261 research outputs found

    “Resistance is futile.” Or is it?:the characterization of the Borg in Star Trek: The Next Generation

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    Abstract. This study analyzes how the Borg are characterized and depicted and how this characterization develops in the science fiction television series Star Trek: The Next Generation (1987–1994). The focus of this study is not to cover the entirety of this series, but instead focus on a few episodes relevant to the study. Furthermore, the study focuses also on what kind of different themes are represented and reflected with the depiction and characterization of the Borg and how these occur. The Borg are an alien, cybernetic humanoid species, typically depicted as antagonists in the Star Trek world. The Borg are also typically depicted as machine-like automatons, linked into a hive mind that is shared within their entire Borg Collective. Therefore, they are typically represented as lacking a sense of individuality. The methodology applied in the study for analyzing the characters and their actions is functional semiotic approach, which is a character-based approach to film and TV analysis. Comprehension of the characters and their interaction with each other are considered to be one of the most important elements in the narrative comprehension and interpretation. Functional semiotic approach can also be used to apply a delicate framework for analyzing the relationships between the characters. The study also adopts the notion of the theory of de-villainization, which includes the concepts of geopolitics and empathic reading. These are used to complement the theoretical framework for the analysis. The process of de-villainization blurs the line between the threshold of a protagonist and an antagonist. Empathic reading requires the understanding of the historical context surrounding a villainized group or population. In the concept of geopolitics, the role of an individual representative of an antagonized group is considered to be of significant importance in how outsiders perceive them. This study suggests that the Borg are first depicted as a nearly indestructible, dangerous threat to humans and other cultures in the world of Star Trek, as they assimilate other species into their collective. However, the Borg are later humanized and depicted in a more ambiguous manner. Eventually, an individual Borg character, Hugh, is even portrayed as a protagonist in the episode “I Borg.” This is done with the characterization of Hugh after he is detached from the Borg Collective. Hugh begins to develop a sense of individuality and appreciation of it. Hugh is also depicted to be an outsider in his appearance in the episode “I Borg.” As an outsider, he questions the actions and behavior of the human characters. This is used to reflect an optimistic view of humanity and traditional humanistic values that are typically seen in a positive light, such as forgiveness, individuality and empathy. Star Trek has often reflected different contemporary and relevant social issues and humanistic values, and this TV series aims to convey these issues and values to the viewer in the characterization of Hugh.Tiivistelmä. Tämä pro gradu -tutkielma analysoi, kuinka Borg-nimisten hahmojen hahmon kuvaus toteutetaan ja esitetään ja kuinka tämä hahmon kuvaus kehittyy scifi-televisiosarjassa Star Trek: The Next Generation (1987–1994). Tutkimuksen tarkoitus ei ole kattaa Borgien esiintymistä koko sarjassa, vaan sen sijaan keskittyä muutamaan tutkimukselle relevanttiin jaksoon. Tutkimus keskittyy lisäksi siihen, minkälaisia teemoja Borgien esittämisellä ja hahmon kuvauksella ilmaistaan ja heijastetaan, sekä kuinka nämä tulevat esille. Borgit ovat maapallon ulkopuolinen, teknologialla vahvistettu, kyberneettinen ihmismäinen laji, jotka esitetään tyypillisesti antagonisteina Star Trekin maailmassa. Borgit esitetään tyypillisesti myös konemaisina, robotteja muistuttavina olentoina, jotka ovat yhteydessä toisiinsa jaetussa tajunnassa ja kollektiivissa. Siitä syystä Borgeilta tyypillisesti puuttuu yksilöllisyyden taju. Tutkimuksessa käytetty metodologia hahmojen analyysiin ja heidän toimimiseensa on toiminnallinen semioottinen lähestymistapa, joka on hahmopohjainen lähestymistapa elokuva- ja TV analyysiin. Hahmojen ja heidän keskinäisen vuorovaikutuksensa ymmärtämistä pidetään yhtenä tärkeimmistä elementeistä narratiivisessa ymmärryksessä ja tulkinnassa. Toiminnallista semioottista lähestymistapaa voidaan käyttää myös tarkan kehyksen luomiseen hahmojen keskinäisten suhteiden analysoinnissa. Tutkimus käyttää myös antagonistien inhimillistämisen teoriaa, johon sisältyy geopolitiikan ja empaattisen lukemisen käsitteet. Näitä käytetään täydentävänä teoreettisena kehyksenä tutkimuksen analyysissä. Antagonistin inhimillistämistä voidaan käyttää protagonistin ja antagonistin rajan sumentamiseen. Empaattinen tulkinta vaatii historiallisen kontekstin ymmärtämistä koskien ryhmää tai populaatiota, jotka tyypillisesti nähdään antagonisteina. Geopolitiikan käsitteessä nähdään, että yksittäisellä edustajalla on merkittävä rooli siinä, kuinka ulkopuoliset mieltävät ryhmän, joka tyypillisesti nähdään antagonisteina. Tutkimuksen analyysi osoittaa, että Borgit kuvataan ensin lähes tuhoutumattomana, vaarallisena uhkana ihmisille ja muille Star Trekin maailman kulttuureille, koska Borgit sulauttavat muita lajeja osaksi heidän kollektiiviaan. Borgit kuitenkin inhimillistetään ja esitetään myöhemmin monitulkinnaisella tavalla. Yksittäistä Borg-hahmoa esitetään jopa protagonistina jaksossa ”I Borg.” Tämä toteutetaan Hugh-nimisen Borgin hahmon kuvauksella sen jälkeen, kun hän erkaantuu Borgien kollektiivista. Tälle hahmolle alkaa kehittyä yksilöllisyyden tunne ja arvostus sitä kohtaan. Hugh kuvataan myös ulkopuolisena hahmona hänen esiintymisessään jaksossa ”I Borg.” Hugh kyseenalaistaa ulkopuolisena hahmona usein ihmishahmojen toimintaa ja käytöstä. Tätä käytetään sellaisten perinteisten humanististen arvojen heijastamiseen, mitkä nähdään tyypillisesti positiivisessa valossa, kuten anteeksiantaminen, yksilöllisyys ja empatia. Star Trek on usein heijastanut erilaisia aikakauden mukaisia ja relevantteja sosiaalisia ongelmia sekä humanistisia arvoja, ja tämä TV-sarja pyrkii ilmaisemaan näitä ongelmia ja arvoja katsojalle Hugh’n hahmon kuvauksella ja esittämisellä

    Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population

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    Background Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. Methods A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival. Results Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4-15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival. Conclusions We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.Peer reviewe

    IGIST - A Kinetic Bioassay for Pertussis Toxin Based on Its Effect on Inhibitory GPCR Signaling

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    Detection of pertussis toxin (PTX) activity is instrumental for the development and manufacturing of pertussis vaccines. These quality and safety measures require thousands of mice annually. Here, we describe Interference in Gαi-mediated Signal Transduction (iGIST), an animal-free kinetic bioassay for detection of PTX, by measuring its effect on inhibitory G protein-coupled receptor (GPCR) signaling. PTX ADP-ribosylates inhibitory α-subunits of the heterotrimeric G proteins, thereby perturbing the inhibitory GPCR signaling. iGIST is based on HEK293 cells coexpressing a somatostatin receptor 2 (SSTR2), which is an inhibitory GPCR controllable by a high-affinity agonist octreotide; and a luminescent 3′5′-cyclic adenosine monophosphate (cAMP) probe. iGIST has a low sensitivity threshold in the pg/mL range of PTX, surpassing by 100-fold in a parallel analysis the currently used in vitro end-point technique to detect PTX, the cluster formation assay (CFA) in Chinese hamster ovary cells. iGIST also detects PTX in complex samples, i.e., a commercial PTX-toxoid-containing pertussis vaccine that was spiked with an active PTX. iGIST has an objective digital readout and is observer independent, offering prospects for automation. iGIST emerges as a promising animal-free alternative to detect PTX activity in the development and manufacturing of pertussis vaccines. iGIST is also expected to facilitate basic PTX research, including identification and characterization of novel compounds interfering with PTX.</p

    Single-Peptide TR-FRET Detection Platform for Cysteine-Specific Post-Translational Modifications

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    Post-translational modifications (PTMs) are one of the most important regulatory mechanisms in cells, and they play key roles in cell signaling both in health and disease. PTM catalyzing enzymes have become significant drug targets, and therefore, tremendous interest has been focused on the development of broad-scale assays to monitor several different PTMs with a single detection platform. Most of the current methodologies suffer from low throughput or rely on antibody recognition, increasing the assay costs, and decreasing the multifunctionality of the assay. Thus, we have developed a sensitive time-resolved Forster resonance energy transfer (TR-FRET) detection method for PTMs of cysteine residues using a single-peptide approach performed in a 384-well format. In the developed assay, the enzyme-specific biotinylated substrate peptide is post-translationally modified at the cysteine residue, preventing the subsequent thiol coupling with a reactive AlexaFluor 680 acceptor dye. In the absence of enzymatic activity, increase in the TR-FRET signal between the biotin-bound Eu(III)-labeled streptavidin donor and the cysteine-coupled AlexaFluor 680 acceptor dye is observed. We demonstrate the detection concept with cysteine modifying S-nitrosylation and ADP-ribosylation reactions using a chemical nitric oxide donor S-nitrosoglutathione and enzymatic ADP-ribosyltransferase PtxS1-subunit of pertussis toxin, respectively. As a proof of concept, three peptide substrates derived from the small GTPase K-Ras and the inhibitory alpha-subunit of the heterotrimeric G-protein G alpha i showed expected functionality in both chemical and enzymatic assays. Measurements yielded signal-to-background ratios of 28.7, 33.0, and 8.7 between the modified and the nonmodified substrates for the three peptides in the S-nitrosylation assay, 5.8 in the NAD(+) hydrolysis assay, and 6.8 in the enzymatic ADP-ribosyltransferase inhibitor dose-response assay. The developed antibody-free assay for cysteine-modifying enzymes provides a detection platform with low nanomolar peptide substrate consumption, and the assay is potentially applicable to investigate various cysteine-modifying enzymes in a high throughput compatible format

    Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin

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    Therapeutic protocols including EGFR antibodies in the context of oxaliplatin-based regimens have variable clinical effect in colorectal cancer. Here, we tested the effect of the EGFR antibody cetuximab in different sequential combinations with oxaliplatin on the growth of colorectal cancer cells in vitro and in vivo. Cetuximab reduced the efficacy of oxaliplatin when administered before oxaliplatin but provided additive effect when administered after oxaliplatin regardless of the KRAS or BRAF mutation status of the cells. Systemic gene expression and protein phosphorylation screens revealed alternatively activated pathways regulating apoptosis, cell cycle and DNA damage response. Functional assays indicated that cetuximab-induced arrest of the cells into the G1 phase of the cell cycle was associated with reduced responsiveness of the cells to subsequent treatment with oxaliplatin. In contrast, oxaliplatin-enhanced responsiveness to subsequent treatment with cetuximab was associated with increased apoptosis, inhibition of STAT3 activity and increased EGFR down-regulation. This preclinical study indicates that optimizing the sequence of administration may enhance the antitumor effect of combination therapy with EGFR antibodies and oxaliplatin

    Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems

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    Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species (vir, vbh, and trw). In a unique case, most rickettsial species encode a T4SS (rvh) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably, while RvhB8-I dimerizes and is structurally similar to other VirB8 proteins, the RvhB8-II dimer interface deviates substantially from other VirB8 structures, potentially preventing RvhB8-I/RvhB8-II heterodimerization. For the rvh T4SS, the evolution of divergent VirB8 paralogs implies a functional diversification that is unknown in other T4SSs. Collectively, our data identify two different constraints (spatiotemporal for Bartonella trw and vir T4SSs and structural for rvh T4SSs) that mediate the functionality of multiple divergent T4SSs within a single bacterium. IMPORTANCE:&nbsp; Assembly of multiprotein complexes at the right time and at the right cellular location is a fundamentally important task for any organism. In this respect, bacteria that express multiple analogous type IV secretion systems (T4SSs), each composed of around 12 different components, face an overwhelming complexity. Our work here presents the first structural investigation on factors regulating the maintenance of multiple T4SSs within a single bacterium. The structural data imply that the T4SS-expressing bacteria rely on two strategies to prevent cross-system interchangeability: (i) tight temporal regulation of expression or (ii) rapid diversification of the T4SS components. T4SSs are ideal drug targets provided that no analogous counterparts are known from eukaryotes. Drugs targeting the barriers to cross-system interchangeability (i.e., regulators) could dysregulate the structural and functional independence of discrete systems, potentially creating interference that prevents their efficient coordination throughout bacterial infection.</p

    Winter Bird Assemblages in Rural and Urban Environments: A National Survey

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    Urban development has a marked effect on the ecological and behavioural traits of many living organisms, including birds. In this paper, we analysed differences in the numbers of wintering birds between rural and urban areas in Poland. We also analysed species richness and abundance in relation to longitude, latitude, human population size, and landscape structure. All these parameters were analysed using modern statistical techniques incorporating species detectability. We counted birds in 156 squares (0.25 km2 each) in December 2012 and again in January 2013 in locations in and around 26 urban areas across Poland (in each urban area we surveyed 3 squares and 3 squares in nearby rural areas). The influence of twelve potential environmental variables on species abundance and richness was assessed with Generalized Linear Mixed Models, Principal Components and Detrended Correspondence Analyses. Totals of 72 bird species and 89,710 individual birds were recorded in this study. On average (±SE) 13.3 ± 0.3 species and 288 ± 14 individuals were recorded in each square in each survey. A formal comparison of rural and urban areas revealed that 27 species had a significant preference; 17 to rural areas and 10 to urban areas. Moreover, overall abundance in urban areas was more than double that of rural areas. There was almost a complete separation of rural and urban bird communities. Significantly more birds and more bird species were recorded in January compared to December. We conclude that differences between rural and urban areas in terms of winter conditions and the availability of resources are reflected in different bird communities in the two environments

    Interplay between manganese and iron in pneumococcal pathogenesis: role of the orphan response regulator RitR

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    Streptococcus pneumoniae (the pneumococcus) is a major human pathogen that is carried asymptomatically in the nasopharynx by up to 70% of the human population. Translocation of the bacteria into internal sites can cause a range of diseases, such as pneumonia, otitis media, meningitis, and bacteremia. This transition from nasopharynx to growth at systemic sites means that the pneumococcus needs to adjust to a variety of environmental conditions, including transition metal ion availability. Although it is an important nutrient, iron potentiates oxidative stress, and it is established that in S. pneumoniae, expression of iron transport systems and proteins that protect against oxidative stress are regulated by an orphan response regulator, RitR. In this study, we investigated the effect of iron and manganese ion availability on the growth of a ritR mutant. Deletion of ritR led to impaired growth of bacteria in high-iron medium, but this phenotype could be suppressed with the addition of manganese. Measurement of metal ion accumulation indicated that manganese prevents iron accumulation. Furthermore, the addition of manganese also led to a reduction in the amount of hydrogen peroxide produced by bacterial cells. Studies of virulence in a murine model of infection indicated that RitR was not essential for pneumococcal survival and suggested that derepression of iron uptake systems may enhance the survival of pneumococci in some niches
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