| 31. |
- Shipilin, Mikhail, et al.
(författare)
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In Situ Surface-Sensitive Investigation of Multiple Carbon Phases on Fe(110) in the Fischer-Tropsch Synthesis
- 2022
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435 .- 2155-5435. ; 12:13, s. 7609-7621
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Tidskriftsartikel (refereegranskat)abstract
- Carbide formation on iron-based catalysts is an integral and, arguably, the most important part of the Fischer–Tropsch synthesis process, converting CO and H2 into synthetic fuels and numerous valuable chemicals. Here, we report an in situ surface-sensitive study of the effect of pressure, temperature, time, and gas feed composition on the growth dynamics of two distinct iron–carbon phases with the octahedral and trigonal prismatic coordination of carbon sites on an Fe(110) single crystal acting as a model catalyst. Using a combination of state-of-the-art X-ray photoelectron spectroscopy at an unprecedentedly high pressure, high-energy surface X-ray diffraction, mass spectrometry, and theoretical calculations, we reveal the details of iron surface carburization and product formation under semirealistic conditions. We provide a detailed insight into the state of the catalyst’s surface in relation to the reaction.
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| 32. |
- Ashton, Susan, et al.
(författare)
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Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:325
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.
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| 33. |
- Axelsson, Emma L., et al.
(författare)
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The role of bodies in infants’ categorical representations of humans and non-human animals
- 2018
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Ingår i: Infant and Child Development. - : John Wiley & Sons. - 1522-7227 .- 1522-7219. ; 27:6
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether bodies are useful cues in infants' category formations, 7-month-old infants were familiarized to images of humans or non-human animals followed by test pairs comprising a familiar category image and a hybrid image with a novel category body. Infants familiarized to humans did not demonstrate a novelty preference for hybrid stimuli with non-human animal bodies. Infants familiarized with non-human animals demonstrated a novelty preference for hybrid stimuli with human bodies, suggesting that there is an asymmetry in infants' category formations of bodies. Compared with infants familiarized to non-human animals, the infants familiarized to humans had a higher proportional fixation count to bodies during familiarization, but the lack of preference for novel category bodies at test suggests that 7-month-old infants' representations of the features of human bodies are likely still developing and they are more likely to form a summary-based categorical representation of non-human animals.
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| 34. |
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| 35. |
- Castell, A, et al.
(författare)
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A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 10064-
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Tidskriftsartikel (refereegranskat)abstract
- MYC is a key player in tumor development, but unfortunately no specific MYC-targeting drugs are clinically available. MYC is strictly dependent on heterodimerization with MAX for transcription activation. Aiming at targeting this interaction, we identified MYCMI-6 in a cell-based protein interaction screen for small inhibitory molecules. MYCMI-6 exhibits strong selective inhibition of MYC:MAX interaction in cells and in vitro at single-digit micromolar concentrations, as validated by split Gaussia luciferase, in situ proximity ligation, microscale thermophoresis and surface plasmon resonance (SPR) assays. Further, MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a KD of 1.6 ± 0.5 μM as demonstrated by SPR. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner with IC50 concentrations as low as 0.5 μM, while sparing normal cells. The response to MYCMI-6 correlates with MYC expression based on data from 60 human tumor cell lines and is abrogated by MYC depletion. Further, it inhibits MYC:MAX interaction, reduces proliferation and induces massive apoptosis in tumor tissue from a MYC-driven xenograft tumor model without severe side effects. Since MYCMI-6 does not affect MYC expression, it is a unique molecular tool to specifically target MYC:MAX pharmacologically and it has good potential for drug development.
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| 36. |
- Cohen, T. J., et al.
(författare)
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A pluvial episode identified in arid Australia during the Medieval Climatic Anomaly
- 2012
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 56, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- Optically stimulated luminescence (OSL) ages from a relict shoreline on Lake Callabonna record a major pluvial episode in southern central Australia between 1050 70 and 1100 60 Common Era (CE), within the Medieval Climatic Anomaly (MCA). During this pluvial interval Lake Callabonna filled to 10e12 times the volume of the largest historical filling (1974) and reached maximum depths of 4e5 m, compared to the 0.5e1.0 m achieved today. Until now there has been no direct evidence for the MCA in the arid interior of Australia. A multi-proxy, analogue-based atmospheric circulation reconstruction indicates that the pluvial episode was associated with an anomalous meridional atmospheric circulation pattern over the Southern extratropics, with high sea-level pressure ridges in the central Indian Ocean and Tasman Sea, and a trough extending from the Southern Ocean into central Australia. A major decline in the mobility of the Australian aboriginal hunter-gatherer coincides with this MCA period, in southern central Australia.
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| 37. |
- Cosgrave, Jan, et al.
(författare)
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Do environmental risk factors for the development of psychosis distribute differently across dimensionally assessed psychotic experiences?
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g. childhood abuse) are associated with the development of PE. However, which specific exposures convey risk for each type or dimension of PE has rarely been explored. The Oxford Wellbeing Life and Sleep (OWLS) survey includes 22 environmental risk factors for psychosis and was designed to examine how environmental risks are associated with specific dimensions of PE. Multivariate logistic regression models were fit using these risk factors to predict six dimensions of PE (perceptual abnormalities, persecutory ideation, bizarre ideas, cognitive disorganisation, delusional mood and negative symptoms). Models were built using only 70% of the data, and then fit to the remaining data to assess their generalisability and quality. 1789 (27.2% men; mean age = 27.6; SD = 10.9) survey responses were analysed. The risk factors predictive of the most PE were anxiety, social withdrawal during childhood and trauma. Cannabis and depression predicted three dimensions with both predicting bizarre ideas and persecutory ideation. Psychological abuse and sleep quality each predicted two dimensions (persecutory ideation and delusional mood). Risk factors predicting one PE dimension were age (predicting cognitive disorganisation), physical abuse (bizarre ideas), bullying and gender (persecutory ideation); and circadian phase (delusional mood). These results lend support for a continuum of psychosis, suggesting environmental risks for psychotic disorders also increase the risk of assorted dimensions of PE. Furthermore, it advocates the use of dimensional approaches when examining environmental exposures for PE given that environmental risks distribute differently across dimensions.
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| 38. |
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| 39. |
- Fazel, S., et al.
(författare)
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Suicides by violent means in individuals taking SSRIs and other antidepressants : A postmortem study in Sweden, 1992-2004
- 2007
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Ingår i: Journal of Clinical Psychopharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0271-0749 .- 1533-712X. ; 27:5, s. 503-506
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Tidskriftsartikel (refereegranskat)abstract
- A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self-poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants.The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (?1 = 7.6, P < 0.01). We found no significant differences in the proportion of violent suicides in the SSRI group compared with the antidepressant-free group by sex or age band (15-24, 25-39, and over 40 years). When subdivided by gender and age-bands, we found specific groups with significantly lower proportions of violent suicides compared with the antidepressants-free group, including men aged 15-24 years. © 2007 Lippincott Williams & Wilkins, Inc.
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| 40. |
- Hales, Susie A., et al.
(författare)
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Imagery-Focused Cognitive Therapy (ImCT) for Mood Instability and Anxiety in a Small Sample of Patients with Bipolar Disorder : a Pilot Clinical Audit
- 2018
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Ingår i: Behavioural and Cognitive Psychotherapy. - : CAMBRIDGE UNIV PRESS. - 1352-4658 .- 1469-1833. ; 46:6, s. 706-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the global impact of bipolar disorder (BD), treatment success is limited. Challenges include syndromal and subsyndromal mood instability, comorbid anxiety, and uncertainty around mechanisms to target. The Oxford Mood Action Psychology Programme (OxMAPP) offered a novel approach within a cognitive behavioural framework, via mental imagery-focused cognitive therapy (ImCT). Aims: This clinical audit evaluated referral rates, clinical outcomes and patient satisfaction with the OxMAPP service. Method: Eleven outpatients with BD received ImCT in addition to standard psychiatric care. Mood data were collected weekly from 6 months pre-treatment to 6 months post-treatment via routine mood monitoring. Anxiety was measured weekly from start of treatment until 1 month post-treatment. Patient feedback was provided via questionnaire. Results: Referral and treatment uptake rates indicated acceptability to referrers and patients. From pre- to post-treatment, there was (i) a significant reduction in the duration of depressive episode relapses, and (ii) a non-significant trend towards a reduction in the number of episodes, with small to medium effect size. There was a large effect size for the reduction in weekly anxiety symptoms from assessment to 1 month follow-up. Patient feedback indicated high levels of satisfaction with ImCT, and underscored the importance of the mental imagery focus. Conclusions: This clinical audit provides preliminary evidence that ImCT can help improve depressive and anxiety symptoms in BD as part of integrated clinical care, with high patient satisfaction and acceptability. Formal assessment designs are needed to further test the feasibility and efficacy of the new ImCT treatment on anxiety and mood instability.
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