| 1. |
- Andersson, H.O., et al.
(författare)
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Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
- 2003
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
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| 2. |
- Andersson, H O
(författare)
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Relevant elements of laboratory competence
- 1998
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Ingår i: Accreditation and Quality Assurance. - 0949-1775 .- 1432-0517. ; 3:7, s. 281-283
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
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| 5. |
- Andersson, L. Mauritz, et al.
(författare)
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Nonadiabatic effects in the photoelectron spectra of HCl and DCl. II. Theory
- 2002
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 65:1
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Tidskriftsartikel (refereegranskat)abstract
- The vibrationally resolved photoelectron spectra of HCl and DCl in the 25-28 eV region were computed using a time-dependent approach for the nuclear dynamics. The spectral features cannot be understood without including a nonadiabatic coupling between the dissociative 3 (2)Sigma(+) state and the bound 4 (2)Sigma(+) state in the adiabatic picture. Alternatively, in the diabatic picture a dissociative two-hole-one-particle state interacts with a bound one-hole state. The molecular system is of intermediate coupling strength, i.e., it cannot be described by a single potential-energy curve. The interaction between a bound and a dissociative state leads to Fano resonances superimposed on a broad back-round, as observed in the experimental spectra [Burmeister et al., Phys. Rev. A 65, 012704 (2001)]. From modified potential-energy curves, all features of the experimental spectra, including Fano resonance parameters and lifetimes, were reproduced. From the simulations we observe that two additional peaks in the experimental DCl spectra should appear if the resolution were to be enhanced to around 10 meV.
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| 6. |
- Andersson, L. Mauritz, et al.
(författare)
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Properties of a discretized coherent state representation and the relation to Gabor analysis
- 2002
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Ingår i: Journal of Physics A. - : IOP Publishing. - 0305-4470 .- 1361-6447. ; 35:36, s. 7787-7801
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Tidskriftsartikel (refereegranskat)abstract
- Properties of a discretized coherent state representation (DCSR) and its connection to Gabor frame analysis are discussed. The DCSR approach was recently shown (Andersson L M 2001 J. Chem. Phys. 115 1158) to yield a practical computational scheme for quantum dynamics, and an iterative scheme for finding the identity operator was proposed. In the present work, we suggest a proof of fast convergence of the iterative scheme for computing the canonical dual to any given countable frame in a Hilbert space. The method of frames is concerned with the use of a non-orthogonal, over-complete set of functions for expansion of an arbitrary function. We also introduce the concept of 'representations of the identity operator' and show how to expand arbitrary vectors using the frame elements, without explicit diagonalization to an orthonormal basis. Numerical examples that illustrate the method are shown.
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| 7. |
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| 8. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
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Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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| 9. |
- Burmeister, F., et al.
(författare)
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A study of the inner-valence ionization region in HCl and DCl
- 2004
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 37:6, s. 1173-1183
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Tidskriftsartikel (refereegranskat)abstract
- An in-depth photoionization study of the inner-valence electrons in HCl and DCl has been performed using synchrotron radiation. A series of photoelectron spectra of HCl were obtained at a resolution of 23 meV over the binding energy range 25-30.5 eV at various excitation energies and at two different electron collection angles relative to the plane of polarization of the undulator radiation. In addition, photoelectron spectra of DCl were recorded at two different excitation energies. These spectra were compared directly with the threshold photoelectron spectra of HCl and DCl that were recorded previously under similar resolution conditions (similar to30 meV). This comparative study reveals new information on the nature of the numerous band systems observed in this binding energy region. In addition, we present the experimental confirmation of the theoretical prediction given by Andersson et al (2001 Phys. Rev. A 65 012705) that a vibrational progression showing interference structure would appear in the main inner-valence ionization band in the photoelectron spectrum of DCl at a resolution of 10 meV.
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| 10. |
- Demichelis, F., et al.
(författare)
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TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort
- 2007
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Ingår i: Oncogene. - Basingstoke : Nature Publ. Group. - 0950-9232 .- 1476-5594. ; 26:31, s. 4596-4599
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.
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| 11. |
- Johansson, M. J., et al.
(författare)
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Modular asymmetric synthesis of P-chirogenic beta-amino phosphine boranes
- 2008
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 73:12, s. 4458-4463
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Tidskriftsartikel (refereegranskat)abstract
- (Chemical Equation Presented) A short concise route to β- aminophosphine boranes is presented via the desymmetrization of prochiral phosphine boranes, forming P-chirogenic aldehydes that are rapidly transformed to the target compounds employing reductive amination under microwave irradiation. This sequence provides a modular route to P-chirogenic P,N ligands, and in addition, the intermediate aldehydes are versatile P-chiral building blocks for ligand design in general. An alternative pathway via the corresponding α-carboxyphosphines is also described. The ligands were subsequently evalutated in the asymmetric conjugate addition of diethylzinc to trans-β-nitrostyrene. © 2008 American Chemical Society.
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| 12. |
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| 13. |
- Ljungdahl, N., et al.
(författare)
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The development of an asymmetric Nicholas reaction using chiral phosphoramidite ligands
- 2008
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Ingår i: Synlett. - : Georg Thieme Verlag KG. - 1437-2096 .- 0936-5214. ; :3, s. 394-398
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Tidskriftsartikel (refereegranskat)abstract
- An asymmetric version of the Nicholas reaction involving the use of chiral phosphoramidite ligands has been developed. Treatment of a cobalt carbonyl complexed propargylic alcohol with two equivalents of the chiral ligand, followed by reaction with a silyl enol ether in the presence of a Lewis acid, afforded, after decomplexation, the desired product in up to 74% ee for the carbon-carbon bond forming step. © Georg Thieme Verlag Stuttgart.
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| 14. |
- Penney, K. L., et al.
(författare)
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mRNA expression signature of Gleason grade predicts lethal prostate cancer
- 2011
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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| 15. |
- Richter, H. O, et al.
(författare)
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Neuroanatomical correlates of voluntary inhibition of accommodation/vergence under monocular open-loop viewing conditions.
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 21:11, s. 3077-3088
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work is to identify human neural circuits involved in inhibition of accommodation/vergence by contrasting the cortical functions subservient to negative voluntary accommodation/vergence (NVA) with those evoked by active fixation in darkness (FIX). Five subjects with normal corrected acuity were studied using positron emission tomography and the H O bolus technique. The dominant right eye viewed a laser speckle pattern (633 nm) whose direction and velocity of motion were determined by the refractive state of the eye. The speckle pattern was presented at a distance of 1.8 m (0.55 D). The non-dominant eye was patched. Subjects performed two tasks counterbalanced for order effects: (i) attempted fixation on the remembered target in darkness with the dominant eye open and ‘fixating’; and (ii) voluntary reduction of the laser speckle flow during each alternate 20-s epoch when a convex +2.0 D lens was placed in front of the right eye causing the speckle pattern to move downwards at 3 °/s. Comparison of the condition of NVA with the condition of FIX indicated widespread occipital activation. Decreases in absolute regional cerebral blood flow occurred in the superior parietal cortex (BA 5), frontal cortex (BA 8 and 10) and within the postcentral/precentral gyrus (BA 1/2/3/4) bilaterally where deactivation clusters eclipsed the presumed neck and shoulder areas. Negative accommodation/vergence appears to be driven by a reduction of parasympathetic tone, and has the effect of shutting down brain regions known to be involved in regulating visual search as well as a centrally controlled eye–head–neck–shoulder motor programme responsible for posturing gaze.
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| 16. |
- Rocha, H., et al.
(författare)
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SooGREEN : Service-oriented optimization of green mobile networks
- 2017
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Ingår i: 2017 15th International Symposium on Modeling and Optimization in Mobile, Ad Hoc, and Wireless Networks, WiOpt 2017. - : Institute of Electrical and Electronics Engineers (IEEE). - 9783901882906
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Konferensbidrag (refereegranskat)abstract
- Today, mobile networks are witnessing an exponential growth of traffic volumes, linked to new services, especially for smart cities and smart-grid. The European Celtic-Plus SooGREEN project, started mid 2015, is targeting to reduce the energy consumption of the services in different mobile architectures in interaction with smart-grid. So GREEN is focused on the services energy consumption modelling and measurement, the dynamic optimization of the mobile access network and of the content delivery, the design of an Energy Efficient Virtualized and Centralized Radio Access Network (RAN), and the bi-directional interaction of the mobile network with the smart-grid. This paper presents insight into the project after its first year, and discusses research trends in green communication networks for the future.
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