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    THE ROLE OF NEURONS AND GLIAL CELLS IN PRODUCTIVE AND LATENT CYTOMEGALOVIRUS INFECTION

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    Cilj istraživanja: Humani citomegalovirus (HCMV) je vodeći uzročnik prirođenih virusnih infekcija koji često uzrokuje trajna oštećenja živčanog sustava u djece. Tipovi stanica i mehanizmi uključeni u uspostavljanje cjeloživotne latencije citomegalovirusa (CMV) u mozgu još uvijek su nepoznati. Glavni cilj ovog istraživanja je razjasniti diseminaciju virusa i stanični tropizam, te imunološke mehanizme koji nadziru infekciju i uspostavljanje latencije CMV-a u mozgu. Materijali i metode: U ovom istraživanju koristili smo mišji model prirođene CMV infekcije, u kojem su novookoćeni miševi inficirani mišjim citomegalovirusom (MCMV). Kako bismo izučavali biologiju infekcije MCMV-om u mozgu, koristili smo rekombinantne reporterske viruse i transgenične miševe koji ispoljavaju rekombinazu Cre ili im nedostaju ključni elementi efektorskih funkcija limfocita T. Tropizam, anatomska lokacija i reaktivacija virusa određeni su imunohistokemijskim metodama. Kako bismo testirali ulogu imunoloških medijatora u sprečavanju infekcije neurona HCMV-om, koristili smo staničnu liniju humanog neuroblastoma SH-SY5Y i organotipsku kulturu tkiva ljudskog fetalnog mozga (hfOBSC). Rezultati: Pokazali smo da je tijekom akutne faze infekcije u novookoćenih miševa hipokampus glavno mjesto produktivne infekcije MCMV-om. Infektivni virus prvo su proizveli astrociti, zatim mikroglije i konačno neuroni, koji su bili glavna mjesta replikacije virusa tijekom kasne faze akutne infekcije. Pokazali smo da su CD4+ limfociti T i citokin IFN-γ potrebni za razrješenje produktivne infekcije u neuronima. Citokin IFN-γ također može spriječiti infekciju stanica SH SY5Y i neurona u hfOBSC HCMV-om. Konačno, pokazali smo da MCMV uspostavlja latenciju u neuronima i da su CD4+ limfociti T ključni za sprječavanje reaktivacije virusa iz neurona. Zaključak: Rezultati ovog istraživanja po prvi put pokazuju da CMV uspostavlja latenciju u neuronima, te da su CD4+ limfociti T i citokin IFN-γ ključni za nadzor produktivne i latentne infekcije u neuronima. Ova studija ima važan translacijski potencijal s obzirom da ukazuje na to da bi poticanje odgovora posredovanog CD4+ limfocitima T moglo spriječiti neurološke posljedice uzrokovane prirođenom CMV infekcijom.Objectives: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infections, frequently accompanied with long-term neurological sequelae in children. The cell types and mechanisms involved in establishing lifelong CMV latency in the brain, from which the virus reactivates intermittently, remain enigmatic. This research aims to elucidate viral dissemination and cell tropism, immune mechanisms controlling the infection, and the establishment of MCMV latency in the brain. Materials and methods: In this research, we used mouse model of congenital CMVinfection, in which newborn mice are infected with MCMV postnatally. To study the biology of MCMV infection in the brain, we utilized recombinant reporter viruses and transgenic mouse lines that express Cre recombinase or lack critical elements of T-cell effector functions. Viral tropism, anatomical location, and reactivation were determined with immunohistochemical methods. We employed human cell line SH-SY5Y and human fetal organotypic brain slices cultures (hfOBSCs) to test the role of immune mechanisms in preventing HCMV infection of neurons. Results: We found that the hippocampus is a major site of productive MCMV infection during the acute phase in newborn mice. Infectious virus was first produced by astrocytes, then microglia, and finally by neurons, which were the major sites of viral replication during the late phase of infection. CD4+ T-cells and IFN-γ were pivotal in resolving a productive infection in neurons. IFN-γ can also suppress HCMV infection of SH-SY5Y cell line and neurons in hfOBSCs. Finally, we show that MCMV establishes latency in neurons and that CD4+ T-cells are crucial to prevent virus reactivation. Conclusion: This research shows for the first time that neuron-restricted cytomegalovirus latency in the central nervous system is regulated by CD4+ T cells and IFN-γ. This study has important translational potential as it demonstrates that boosting CD4+ T-cell-mediated immunity could prevent neurological sequelae following congenital CMV infection

    Določitev kanabidoidnih receptorjev v celičnih linijah raka dojke

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    Breast cancer is the most common malignancy in women across the globe, with over 1.5 million new cases reported yearly. Apart from invasive methods, phenotype-specific system therapy is used in suppression of disease development and recurrence. Recent research revealed that the endocannabinoid system (ECS) is involved in many diseases, including cancer. The endocannabinoid receptors are receptors associated with G-proteins, which are found in the central nervous system (Type 1 receptor, CB1) and the immune system (Type 2 receptor, CB2). While some cannabinoids (such as tetrahydrocannabinol, THC) are associated with psychotropic effects when bound to (CB1), others (such as cannabinol, CBD) have a plethora of biological effects, indicating their potential therapeutic value. In this Master Thesis we aimed to reveal (1) the expression levels of cannabinoid receptors and (2) the effects of cannabidiol (CBD) on cell viability alone, or in combination with commonly used phenotype-specific therapeutic on selected breast cancer cells. We hypothesized that the selected breast cancer cell lines express CBs on a protein level and that receptor CB1 and CB2 levels would correspond to the biological effects of CBD on cell viability. We evaluated the expression of CB1 and CB2 in breast cancer cell lines of different subtypes and receptor status (ER+/PR+/HER2-, ER-/PR-/HER2+ and triple-negative). The expression levels of CB1 and CB2 receptor proteins were analyzed using western blot (WB) and immunocytochemistry (ICC) method, comparing two different sets of primary antibodies. We tested one of the most used commercial polyclonal antibodies (manufactured by Abcam) against both CBs, and were among the first to test the new monoclonal antibody (manufactured by Santa Cruz Biotechnology) against both CBs. Both sets of antibodies successfully detected CBs in selected cell lines with the WB method, with rather different specificity. No constant pattern of expression was observed with the ICC method, as receptor staining highly varied amongst tested cell lines and antibodies. With the cell viability assay, we also tested the therapeutic potential of cannabidiol (CBD) alone, or in combination with common phenotype-specific therapeutics. Tamoxifen was used for hormone receptor-positive (ER+, PR+) T-47D, Herceptin (HER) for human epidermal growth factor 2 receptor positive (HER+) SK-BR-3 and cisplatin (CIS) for triple-negative (ER-, PR-, HER-) MDA-MB-231 cell line. CBD treatment alone was shown to decrease cell viability in all tested cell lines, in either a concentration-dependent (T-47D) or threshold response (SK-BR-3, MDA-MB-231) manner. To our knowledge, we were the first to test and show CBD effects in combination with the above listed therapeutics. Possible synergism between CBD and therapeutics was observed in all tested cell lines, which holds a promising potential for further exploitation of ECS in treatment of breast cancer.Rak dojke je najpogostejša malignost pri ženskah, saj je letno na svetu diagnosticiranih več kot 1,5 milijona novih primerov bolezni. Opredeljeni so bili različni dejavniki tveganja, kot so hormonski in genski dejavniki ter življenjski slog, za katere je dokazano, da povečujejo verjetnost za nastanek raka dojke. Glede na prisotnost molekularnega markerja so opredeljeni trije podtipi bolezni: za hormonski receptor pozitivni (HR+), za humani epidermalni rastni faktor 2 pozitivni (HER2+) in trojno negativni rak dojke. Podtipi delujejo kot vodilo pri diagnozi, prognozi in sistematičnem zdravljenju bolezni. Sistematično zdravljenje se uporablja za zaustavitev razvoja in preprečitev ponovitve bolezni. Najpogostejši podtip raka dojke je HR+, s prevalenco med 60 in 70 %. Znotraj podtipa HR+ je opaženo izražanje estrogenskega (ER) in progesteronskega receptorja (PR), ki služita kot markera in tarči za zdravljenje. Standardno sistemsko terapijo sestavljajo zaviralci jajčnikov (OS), inhibitorji aromataze (AIs) in selektivni modulatorji estrogenskih receptorjev (SERM). Tamoksifen (TAM), nesteroidni antagonist ER, ki ima sposobnost vezave na ER-receptorje v nanomolarni koncentraciji, je najbolj pogosto uporabljeno zdravilo za HR+ rak dojke. Drugi najpogostejši podtip je HER2+, s prevalenco med 20 in 30 %. Značilno je prekomerno izražanje receptorja HER2. Zlati standard v zdravljenju podtipa HER2+ je humanizirano monoklonsko protitelo, ki cilja zunajcelično domeno HER2, trastuzumab (blagovna znamka Herceptin, HER). Pred razvojem trastuzumaba je bil zaradi pomanjkanja sistemske terapije ta fenotip povezan z zelo slabo prognozo. Tretji znani podtip je trojno negativni rak dojke, ki je najmanj pogost, a najbolj agresiven fenotip, povezan s slabo prognozo. V primerjavi s podtipoma ER+ in HER2+ trojno negativni rak nima molekularne tarče, ki bi zavrla razvoj bolezni. Standardna terapija pri trojno negativnem raku je kombinacija kemoterapije in radioterapije. Cisplatin (CIS) je eden od prvih odkritih kemoterapevtikov s klinično uporabo iz poznih sedemdestih let prejšnjega stoletja. CIS zavira celično delitev s tvorbo dvojnih prelomov DNA, ki jih rakave celice ne morejo uspešno popraviti zaradi pogosto mutiranih mehanizmov popravljanja poškodb DNA. Endokanabinoidni sistem (ECS) je sestavljen iz kanabinoidnih receptorjev (CBs), endogenih kanabinoidov in encimov, vključenih v biosintzne in razgradne poti endokanabinoidov. Doslej so odkrili dve vrsti receptorjev: kanabinoidni receptor tipa 1 (CB1) in kanabinoidni receptor tipa 2 (CB2). Oba receptorja sta povezana z G-proteini (GPCR), in sodelujeta pri različnih celičnih mehanizmih in v nevronih pri kognitivnih procesih. CB1 je bil prvi odkriti receptor ECS, ki vsebuje 2 znani izoobliki, se je pretežno izraža v centralnem in perifernem živčnem sistemu. Izražanje ni omejeno samo na živčni sistem, prisotno je tudi v drugih perifernih tkivih, kot so kardiovaskularni, gastrointestinalni, imunski sistem itd. Vloga CB1 v perifernih tivih še ni dovolj poznana. Dokazano je, da je receptor CB1 lokaliziran na plazemski membrani, vendar so raziskave pokazale, da obstajajo internalizirani (endosomi) in intracelularni predvsem mitohondrijski, pa tudi lizosomski receptorji. Po aktivaciji CB1 lahko deluje inhibitorno ali aktivacijsko na različne encime in signalne poti, ki posledično spodbujajo celično preživetje ali smrt, odvisno od vrste vezanega liganda in celičnega okolja. Drugi odkriti receptor ECS je CB2, ki se enako nahaja v dveh znanih izooblikah in se pretežno izraža v imunskem sistemu (v celicah, kot so bazofilci, eozinofilci, NK-celice, nevtrofilci, makrofagi, itd.). Nove raziskave so pokazale, da je receptor CB2 prisoten tudi v periferiji in v možganih. Čeprav signalne poti CB2 niso tako dobro poznane kot pri CB1, je glavna vloga CB2 pri sprožitvi provnetnih ali protivnetnih učinkov imunskih celic. Obstajajo tri vrste spojin, ki lahko sprožijo aktivacijo ECS: endokanabinoidi, fitokanabinoidi in sintetični kanabinoidi. Endokanabinoidi so endogeno sintetizirane signalne lipidne molekule, ki imajo sposobnost vezave na CB-receptorje. Anandamid (AEA) in 2-arahidonoilglicerol (2-AG) sta najbolj znana endokanabinoida, ki delujeta kot agonista CB-receptorjev, imata različne lastnosti, način delovanja, pot sinteze in razgradnje. Fitokanabinoide najdemo pretežno v rastlini C.sativa L., ki vsebuje več kot 120 kanabinoidov. Najbolj pogost fitokanabinoid je Δ9-tetrahidrokanabinol (Δ9-THC), psihoaktivna spojina, in kanabidiol (CBD), ki je zaradi svojih potencialnih terapevtskih lastnosti postal zanimiv v zadnjih letih. Tretja vrsta kanabinoidov so sintetični kanabinoidi, ki so sintetizirani mimetiki fito in endokanabinoidov. Sintetične kanabinoide so razvili za eksperimentalne in terapevtske namene. Povezava med ECS in njegovim potencialom kot terapevtsko tarčo so prvič opazili pred 35 leti. Pri nekaterih boleznih je ECS spremenjen, stopnje izražanja CB-receptorjev so različne, prav tako ravni endokanabinoidov. Danes obstajajo dokazi o pozitivnih učinkih kanabinoidov pri zdravljenju nevropatske bolečine, multiple skleroze (MS), epilepsije in raka (paliativno zdravljenje). Pri zdravljenju zgoraj navedenih patologij je bilo odobrenih več zdravil na osnovi kanabinoidov, kot so Nabilon, Dronabinol, Nabiximols, itd. Potencial kanabinoidov pri zdravljenju intenzivo proučuje, klinična preskušanja pa potekajo pri boleznih z različnimi nevrološkimi motnjami (Parkinsonova, Alzheimerjeva, Huntingtonova), psihičnimi motnjami, posttravmatskimi stresnimi motnjami (PTSP), Tourettovim sindromom, anksioznimi motnjami, glavkomu in raku (možgani, dojka, prostata, kosti, koža, maternični vrat, trebušna slinavka, levkemija itd.). Razen paliativne terapije raka so različni in vivo ter in vitro poskusi pokazali, da imajo kanabinoidi protitumorske učinke ter da vplivajo na celične procese, kot so celični cikel, proliferacija, smrt, migracija/invazija rakavih celic in angiogeneza/metastaziranje. Namen dela, cilji in hipoteze V magistrskem delu smo želeli (1) določiti ravni izražanja kanabinoidnih receptorjev in (2) učinke samega kanabidiola (CBD) ali v kombinaciji s pogostim za fenotip specifičnim terapevtikom na izbrane celice raka dojke. Predpostavili smo, da bosta raven izražanja receptorjev CB1 in CB2 ustrezala biološkim vplivom CBD-ja na preživetje celic. Rezultati Ad 1. V sklopu naloge smo preizkusili eno od najbolj uporabljenih komercialnih poliklonskih protiteles proti CB1 in proti CB2 (proizvajalca Abcam) in bili med prvimi, ki smo testirali novo monoklonsko protitelo proti CB1 in proti CB2 (proizvajalca Santa Cruz Biotechnology). Določili smo specifičnost izbranih protiteles in ovrednotili izražanje CB1 in CB2 v izbranih celičnih linijah raka dojke različnih podtipov in z različnim statusom receptorjev. Izbrali smo humane nesmrtne celične linije raka dojke: MCF-7 (ER+/PR+/HER2-), MDA-MB-231 (trojno-negativna), MDA-MB-361 (ER+/PR+/HER2-), SK-BR-3 (ER-/PR-/HER2+) in T-47D (ER+/PR+/HER2-). Celice smo gojili po protokolih ATCC in dobili pričakovane morfologije. Izražanje CB-receptorjev smo določili z dvema izbranima metodama: z metodo prenosa western (WB) in imunocitokemijo (ICC). Za analizo s prenosom western smo iz celičnih linij pridobili celične oborine, iz katerih smo ekstrahirali proteine z RIPA pufrom. Za pozitivne kontrolne celice smo izbrali nerakotvorno celično linijo MCF-10 in celice, izolirane iz pacienta z možganskim tumorjem (glioblastomom). Oba seta protiteles se vežeta na CB1 in CB2, a z različnima intenzitetama v izbranih celičnih linijah raka dojke. Protitelo proti CB1 podjetja Abcam lahko zazna CB1 samo v dimerni obliki, s signali, ki ustrezajo dvojni molekulski masi CB1. Pri protitelesu proti CB2 proizvajalca Abcam opazimo dimerne in monomerne signale. Protitelesa proti CB1 in CB2 proizvajalca Santa Cruz uspešno zaznajo signale specifične velikosti za CB-receptorje. Rezultate smo kvantificirali in normalizirali glede na hišni protein GAPDH. Tu prvič poročamo o izražanju CB-receptorjev v celičnih linijah SK-BR-3 in MDA-MB-361. Pokazali smo, da poleg CB2 celice SK-BR-3 izražajo tudi CB1. Pokazali smo tudi, da celična linija MDA-MB-361 izraža oba CB-receptorja, vendar z različno intenzivnostjo. Pri imunocitokemijskih rezultatih ni bilo enotnega obarvanja med testiranima celičnima linijama raka dojk. Protitelesa podjetja Santa Cruz proti CB1 so neustrezna za metodo ICC in rezultati niso primerljivi z WB. Pri Abcamovom protitelesu proti CB1 in Santa Cruzovemu proti CB2 smo opazili signal, vendar je potrebna dodatna validacija zaradi nespecifičnosti in opažene neobičajne lokalizacije (jedrno barvanje). Ad 2. Drugi cilj naloge je bil ugotoviti vpliv CBD na celično viabilnost, samostojno ali kombinaciji z specifičnim terapevtikom, kar smo določali s testom MTT. Za ER+ smo zbrali linijo T-47D in terapevtik tamoksifen, za HER+ SK-BR-3 in terapevtik Herceptin ter za trojno negativno MDA-MB-231 in terapevtik cisplatin. Metabolni testi so pokazali, da CBD zmanjšajo viabilnost celic v vseh testiranih celičnih linijah, bodisi na način, ki je odvisen od koncentracije (T-47D) ali praga odgovora (SK-BR-3, MDA-MB-231). Za vse tri linije smo izračunali vrednosti IC50 za CBD. Po našem vedenju smo bili prvi, ki smo testirali in prikazali CBD v kombinacijski terapiji z zgoraj navedenimi terapevtiki (TAM, HER, CIS). Možen sinergizem med CBD in terapevtiki smo opazili v vseh preizkušenih celičnih linijah, kar je obetavno za nadaljnje raziskave vpliva ECS pri zdravljenju raka dojke

    THE ROLE OF NEURONS AND GLIAL CELLS IN PRODUCTIVE AND LATENT CYTOMEGALOVIRUS INFECTION

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    Cilj istraživanja: Humani citomegalovirus (HCMV) je vodeći uzročnik prirođenih virusnih infekcija koji često uzrokuje trajna oštećenja živčanog sustava u djece. Tipovi stanica i mehanizmi uključeni u uspostavljanje cjeloživotne latencije citomegalovirusa (CMV) u mozgu još uvijek su nepoznati. Glavni cilj ovog istraživanja je razjasniti diseminaciju virusa i stanični tropizam, te imunološke mehanizme koji nadziru infekciju i uspostavljanje latencije CMV-a u mozgu. Materijali i metode: U ovom istraživanju koristili smo mišji model prirođene CMV infekcije, u kojem su novookoćeni miševi inficirani mišjim citomegalovirusom (MCMV). Kako bismo izučavali biologiju infekcije MCMV-om u mozgu, koristili smo rekombinantne reporterske viruse i transgenične miševe koji ispoljavaju rekombinazu Cre ili im nedostaju ključni elementi efektorskih funkcija limfocita T. Tropizam, anatomska lokacija i reaktivacija virusa određeni su imunohistokemijskim metodama. Kako bismo testirali ulogu imunoloških medijatora u sprečavanju infekcije neurona HCMV-om, koristili smo staničnu liniju humanog neuroblastoma SH-SY5Y i organotipsku kulturu tkiva ljudskog fetalnog mozga (hfOBSC). Rezultati: Pokazali smo da je tijekom akutne faze infekcije u novookoćenih miševa hipokampus glavno mjesto produktivne infekcije MCMV-om. Infektivni virus prvo su proizveli astrociti, zatim mikroglije i konačno neuroni, koji su bili glavna mjesta replikacije virusa tijekom kasne faze akutne infekcije. Pokazali smo da su CD4+ limfociti T i citokin IFN-γ potrebni za razrješenje produktivne infekcije u neuronima. Citokin IFN-γ također može spriječiti infekciju stanica SH SY5Y i neurona u hfOBSC HCMV-om. Konačno, pokazali smo da MCMV uspostavlja latenciju u neuronima i da su CD4+ limfociti T ključni za sprječavanje reaktivacije virusa iz neurona. Zaključak: Rezultati ovog istraživanja po prvi put pokazuju da CMV uspostavlja latenciju u neuronima, te da su CD4+ limfociti T i citokin IFN-γ ključni za nadzor produktivne i latentne infekcije u neuronima. Ova studija ima važan translacijski potencijal s obzirom da ukazuje na to da bi poticanje odgovora posredovanog CD4+ limfocitima T moglo spriječiti neurološke posljedice uzrokovane prirođenom CMV infekcijom.Objectives: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infections, frequently accompanied with long-term neurological sequelae in children. The cell types and mechanisms involved in establishing lifelong CMV latency in the brain, from which the virus reactivates intermittently, remain enigmatic. This research aims to elucidate viral dissemination and cell tropism, immune mechanisms controlling the infection, and the establishment of MCMV latency in the brain. Materials and methods: In this research, we used mouse model of congenital CMVinfection, in which newborn mice are infected with MCMV postnatally. To study the biology of MCMV infection in the brain, we utilized recombinant reporter viruses and transgenic mouse lines that express Cre recombinase or lack critical elements of T-cell effector functions. Viral tropism, anatomical location, and reactivation were determined with immunohistochemical methods. We employed human cell line SH-SY5Y and human fetal organotypic brain slices cultures (hfOBSCs) to test the role of immune mechanisms in preventing HCMV infection of neurons. Results: We found that the hippocampus is a major site of productive MCMV infection during the acute phase in newborn mice. Infectious virus was first produced by astrocytes, then microglia, and finally by neurons, which were the major sites of viral replication during the late phase of infection. CD4+ T-cells and IFN-γ were pivotal in resolving a productive infection in neurons. IFN-γ can also suppress HCMV infection of SH-SY5Y cell line and neurons in hfOBSCs. Finally, we show that MCMV establishes latency in neurons and that CD4+ T-cells are crucial to prevent virus reactivation. Conclusion: This research shows for the first time that neuron-restricted cytomegalovirus latency in the central nervous system is regulated by CD4+ T cells and IFN-γ. This study has important translational potential as it demonstrates that boosting CD4+ T-cell-mediated immunity could prevent neurological sequelae following congenital CMV infection

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We 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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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