affect method performance. In 2004, the FDA first introduced Quality by Design (QbD), the purpose of which is to improve the quality of the drug product by designing it directly into the pharmaceutical process. In June 2018, ICH announced a new ICH Q14 guideline that will include the use of QbD for analytical methods, called Analytical Quality by Design (AQbD). In the introduction part, as a review scientific article, we introduced the theoretical background of AQbD and presented in detail the recent cases, which systematically show the methodology of the AQbD approach to the development and optimization of HPLC methods. In chapter one of experimental part, we focused on the HPLC method from the EP for the determination of related substances in celecoxib. Using the prescribed analytical method the system suitability test (SST) criteria cannot be met: inadequate resolution between celecoxib and impurity B, barely adequate resolution between impurity A and celecoxib. Using the Design of Experiments (DoE) we optimized the pharmacopeial method within the acceptable limits prescribed in the EP. Four critical method parameters were varied using DoE: the ratio of methanol and acetonitrile in the mobile phase, column temperature and mobile phase flow rate. We determined the sweet spot, in which both resolution meet the SST criteria. However, the sweet spot was narrow and the analysis time had to be increased for a factor of 1.5. In chapter two, we started with the development and optimization of a new HPLC method for celecoxib, since the pharmacopeial optimized method was too long and non-robust. In the USP forum, we found the HPLC method for celecoxib capsules, that can be used for the determination of six process related impurities but not also impurity A, as it was not separated from the peak of celecoxib. Our goal was to develop one HPLC method able to determine all seven process related impurities of celecoxib from EP and USP. Due to structural similarity of some investigated process-related impurities (positional isomers), we had to find a more suitable stationary phase for their separation. Using a chiral column in reversed phase, we achieved satisfactory separations. In order to optimize the method and determine the design space, we performed 17 experiments according to a central composite face design, in which the values of three CMPs (the ratio of acetonitrile in the mobile phase, column temperature and mobile phase flow rate) were varied. Three critical resolutions and the retention time of the last eluting impurity were monitored as CMAs. Using the multiple linear regression (MLR) method, we established a statistically significant mathematical model with excellent prediction abilities. Using the Monte Carlo simulations method, we determined the design space, in which all responses meet the criteria with 99 % probability. We also determined a combination of factors that give the optimal response and confirmed the suitable precision, accuracy, linearity and sensitivity of the developed HPLC method. In chapter three, we focused on the HPLC method from the EP for the determination of related substances in ropinirole hydrochloride. The pharmacopeial method did not separate two pairs of impurities and the analysis time was too long. A UHPLC analytical technique was used to develop a new method. Due to a relatively large number of CMPs (buffer molarity, buffer pH, ratio of methanol in the mobile phase, column temperature, initial ratio of organic phase and gradient slope) we performed 19 experiments according to a fractional factorial screening design. Using DoE, we determined the effects of factors, among which the ratio of methanol in the mobile phase, column temperature and gradient slope turned out as highly significant. In this step, we already determined the optimal values for the three less significant factors. In the method optimization step, we performed 17 experiments according to a central composite face-centered response-surface design. Using the MLR method, we established a statistically significant mathematical model with very good prediction abilities. Using the Monte Carlo simulations method, we determined two design spaces according to the elution order of impurity C and unknown degradation impurity. For the final method, we chose the optimal combination of factors from the wider design space and confirmed the suitable precision, accuracy, linearity and sensitivity of the developed UHPLC method. Using AQbD, we developed and optimized two new robust methods, which eliminate the issues of the existing pharmacopeial methods. Using DoE reduced the number of experiments that would otherwise be performed if using OFAT approach, and that the established mathematical model allowed us to obtain detailed information on the effects of factors and factor interactions on a particular response, which is impossible to determine using OFAT. Using DoE, we determined the design space. In the case of ropinirole hydrochloride, we significantly shortened the analysis time and reduced organic solvent consumption, which is in line with current trends of analytical chemistry. For both cases, we have proven the effectiveness of the AQbD approach to the development and optimization of HPLC methods
Soft biometrics and their application in person recognition at a distance
No full textSoft biometric information extracted from a human body (e.g., height, gender, skin color, hair color, and so on) is ancillary information easily distinguished at a distance but it is not fully distinctive by itself in recognition tasks. However, this soft information can be explicitly fused with biometric recognition systems to improve the overall recognition when confronting high variability conditions. One significant example is visual surveillance, where face images are usually captured in poor quality conditions with high variability and automatic face recognition systems do not work properly. In this scenario, the soft biometric information can provide very valuable information for person recognition. This paper presents an experimental study of the benefits of soft biometric labels as ancillary information based on the description of human physical features to improve challenging person recognition scenarios at a distance. In addition, we analyze the available soft biometric information in scenarios of varying distance between camera and subject. Experimental results based on the Southampton multibiometric tunnel database show that the use of soft biometric traits is able to improve the performance of face recognition based on sparse representation on real and ideal scenarios by adaptive fusion rules
Conceptual, methodological and computational issues concerning the compartmental modeling of a complex biological system: postprandial inter-organ metabolism of dietary nitrogen in humans.
No full textA multi-compartmental model has been developed to describe dietary nitrogen (N) postprandial distribution and metabolism in humans. This paper details the entire process of model development, including the successive steps of its construction, parameter estimation and validation. The model was built using experimental data on dietary N kinetics in certain accessible pools of the intestine, blood and urine in healthy adults fed a [15N]-labeled protein meal. A 13-compartment, 21-parameter model was selected from candidate models of increasing order as being the minimum structure able to properly fit experimental data for all sampled compartments. Problems of theoretical identifiability and numerical identification of the model both constituted mathematical challenges that were difficult to solve because of the large number of unknown parameters and the few experimental data available. For this reason, new robust and reliable methods were applied, which enabled (i) a check that all model parameters could theoretically uniquely be determined and (ii) an estimation of their numerical values with satisfactory precision from the experimental data. Finally, model validation was completed by first verifying its a posteriori identifiability and then carrying out external validation
Dr. Edwin Wright Collection: Author Unknown
No full textNotes - The author relates several short stories about his neighbours including Alex McDonell, homesteading and life around Meanook and Athabasca (1 page
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
