Kravsammanställning samt utvärdering avbildvisningsprogramför diagnostik inom telepatologi : En fallstudiemed SIV-metoden som tillvägagångssätt

De flesta har i sin närhet någon som drabbats av cancer och sjukdomsfallen har ökat genom åren. Den yrkesgrupp som ställer diagnos av denna sjukdom är patologer. Bristen på patologer är idagsläget stor och det finns därför ett behov av att finna effektiva lösningar för att möta denna brist och en ökande mängd patienter. För att digitalisera vävnadsproven som diagnostiseras, scannas dessa in med en glasscanner. Dessa digitala bildfiler kan sedan visas i ett bildvisningsprogram och delas digitalt mellan patologer på distans. Detta begrepp kallas för telepatologi. Studien utgår utifrån följande frågeställningar: Vilka krav är väsentliga och bör ingå i en utvärdering för bildvisningsprogram avsedda för diagnostik inom telepatologi? Vilket bildvisningsprogram är mest lämpat att implementeras i ett webbaserat system baserat på dessa väsentliga krav? Syftet med studien är att undersöka vilka krav som är väsentliga och bör ingå i en utvärdering av bildvisningsprogram avsedda för diagnostik inom telepatologi, samt att utföra en utvärdering av ett urval bildvisningsprogramvaror med hjälp av dessa krav. En fallstudie genomfördes med datainsamlingsmetoderna: intervjuer med två personer från studiens samarbetspartner CGM, Frågeformulär där Sveriges patologer var respondenter samt dokumentstudier för att samla in information gällande bildvisningsprogrammen. Studien tillämpar utvalda delar ur Anders G. Nilssons SIV-metod som tillvägagångsätt för att samla in krav samt för att göra ett urval av bildvisningsprogram som sedan utvärderas gentemot dessa krav. Resultaten av datainsamlingarna analyserades och ledde till ett kravdokument med väsentliga krav.Tre så kallade utslagsgivande faktorer bland dessa krav var att bildvisningsprogrammet måste vara webbaserat utan installation på klient, funktioner för in- och ut-zoomning samt panorering måste finnas. Utvärderingen av utvalda bildvisningsprogram visade slutligen att OpenSlide var mest lämpad att implementeras i ett webbaserat system.

Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.

African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV(agmVer90) to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.

Expansion of a subset of CD14(high)CD16(neg)CCR2(low/neg) monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection

Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes express the CD14(++)CD16(-) CCR2(+) phenotype and migrate to inflammatory sites by quickly responding to CCL2 signaling. Here, we identified and characterized the expansion of a novel monocyte subset during HIV and SIV infection, which were undistinguishable from classical monocytes, based on CD14 and CD16 expression, but expressed significantly lower surface CCR2. Transcriptome analysis of sorted cells demonstrated that the CCR2(low/neg) cells are a distinct subpopulation and express lower levels of inflammatory cytokines and activation markers than their CCR2(high) counterparts. They exhibited impaired phagocytosis and greatly diminished chemotaxis in response to CCL2 and CCL7. In addition, these monocytes are refractory to SIV infection and suppress CD8(+) T cell proliferation in vitro. These cells express higher levels of STAT3 and NOS2, suggesting a phenotype similar to monocytic myeloid-derived cells, which suppress expansion of CD8(+) T cells in vivo. They may reflect an antiproliferative response against the extreme immune activation observed during HIV and SIV infections. In addition, they may suppress antiviral responses and thus, have a role in AIDS pathogenesis. Antiretroviral therapy in infected macaque and human subjects caused this population to decline, suggesting that this atypical phenotype is linked to viral replication. J. Leukoc. Biol. 91: 803-816; 2012.

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity

The accessory protein negative factor (Nef) from human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is required for optimal viral infectivity and the progression to acquired immunodeficiency syndrome (AIDS). Nef interacts with the endocytic machinery, resulting in the down-regulation of cluster of differentiation antigen 4 (CD4) and major histocompatibility complex class I (MHCI) molecules on the surface of infected cells. Mutations in the C-terminal flexible loop of Nef result in a lower rate of internalization by this viral protein. However, no loop-dependent binding of Nef to adaptor protein-2 (AP-2), which is the adaptor protein complex that is required for the internalization of proteins from the plasma membrane, could be demonstrated. In this study we investigated the relevance of different motifs in Nef from SIVmac239 for its internalization, CD4 down-regulation, binding to components of the trafficking machinery, and viral infectivity. Our data suggest that the binding of Nef to the catalytic subunit H of the vacuolar membrane ATPase (V-ATPase) facilitates its internalization. This binding depends on the integrity of the whole flexible loop. Subsequent studies on Nef mutant viruses revealed that the flexible loop is essential for optimal viral infectivity. Therefore, our data demonstrate how Nef contacts the endocytic machinery in the absence of its direct binding to AP-2 and suggest an important role for subunit H of the V-ATPase in viral infectivity.

Joannis Dominici Bonomi Carmina : Epigrammatum libri tres ; Mysteriorum liber ; Imagines, sivè Emblemata.

Mode of access: Internet.

Historia polemica de graecorum schismate ex ecclesiasticis monumentis concinnata, labore et stvdio P. Laurentii Cozza ... in qva praeter historiam exactè digestam, omnes & singulae controversiae post concilium Constantinopolitanum i.usque ad Florentinum, sivè occasione haeresis, sive schismatis inter Ecclesiam orientalem, & Romanam occidentalem exortae, summâ cum diligentia discutiuntur ...

Mode of access: Internet.

D. celeberrimi don Laurentii Matthaeu et Sanz ... Tractatus de regimine regni Valentiae sivè selectarum interpretationum ad principaliores foros eiusdem ...

Mode of access: Internet.

D. celeberrimi don Laurentij Matthaeu et Sanz ... Tractatus de regimine regni Valentiae sivè selectarum interpretationum ad principaliores foros eiusdem : tribus libris contentus et explicatus ...

Mode of access: Internet.

Engineering an Ecosystem : Taking Cues from Nature’s Paradigm to Build Tissue in the Lab and the Body

This manuscript took a 'top down' approach to understanding survival of inhabitant cells in the ecosystem bone, working from higher to lower length and time scales through the hierarchical ecosystem of bone. Our working hypothesis is that nature “engineered” the skeleton using a 'bottom up' approach,where mechanical properties of cells emerge from their adaptation to their local me-chanical milieu. Cell aggregation and formation of higher order anisotropic struc- ture results in emergent architectures through cell differentiation and extracellular matrix secretion. These emergent properties, including mechanical properties and architecture, result in mechanical adaptation at length scales and longer time scales which are most relevant for the survival of the vertebrate organism [Knothe Tate and von Recum 2009]. We are currently using insights from this approach to har-ness nature’s regeneration potential and to engineer novel mechanoactive materials [Knothe Tate et al. 2007, Knothe Tate et al. 2009]. In addition to potential applications of these exciting insights, these studies may provide important clues to evolution and development of vertebrate animals. For instance, one might ask why mesenchymal stem cells condense at all? There is a putative advantage to self-assembly and cooperation, but this advantage is somewhat outweighed by the need for infrastructural complexity (e.g., circulatory systems comprised of specific differentiated cell types which in turn form conduits and pumps to overcome limitations of mass transport via diffusion, for example; dif-fusion is untenable for multicellular organisms larger than 250 microns in diameter. A better question might be: Why do cells build skeletal tissue? Once cooperatingcells in tissues begin to deplete local sources of food in their aquatic environment, those that have evolved a means to locomote likely have an evolutionary advantage. Once the environment becomes less aquarian and more terrestrial, self-assembled organisms with the ability to move on land might have conferred evolutionary ad-vantages as well. So did the cytoskeleton evolve several length scales, enabling the emergence of skeletal architecture for vertebrate animals? Did the evolutionary advantage of motility over noncompliant terrestrial substrates (walking on land) favor adaptations including emergence of intracellular architecture (changes in the cytoskeleton and upregulation of structural protein manufacture), inter-cellular con- densation, mineralization of tissues, and emergence of higher order architectures?How far does evolutionary Darwinism extend and how can we exploit this knowl- edge to engineer smart materials and architectures on Earth and new, exploratory environments?[Knothe Tate et al. 2008]. We are limited only by our ability to imagine. Ultimately, we aim to understand nature, mimic nature, guide nature and/or exploit nature’s engineering paradigms without engineer-ing ourselves out of existence.

Estudio diacrónico comparativo de los usos y la semántica de la preposición DE en dos novelas españolas: Libro del caballero Zifar y El ingenioso hidalgo don Quijote de la Mancha

Prepositioner är välkända för sin polysemi eller betydelsemångfald, och utgångspunkten för den här uppsatsen har varit ett intresse av att undersöka om det är möjligt att för en av de mest mångtydiga spanska prepositionerna, DE, finna en sammanhängande semantisk struktur, eller om det är nödvändigt att se de olika betydelserna som inbördes orelaterade. För att utreda den här frågan och ge den ett diakroniskt perspektiv undersöker jag i den här uppsatsen användningen av den spanska prepositionen DE i två romaner ur den spanska litteraturhistorien, Libro del caballero Zifar och El ingenioso hidalgo don Quijote de la Mancha, del I. Uppsatsen består av tre delar. I kapitel två ger jag en teoretisk översikt över spanskans prepositionssystem och prepositionerna beskrivs både ur syntaktisk och semantisk synvinkel. Dessutom presenteras den kognitiva grammatiken och dess synsätt på prepositioner. Huvuddelen av arbetet koncentrerar sig på att presentera prepositionen DE på två sätt och enligt två skilda metoder. I kapitel tre presenteras de olika kontextuella användningarna av DE enligt den traditionella, historisk-komparativa metoden. Med utgångspunkt i dessa kontextuella användningar ställer jag i kapitel fyra med stöd av den kognitiva grammatikens begreppssystem upp en semantisk nätverksmodell av de olika betydelser som jag fastställt för DE i den funktionella analysen. För den semantiska beskrivningen har jag använt mig av den kognitiva grammatiken, eftersom denna grammatikuppfattning i motsats till den traditionella grammatiken ser polysemin som regel och utgångspunkt i den semantiska strukturen. Analysdelen av uppsatsen inleds med den funktionella presentationen av användningarna av DE av två grundläggande skäl: För det första anser jag det ändamålsenligt att för den semantiska beskrivningen ha en solid bas av exempel där användningen av DE analyserats med hänsyn till kontexten. Kapitel tre är därför indelat i fyra huvuddelar, enligt vilken ordklass DEs huvudord tillhör, t.ex.: substantiv, adjektiv, verb. I exemplen i den fjärde gruppen fungerar prepositionsfrasen som inleds av DE som en mer fristående bestämning på frasnivå, där huvudordets ordklasstillhörighet inte är av avgörande betydelse. För det andra utgår jag från att en viss utveckling av DE har skett under de 300 år som tidsmässigt skiljer de båda romanerna åt, både vad gäller dess användning och dess semantik. För att komma underfund med och beskriva utsträckningen hos denna utveckling är det nödvändigt att den komparativa delen presenteras innan den semantiska beskrivningen kan inledas. Resultaten av den komparativa analysen är att ett antal smärre skillnader i användningen förekommer, men detta till trots har ingen betydande semantisk utveckling kunnat iakttas. Detta innebär att den semantiska beskrivningen av DE kan göras utifrån ett relativt enhetligt material. Jag har följaktligen också kunnat ställa upp en enhetlig semantisk nätverksmodell av tolv olika, relaterade betydelser hos DE. Utgående från mitt material är det sålunda möjligt att se DEs polysemi som ett sammanhängande nätverk, trots att vissa av betydelserna kan verka sinsemellan motstridiga och att 300 år skiljer åt de två böckerna. Nyckelord: prepositioner, DE: semantik och användning, polysemi, kognitiv grammatik, diakroni

Anpassning i språkkontakt : Morfologisk och ortografisk anpassning av engelska lånord i svenskan

The study investigates the formal integration of English loanwords into the Swedish language system. The aim has been to analyse and describe the morphological/morphosyntactic and the orthographical integration of the loanwords. I have studied how the foreign language elements get accommodated to Swedish and which factors are relevant in the integration. The material for the study consists of Swedish newspapers published in Sweden and Finland in paper format (with a focus on the years 1975 and 2000) and newspapers in digital format on the net. The theoretical frame for the study is contact linguistics. The study is based on a sociolinguistic, structural and language political perspective on what language is, and what language contact is. The method used is usage-based linguistic analysis. In the morphological study of the loanwords, I have made both a quantitative and a qualitative study. I have analysed the extent to which loanwords show some indication of integration in Swedish, and to what extent they show no signs of integration at all. I have also analysed integration in relation to word classes i.e., how nouns, adjectives and verbs integrate and which factors are relevant for the result of the integration. The result shows that most loanwords (36 %) do not show any signs of being formally integrated in Swedish. They undergo neither inflectional, nor derivational changes. One fifth of the loanwords are inflected according to the rules of Swedish grammar. Nouns are generally more often than verbs placed in positions in the sentence where no formal adaption is needed. Almost all of the verbs in the material are inflected according to Swedish rules of grammar. Only 3 % of the loanwords are inflected according to English rules or are placed in an ungrammatical position in the sentence. The orthographical study shows that English loanwords very seldom get adapted to Swedish orthography. Some English vowel and consonant graphemes are replaced with Swedish ones, for example a, ay and ai are replaced with aj or ej (mail → mejl). The study also indicates that morphological integration is related to orthographical integration: loanwords that are inflected according to Swedish grammar are more likely to be orthographical integrated than loanwords that are inflected according to English grammar. The results also shows that the integration of loanwords are affected by mostly language structural factors and language political factors.