573 research outputs found
The âOld Testamentâ as the origin of the patriarchy: A comparison of the German and Swedish debate
This article explores and compares two similar debates in Germany and Sweden during the 1980s, in which feminists blamed the Hebrew Bible, or âOld Testamentâ, for being the origin of the patriarchy. In Germany, the psychologist and pedagogue Gerda Weiler articulated the discourse in several writings, which led to a scholarly debate on anti-Jewish tendencies within Christian femiÂnist theology. In Sweden, the debate mainly became a media event, initiated by the author Birgitta Onsell. Instead of criticising the discourse, as in the German debate, other actors reinforced it, for example by highlighting Jesus as a feminist and a contrast to the Old Testament religion. The article further examines ideological consequences of the discourse, including the interdiscursive link to the notion of Judaism as responsible for the patriarchal moral that enabled the Holocaust, also expressed in the public sphere in Germany and Sweden
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A meditation on the similarities and differences of the camera and the human eye
Konst som resurs i vÄrden : En forskningsstudie om hur Region SkÄnes konstsamling kan tillgÀngliggöras för patienter, personal och besökare
Virtualiteter : sex essÀer
Sex forskare frÄn olika humanistiska discipliner skriver varsin essÀ kring temat virtualitet
Pharmacophore and receptor models for neurokinin receptors
Three neurokinin (NK) antagonist pharmacophore models (Models 1â3) accounting for hydrogen bonding groups in the `head' and `tail' of NK receptor ligands have been developed by use of a new procedure for treatment of hydrogen bonds during superimposition. Instead of modelling the hydrogen bond acceptor vector in the strict direction of the lone pair, an angle is allowed between the hydrogen bond acceptor direction and the ideal lone pair direction. This approach adds flexibility to hydrogen bond directions and produces more realistic RMS values. By using this approach, two novel pharmacophore models were derived (Models 2 and 3) and a hydrogen bond acceptor was added to a previously published NK2 pharmacophore model [Poulsen et al., J. Comput.-Aided Mol. Design, 16 (2002) 273] (Model 1). Model 2 as well as Model 3 are described by seven pharmacophore elements: three hydrophobic groups, three hydrogen bond acceptors and a hydrogen bond donor. Model 1 contains the same hydrophobic groups and hydrogen bond donor as Models 2 and 3, but only one hydrogen bond acceptor. The hydrogen bond acceptors and donor are represented as vectors. Two of the hydrophobic groups are always aromatic rings whereas the other hydrophobic group can be either aromatic or aliphatic. In Model 1 the antagonists bind in an extended conformation with two aromatic rings in a parallel displaced and tilted conformation. Model 2 has the same two aromatic rings in a parallel displaced conformation whereas Model 3 has the rings in an edge to face conformation. The pharmacophore models were evaluated using both a structure (NK receptor homology models) and a ligand based approach. By use of exhaustive conformational analysis (MMFFs force field and the GB/SA hydration model) and least-squares molecular superimposition studies, 21 non-peptide antagonists from several structurally diverse classes were fitted to the pharmacophore models. More antagonists could be fitted to Model 2 with a low RMS and a low conformational energy penalty than to Models 1 and 3. Pharmacophore Model 2 was also able to explain the NK1, NK2 and NK3 subtype selectivity of the compounds fitted to the model. Three NK 7TM receptor models were constructed, one for each receptor subtype. The location of the antagonist binding site in the three NK receptor models is identical. Compounds fitted to pharmacophore Model 2 could be docked into the NK1, NK2 and NK3 receptor models after adjustment of the conformation of the flexible linker connecting the head and tail. Models 1 and 3 are not compatible with the receptor models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42969/1/10822_2004_Article_5257316.pd
Forum för humanistisk-samhÀllsvetenskaplig hÀlsoforskning: Forskarkonferens kring temat Program och praktik
Med temat program och praktik vill vi sÀrskilt uppmana forskare att reflektera över vad som sÀgs och vad som görs inom hÀlso-, medicin- och sjukdomsrelaterade verksamheter, sÄvÀl i nutid som i det förflutna. Med program avses till exempel vÄrdpolitiska uttalanden och viljeyttringar av olika slag, beskrivningar eller bilder av hur t.ex. vÄrd och omhÀndertagande bör vara beskaffad, lÀroböckers beskrivningar av önskvÀrda metoder, vÄrdformer, omhÀndertaganden, ingrepp etc., eller andra sorters vÀgledande utsagor, bl.a. i massmedia, som anger hur nÄgot bör vara beskaffat, ska utföras eller pÄ annat sÀtt riktas mot en önskvÀrd omsÀttning i handling. Med praktik menas t.ex. handlingar, handgrepp och genomförande, tysta eller fotade i nÄgot slags program. HÀr ingÄr ocksÄ upplevda och beskrivna relationer mellan t.ex. vÄrdtagare, klient eller kund och olika vÄrdgivare eller producenter av vÄrd, behandling och omhÀndertagande eller andra aktiviteter, rum eller materiella alt. immateriella produkter inom medicin- och hÀlsofÀltet. Konferensen vill gÀrna att deltagarna reflekterar över dessa tvÄ begrepp, vart och ett eller i relation till varandra i empiriskt, metodologiskt, kÀllkritiskt eller annat avseende. Konferensen vÀlkomnar ocksÄ bidrag om de epistemologiska, etiska och representationsteoretiska perspektiv och paradigm som ligger bakom, uttrycks genom eller utesluts frÄn sÄdana program och praktiker som angivits ovan
Investigation of D1 ReceptorâAgonist Interactions and D1/D2 Agonist Selectivity Using a Combination of Pharmacophore and Receptor Homology Modeling
The aim of this study was to use a combined structure and pharmacophore modeling approach to extract information regarding dopamine D1 receptor agonism and D1/D2 agonist selectivity. A 3D structure model of the D1 receptor in its agonist-bound state was constructed with a full D1 agonist present in the binding site. Two different binding modes were identified using (+)-doxanthrine or SKF89626 in the modeling procedure. The 3D model was further compared with a selective D1 agonist pharmacophore model. The pharmacophore feature arrangement was found to be in good agreement with the binding site composition of the receptor model, but the excluded volumes did not fully reflect the shape of the agonist binding pocket. A new receptor-based pharmacophore model was developed with forbidden volumes centered on atom positions of amino acids in the binding site. The new pharmacophore model showed a similar ability to discriminate as the previous model. A comparison of the 3D structures and pharmacophore models of D1 and D2 receptors revealed differences in shape and ligand-interacting features that determine selectivity of D1 and D2 receptor agonists. A hydrogen bond pharmacophoric feature (Ser-TM5) was shown to contribute most to the selectivity. Non-conserved residues in the binding pocket that strongly contribute to D1/D2 receptor agonist selectivity were also identified; those were Ser/Cys3.36, Tyr/Phe5.38, Ser/Tyr5.41, and Asn/His6.55 in the transmembrane (TM) helix region, together with Ser/Ile and Leu/Asn in the second extracellular loop (EC2). This work provides useful information for the design of new selective D1 and D2 agonists. The combined receptor structure and pharmacophore modeling approach is considered to be general, and could therefore be applied to other ligandâprotein interactions for which experimental information is limited
Investigation of D2 ReceptorâAgonist Interactions Using a Combination of Pharmacophore and Receptor Homology Modeling
A combined modeling approach was used to identify structural factors that underlie the structureâactivity relationships (SARs) of full dopamine D2 receptor agonists and structurally similar inactive compounds. A 3D structural model of the dopamine D2 receptor was constructed, with the agonist (â)-(R)-2-OH-NPA present in the binding site during the modeling procedure. The 3D model was evaluated and compared with our previously published D2 agonist pharmacophore model. The comparison revealed an inconsistency between the projected hydrogen bonding feature (Ser-TM5) in the pharmacophore model and the TM5 region in the structure model. A new refined pharmacophore model was developed, guided by the shape of the binding site in the receptor model and with less emphasis on TM5 interactions. The combination of receptor and pharmacophore modeling also identified the importance of His3936.55 for agonist binding. This convergent 3D pharmacophore and protein structure modeling strategy is considered to be general and can be highly useful in less well-characterized systems to explore ligandâreceptor interactions. The strategy has the potential to identify weaknesses in the individual models and thereby provides an opportunity to improve the discriminating predictivity of both pharmacophore searches and structure-based virtual screens
NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy
Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions
Young people's understanding of European values: enhancing abilities, supporting participation and voice
This report is prepared as part of the Jean Monnet Network on Citizenship Education in the Context of European Values. It investigates: the knowledge of young people in European countries about civil society, its principles, citizenship, European values and the European Union; and the citizenship experiences and young peopleâs attitudes to European values and institutions, their willingness to participate in societal life and spread democratic ideas, Europeanism and global responsibility.
Understanding values has always been important. In a time when we are exposed to so many different explanations and commentaries, when social media allow and almost require instantaneous responses, that seem to have to be short, pithy, emphatic. Opinions appear as sharper, less nuanced, insistent. Conspiracy theories can become magnified, imperative and divisive. Young people in particular need to develop the resilience to resist the subversion of values, and have, in some senses, fewer resources and experiences to do so. Yet many of them can do this, and can display depths of understanding and tolerances of diversity.
Presentation of the analysis:
A: The demographic characteristics of the survey population.
This gives a short description of the data set: the countries surveyed, the distribution of ages and gender, the population of the locations, and parental occupations
B: A pattern of rights.
This section provides an overview of how young people referred to values across Europe as a whole. The intensity of discussions is analysed, and the number of overall individual references are given, contrasting these with the number of individual young people who made multiple references to the same value.
C The European values in depth.
The first level of detailed analysis is of the value. Each is introduced in turn, and for each there is
âą an overview of the value in the current European context: its source in the Convention and the Charter, and its development and contemporary meaning;
âą an analysis of how young people discussed the value â
âą differences in different Regions of Europe, and
âą differences in the characteristic descriptions, by timing, location, and type of othering (described in statistics and by illustrative quotations of remarks by young people)
âą a discussion of the implications of this for pedagogic practice about furthering the understanding of the specific value.
D An analysis of regional and other factors.
E Teaching issues.
We draw together the implications of the analysis for educating young people about understanding these values
F Conclusions and recommendations.
We conclude by summarising our principal conclusions, and making recommendations at teacher/lecturer, school/college, state and European level
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