| 1. |
- Andersson, Erik, et al.
(författare)
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A Randomized Controlled Trial of Guided Internet-delivered Cognitive Behavioral Therapy for Erectile Dysfunction
- 2011
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Ingår i: Journal of Sexual Medicine. - : Wiley-Blackwell. - 1743-6095 .- 1743-6109. ; 8:10, s. 2800-2809
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Men with erectile dysfunction are often worried about their condition, have interpersonal difficulties, and have a reduced quality of life. Internet-delivered cognitive behavior therapy (ICBT) has been shown effective for a number of health problems but evidence is limited concerning the treatment of erectile dysfunction. less thanbrgreater than less thanbrgreater thanAim. The study investigated the effects of ICBT for erectile dysfunction. less thanbrgreater than less thanbrgreater thanMethods. Seventy-eight men were included in the study and randomized to either ICBT or to a control group, which was an online discussion group. Treatment consisted of a 7-week Web-based program with e-mail-based therapist support. Each therapist spent an average of 55 minutes per participant. less thanbrgreater than less thanbrgreater thanMain Outcome Measure. The International Index of Erectile Functioning five-item version was administered via the telephone at pretreatment, post-treatment, and 6 months after receiving ICBT. less thanbrgreater than less thanbrgreater thanResults. At post-treatment, the treatment group had significantly greater improvements with regard to erectile performance compared with the control group. Between-group differences at post-treatment were small (d = 0.1), but increased at the 6-month follow-up (d = 0.88). less thanbrgreater than less thanbrgreater thanConclusions. This study provides support for the use of ICBT as a possible treatment format for erectile dysfunction.
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| 2. |
- Barlow, Nicholas, et al.
(författare)
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Macrocyclic Peptidomimetics as Inhibitors of Insulin-Regulated Aminopeptidase (IRAP)
- 2020
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Ingår i: RSC Medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 11:2, s. 234-244
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Tidskriftsartikel (refereegranskat)abstract
- Macrocyclic analogues of the linear hexapeptide, angiotensin IV (AngIV) have proved to be potent inhibitors of insulin-regulated aminopeptidase (IRAP, oxytocinase, EC 3.4.11.3). Along with higher affinity, macrocycles may also offer better metabolic stability, membrane permeability and selectivity, however predicting the outcome of particular cycle modifications is challenging. Here we describe the development of a series of macrocyclic IRAP inhibitors with either disulphide, olefin metathesis or lactam bridges and variations of ring size and other functionality. The binding mode of these compounds is proposed based on molecular dynamics analysis. Estimation of binding affinities (∆G) and relative binding free energies (∆∆G) with the linear interaction energy (LIE) method and free energy perturbation (FEP) method showed good general agreement with the observed inhibitory potency. Experimental and calculated data highlight the cumulative importance of an intact N-terminal peptide, the specific nature of the macrocycle, the phenolic oxygen and the C-terminal functionality.
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| 3. |
- Hallberg, Jonas, et al.
(författare)
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Towards second-generation smart card-based authentication in health information systems : the secure server model.
- 2001
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Ingår i: Medinfo. - 1569-6332. ; 10:Pt 2, s. 1257-1261
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Tidskriftsartikel (refereegranskat)abstract
- Conventional smart card-based authentication systems used in health care alleviate some of the security issues in user and system authentication. Existing models still do not cover all security aspects. To enable new protective measures to be developed, an extended model of the authentication process is presented. This model includes a new entity referred to as secure server. Assuming a secure server, a method where the smart card is aware of the status of the terminal integrity verification becomes feasible. The card can then act upon this knowledge and restrict the exposure of sensitive information to the terminal as required in order to minimize the risks. The secure server model can be used to illuminate the weaknesses of current approaches and the need for extensions which alleviate the resulting risks.
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| 4. |
- Hallberg, Mathias, 1971-, et al.
(författare)
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Angiotensin Peptides as AT2 Receptor Agonists
- 2017
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Ingår i: Current protein and peptide science. - : Bentham Science Publishers Ltd.. - 1389-2037 .- 1875-5550. ; 18:8, s. 809-818
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Forskningsöversikt (refereegranskat)abstract
- In 2004, the first nonpeptide selective angiotensin II type 2 receptor (AT2R) agonist was reported. This nonpeptide (C21), which, exerts anti-inflammatory and antifibrotic actions in vivo, has been extensively explored and is currently in clinical trials. Subsequently, a large number of related drug-like AT2R agonists have been disclosed. Reviews that summarize known structure-activity relationships (SAR) of nonpeptide AT2R agonists have recently appeared in the literature; however, very few reviews discuss the role of angiotensin peptides as AT2R agonists. Furthermore, to date, there have been no reports focusing on the medicinal chemistry perspective of peptide AT2R agonists. In the present review, reports on linear and conformationally constrained Ang II analogues, with a focus on AT2R selective ligands that are proven to act as agonists at the AT2 receptor are summarized. The impact of truncations and macrocyclizations of Ang II analogues and of incorporation of scaffolds that mimic secondary structures into Ang II related peptides is highlighted. A survey of the efforts to transform the nonselective octapeptide Ang II to more drug-like selective AT2R agonists is presented. The relationship between the structures of the AT2R agonists and their affinity to the AT2R is briefly discussed and common pharmacophore elements of AT2R selective Ang II peptide analogues and selective nonpeptide AT2R agonists are compared.
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| 5. |
- Reddy Vanga, Sudarsana, et al.
(författare)
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Structural Basis of Inhibition of Human Insulin-Regulated Aminopeptidase (IRAP) by Aryl Sulfonamides
- 2018
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Ingår i: ACS Omega. - : AMER CHEMICAL SOC. - 2470-1343. ; 3:4, s. 4509-4521
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Tidskriftsartikel (refereegranskat)abstract
- The insulin-regulated aminopeptidase (IRAP) is a membrane-bound zinc metallopeptidase with many important regulatory functions. It has been demonstrated that inhibition of IRAP by angiotensin IV (Ang IV) and other peptides, as well as more druglike inhibitors, improves cognition in several rodent models. We recently reported a series of aryl sulfonamides as small-molecule IRAP inhibitors and a promising scaffold for pharmacological intervention. We have now expanded with a number of derivatives, report their stability in liver microsomes, and characterize the activity of the whole series in a new assay performed on recombinant human IRAP. Several compounds, such as the new fluorinated derivative 29, present submicromolar affinity and high metabolic stability. Starting from the two binding modes previously proposed for the sulfonamide scaffold, we systematically performed molecular dynamics simulations and binding affinity estimation with the linear interaction energy method for the full compound series. The significant agreement with experimental affinities suggests one of the binding modes, which was further confirmed by the excellent correlation for binding affinity differences between the selected pair of compounds obtained by rigorous free energy perturbation calculations. The new experimental data and the computationally derived structure-activity relationship of the sulfonamide series provide valuable information for further lead optimization of novel IRAP inhibitors.
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| 6. |
- Andersson, Dennis, et al.
(författare)
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Exploratory Sequential Data Analysis of a Cyber Defence Exercise
- 2011
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Ingår i: Proceedings of the International Defense and Homeland Security Simulation Workshop (DHSS) 2011. - : Caltek s.r.l.. ; , s. 27-32
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Konferensbidrag (refereegranskat)abstract
- Baltic Cyber Shield 2010 (BCS), a multi-national civilmilitary cyber defence exercise (CDX), aimed to improve the capability of performing a CDX and investigate how IT attacks and defence of critical infrastructure can be studied. The exercise resulted in a massive dataset to be analyzed and many lessons learned in planning and executing a large-scale multinational CDX. A reconstruction & exploration (R&E) approach was used to capture incidents such as attacks and defensive counter-measures during the exercise. This paper introduces the usage of R&E combined with exploratory sequential data analysis (ESDA) and discusses benefits and limitations of using these methods for analyzing multi-national cyber defence exercises. Using ESDA we were able to generate statistical data on attacks from BCS, such as number of reported attacks by the attackers and the defenders on different type of services. Initial results from these explorations will be analyzed and discussed.
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| 7. |
- Bengtsson, Stefan L., 1978-, et al.
(författare)
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Immersion and ritual in Object-Oriented Didactics and Sensuous Learning
- 2021
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Konferensbidrag (refereegranskat)abstract
- Environmental and sustainability education (ESE) that wants to address existing environmental and sustainability challenges is basically critical, that is if it wants to change through education and learning contemporary ways of being in the world (cf Hart & Nolan 1999). This change is often framed in terms of transformation, where something is changed into something else, yet, that change of that something (van Poeck, König & Wals 2018; Lundegård & Wickman 2009), for example the process, is partially a retainment of something (Mezirow 2000). For example, it is still the social, learner, knowledge or custom that was transformed, highlighting its continuity. This focus on retainment and continuity has recently been challenged through the concept of transgressive learning (e.g. Lotz-Sisitka et al. 2015), where the focus is rather of abandonment and discontinuity of ways of being through learning (Bengtsson 2019). Transgression is by the presenting authors seen as a means of potentially subverting the reproduction of coloniality of Western thought (Chaves et al. 2015), pertaining anthropocentrism (Kopnina 2012) and capitalism/neoliberalism (Hursh, Henderson & Greenwood 2015) in and through ESE.This paper aims to contribute to a theoretical and practical development of didactical means for transgression, particularly by providing alternative pedagogical and didactical entry points for understanding learning as not primarily rational but by highlighting aesthetics and the sensuous learner. In this effort, the paper combines the theoretical outlooks of sensuous learning (Hallberg 2015, 2017, 2018) and object-oriented learning (Bengtsson 2018) in order to develop further a object-oriented didactics of ESE (Bengtsson, Lysgaard, Jordt-Joergensen 2019). The effort is here to provide theoretical and practical means for engaging with withdrawn and uncanny objects of education through sensuous learning. Drawing on the initial considerations of object-oriented didactics (Bengtsson, Lysgaard, Jordt-Joergensen 2019) holding that the real object of education is not congruent with the content of education and that the educative substance (Bildungsgehalt) of the object of education is indeterminate (located in an open future) and infinite (given that the qualities of the object of education are always larger than any attempts to reduce it to a content of education), sensuous learning is here to provide entry points for understanding how the indeterminate and infinite qualities of the object of education can be rendered sensible.The paper will address the following research questions:How can didactic intervention engage with the surplus of the educative substance (Bildungssubstanz) of the object of education? (Practical question)How can senouse learning sensitize the learner and teacher to the indeterminate potential of the educative substance of the object as that substance is according to the axioms of object-oriented learning located in a future still to come? (Practical and theoretical question)How can we understand the contribution of object-oriented didactics to the production of a Sensuous Society (Hallberg 2017) and Ecological Bildung (Bengtsson, Lysgaard, Jordt-Joergensen 2019). How is this link actualized in didactical intervention and in learning? (Theoretical question)MethodThe paper represents a theoretical development of existing conceptions of a) transgressive learning, b) dark pedagogy and c) sensuous learning. In particular, it induces insights and perspectives from theory and methods in performance art and arts-based research into pedagogical and didactical research. Findings and models developed in Sisters Academy ́s school takeovers and boarding schools formats offer rich and innovative approaches to facilitating sensuous learning that are taken as inspiration for the development of object-oriented didactics. The Takeover format is meant to immerse the entire school into the sensuous and poetic and thus 'leave no one behind' in an attempt to democratize' the aesthetic. It is this all-embracing immersion that allows such democratization. However, the modes of participation can largely differ and is never forced and thus based on individual navigation within the overall educational experiment. This paper will in particular focus on two aspects of sensuous learning: immersion and the ritual. By engaging with approaches and models to immersion and the ritual, this paper is to explore in an open and creative manner how immersion and the ritual could be integrated into didactical interventions. Immersion, refers here also to the possibility of an immersion of the whole sensory spectrum, where the ritual might address different senses. The ritual is in this sense open and not already focused on particular senses or what is to be sensed.Expected OutcomesBy rendering partially sensible the object of education through didactic intervention, sensuous learning is resensitizing the learner to what in sensuous learning is called “Poetic Self” (Hallberg 2017, 2018) and in dark pedagogy is called “Future Self of Essence” (Bengtsson 2019b). Accordingly, educational substance (Bildungsgehalt) of the object of education to be engaged with in sensuous learning is not strictly speaking that of the object or “for me”. Instead, sensuous learning can be seen to lead to a transgression where the learner loses or ruins “its self”/”itself” (Bataille 1988). The poetic self is in this sense not engaging in the process of autopoiesis, i.e. self-reproduction and self-maintenance, finds itself caught up in “some thing”/”something”. The openness of the ritual and the process of object-oriented didactic gesture points here also the uncanny/unhomely (unheimlich) aspect of learning that is resensitizing to the Poetic Self/Future Self. The uncanniness refers here to a conception of self that is not strictly “in place”, but alienated and hence a self sensing self that is both itself and not-itself. Accordingly, the paper is to provide a reconception of understanding the positionality and limit of the self at the core of our understanding of learning. The combination of sensuous learning and object oriented didactics is in the context above to provide ecologically oriented entry points for ESE and for developing further transgressive learning.
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| 8. |
- Borhade, Sanjay R, et al.
(författare)
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Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Arylsulfonamides
- 2014
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 3:6, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- The inhibition of insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) by angiotenesin IV is known to improve memory and learning in rats. Screening 10 500 low-molecular-weight compounds in an enzyme inhibition assay with IRAP from Chinese Hamster Ovary (CHO) cells provided an arylsulfonamide (N-(3-(1H-tetrazol-5-yl)phenyl)-4-bromo-5-chlorothiophene-2-sulfonamide), comprising a tetrazole in the meta position of the aromatic ring, as a hit. Analogues of this hit were synthesized, and their inhibitory capacities were determined. A small structure-activity relationship study revealed that the sulfonamide function and the tetrazole ring are crucial for IRAP inhibition. The inhibitors exhibited a moderate inhibitory potency with an IC50=1.1±0.5 μm for the best inhibitor in the series. Further optimization of this new class of IRAP inhibitors is required to make them attractive as research tools and as potential cognitive enhancers.
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| 9. |
- Bäck, Marcus, et al.
(författare)
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Design, synthesis and SAR of potent statine-based BACE-1 inhibitors : Exploration of P1 phenoxy and benzyloxy residues
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:21, s. 9471-9486
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Tidskriftsartikel (refereegranskat)abstract
- Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modi. cation introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.
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| 10. |
- Chatzittofis, Andreas, et al.
(författare)
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HPA axis dysregulation in men with hypersexual disorder
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 63, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5 mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels >= 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Asberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.
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